|
1
|
Urabe M, Ikezawa K, Seiki Y, Watsuji K, Kawamoto Y, Hirao T, Kai Y, Takada R, Yamai T, Mukai K, Nakabori T, Uehara H, Ohkawa K. Comparison of sedation with pentazocine or pethidine hydrochloride for endoscopic ultrasonography in outpatients: A single-center retrospective study. DEN OPEN 2025; 5:e70048. [PMID: 39741901 PMCID: PMC11687558 DOI: 10.1002/deo2.70048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 12/02/2024] [Accepted: 12/12/2024] [Indexed: 01/03/2025]
Abstract
Objectives Endoscopic ultrasonography (EUS) plays an important role in the diagnosis of pancreatobiliary diseases. However, an appropriate sedation method for EUS has not been established. Therefore, this study aimed to examine the safety and complications of sedation with pentazocine or pethidine hydrochloride for outpatient diagnostic EUS. Methods We retrospectively reviewed 1302 consecutive cases in our department that underwent outpatient diagnostic EUS between April 2019 and September 2021. Until June 2020, EUS was performed under sedation with midazolam and pentazocine (pentazocine group) in principle; after June 2020, sedation with midazolam and pethidine hydrochloride (pethidine hydrochloride group) was used. A cohort of patients with comparable backgrounds was identified using propensity score matching. Results A total of 486 cases were included in this study. Sedation-related adverse events during the endoscopic procedures were not significantly different between the groups. The median time spent in the recovery room after EUS was significantly shorter in the pethidine hydrochloride group than in the pentazocine group (69 versus vs. 77 min; p < 0.001). The frequency of nausea or vomiting after EUS was significantly lower in the pethidine hydrochloride group than in the pentazocine group (0% [0/486] vs. 6.2% [29/486]; p < 0.001). The frequency of readmission to the recovery room after discharge was significantly lower in the pethidine group than in the pentazocine group (0 [0%] vs. 18 [3.7%], respectively; p < 0.001). Conclusions The combination of midazolam and pethidine hydrochloride is a more favorable anesthetic than the combination of midazolam and pentazocine for diagnostic EUS in outpatients.
Collapse
Affiliation(s)
- Makiko Urabe
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Kenji Ikezawa
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Yusuke Seiki
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Ko Watsuji
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Yasuharu Kawamoto
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Takeru Hirao
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Yugo Kai
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Ryoji Takada
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Takuo Yamai
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Kaori Mukai
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Tasuku Nakabori
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Hiroyuki Uehara
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| | - Kazuyoshi Ohkawa
- Department of Hepatobiliary and Pancreatic OncologyOsaka International Cancer InstituteOsakaJapan
| |
Collapse
|
|
2
|
Huang L, Han Q, Zhao L, Wang Z, Dai G, Shi Y. Development and Validation of the Predictive and Prognostic ChemoResist Signature in Resected Pancreatic Ductal Adenocarcinoma: Multicohort Study. Ann Surg 2025; 281:632-644. [PMID: 39676652 DOI: 10.1097/sla.0000000000006610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2024]
Abstract
OBJECTIVE To develop and validate a signature to precisely predict prognosis in pancreatic ductal adenocarcinoma (PDAC) undergoing resection and adjuvant chemotherapy. BACKGROUND PDAC is largely heterogeneous and responds discrepantly to treatment. METHODS A total of 551 consecutive patients with PDAC from 3 different cohorts of tertiary centers were initially enrolled. Genetic events of the 4 most commonly mutated genes in PDAC and expressions of 12 PI3K/AKT/mammalian target of rapamycin (mTOR) pathway markers were examined. A 9-feature signature for the prediction of chemotherapy benefits was constructed in the training cohort using the least absolute shrinkage and selection operator Cox regression model and validated in 2 independent cohorts. RESULTS Utilizing the least absolute shrinkage and selection operator model, a predictive and prognostic signature, named ChemoResist, was established based on KRAS single nucleotide variant (SNV), phosphatase and tensin homologue (PTEN), and mTOR expressions, and 6 clinicopathologic features. Significant differences in survival were observed between high and low-ChemoResist patients receiving chemotherapy in both the training [median overall survival (OS), 17 vs 42 months, P < 0.001; median disease-free survival (DFS), 10 vs 23 months, P < 0.001] and validation cohorts (median OS, 18 vs 35 months, P = 0.034; median DFS, 11 vs 20 months, P = 0.028). The ChemoResist classifier also significantly differentiated patient survival in whole patients regardless of chemotherapy. Multivariable-adjusted analysis substantiated the ChemoResist signature as an independent predictive and prognostic factor. For predicting 2-year OS, the ChemoResist classifier had significantly higher areas under the curve than TNM stage (0.788 vs 0.636, P < 0.001), other clinicopathologic characteristics (0.505-0.668), and single molecular markers (0.507-0.591) in the training cohort. Furthermore, patients with low ChemoResist scores exhibited a more favorable response to adjuvant chemotherapy compared with those with high ChemoResist scores (hazard ratio for OS: training, 0.22 vs 0.57; validation, 0.26 vs 0.50; hazard ratio for DFS: training, 0.35 vs 0.54; validation, 0.18 vs 0.59). The ChemoResist signature was further validated in the total cohort undergoing R0 resection. CONCLUSIONS The ChemoResist signature could precisely predict survival in PDAC undergoing resection and chemotherapy, and its predictive value surpassed the TNM stage and other clinicopathologic factors. Moreover, the ChemoResist classifier could assist with identifying patients who would more likely benefit from adjuvant chemotherapy.
Collapse
Affiliation(s)
- Lei Huang
- Department of Gastroenterology, National Clinical Research Center for Digestive Diseases, Shanghai Institute of Pancreatic Diseases, The First Affiliated Hospital of Naval Medical University/Changhai Hospital, Naval Medical University, Shanghai, China
- Changhai Clinical Research Unit,National Key Laboratory of Immunity and Inflammation, The First Affiliated Hospital of Naval Medical University/Changhai Hospital, Naval Medical University, Shanghai, China
| | - Quanli Han
- Department of Medical Oncology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Liangchao Zhao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhikuan Wang
- Department of Medical Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Guanghai Dai
- Department of Medical Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yan Shi
- Department of General Surgery, Shanghai Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| |
Collapse
|
|
3
|
Stoop TF, Sugawara T, Oba A, Feld IM, van Roessel S, van Veldhuisen E, Wu YHA, Nishino J, Ali M, Alseidi A, Sauvanet A, Mirabella A, Sa Cunha A, Kokkola A, Groot Koerkamp B, Pietrasz D, Kleive D, Butturini G, Malleo G, van Laarhoven HWM, Frigerio I, Dembinski J, He J, Gagnière J, Kleeff J, Ramia JM, Roberts KJ, Labori KJ, Marino MV, Falconi M, B Mortensen M, Lesurtel M, Bonds M, Chatzizacharias N, Strobel O, Turrini O, Griffin O, Franklin O, Pfeiffer P, Schulick RD, Salvia R, de Wilde RF, Dokmak S, Rodriguez Franco S, Augustinus S, Burgdorf SK, Crippa S, Hackert T, Tarvainen T, Burns WR, Messersmith W, Wilmink JW, Burkhart RA, Del Chiaro M, Besselink MG. Adjuvant Chemotherapy After Resection of Localized Pancreatic Adenocarcinoma Following Preoperative FOLFIRINOX. JAMA Oncol 2025; 11:276-287. [PMID: 39847363 PMCID: PMC11926629 DOI: 10.1001/jamaoncol.2024.5917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2025]
Abstract
Importance The effect of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) chemotherapy on overall survival (OS) is unclear because current studies do not account for the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen. Objective To investigate the association of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX with OS, taking into account the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen. Design, Setting, and Participants This retrospective cohort study included patients with localized pancreatic adenocarcinoma treated with 2 to 11 cycles of preoperative (m)FOLFIRINOX followed by resection across 48 centers in 20 countries from 2010 to 2018. Patients who died within 3 months after surgery were excluded (landmark). Data were analyzed from February 1 to December 31, 2023. Exposures Preoperative (m)FOLFIRINOX chemotherapy followed by resection and eventually followed by adjuvant chemotherapy. Main Outcomes and Measures The primary outcome was OS, calculated from the 3-month landmark. Cox regression analysis, including interaction analyses, was performed to investigate the association of adjuvant chemotherapy with OS. Results Overall, 767 patients were included after resection of pancreatic adenocarcinoma (median [IQR] age, 62 [55-67] years; 404 [52.7%] male). Adjuvant chemotherapy was independently associated with prolonged OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87), confirmed by adjusted OS curves. The interaction analysis to assess estimated treatment effect across subgroups was not statistically significant. The forest plot and interaction test suggest that the association of adjuvant chemotherapy was lower among patients receiving 8 or more cycles of preoperative (m)FOLFIRINOX, those who had radiological response, and those with ypN0 disease. Compared to no adjuvant chemotherapy, both adjuvant (m)FOLFIRINOX (HR, 0.57; 95% CI, 0.40-0.80) and other multiagent adjuvant regimens (HR, 0.61; 95% CI, 0.41-0.92) were associated with prolonged OS, whereas single-agent adjuvant chemotherapy was not (HR, 0.75; 95% CI, 0.55-1.03). Conclusions and Relevance In this cohort study, adjuvant (m)FOLFIRINOX and other multiagent chemotherapy regimens were associated with improved OS following resection of localized pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX, whereas single-agent adjuvant chemotherapy was not. The impact of adjuvant chemotherapy on OS may be lower in subgroups such as patients with 8 or more preoperative cycles of (m)FOLFIRINOX, those having radiological response, and those with ypN0.
Collapse
Affiliation(s)
- Thomas F Stoop
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Toshitaka Sugawara
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Atsushi Oba
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Isabel M Feld
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Stijn van Roessel
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Eran van Veldhuisen
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Y H Andrew Wu
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland
| | - Jo Nishino
- Division of Bioinformatics, Research Institute National Cancer Center Japan, Tokyo, Japan
| | - Mahsoem Ali
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Adnan Alseidi
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Alain Sauvanet
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, Clichy, France
| | - Antonello Mirabella
- General Surgery Department, Azienda Ospedaliera, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
| | - Antonio Sa Cunha
- Department of Hepato-Biliary-Pancreatic Surgery, Liver Transplant Center, Université Paris-Sud, Université Paris-Saclay, Villejuif, France
| | - Arto Kokkola
- Department of Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Daniel Pietrasz
- Department of Hepato-Biliary-Pancreatic Surgery, Liver Transplant Center, Université Paris-Sud, Université Paris-Saclay, Villejuif, France
| | - Dyre Kleive
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | | | - Giuseppe Malleo
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Hanneke W M van Laarhoven
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands
| | | | - Jeanne Dembinski
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, Clichy, France
| | - Jin He
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland
| | - Johan Gagnière
- Department of Digestive and Hepatobiliary Surgery-Liver Transplantation, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France
| | - Jörg Kleeff
- Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle, Germany
| | - Jose M Ramia
- Department of Surgery, Hospital General Universitario de Alicante, Alicante, Spain
| | - Keith J Roberts
- Hepato-Pancreato-Biliary Unit, Department of Surgery, University Hospitals of Birmingham, Birmingham, United Kingdom
| | - Knut J Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Marco V Marino
- General Surgery Department, Azienda Ospedaliera, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
| | - Massimo Falconi
- Department of Pancreatic Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milano, Italy
| | - Michael B Mortensen
- Department of Surgery, Odense Pancreas Center, Odense University Hospital, Odense, Denmark
| | - Mickaël Lesurtel
- Department of Hepato-Biliary-Pancreatic Surgery, Liver Transplant Center, Université Paris-Sud, Université Paris-Saclay, Villejuif, France
| | - Morgan Bonds
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Nikolaos Chatzizacharias
- Hepato-Pancreato-Biliary Unit, Department of Surgery, University Hospitals of Birmingham, Birmingham, United Kingdom
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Olivier Turrini
- Department of Surgical Oncology, Aix-Marseille University, Institut Paoli-Calmettes, CRCM, Marseille, France
| | - Oonagh Griffin
- National Surgical Center for Pancreatic Cancer, St. Vincent's University Hospital, Dublin, Ireland
| | - Oskar Franklin
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
- Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
| | - Per Pfeiffer
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Richard D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Roeland F de Wilde
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Safi Dokmak
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, Clichy, France
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
| | - Simone Augustinus
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Stefan K Burgdorf
- Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Stefano Crippa
- Department of Pancreatic Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milano, Italy
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Timo Tarvainen
- Department of Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - William R Burns
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland
| | - Wells Messersmith
- Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora
| | - Johanna W Wilmink
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands
| | - Richard A Burkhart
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora
| | - Marc G Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| |
Collapse
|
|
4
|
Pitman MB. The World Health Organization Reporting System for Pancreaticobiliary Cytopathology: Review and Comparison to the Papanicolaou Society of Cytopathology System. Arch Pathol Lab Med 2025; 149:e39-e46. [PMID: 38190275 DOI: 10.5858/arpa.2023-0411-ra] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/24/2023] [Indexed: 01/10/2024]
Abstract
CONTEXT.— The World Health Organization (WHO) Reporting System for Pancreaticobiliary Cytopathology (WHO System) is the product of a joint venture between the World Health Organization, the International Academy of Cytology, and the International Agency for Research on Cancer. The WHO System revises the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSC System) and replaces the 6-tiered system with a 7-tiered system. OBJECTIVE.— To explain the WHO System and the differences with the PSC System. DATA SOURCES.— The WHO System and the PSC System of Reporting Pancreaticobiliary Cytopathology. CONCLUSIONS.— The diagnostic categories of the WHO System are "Insufficient/Inadequate/Nondiagnostic"; "Benign (Negative for Malignancy)"; "Atypical"; "Pancreaticobiliary Neoplasm, Low Risk/Low Grade (PaN-Low)"; "Pancreatic Neoplasm, High Risk/High Grade (PaN-High)"; "Suspicious for Malignancy"; and "Malignant." In the WHO System, the "benign" category includes both nonneoplastic and neoplastic lesions, so the "Neoplastic: Benign" category of the PSC system has been eliminated. Low-grade malignancies, pancreatic neuroendocrine tumors (PanNETs), and solid-pseudopapillary neoplasm (SPN) classified as "Neoplastic: Other" in the PSC System are classified as "Malignant" in the WHO System, leaving in the "Neoplasm" category intraductal lesions, which are divided into 2 new diagnostic categories: "Pancreaticobiliary Neoplasm (PaN)-Low Risk/Grade" and "PaN-High Risk/Grade." As with the PSC System, the WHO System advocates close correlation with imaging and encourages incorporation of ancillary testing into the final diagnosis, such as biochemical (carcinoembryonic antigen [CEA] and amylase) and molecular testing. The WHO System includes risk of malignancy per category, and reporting and diagnostic management options that recognize the variations in resources of low- and middle-income countries.
Collapse
Affiliation(s)
- Martha B Pitman
- From the Department of Pathology, Harvard Medical School, Boston, Massachusetts; and the Department of Pathology, Massachusetts General Hospital, Boston
| |
Collapse
|
|
5
|
Cloyd JM, Sarna A, Arango MJ, Bates SE, Bhutani MS, Bloomston M, Chung V, Dotan E, Ferrone CR, Gambino PF, Goenka AH, Goodman KA, Hall WA, He J, Hogg ME, Jayaraman S, Kambadakone A, Katz MHG, Khorana AA, Ko AH, Koay EJ, Kooby DA, Krishna SG, Larsson LK, Lee RT, Maitra A, Massarweh NN, Mikhail S, Muzaffar M, O’Reilly EM, Palta M, Petzel MQB, Philip PA, Reyngold M, Santa Mina D, Sohal DPS, Sundaresan TK, Tsai S, Turner KL, Vreeland TJ, Walston S, Washington MK, Williams TM, Wo JY, Snyder RA. Best Practices for Delivering Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma. JAMA Surg 2025; 160:172-180. [PMID: 39630427 PMCID: PMC11618571 DOI: 10.1001/jamasurg.2024.5191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 09/01/2024] [Indexed: 12/08/2024]
Abstract
Importance Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined. Objective To develop consensus best practices for delivering NT to patients with localized PDAC. Design, Setting, and Participants This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature and expert opinion. An interdisciplinary panel was formed including 47 North American experts from surgical, medical, and radiation oncology, radiology, pathology, gastroenterology, integrative oncology, anesthesia, pharmacy, nursing, cancer care delivery research, and nutrition as well as patient and caregiver stakeholders. Main Outcome and Measures Statements that reached 75% agreement or greater were included in final consensus statements. Results Of the 47 participating panel members, 27 (57.64%) were male, and the mean (SD) age was 47.6 (8.2) years. Physicians reported completing training a mean (SD) 14.6 (8.6) years prior and seeing a mean (SD) 110.6 (38.4) patients with PDAC annually; 35 (77.7%) were in academic practice. Final consensus was reached on 82 best practices for delivering NT. Of these, 38 statements focused on pre-NT practices, including diagnosis and staging (n = 15), evaluation and optimization (n = 20), and decision-making (n = 3); 29 statements defined best practices during NT, including initiation (n = 3), delivery of therapy (n = 8), restaging practices (n = 12), and management of complications during NT (n = 6); and 15 best practices were identified to guide treatment post-NT, focusing on surgery (n = 7), pathology (n = 4), and follow-up (n = 3). Conclusions Using a modified Delphi consensus technique, best practice guidelines were developed focusing on the optimal standards for delivering NT to patients with localized PDAC. Given the prognostic importance of completing multimodality therapy, efforts to standardize and optimize the delivery of NT represent an immediate opportunity to decrease care variation and improve outcomes for patients with PDAC. Future research should focus on validating and implementing best practice standards into clinical practice.
Collapse
Affiliation(s)
- Jordan M. Cloyd
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus
| | - Angela Sarna
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus
| | | | - Susan E. Bates
- Columbia University Irving Medical Center, New York, New York
| | | | | | | | - Efrat Dotan
- Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | | | | | | | | | | | - Jin He
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Shiva Jayaraman
- St Joseph’s Health Centre Toronto, University of Toronto, Toronto, Ontario, Canada
| | | | | | - Alok A. Khorana
- Cleveland Clinic and Case Comprehensive Cancer Center, Cleveland, Ohio
| | | | - Eugene J. Koay
- The University of Texas MD Anderson Cancer Center, Houston
| | | | | | | | | | - Anirban Maitra
- The University of Texas MD Anderson Cancer Center, Houston
| | | | - Sameh Mikhail
- Zangmeister Center, American Oncology Network, Columbus, Ohio
| | | | | | | | | | | | | | - Daniel Santa Mina
- St Joseph’s Health Centre Toronto, University of Toronto, Toronto, Ontario, Canada
| | | | | | - Susan Tsai
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus
| | | | | | - Steve Walston
- The Ohio State University Wexner Medical Center, Wooster
| | | | | | | | | |
Collapse
|
|
6
|
Ishiwatari H, Kobayashi Y, Kawaguchi S, Iwashita T, Kaneko J, Ito J, Ishikawa K, Sato J, Niiya F, Endo S, Satoh T, Uemura S, Mori K. Assessment of safety and patency of 7-mm covered metal stents for preoperative biliary drainage in pancreatic cancer: Prospective multicenter study. Endosc Int Open 2025; 13:a25031995. [PMID: 40007658 PMCID: PMC11855238 DOI: 10.1055/a-2503-1995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 11/19/2024] [Indexed: 02/27/2025] Open
Abstract
Background and study aims For preoperative biliary drainage of pancreatic cancer (PC), a 10-mm diameter metal stent (MS) is commonly used; however, the rate of pancreatitis is high. It is hypothesized that smaller-diameter MS may reduce the rate of pancreatitis. Therefore, we conducted a multicenter prospective study to evaluate the efficacy and safety of 7-mm MS. Patients and methods Patients requiring initial biliary drainage for obstructive jaundice caused by PC and scheduled for surgery from six facilities were included. After endoscopic retrograde cholangiography, a 7-mm MS was placed at the site of biliary obstruction. The primary endpoint was the rate of pancreatitis, and the secondary endpoints included early and late adverse events (AEs). The pancreatitis rate was assumed to be 18% and 5% with 10- and 7-mm MS, respectively; with a power of 80% and one-sided significance level of 10%, the planned enrollment was 38 patients. If pancreatitis occurred in no more than three patients, this indicates that the 7-mm MS effectively reduced incidence of pancreatitis. Results Overall, 38 patients were enrolled, and 35 patients in whom a 7-mm MS was successfully placed were analyzed. All MS were placed after sphincterotomy. Pancreatitis occurred in four patients (11.4%) and no early AEs were observed. Surgery was performed in 24 patients and late AEs included stent occlusion in eight patients (23%) and cholecystitis in four patients (11%). Conclusions The 7-mm MS did not reduce incidence of pancreatitis among surgical candidates for PC.
Collapse
Affiliation(s)
| | - Yousuke Kobayashi
- Department of Gastroenterology, Seirei Hamamatsu Hospital, Hamamatsu, Japan
| | - Shinya Kawaguchi
- Department of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
| | - Takuji Iwashita
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Junichi Kaneko
- Department of Gastroenterology, Iwata City Hospital, Iwata, Japan
| | - Jun Ito
- Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Kazuma Ishikawa
- Division of Endoscopy, Shizuoka Cancer Center, Nagaizumi, Japan
| | - Junya Sato
- Division of Endoscopy, Shizuoka Cancer Center, Nagaizumi, Japan
| | - Fumitaka Niiya
- Division of Endoscopy, Shizuoka Cancer Center, Nagaizumi, Japan
| | - Shinya Endo
- Department of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
| | - Tatsunori Satoh
- Department of Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
| | - Shinya Uemura
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Keita Mori
- Division of Clinical Trials, Shizuoka Cancer Center, Sunto-gun, Japan
| |
Collapse
|
|
7
|
Rangelova E, Stoop TF, van Ramshorst TME, Ali M, van Bodegraven EA, Javed AA, Hashimoto D, Steyerberg E, Banerjee A, Jain A, Sauvanet A, Serrablo A, Giani A, Giardino A, Zerbi A, Arshad A, Wijma AG, Coratti A, Zironda A, Socratous A, Rojas A, Halimi A, Ejaz A, Oba A, Patel BY, Björnsson B, Reames BN, Tingstedt B, Goh BKP, Payá-Llorente C, Del Pozo CD, González-Abós C, Medin C, van Eijck CHJ, de Ponthaud C, Takishita C, Schwabl C, Månsson C, Ricci C, Thiels CA, Douchi D, Hughes DL, Kilburn D, Flanking D, Kleive D, Silva DS, Edil BH, Pando E, Moltzer E, Kauffman EF, Warren E, Bozkurt E, Sparrelid E, Thoma E, Verkolf E, Ausania F, Giannone F, Hüttner FJ, Burdio F, Souche FR, Berrevoet F, Daams F, Motoi F, Saliba G, Kazemier G, Roeyen G, Nappo G, Butturini G, Ferrari G, Kito Fusai G, Honda G, Sergeant G, Karteszi H, Takami H, Suto H, Matsumoto I, Mora-Oliver I, Frigerio I, Fabre JM, Chen J, Sham JG, Davide J, Urdzik J, de Martino J, Nielsen K, Okano K, Kamei K, Okada K, Tanaka K, Labori KJ, Goodsell KE, Alberici L, Webber L, Kirkov L, de Franco L, Miyashita M, Maglione M, Gramellini M, Ramera M, Amaral MJ, Ramaekers M, Truty MJ, van Dam MA, Stommel MWJ, Petrikowski M, Imamura M, Hayashi M, D'Hondt M, Brunner M, Hogg ME, Zhang C, Suárez-Muñoz MÁ, Luyer MD, Unno M, Mizuma M, Janot M, Sahakyan MA, Jamieson NB, Busch OR, Bilge O, Belyaev O, Franklin O, Sánchez-Velázquez P, Pessaux P, Holka PS, Ghorbani P, Casadei R, Sartoris R, Schulick RD, Grützmann R, Sutcliffe R, Mata R, Patel RB, Takahashi R, Rodriguez Franco S, Cabús SS, Hirano S, Gaujoux S, Festen S, Kozono S, Maithel SK, Chai SM, Yamaki S, van Laarhoven S, Mieog JSD, Murakami T, Codjia T, Sumiyoshi T, Karsten TM, Nakamura T, Sugawara T, Boggi U, Hartman V, de Meijer VE, Bartholomä W, Kwon W, Koh YX, Cho Y, Takeyama Y, Inoue Y, Nagakawa Y, Kawamoto Y, Ome Y, Soonawalla Z, Uemura K, Wolfgang CL, Jang JY, Padbury R, Satoi S, Messersmith W, Wilmink JW, Abu Hilal M, Besselink MG, Del Chiaro M. The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study. Ann Oncol 2025:S0923-7534(25)00004-3. [PMID: 39814200 DOI: 10.1016/j.annonc.2024.12.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 10/26/2024] [Accepted: 12/23/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. PATIENTS AND METHODS This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. RESULTS Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement. CONCLUSIONS Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.
Collapse
Affiliation(s)
- E Rangelova
- Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
| | - T F Stoop
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
| | - T M E van Ramshorst
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Surgery, Fondazione Poliambulanza, Instituto Ospedaliero, Brescia, Italy
| | - M Ali
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - E A van Bodegraven
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - A A Javed
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, USA
| | - D Hashimoto
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - E Steyerberg
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - A Banerjee
- HPB & Liver Transplant Unit, Royal Free Hospital, London, UK
| | - A Jain
- Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, USA
| | - A Sauvanet
- Department of HPB Surgery and Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, Clichy, France
| | - A Serrablo
- HPB Surgical Division, Miguel Servet University Hospital, Zaragoza, Spain
| | - A Giani
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - A Giardino
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - A Zerbi
- Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - A Arshad
- Hepatopancreatobiliary Unit, University Hospitals Southampton NHS Trust, Southampton General Hospital, Southampton, UK
| | - A G Wijma
- Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - A Coratti
- General and Emergency Surgery Unit, Misericordia Hospital, Azienda USL Toscana Sud-Est, Grosseto, Italy
| | - A Zironda
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - A Socratous
- Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - A Rojas
- Department of Surgery, NorthShore University Health System, Evanston, USA
| | - A Halimi
- Department of Surgery, Umeå University, Umeå, Sweden; Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - A Ejaz
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, USA
| | - A Oba
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo; Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - B Y Patel
- Hepatopancreatobiliary Unit, University Hospitals Southampton NHS Trust, Southampton General Hospital, Southampton, UK
| | - B Björnsson
- Department of Surgery, Linköping University Hospital, Linköping, Sweden
| | - B N Reames
- Department of Surgery, University of Nebraska Medical Center, Omaha, USA
| | - B Tingstedt
- Department of Clinical Sciences Lund, Surgery, Lund University, Skåne University Hospital, Lund, Sweden
| | - B K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - C Payá-Llorente
- General and Digestive Surgery, Hospital Doctor Peset, Valencia, Spain
| | - C D Del Pozo
- General and Digestive Surgery, Hospital Doctor Peset, Valencia, Spain
| | - C González-Abós
- Hepatobiliopancreatic Department, Hospital Clinic de Barcelona, Barcelona, Spain
| | - C Medin
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - C H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - C de Ponthaud
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - C Takishita
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - C Schwabl
- Department of Radiology, Medical University Innsbruck, Innsbruck, Austria
| | - C Månsson
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - C Ricci
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy; Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - C A Thiels
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - D Douchi
- Department of Surgery, Tohoku University, Sendai, Japan
| | - D L Hughes
- Department of Hepatobiliary and Pancreatic Surgery, Oxford Radcliffe Hospitals NHS Foundation Trust, Oxford, UK
| | - D Kilburn
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - D Flanking
- Department of Upper Abdominal Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden
| | - D Kleive
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| | - D S Silva
- HEBIPA Surgery, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - B H Edil
- Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, USA
| | - E Pando
- Universitat Autónoma de Barcelona, Barcelona, Spain; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - E Moltzer
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - E F Kauffman
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - E Warren
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - E Bozkurt
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - E Sparrelid
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - E Thoma
- Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany
| | - E Verkolf
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - F Ausania
- Hepatobiliopancreatic Department, Hospital Clinic de Barcelona, Barcelona, Spain; Instituto de Investigaciones Biomédicas August Pi I Sunyer (IDIBAPS), Barcelona, Spain
| | - F Giannone
- Department of Visceral and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France
| | - F J Hüttner
- Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany
| | - F Burdio
- Department of Surgery, Hepatobiliary and Pancreatic Unit, Hospital del Mar de Barcelona, Barcelona, Spain; Hospital del Mar Research Institute (IMIM), University Pompeu-Fabra, Barcelona, Spain
| | - F R Souche
- Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France
| | - F Berrevoet
- Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, Ghent, Belgium
| | - F Daams
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - F Motoi
- Department of Surgery, Yamagata University, Yamagata, Japan
| | - G Saliba
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - G Kazemier
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands
| | - G Roeyen
- Department of HPB, Endocrine and Transplantation Surgery, University Hospital Antwerp, Antwerp, Belgium
| | - G Nappo
- Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - G Butturini
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - G Ferrari
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - G Kito Fusai
- HPB & Liver Transplant Unit, Royal Free Hospital, London, UK
| | - G Honda
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - G Sergeant
- Department of Abdominal Surgery, Jessa Hospital, Faculty of Medicine and Health Sciences, Universiteit Hasselt, Hasselt, Belgium
| | - H Karteszi
- Department of Radiology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - H Takami
- Department of Gastroenterological Surgery (Surgery II), Nagoya University, Nagoya, Japan
| | - H Suto
- Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan
| | - I Matsumoto
- Department of Surgery, Kindai University, Osakasayama, Japan
| | - I Mora-Oliver
- Department of Surgery, Liver and Pancreato-Biliary Unit, Hospital Clínico Universitario Valencia, Biomedical Research Institute, INCLIVA, Valencia, Spain
| | - I Frigerio
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - J M Fabre
- Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France
| | - J Chen
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - J G Sham
- Department of Surgery, University of Washington, Seattle, USA; Fred Hutchinson Cancer Center, Seattle, USA
| | - J Davide
- HEBIPA Surgery, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - J Urdzik
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - J de Martino
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - K Nielsen
- Department of Hepatopancreatobiliary Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - K Okano
- Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan
| | - K Kamei
- Department of Surgery, Kindai University, Osakasayama, Japan
| | - K Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - K Tanaka
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - K J Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - K E Goodsell
- Department of Surgery, University of Washington, Seattle, USA
| | - L Alberici
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - L Webber
- Department of Upper GI Surgery, Fiona Stanley Hospital, Perth, Austria
| | - L Kirkov
- Oncologic & Minimally-Invasive Digestive Surgery, CHU Montpellier, University of Montpellier, Montpellier, France
| | - L de Franco
- General and Emergency Surgery Unit, Misericordia Hospital, Azienda USL Toscana Sud-Est, Grosseto, Italy
| | - M Miyashita
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - M Maglione
- Department of Visceral, Transplant, and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - M Gramellini
- Humanitas University, Department of Biomedical Sciences, Milan, Italy; Pancreatic Surgery Unit, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - M Ramera
- Department of Surgery, Fondazione Poliambulanza, Instituto Ospedaliero, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - M J Amaral
- General Surgery Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - M Ramaekers
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - M J Truty
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - M A van Dam
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - M W J Stommel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - M Petrikowski
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - M Imamura
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Hokkaido, Japan
| | - M Hayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University, Nagoya, Japan
| | - M D'Hondt
- Department of Digestive and Hepatobiliary-Pancreatic Surgery, Groeninge Hospital, Kortrijk, Belgium
| | - M Brunner
- Department of Surgery, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen Nürnberg, Erlangen, Germany
| | - M E Hogg
- Department of Surgery, NorthShore University Health System, Evanston, USA
| | - C Zhang
- Department of Surgery, University of Nebraska Medical Center, Omaha, USA
| | - M Á Suárez-Muñoz
- HPB Surgical Unit, University Hospital Virgen de la Victoria, Málaga, Spain
| | - M D Luyer
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - M Unno
- Department of Surgery, Tohoku University, Sendai, Japan
| | - M Mizuma
- Department of Surgery, Tohoku University, Sendai, Japan
| | - M Janot
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - M A Sahakyan
- The Intervention Center, Oslo University Hospital, Rigshospitalet, Oslo, Norway
| | - N B Jamieson
- Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - O R Busch
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - O Bilge
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - O Belyaev
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - O Franklin
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Surgery, Umeå University, Umeå, Sweden
| | - P Sánchez-Velázquez
- Department of Surgery, Hepatobiliary and Pancreatic Unit, Hospital del Mar de Barcelona, Barcelona, Spain; Hospital del Mar Research Institute (IMIM), University Pompeu-Fabra, Barcelona, Spain
| | - P Pessaux
- Department of Visceral and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France
| | - P S Holka
- Department of Clinical Sciences Lund, Surgery, Lund University, Skåne University Hospital, Lund, Sweden
| | - P Ghorbani
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - R Casadei
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy; Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - R Sartoris
- Department of Radiology, APHP Beaujon Hospital, University of Paris Cité, Clichy, France
| | - R D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
| | - R Grützmann
- The Intervention Center, Oslo University Hospital, Rigshospitalet, Oslo, Norway
| | - R Sutcliffe
- Department of Hepatopancreatobiliary Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - R Mata
- Universitat Autónoma de Barcelona, Barcelona, Spain; Department of Hepato-Pancreato-Biliary and Transplant Surgery, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - R B Patel
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, USA
| | - R Takahashi
- Department of Surgery, Yamagata University, Yamagata, Japan
| | - S Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
| | - S S Cabús
- Department of HPB Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - S Hirano
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - S Gaujoux
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - S Festen
- Department of Surgery, OLVG, Amsterdam, The Netherlands
| | - S Kozono
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - S K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - S M Chai
- Department of Anatomical Pathology, PathWest Laboratory Medicine, Perth, Australia
| | - S Yamaki
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - S van Laarhoven
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of HPB Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - J S D Mieog
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - T Murakami
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Hokkaido, Japan
| | - T Codjia
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
| | - T Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - T M Karsten
- Department of Surgery, OLVG, Amsterdam, The Netherlands
| | - T Nakamura
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - T Sugawara
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo
| | - U Boggi
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - V Hartman
- Department of HPB, Endocrine and Transplantation Surgery, University Hospital Antwerp, Antwerp, Belgium
| | - V E de Meijer
- Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - W Bartholomä
- Department of Radiology, Linköping University, Linköping, Sweden
| | - W Kwon
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Y X Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
| | - Y Cho
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Y Takeyama
- Department of Surgery, Kindai University, Osakasayama, Japan
| | - Y Inoue
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Y Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Y Kawamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Y Ome
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Z Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford Radcliffe Hospitals NHS Foundation Trust, Oxford, UK
| | - K Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - C L Wolfgang
- Department of Surgical Oncology, Department of Surgery, New York University Medical Center, New York, USA
| | - J Y Jang
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - R Padbury
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - S Satoi
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA; Department of Surgery, Kansai Medical University, Osaka, Japan
| | - W Messersmith
- Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, USA
| | - J W Wilmink
- Cancer Center Amsterdam, Amsterdam, The Netherlands; Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, The Netherlands
| | - M Abu Hilal
- Department of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, Peschiera, Italy
| | - M G Besselink
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - M Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, USA
| |
Collapse
|
|
8
|
Ji Jang H, Soo Lee S, Baek S, Jeong B, Wook Kim D, Hee Kim J, Jung Kim H, Ho Byun J, Lee W, Cheol Kim S. Prognostic implication of extra-pancreatic organ invasion in resectable pancreas ductal adenocarcinoma in the pancreas tail. Eur J Radiol 2024; 181:111715. [PMID: 39241306 DOI: 10.1016/j.ejrad.2024.111715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 07/26/2024] [Accepted: 08/31/2024] [Indexed: 09/09/2024]
Abstract
OBJECTIVES To assess the prognostic significance of extra-pancreatic organ invasion in patients with resectable pancreatic ductal adenocarcinoma (PDAC) in the pancreas tail. MATERIALS & METHODS This retrospective study included patients with resectable PDAC in the pancreas tail who received upfront surgery between 2014 and 2020 at a tertiary institution. Preoperative pancreas protocol computed tomography (CT) scans evaluated tumor size, peripancreatic tumor infiltration, suspicious metastatic lymph nodes, and extra-pancreatic organ invasion. The influence of extra-pancreatic organ invasion, detected by CT or postoperative pathology, on pathologic resection margin status was evaluated using logistic regression. The impact on recurrence-free survival (RFS) was analyzed using multivariable Cox proportional hazard models (clinical-CT and clinical-pathologic). RESULTS The study included 158 patients (mean age, 65 years ± 8.8 standard deviation; 93 men). Extra-pancreatic organ invasion identified by either CT (p = 0.92) or pathology (p = 0.99) was not associated with a positive resection margin. Neither CT (p = 0.42) nor pathological (p = 0.64) extra-pancreatic organ invasion independently correlated with RFS. Independent predictors for RFS included suspicious metastatic lymph node (hazard ratio [HR], 2.05; 95 % confidence interval [CI], 1.08-3.9; p = 0.03) on CT in the clinical-CT model, pathological T stage (HR, 2.97; 95 % confidence interval [CI], 1.39-6.35; p = 0.005 for T2 and HR, 3.78; 95 % CI, 1.64-8.76; p = 0.002 for T3) and adjuvant therapy (HR, 0.62; 95 % confidence interval [CI], 0.42-0.92; p = 0.02) in the clinical-pathologic model. CONCLUSION Extra-pancreatic organ invasion does not independently influence pathologic resection margin status and RFS in patients with resectable PDAC in the pancreas tail after curative-intent resection; therefore, it should not be considered a high-risk factor.
Collapse
Affiliation(s)
- Hyeon Ji Jang
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
| | - Seunghee Baek
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Boryeong Jeong
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Dong Wook Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jin Hee Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| |
Collapse
|
|
9
|
Giuliante F, Panettieri E, Campisi A, Coppola A, Vellone M, De Rose AM, Ardito F. Treatment of oligo-metastatic pancreatic ductal adenocarcinoma to the liver: is there a role for surgery? A narrative review. Int J Surg 2024; 110:6163-6169. [PMID: 38818688 PMCID: PMC11486948 DOI: 10.1097/js9.0000000000001665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Accepted: 05/09/2024] [Indexed: 06/01/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a prognostically unfavorable malignancy that presents with distant metastases at the time of diagnosis in half of patients. Even if patients with metastatic PDAC have not been traditionally considered candidates for surgery, an increasing number of researchers have been investigating the efficacy of surgical treatment for patients with liver-only oligometastases from PDAC, showing promising results in extremely selected patients, mainly with metachronous metastases after perioperative chemotherapy. Nevertheless, a standardized definition of oligometastatic disease should be adopted and additional investigations focusing on the role of perioperative chemotherapy and tumor biology are warranted to reliably assess the role of resection for PDAC metastatic to the liver.
Collapse
Affiliation(s)
- Felice Giuliante
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | - Elena Panettieri
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Andrea Campisi
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | | | - Maria Vellone
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | - Agostino M. De Rose
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| | - Francesco Ardito
- Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli ‘IRCCS’, Università Cattolica del Sacro Cuore
| |
Collapse
|
|
10
|
Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1724-1785. [PMID: 39389105 DOI: 10.1055/a-2338-3716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
| |
Collapse
|
|
11
|
Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e874-e995. [PMID: 39389103 DOI: 10.1055/a-2338-3533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
| |
Collapse
|
|
12
|
Salmi L, Otis-Green S, Hayden A, Taylor LP, Reblin M, Kwan BM. Identifying research priorities and essential elements of palliative care services for people facing malignant brain tumors: A participatory co-design approach. Neurooncol Pract 2024; 11:556-565. [PMID: 39279776 PMCID: PMC11398937 DOI: 10.1093/nop/npae052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/18/2024] Open
Abstract
Background Primary malignant brain tumors (ie, brain cancer) impact the quality of life (QoL) for patients and care partners in disease-specific ways involving cognition and communication. Palliative care (PC) addresses patient/care partner QoL, but it is not known how PC may address the unique needs of brain cancer patients. The purpose of this project was to identify brain cancer PC research priorities using participatory co-design methods. Methods Participatory co-design included the formation of a longitudinal, collaborative advisory group, engagement frameworks, design-thinking processes, and social media-based engagement over a 1-year period. Community-identified brain cancer QoL needs and research priorities were mapped to proposed "essential elements" of brain cancer PC services. Results We engaged an estimated 500 patients, care partners, healthcare professionals, and others with an interest in QoL and PC services for people with malignant brain tumors. Research priorities included testing the early introduction of PC services designed to address the unique QoL needs of brain cancer patients and care partners. Essential elements of brain cancer PC include: (1) addressing brain cancer patients' unique range of QoL needs and concerns, which change over time, (2) tailoring existing services and approaches to patient needs and concerns, (3) enhancing the involvement of interprofessional care team members, and (4) optimizing timing for PC services. This was the first participatory research effort exploring brain cancer patient and care partner QoL needs and PC services. Conclusions The brain tumor community calls for research testing PC service models for patients that incorporate the "essential elements" of palliative care.
Collapse
Affiliation(s)
- Liz Salmi
- Department of General Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | | | - Adam Hayden
- Independent researcher, unaffiliated, Greenwood, Indiana, USA
| | - Lynne P Taylor
- Departments of Neurology, Neurologic Surgery and Medicine, University of Washington School of Medicine, Seattle, Washington, USA
| | - Maija Reblin
- Department of Family Medicine, University of Vermont, Burlington, Vermont, USA
| | - Bethany M Kwan
- Adult & Child Center for Outcomes Research and Delivery Science (ACCORDS) and Department of Family Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| |
Collapse
|
|
13
|
Taherian M, Katz MHG, Prakash LR, Wei D, Tong YT, Lai Z, Chatterjee D, Wang H, Kim M, Tzeng CWD, Ikoma N, Wolff RA, Zhao D, Koay EJ, Maitra A, Wang H. The Association between Sampling and Survival in Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreaticoduodenectomy. Cancers (Basel) 2024; 16:3312. [PMID: 39409932 PMCID: PMC11476037 DOI: 10.3390/cancers16193312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/12/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limited data are available for the association between the sampling and survival in these patients. We examined the association of the entire submission of the tumor (ESOT) and the entire submission of the pancreas (ESOP) with disease-free survival (DFS) and overall survival (OS), as well as their correlations with clinicopathologic features, for 627 patients with PDAC who received NAT and pancreaticoduodenectomy. We demonstrated that both ESOT and ESOP were associated with lower ypT, less frequent perineural invasion, and better tumor response (p < 0.05). ESOP was also associated with a smaller tumor size (p < 0.001), more lymph nodes (p < 0.001), a lower ypN stage (p < 0.001), better differentiation (p = 0.02), and less frequent lymphovascular invasion (p = 0.009). However, since ESOP and ESOT were primarily conducted for cases with no grossly identifiable tumor or minimal residual carcinoma in initial sections, potential bias cannot be excluded. Both ESOT and ESOP were associated with less frequent recurrence/metastasis and better DFS and OS (p < 0.05) in the overall study population. ESOP was associated with better DFS and better OS in patients with ypT0/ypT1 or ypN0 tumors and better OS in patients with complete or near-complete response (p < 0.05). ESOT was associated with better OS in patients with ypT0/ypT1 or ypN0 tumors (p < 0.05). Both ESOT and ESOP were independent prognostic factors for OS according to multivariate survival analyses. Therefore, accurate pathologic evaluation using ESOP and ESOT is associated with the prognosis in PDAC patients with complete or near-complete pathologic response and ypT0/ypT1 tumor after NAT.
Collapse
Affiliation(s)
- Mehran Taherian
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.T.); (D.W.); (Y.T.T.); (Z.L.); (D.C.)
| | - Matthew H. G. Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.H.G.K.); (L.R.P.); (M.K.); (C.-W.D.T.); (N.I.)
| | - Laura R. Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.H.G.K.); (L.R.P.); (M.K.); (C.-W.D.T.); (N.I.)
| | - Dongguang Wei
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.T.); (D.W.); (Y.T.T.); (Z.L.); (D.C.)
| | - Yi Tat Tong
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.T.); (D.W.); (Y.T.T.); (Z.L.); (D.C.)
| | - Zongshan Lai
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.T.); (D.W.); (Y.T.T.); (Z.L.); (D.C.)
| | - Deyali Chatterjee
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.T.); (D.W.); (Y.T.T.); (Z.L.); (D.C.)
| | - Hua Wang
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (H.W.); (R.A.W.); (D.Z.)
| | - Michael Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.H.G.K.); (L.R.P.); (M.K.); (C.-W.D.T.); (N.I.)
| | - Ching-Wei D. Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.H.G.K.); (L.R.P.); (M.K.); (C.-W.D.T.); (N.I.)
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.H.G.K.); (L.R.P.); (M.K.); (C.-W.D.T.); (N.I.)
| | - Robert A. Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (H.W.); (R.A.W.); (D.Z.)
| | - Dan Zhao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (H.W.); (R.A.W.); (D.Z.)
| | - Eugene J. Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Anirban Maitra
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.T.); (D.W.); (Y.T.T.); (Z.L.); (D.C.)
| | - Huamin Wang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.T.); (D.W.); (Y.T.T.); (Z.L.); (D.C.)
| |
Collapse
|
|
14
|
Ishiwatari H, Sato J, Sakamoto H, Doi T, Ono H. Current status of preoperative endoscopic biliary drainage for distal and hilar biliary obstruction. Dig Endosc 2024; 36:969-980. [PMID: 38629308 DOI: 10.1111/den.14786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 02/18/2024] [Indexed: 11/20/2024]
Abstract
The purpose of preoperative biliary drainage (PBD) is to reduce complications during the perioperative period. The extrahepatic bile duct comprises distal and hilar bile ducts and assessing the need for PBD must be considered separately for each duct, as surgical procedures and morbidities vary. The representative disease-causing distal bile duct obstruction is pancreatic cancer. A randomized controlled trial has revealed that PBD carries the risk of recurrent cholangitis and pancreatitis before surgery, thus eliminating the need for PBD when early surgery is feasible. However, neoadjuvant therapy has seen a rise in recent years, resulting in longer preoperative waiting periods and an increased demand for PBD. In such cases, metal stents are preferable to plastic stents due to their lower stent occlusion rates. When endoscopic transpapillary biliary drainage (EBD) is not viable, endoscopic ultrasound-guided biliary drainage may be a suitable substitute. In the hilar bile duct, the representative disease-causing obstruction is hilar cholangiocarcinoma. PBD's necessity has long been a subject of contention. In spite of earlier criticisms of routine PBD, recent views have emerged recommending PBD, particularly when major hepatectomy is required, to prevent postoperative liver failure. Given the risk of tumor seeding associated with percutaneous transhepatic biliary drainage, EBD is preferable. Nevertheless, as its shortcomings involve recurrent cholangitis until surgery due to stent or tube obstruction, it is necessary to seek out novel approaches to circumvent complications. In this review we summarize the current evidence for PBD in patients with distal and hilar biliary obstruction.
Collapse
Affiliation(s)
| | - Junya Sato
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Hiroki Sakamoto
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takuya Doi
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| |
Collapse
|
|
15
|
Yang DH, Park SH, Yoon S. Differential Diagnosis of Pancreatic Cancer and its Mimicking Lesions. JOURNAL OF THE KOREAN SOCIETY OF RADIOLOGY 2024; 85:902-915. [PMID: 39416316 PMCID: PMC11473986 DOI: 10.3348/jksr.2023.0100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 12/02/2023] [Accepted: 02/12/2024] [Indexed: 10/19/2024]
Abstract
Pancreatic cancer is usually detected through contrast-enhanced CT and MRI. However, pancreatic cancer is occasionally overlooked because of its small size or is misdiagnosed as other conditions due to atypical imaging features that present diagnostic challenges. Considering the rapid growth and poor prognosis associated with pancreatic cancer, the ability to accurately detect and differentiate pancreatic lesions is crucial for appropriate surgical intervention. Reviewing diverse challenging cases of pancreatic cancer at an early stage and other mimicking lesions may help us accurately interpret the imaging features of pancreatic cancer on CT and MRI scans. Therefore, we aimed to illustrate various imaging features of pancreatic cancer and its mimicking lesions and provide valuable insights for differential diagnosis.
Collapse
|
|
16
|
Manne A, Esnakula A, Sheel A, Sara A, Manne U, Paluri RK, He K, Yang W, Sohal D, Kasi A, Noonan AM, Mittra A, Hays J, Roychowdhury S, Malalur P, Rahman S, Jin N, Cloyd JM, Tsai S, Ejaz A, Pitter K, Miller E, Thanikachalam K, Dillhoff M, Yu L. Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts Treatment Response and Outcomes. Int J Mol Sci 2024; 25:9041. [PMID: 39201728 PMCID: PMC11354508 DOI: 10.3390/ijms25169041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 08/13/2024] [Accepted: 08/19/2024] [Indexed: 09/03/2024] Open
Abstract
Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes.
Collapse
Affiliation(s)
- Ashish Manne
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - Ashwini Esnakula
- Department of Pathology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA;
| | - Ankur Sheel
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - Amir Sara
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - Upender Manne
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Ravi Kumar Paluri
- Division of Hematology-Oncology, Department of Internal Medicine, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27103, USA
| | - Kai He
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - Wancai Yang
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
| | - Davendra Sohal
- Department of Internal Medicine, Division of Hematology/Oncology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
| | - Anup Kasi
- Division of Medical Oncology, University of Kansas Cancer Center, Westwood, KS 66205, USA
| | - Anne M. Noonan
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - Arjun Mittra
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - John Hays
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - Sameek Roychowdhury
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - Pannaga Malalur
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - Shafia Rahman
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - Ning Jin
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA
| | - Jordan M. Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43221, USA
| | - Susan Tsai
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43221, USA
| | - Aslam Ejaz
- Department of Surgical Oncology, University of Illinois College of Medicine, Chicago, IL 60612, USA
| | - Kenneth Pitter
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA (E.M.)
| | - Eric Miller
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43210, USA (E.M.)
| | - Kannan Thanikachalam
- Center of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY 14203, USA
| | - Mary Dillhoff
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center (OSU-CCC), Columbus, OH 43221, USA
| | - Lianbo Yu
- Center of Biostatistics and Bioinformatics, The Ohio State University, Columbus, OH 43210, USA
| |
Collapse
|
|
17
|
Schouten TJ, van Goor IWJM, Dorland GA, Besselink MG, Bonsing BA, Bosscha K, Brosens LAA, Busch OR, Cirkel GA, van Dam RM, Festen S, Groot Koerkamp B, van der Harst E, de Hingh IHJT, Intven MPW, Kazemier G, Liem MSL, van Lienden KP, Los M, de Meijer VE, Patijn GA, Schreinemakers JMJ, Stommel MWJ, van Tienhoven GJ, Verdonk RC, Verkooijen HM, van Santvoort HC, Molenaar IQ, Daamen LA. The Value of Biological and Conditional Factors for Staging of Patients with Resectable Pancreatic Cancer Undergoing Upfront Resection: A Nationwide Analysis. Ann Surg Oncol 2024; 31:4956-4965. [PMID: 38386198 PMCID: PMC11236903 DOI: 10.1245/s10434-024-15070-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 01/31/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND Novel definitions suggest that resectability status for pancreatic ductal adenocarcinoma (PDAC) should be assessed beyond anatomical criteria, considering both biological and conditional factors. This has, however, yet to be validated on a nationwide scale. This study evaluated the prognostic value of biological and conditional factors for staging of patients with resectable PDAC. PATIENTS AND METHODS A nationwide observational cohort study was performed, including all consecutive patients who underwent upfront resection of National Comprehensive Cancer Network resectable PDAC in the Netherlands (2014-2019) with complete information on preoperative carbohydrate antigen (CA) 19-9 and Eastern Cooperative Oncology Group (ECOG) performance status. PDAC was considered biologically unfavorable (RB+) if CA19-9 ≥ 500 U/mL and favorable (RB-) otherwise. ECOG ≥ 2 was considered conditionally unfavorable (RC+) and favorable otherwise (RC-). Overall survival (OS) was assessed using Kaplan-Meier and Cox-proportional hazard analysis, presented as hazard ratios (HRs) with 95% confidence interval (CI). RESULTS Overall, 688 patients were analyzed with a median overall survival (OS) of 20 months (95% CI 19-23). OS was 14 months (95% CI 10 months-median not reached) in 20 RB+C+ patients (3%; HR 1.61, 95% CI 0.86-2.70), 13 months (95% CI 11-15) in 156 RB+C- patients (23%; HR 1.86, 95% CI 1.50-2.31), and 21 months (95% CI 12-41) in 47 RB-C+ patients (7%; HR 1.14, 95% CI 0.80-1.62) compared with 24 months (95% CI 22-27) in 465 patients with RB-C- PDAC (68%; reference). CONCLUSIONS Survival after upfront resection of anatomically resectable PDAC is worse in patients with CA19-9 ≥ 500 U/mL, while performance status had no impact. This supports consideration of CA19-9 in preoperative staging of resectable PDAC.
Collapse
Affiliation(s)
- Thijs J Schouten
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - Iris W J M van Goor
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
- Department of Radiation Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Galina A Dorland
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - Marc G Besselink
- Amsterdam UMC, Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Koop Bosscha
- Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Olivier R Busch
- Amsterdam UMC, Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Geert A Cirkel
- Department of Medical Oncology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
- Department of Medical Oncology, Meander Medical Center, Amersfoort, The Netherlands
| | - Ronald M van Dam
- Department of Surgery, Maastricht UMC+,, Maastricht, The Netherlands
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
- Department of General and Visceral Surgery, University Hospital Aachen, Aachen, Germany
| | | | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | | | - Ignace H J T de Hingh
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Martijn P W Intven
- Department of Radiation Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Geert Kazemier
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Mike S L Liem
- Department of Surgery, Medical Spectrum Twente, Enschede, The Netherlands
| | - Krijn P van Lienden
- Department of Interventional Radiology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Maartje Los
- Department of Medical Oncology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Vincent E de Meijer
- Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Gijs A Patijn
- Department of Surgery, Isala Clinics, Zwolle, The Netherlands
| | | | - Martijn W J Stommel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Geert Jan van Tienhoven
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Amsterdam UMC, Department of Radiation Oncology, location University of Amsterdam, Amsterdam, The Netherlands
| | - Robert C Verdonk
- Department of Gastroenterology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Helena M Verkooijen
- Imaging Division, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - Lois A Daamen
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands.
- Imaging Division, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
| |
Collapse
|
|
18
|
Shindo Y, Ioka T, Tokumitsu Y, Matsui H, Nakajima M, Kimura Y, Watanabe Y, Tomochika S, Nakagami Y, Tsunedomi R, Iida M, Takahashi H, Nagano H. Safety and Feasibility of Neoadjuvant-Modified FOLFIRINOX in Elderly Patients with Pancreatic Cancer. Cancers (Basel) 2024; 16:2522. [PMID: 39061162 PMCID: PMC11275028 DOI: 10.3390/cancers16142522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 07/01/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
The optimal treatment strategy for neoadjuvant chemotherapy in elderly patients with pancreatic cancer (PC) remains unclear. Hence, this study was aimed at evaluating the safety and feasibility of neoadjuvant-modified FOLFIRINOX (mFOLFIRINOX) in elderly patients with PC. We retrospectively collected data from 62 patients who received neoadjuvant mFOLFIRINOX between May 2015 and October 2023 and comparatively analyzed the clinicopathological data and outcomes between the non-elderly group (age: <75 years) and elderly group (age: >75 years). The non-elderly and elderly groups comprised 39 and 23 patients, respectively. Although elevated levels of aspartate aminotransferase (p = 0.0173) and alanine aminotransferase (p = 0.0378) and nausea (p = 0.0177) were more frequent in the elderly group, the incidence of severe adverse events was similar between the groups. Intergroup differences in resection rate (p = 0.3381), postoperative severe complication rates (p = 0.2450), and postoperative hospital stay (p = 0.3496) were not significant. Furthermore, no significant intergroup differences were found in survival in either the whole or the resection cohorts. The perioperative and postoperative outcomes of elderly patients treated with neoadjuvant mFOLFIRINOX were comparable with those of non-elderly patients. Neoadjuvant mFOLFIRINOX should be considered a feasible option for elderly patients with PC.
Collapse
Affiliation(s)
- Yoshitaro Shindo
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| | - Tatsuya Ioka
- Department of Oncology Center, Yamaguchi University Hospital, Ube 755-8505, Yamaguchi, Japan;
| | - Yukio Tokumitsu
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| | - Hiroto Matsui
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| | - Masao Nakajima
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| | - Yuta Kimura
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| | - Yusaku Watanabe
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| | - Shinobu Tomochika
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| | - Yuki Nakagami
- Department of Data Science, Shimonoseki City University, Shimonoseki 751-8510, Yamaguchi, Japan;
| | - Ryouichi Tsunedomi
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| | - Michihisa Iida
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| | - Hidenori Takahashi
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Yamaguchi, Japan; (Y.S.); (Y.T.); (H.M.); (M.N.); (Y.K.); (Y.W.); (S.T.); (R.T.); (M.I.); (H.T.)
| |
Collapse
|
|
19
|
Carpenter EL, Van Decar SG, McCarthy PM, Valdera FA, Adams AM, O'Shea AE, Smolinsky T, Thomas K, Clifton GT, Newhook TE, Peoples GE, Nelson DW, Vreeland TJ. The benefit of adjuvant chemotherapy following pancreaticoduodenectomy for pancreatic adenocarcinoma depends on response to neoadjuvant therapy. J Surg Oncol 2024; 130:109-116. [PMID: 38801055 DOI: 10.1002/jso.27689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 04/15/2024] [Accepted: 05/11/2024] [Indexed: 05/29/2024]
Abstract
BACKGROUND The benefit of adjuvant therapy (AT) remains unclear in pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and surgical resection. METHODS The 2019 National Cancer Database was queried for patients with non-metastatic PDAC who received NAT followed by pancreaticoduodenectomy. Only patients with data regarding receipt of AT were included. Patients were classified if they had nodal down-staging specifically, or any downstaging (Tumor, Nodal, or overall). Propensity score matching (PSM) adjusted for pretreatment covariate imbalance between groups. The weighted Kaplan-Meier method and log-rank test were used to estimate the cumulative survival. RESULTS After exclusion criteria and PSM, a total of 2784 patients remained; 1689 (60.7%) received AT and 1095 (39.3%) did not receive AT. Among all, those with additional AT had a significantly improved overall survival (OS) (p < 0.001). Upon evaluation of patients without downstaging after NAT, those who received AT had improved OS (no nodal downstaging or any downstaging; p = 0.002; p = 0.001). When evaluating patients with downstaging after NAT, those receiving AT did not have improved OS (nodal downstaging or any downstaging: p = 0.352; p = 0.99). CONCLUSION Response to NAT appears to correlate with the benefit of AT following pancreaticoduodenectomy; patients who have a favorable response to NAT may not benefit from AT.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | - Timothy E Newhook
- The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | | | | | | |
Collapse
|
|
20
|
Centeno BA, Saieg M, Siddiqui MT, Perez-Machado M, Layfield LJ, Weynand B, Reid MD, Stelow EB, Lozano MD, Fukushima N, Cree IA, Mehrotra R, Schmitt FC, Field AS, Pitman MB. The World Health Organization Reporting System for Pancreaticobiliary Cytopathology: Overview and Summary. Cancer Cytopathol 2024; 132:396-418. [PMID: 38709670 DOI: 10.1002/cncy.22806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/12/2024] [Accepted: 01/17/2024] [Indexed: 05/08/2024]
Abstract
The recently published WHO Reporting System for Pancreaticobiliary Cytopathology (World Health Organization [WHO] System) is an international approach to the standardized reporting of pancreaticobiliary cytopathology, updating the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSC System). Significant changes were made to the categorization of benign neoplasms, intraductal neoplasms, mucinous cystic neoplasms, and malignant neoplasms considered low grade. Benign neoplasms, such as serous cystadenoma, categorized as Neoplastic: benign in the PSC system, are categorized as Benign/negative for malignancy in the WHO system. Pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, and gastrointestinal stromal tumor, categorized as Neoplastic: other in the PSC system, are categorized as Malignant in the WHO System in accord with their classification in the 5th edition WHO Classification of Digestive System Tumours (2019). The two new categories of Pancreaticobiliary Neoplasm Low-risk/grade and Pancreaticobiliary Neoplasm High-risk/grade are mostly limited to intraductal neoplasms and mucinous cystic neoplasms. Low-risk/grade lesions are mucinous cysts, with or without low-grade epithelial atypia. High-risk/grade lesions contain neoplastic epithelium with high-grade epithelial atypia. Correlation with clinical, imaging, and ancillary studies remains a key tenet. The sections for each entity are written to highlight key cytopathological features and cytopathological differential diagnoses with the pathologist working in low resource setting in mind. Each section also includes the most pertinent ancillary studies useful for the differential diagnosis. Sample reports are provided for each category. Finally, the book provides a separate section with risk of malignancy and management recommendations for each category to facilitate decision-making for clinicians.
Collapse
Affiliation(s)
| | - Mauro Saieg
- Santa Casa Medical School, Sao Paulo, Brazil
| | - Momin T Siddiqui
- Department of Pathology, Weill Cornell Medicine, New York, New York, USA
| | - Miguel Perez-Machado
- Department of Cellular Pathology, Royal Free Hampstead NHS Trust, London, England
| | - Lester J Layfield
- Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, Missouri, USA
| | - Birgit Weynand
- Department of Pathology, University Hospitals Leuven, Leuven, Belgium
| | - Michelle D Reid
- Department of Pathology, Emory University Hospital, Atlanta, Georgia, USA
| | - Edward B Stelow
- Department of Pathology, University of Virginia Hospital, Charlottesville, Virginia, USA
| | - Maria D Lozano
- Department of Pathology, Clinica University of Navarra, Pamplona, Spain
| | - Noriyoshi Fukushima
- Department of Diagnostic Pathology, Jichi Medical University Hospital, Shimotsuke, Japan
| | - Ian A Cree
- International Agency for Research on Cancer [IARC], World Health Organization, Lyon, France
| | - Ravi Mehrotra
- Indian Cancer Genomic Atlas, Centre for Health, Innovation and Policy Foundation, Noida, Uttar Pradesh, India
| | - Fernando C Schmitt
- Faculty of Medicine, Department of Pathology, University of Porto, Porto, Portugal
- CINTESIS@RISE, Porto University, Porto, Portugal
| | - Andrew S Field
- Department of Anatomical Pathology, St Vincent's Hospital, Sydney, New South Wales, Australia
- University of New South Wales Sydney and University of Notre Dame, Sydney, New South Wales, Australia
| | - Martha B Pitman
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
|
21
|
Brown ZJ, Shannon AH, Cloyd JM. Neoadjuvant therapy for localized pancreatic ductal adenocarcinoma. Minerva Surg 2024; 79:315-325. [PMID: 38385797 DOI: 10.23736/s2724-5691.23.10150-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor with poor prognosis and rising incidence globally. Multimodal therapy that includes surgical resection and chemotherapy with or without radiation offers the best chance for optimal outcomes. The development of established criteria for anatomic staging of local primary tumors into potentially resectable (PR), borderline resectable (BR), and locally advanced (LA) has greatly clarified the optimal treatment strategies. While upfront surgical resection was traditionally the recommended approach for localized PDAC, increasingly neoadjuvant therapy (NT) is recommended prior to surgery. Whereas NT can lead to downstaging that facilitates surgical resection for BR/LA cancers, NT also enhances patient selection for surgery, improves margin-negative resection rates, and increases the odds of completing multimodality therapy for all patients with PDAC. Herein, we review the rationale for NT for localized PDAC and summarize existing and ongoing literature.
Collapse
Affiliation(s)
- Zachary J Brown
- Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Alexander H Shannon
- Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jordan M Cloyd
- Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH, USA -
| |
Collapse
|
|
22
|
K GB, Koyyala VPB. The Role of Neoadjuvant and Adjuvant Chemotherapy in Pancreatic Cancer. Indian J Surg Oncol 2024; 15:315-321. [PMID: 38818012 PMCID: PMC11133239 DOI: 10.1007/s13193-024-01938-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 03/30/2024] [Indexed: 06/01/2024] Open
Abstract
Pancreatic cancer is an aggressive malignancy. Recurrences are very high despite high-quality surgery necessitating adjuvant therapy. The evolution of adjuvant therapy took several decades and gradually evolved from single-agent chemotherapy to multi-agent chemotherapy. The two important agents that are active in pancreatic cancer are 5-fluorouracil and gemcitabine, and with several combinations showing better results in the subsequent trials, the most recent trial PRODIGE 24 shows a median survival of 54.4 months. The role of neoadjuvant therapy is still evolving in resectable cancers. The role of adjuvant radiotherapy is not well defined due to controversial results from historical trials.
Collapse
Affiliation(s)
- Govind Babu K
- HCG Hospitals St. Johns Medical College and Hospital, Bangalore, Karnataka India
| | | |
Collapse
|
|
23
|
Dekker EN, van Dam JL, Janssen QP, Besselink MG, DeSilva A, Doppenberg D, van Eijck CHJ, Nasar N, O'Reilly EM, Paniccia A, Prakash LR, Tzeng CWD, Verkolf EMM, Wei AC, Zureikat AH, Katz MHG, Groot Koerkamp B. Improved Clinical Staging System for Localized Pancreatic Cancer Using the ABC Factors: A TAPS Consortium Study. J Clin Oncol 2024; 42:1357-1367. [PMID: 38315954 DOI: 10.1200/jco.23.01311] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 10/03/2023] [Accepted: 11/14/2023] [Indexed: 02/07/2024] Open
Abstract
PURPOSE Previous studies suggest that besides anatomy (A: resectable, borderline resectable [BR], or locally advanced [LA]) also biologic (B: carbohydrate antigen 19-9 [CA 19-9]) and conditional (C: performance status) factors should be considered when staging patients with localized pancreatic ductal adenocarcinoma (PDAC). The prognostic value of the combined ABC factors has not been quantitatively validated. METHODS In this retrospective cohort study, we evaluated patients with localized PDAC treated with initial (modified) fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) at five high-volume pancreatic cancer centers in the United States and the Netherlands (2012-2019). Multivariable Cox proportional hazards analysis was used to investigate the impact of the ABC factors for overall survival (OS). RESULTS Overall, 1,835 patients with localized PDAC were included. Tumor stage at diagnosis was potentially resectable in 346 (18.9%), BR in 531 (28.9%), and LA in 958 (52.2%) patients. The baseline CA 19-9 was >500 U/mL in 559 patients (32.5%). Performance status was ≥1 in 1,110 patients (60.7%). Independent poor prognostic factors for OS were BR disease (hazard ratio [HR], 1.26 [95% CI, 1.06 to 1.50]), LA disease (HR, 1.71 [95% CI, 1.45 to 2.02]), CA 19-9 >500 U/mL (HR, 1.36 [95% CI, 1.21 to 1.52]), and WHO performance status ≥1 (HR, 1.31 [95% CI, 1.16 to 1.47]). Patients were assigned 1 point for each poor ABC factor and 2 points for LA disease. The median OS for patients with score 0-4 was 49.7, 29.9, 22.0, 19.1, and 14.9 months with corresponding 5-year OS rates of 47.0%, 28.9%, 19.2%, 9.3%, and 4.8%, respectively. CONCLUSION The ABC factors of tumor anatomy, CA 19-9, and performance status at diagnosis were independent prognostic factors for OS in patients with localized PDAC treated with initial (m)FOLFIRINOX. Staging of patients with localized PDAC at diagnosis should be based on anatomy, CA 19-9, and performance status.
Collapse
Affiliation(s)
- Esther N Dekker
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Jacob L van Dam
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Quisette P Janssen
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Annissa DeSilva
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Deesje Doppenberg
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | | | - Naaz Nasar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Eileen M O'Reilly
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Alessandro Paniccia
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Laura R Prakash
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eva M M Verkolf
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amer H Zureikat
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Matthew H G Katz
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| |
Collapse
|
|
24
|
Miao Q, Wang X, Cui J, Zheng H, Xie Y, Zhu K, Chai R, Jiang Y, Feng D, Zhang X, Shi F, Tan X, Fan G, Liang K. Artificial intelligence to predict T4 stage of pancreatic ductal adenocarcinoma using CT imaging. Comput Biol Med 2024; 171:108125. [PMID: 38340439 DOI: 10.1016/j.compbiomed.2024.108125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 02/02/2024] [Accepted: 02/05/2024] [Indexed: 02/12/2024]
Abstract
BACKGROUND The accurate assessment of T4 stage of pancreatic ductal adenocarcinoma (PDAC) has consistently presented a considerable difficulty for radiologists. This study aimed to develop and validate an automated artificial intelligence (AI) pipeline for the prediction of T4 stage of PDAC using contrast-enhanced CT imaging. METHODS The data were obtained retrospectively from consecutive patients with surgically resected and pathologically proved PDAC at two institutions between July 2017 and June 2022. Initially, a deep learning (DL) model was developed to segment PDAC. Subsequently, radiomics features were extracted from the automatically segmented region of interest (ROI), which encompassed both the tumor region and a 3 mm surrounding area, to construct a predictive model for determining T4 stage of PDAC. The assessment of the models' performance involved the calculation of the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS The study encompassed a cohort of 509 PDAC patients, with a median age of 62 years (interquartile range: 55-67). The proportion of patients in T4 stage within the model was 16.9%. The model achieved an AUC of 0.849 (95% CI: 0.753-0.940), a sensitivity of 0.875, and a specificity of 0.728 in predicting T4 stage of PDAC. The performance of the model was determined to be comparable to that of two experienced abdominal radiologists (AUCs: 0.849 vs. 0.834 and 0.857). CONCLUSION The automated AI pipeline utilizing tumor and peritumor-related radiomics features demonstrated comparable performance to that of senior abdominal radiologists in predicting T4 stage of PDAC.
Collapse
Affiliation(s)
- Qi Miao
- Department of Radiology, The First Hospital of China Medical University, Shenyang, China
| | - Xuechun Wang
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Jingjing Cui
- Department of Research and Development, United Imaging Intelligence (Beijing) Co., Ltd., Bejing, China
| | - Haoxin Zheng
- Department of Computer Science, University of California, Los Angeles, USA
| | - Yan Xie
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Kexin Zhu
- Department of Radiology, The First Hospital of China Medical University, Shenyang, China
| | - Ruimei Chai
- Department of Radiology, The First Hospital of China Medical University, Shenyang, China
| | - Yuanxi Jiang
- Department of Radiology, The First Hospital of China Medical University, Shenyang, China
| | - Dongli Feng
- Department of Radiology, The First Hospital of China Medical University, Shenyang, China
| | - Xin Zhang
- Department of Radiology, The First Hospital of China Medical University, Shenyang, China
| | - Feng Shi
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Xiaodong Tan
- Department of General Surgery/Pancreatic and Thyroid Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Guoguang Fan
- Department of Radiology, The First Hospital of China Medical University, Shenyang, China.
| | - Keke Liang
- Department of General Surgery/Pancreatic and Thyroid Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
| |
Collapse
|
|
25
|
Doppenberg D, Stoop TF, van Dieren S, Katz MHG, Janssen QP, Nasar N, Prakash LR, Theijse RT, Tzeng CWD, Wei AC, Zureikat AH, Groot Koerkamp B, Besselink MG. Serum CEA as a Prognostic Marker for Overall Survival in Patients with Localized Pancreatic Adenocarcinoma and Non-Elevated CA19-9 Levels Treated with FOLFIRINOX as Initial Treatment: A TAPS Consortium Study. Ann Surg Oncol 2024; 31:1919-1932. [PMID: 38170408 DOI: 10.1245/s10434-023-14680-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 11/13/2023] [Indexed: 01/05/2024]
Abstract
INTRODUCTION About 25% of patients with localized pancreatic adenocarcinoma have non-elevated serum carbohydrate antigen (CA) 19-9 levels at baseline, hampering evaluation of response to preoperative treatment. Serum carcinoembryonic antigen (CEA) is a potential alternative. METHODS This retrospective cohort study from five referral centers included consecutive patients with localized pancreatic adenocarcinoma (2012-2019), treated with one or more cycles of (m)FOLFIRINOX, and non-elevated CA19-9 levels (i.e., < 37 U/mL) at baseline. Cox regression analyses were performed to assess prognostic factors for overall survival (OS), including CEA level at baseline, restaging, and dynamics. RESULTS Overall, 277 patients were included in this study. CEA at baseline was elevated (≥5 ng/mL) in 53 patients (33%) and normalized following preoperative therapy in 14 patients (26%). In patients with elevated CEA at baseline, median OS in patients with CEA normalization following preoperative therapy was 33 months versus 19 months in patients without CEA normalization (p = 0.088). At time of baseline, only elevated CEA was independently associated with (worse) OS (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.04-1.98). At time of restaging, elevated CEA at baseline was still the only independent predictor for (worse) OS (HR 1.44, 95% CI 1.04-1.98), whereas elevated CEA at restaging (HR 1.16, 95% CI 0.77-1.77) was not. CONCLUSIONS Serum CEA was elevated in one-third of patients with localized pancreatic adenocarcinoma having non-elevated CA19-9 at baseline. At both time of baseline and time of restaging, elevated serum CEA measured at baseline was the only predictor for (worse) OS. Therefore, serum CEA may be a useful tool for decision making at both initial staging and time of restaging in patients with non-elevated CA19-9.
Collapse
Affiliation(s)
- Deesje Doppenberg
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Thomas F Stoop
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Susan van Dieren
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
| | - Matthew H G Katz
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Quisette P Janssen
- Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Naaz Nasar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Laura R Prakash
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rutger T Theijse
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Amer H Zureikat
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Marc G Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
- Cancer Center Amsterdam, Amsterdam, the Netherlands.
| |
Collapse
|
|
26
|
Turner KM, Wilson GC, Patel SH, Ahmad SA. ASO Practice Guidelines Series: Management of Resectable, Borderline Resectable, and Locally Advanced Pancreas Cancer. Ann Surg Oncol 2024; 31:1884-1897. [PMID: 37980709 DOI: 10.1245/s10434-023-14585-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 10/29/2023] [Indexed: 11/21/2023]
Abstract
Pancreatic adenocarcinoma is an aggressive disease marked by high rates of both local and distant failure. In the minority of patients with potentially resectable disease, multimodal treatment paradigms have allowed for prolonged survival in an increasingly larger pool of well-selected patients. Therefore, it is critical for surgical oncologists to be abreast of current guideline recommendations for both surgical management and multimodal therapy for pancreas cancer. We discuss these guidelines, as well as the underlying data supporting these positions, to offer surgical oncologists a framework for managing patients with pancreatic adenocarcinoma.
Collapse
Affiliation(s)
- Kevin M Turner
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Gregory C Wilson
- Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Sameer H Patel
- Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Syed A Ahmad
- Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
| |
Collapse
|
|
27
|
Wiessner JR, Orben F, Schäfer A, Fricke L, Schneider G, Reichert M, Herner A, Mayr U, Phillip V, Treiber M, von Figura G, Abdelhafez M, Schmid RM, Schlag C. Comparison of endoscopic ultrasound-guided fine-needle aspiration and fine-needle biopsy to generate pancreatic cancer organoids: Randomized trial. Endosc Int Open 2024; 12:E361-E366. [PMID: 38464982 PMCID: PMC10919996 DOI: 10.1055/a-2257-3171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 12/19/2023] [Indexed: 03/12/2024] Open
Abstract
Background and study aims The prognosis for pancreatic cancer remains poor. Molecular diagnostics and customized therapies are becoming increasingly important in clinical routine. Patient-derived, predictive model systems such as organoids have the potential to substantially increase the depth of information from biopsy material by functional and molecular characterization. We compared the extent to which the use of fine-needle aspiration needles (FNA, 22G) or fine-needle biopsy needles (FNB, 22G) influences the generation of pancreatic cancer patient-derived organoids (PDOs) to establish endoscopic standards of organoid technology. Patients and methods Endoscopic ultrasound (EUS)-guided punctures by EUS-FNA and EUS-FNB of pancreatic masses highly suspicious for adenocarcinoma (detected by computed tomography and/or magnetic resonance imaging) were prospectively evaluated. Consecutive patients received EUS-FNA and EUS-FNB in a randomized order without the need to exchange the needle shaft (only the inner needle type (FNA/-B) was exchanged) between the passes. With each needle type, the specimens for histological analysis and for PDOs were obtained separately. Results Fifty patients were enrolled in the study. Histology revealed malignancy in 42 of 50 cases (84%). In total PDOs were generated from 17 patients (34%). Of these, nine were established by FNB only, two by FNA only, and six by both FNA and FNB. Histology revealed malignancy in 13 of 17 PDO cases (76%). In two histologically false-negative cases, PDOs could be established. Conclusions EUS-FNB was superior to EUS-FNA in terms of successful generation of PDOs, although it failed to show statistical significance.
Collapse
Affiliation(s)
- Johannes Roman Wiessner
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
| | - Felix Orben
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
| | - Arlett Schäfer
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
| | - Lisa Fricke
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
| | - Günter Schneider
- Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Gottingen, Germany
- Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Chair of Translational Cancer Research and Institute of Experimental Cancer Therapy, München, Germany
- CCC-N (Comprehensive Cancer Center Lower Saxony), Medizinische Hochschule Hannover, Hannover, Germany
| | - Maximilian Reichert
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
- Translational Pancreatic Cancer Center, Medical Clinic and Polyclinic II, Technical University of Munich, München, Germany
- German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Partner Site Munich, DKFZ, Heidelberg, Germany
- Center for Protein Assemblies (CPA), Technical University of Munich, 85747, Garching, Germany
| | - Alexander Herner
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zürich, Switzerland
| | - Ulrich Mayr
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
| | - Veit Phillip
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
| | - Matthias Treiber
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
| | - Guido von Figura
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
| | - Mohamed Abdelhafez
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
| | - Roland M. Schmid
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
| | - Christoph Schlag
- Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zürich, Switzerland
| |
Collapse
|
|
28
|
Pacheco-Barcia V, Custodio-Cabello S, Carrasco-Valero F, Palka-Kotlowska M, Mariño-Mendez A, Carmona-Bayonas A, Gallego J, Martín AJM, Jimenez-Fonseca P, Cabezon-Gutierrez L. Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial. World J Gastrointest Oncol 2024; 16:386-397. [PMID: 38425396 PMCID: PMC10900150 DOI: 10.4251/wjgo.v16.i2.386] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/14/2023] [Accepted: 01/10/2024] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND The prognostic value of the Systemic Inflammation Response Index (SIRI) in advanced pancreatic cancer is recognized, but its correlation with patients´ nutritional status and outcomes remains unexplored. AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer. METHODS The PANTHEIA-Spanish Society of Medical Oncology (SEOM) study is a multicentric (16 Spanish hospitals), observational, longitudinal, non-interventional initiative, promoted by the SEOM Real World-Evidence work group. This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI. The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers. Patients with pathologically confirmed metastatic pancreatic adenocarcinoma, treated from January 2020 to January 2023, were included. The index was calculated using the product of neutrophil and monocyte counts, divided by lymphocyte counts, obtained within 15 days before initiation chemotherapy. This study evaluated associations between overall survival (OS), SIRI and weight loss. RESULTS A total of 50 patients were included. 66% of these patients were male and the median age was 66 years. Metastasis sites: 36% liver, 12% peritoneal carcinomatosis, 10% lung, and 42% multiple locations. Regarding the first line palliative chemotherapy treatments: 50% received gemcitabine plus nab-paclitaxel; 28%, modified fluorouracil, leucovorin, irinotecan and oxaliplatin, and 16% were administered gemcitabine. 42% had a weight loss > 5% in the three months (mo) preceding diagnosis. 21 patients with a SIRI ≥ 2.3 × 103/L exhibited a trend towards a lower median OS compared to those with a SIRI < 2.3 × 103/L (4 vs 18 mo; P < 0.000). Among 21 patients with > 5% weight loss before diagnosis, the median OS was 6 mo, in contrast to 19 mo for those who did not experience such weight loss (P = 0.003). Patients with a weight loss > 5% showed higher SIRI levels. This difference was statistically significant (P < 0.000). For patients with a SIRI < 2.3 × 103/L, those who did not lose > 5% of their weight had an OS of 20 mo, compared to 11 mo for those who did (P < 0.001). No association was found between carbohydrate antigen 19-9 levels ≥ 1000 U/mL and weight loss. CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss. An elevated SIRI is suggested as a predictor of survival, emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.
Collapse
Affiliation(s)
- Vilma Pacheco-Barcia
- Department of Medical Oncology, Hospital Universitario de Torrejon, Madrid 28850, Spain
| | - Sara Custodio-Cabello
- Department of Medical Oncology, Hospital Universitario de Torrejon, Madrid 28850, Spain
| | - Fatima Carrasco-Valero
- Department of Internal Medicine, Hospital Universitario de Torrejon, Madrid 28850, Spain
| | - Magda Palka-Kotlowska
- Department of Medical Oncology, Hospital Universitario de Torrejon, Madrid 28850, Spain
| | - Axel Mariño-Mendez
- Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo 33011, Spain
| | - Alberto Carmona-Bayonas
- Department of Medical Oncology, Hospital Universitario Morales Meseguer, University of Murcia, Murcia 30001, Spain
| | - Javier Gallego
- Department of Medical Oncology, Hospital General Universitario de Elche, Elche 03202, Spain
| | - A J Muñoz Martín
- Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Universidad Complutense Madrid, Madrid 28007, Spain
| | - Paula Jimenez-Fonseca
- Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo 33011, Spain
| | - Luis Cabezon-Gutierrez
- Department of Medical Oncology, Hospital Universitario de Torrejon, Madrid 28850, Spain
- Universidad Francisco de Vitoria, Madrid 28223, Spain
| |
Collapse
|
|
29
|
Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, van Tienhoven G, van Santvoort HC, Molenaar IQ, Wilmink JW, Del Chiaro M, Katz MHG, Hackert T, Besselink MG. Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer. Nat Rev Gastroenterol Hepatol 2024; 21:101-124. [PMID: 38036745 DOI: 10.1038/s41575-023-00856-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/05/2023] [Indexed: 12/02/2023]
Abstract
Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.
Collapse
Affiliation(s)
- Thomas F Stoop
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Rutger T Theijse
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands
- Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Leonard W F Seelen
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
| | - Christopher L Wolfgang
- Division of Surgical Oncology, Department of Surgery, New York University Medical Center, New York City, NY, USA
| | - Geertjan van Tienhoven
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Radiation Oncology, Amsterdam, Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - Johanna W Wilmink
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, Netherlands
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Marc G Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands.
- Cancer Center Amsterdam, Amsterdam, Netherlands.
| |
Collapse
|
|
30
|
Wang G, Lei W, Duan S, Cao A, Shi H. Preoperative evaluating early recurrence in resectable pancreatic ductal adenocarcinoma by using CT radiomics. Abdom Radiol (NY) 2024; 49:484-491. [PMID: 37955726 DOI: 10.1007/s00261-023-04074-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 09/23/2023] [Accepted: 09/25/2023] [Indexed: 11/14/2023]
Abstract
OBJECTIVE To investigate the feasibility of a radiomics model based on contrast-enhanced CT for preoperatively predicting early recurrence after curative resection in patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS One hundred and eighty-six patients with resectable PDAC who underwent curative resection were included and allocated to training set (131 patients) and validation set (55 patients). Radiomics features were extracted from arterial phase and portal venous phase images. The Mann-Whitney U test and least absolute shrinkage and selection operator (LASSO) regression were used for feature selection and radiomics signature construction. The radiomics model based on radiomics signature and clinical features was developed by the multivariate logistic regression analysis. Performance of the radiomics model was investigated by the area under the receiver operating characteristic (ROC) curve. RESULTS The radiomics signature, consisting of three arterial phase and three venous phase features, showed optimal prediction performance for early recurrence in both training (AUC = 0.73) and validation sets (AUC = 0.66). Multivariate logistic analysis identified the radiomics signature (OR, 2.58; 95% CI 2.36-3.17; p = 0.002) and clinical stage (OR, 1.60; 95% CI 1.15-2.30; p = 0.007) as independent predictors. The AUC values for risk evaluation of early recurrence using the radiomics model incorporating clinical stage were 0.80 (training set) and 0.75 (validation set). CONCLUSION The radiomics-based model integrating with clinical stage can predict early recurrence after upfront surgery in patients with resectable PDAC.
Collapse
Affiliation(s)
- Gang Wang
- Department of Radiotherapy, The Second Affiliated Hospital of Xuzhou Medical University, 32 Meijian Road, Xuzhou, People's Republic of China
| | - Weijie Lei
- Department of Radiotherapy, The Second Affiliated Hospital of Xuzhou Medical University, 32 Meijian Road, Xuzhou, People's Republic of China
| | - Shaofeng Duan
- GE Healthcare, Pudong New Town, 1 Huatuo Road, Shanghai, People's Republic of China
| | - Aihong Cao
- Department of Radiology, The Second Affiliated Hospital of Xuzhou Medical University, 32 Meijian Road, Xuzhou, People's Republic of China.
| | - Hongyuan Shi
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, People's Republic of China.
| |
Collapse
|
|
31
|
Sugawara T, Rodriguez Franco S, Sherman S, Torphy RJ, Colborn K, Franklin O, Ishida J, Grandi S, Al-Musawi MH, Gleisner A, Schulick RD, Del Chiaro M. Neoadjuvant Chemotherapy Versus Upfront Surgery for Resectable Pancreatic Adenocarcinoma: An Updated Nationwide Study. Ann Surg 2024; 279:331-339. [PMID: 37226812 DOI: 10.1097/sla.0000000000005925] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
OBJECTIVE The objective of this study was to assess the association of survival with neoadjuvant chemotherapy (NAC) in resectable pancreatic adenocarcinoma (PDAC). BACKGROUND The early control of potential micrometastases and patient selection using NAC has been advocated for patients with PDAC. However, the role of NAC for resectable PDAC remains unclear. METHODS Patients with clinical T1 and T2 PDAC were identified in the National Cancer Database from 2010 to 2017. Kaplan-Meier estimates, and Cox regression models were used to compare survival. To address immortal time bias, landmark analysis was performed. Interactions between preoperative factors and NAC were investigated in subgroup analyses. A propensity score analysis was performed to compare survival between multiagent NAC and upfront surgery. RESULTS In total, 4041 patients were treated with upfront surgery and 1,175 patients were treated with NAC (79.4% multiagent NAC, 20.6% single-agent NAC). Using a landmark time of 6 months after diagnosis, patients treated with multiagent NAC had longer median overall survival compared with upfront surgery and single-agent NAC. (35.8 vs 27.1 vs 27.4 mo). Multiagent NAC was associated with lower mortality rates compared with upfront surgery (adjusted hazard ratio, 0.77; 95% CI, 0.70-0.85), whereas single-agent NAC was not. The association of survival with multiagent NAC were consistent in analyses using the matched data sets. Interaction analysis revealed that the association between multiagent NAC and a lower mortality rate did not significantly differ across age, facility type, tumor location, CA 19-9 levels, and clinical T/N stages. CONCLUSIONS The findings suggest that multiagent NAC followed by resection is associated with improved survival compared with upfront surgery.
Collapse
Affiliation(s)
- Toshitaka Sugawara
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Samantha Sherman
- Department of Surgery, Parkview Hospital Randallia, Fort Wayne, IN
| | - Robert J Torphy
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Kathryn Colborn
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
- Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, CO
- Surgical Outcomes and Applied Research Program, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
| | - Oskar Franklin
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden
| | - Jun Ishida
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Samuele Grandi
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | | | - Ana Gleisner
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
- University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO
| | - Richard D Schulick
- Surgical Outcomes and Applied Research Program, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
- University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
- University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO
| |
Collapse
|
|
32
|
Heiling HM, Rashid NU, Li Q, Peng XL, Yeh JJ, Ibrahim JG. Efficient computation of high-dimensional penalized generalized linear mixed models by latent factor modeling of the random effects. Biometrics 2024; 80:ujae016. [PMID: 38497825 PMCID: PMC10946237 DOI: 10.1093/biomtc/ujae016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 11/22/2023] [Accepted: 02/16/2024] [Indexed: 03/19/2024]
Abstract
Modern biomedical datasets are increasingly high-dimensional and exhibit complex correlation structures. Generalized linear mixed models (GLMMs) have long been employed to account for such dependencies. However, proper specification of the fixed and random effects in GLMMs is increasingly difficult in high dimensions, and computational complexity grows with increasing dimension of the random effects. We present a novel reformulation of the GLMM using a factor model decomposition of the random effects, enabling scalable computation of GLMMs in high dimensions by reducing the latent space from a large number of random effects to a smaller set of latent factors. We also extend our prior work to estimate model parameters using a modified Monte Carlo Expectation Conditional Minimization algorithm, allowing us to perform variable selection on both the fixed and random effects simultaneously. We show through simulation that through this factor model decomposition, our method can fit high-dimensional penalized GLMMs faster than comparable methods and more easily scale to larger dimensions not previously seen in existing approaches.
Collapse
Affiliation(s)
- Hillary M Heiling
- Department of Biostatistics, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, United States
| | - Naim U Rashid
- Department of Biostatistics, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, United States
| | - Quefeng Li
- Department of Biostatistics, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, United States
| | - Xianlu L Peng
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
| | - Jen Jen Yeh
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
- Department of Surgery, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, United States
- Department of Pharmacology, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, United States
| | - Joseph G Ibrahim
- Department of Biostatistics, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, United States
| |
Collapse
|
|
33
|
Pourali G, Donyadideh G, Mehrabadi S, Hamid F, Hassanian SM, Ferns GA, Khazaei M, Avan A. Clinical practice guidelines for interventional treatment of pancreatic cancer. RECENT ADVANCES IN NANOCARRIERS FOR PANCREATIC CANCER THERAPY 2024:345-373. [DOI: 10.1016/b978-0-443-19142-8.00008-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
|
|
34
|
Shao Z, Chen X, Qiu H, Xu M, Wen X, Chen Z, Liu Z, Ding X, Zhang L. CircNEK6 promotes the progression of pancreatic ductal adenocarcinoma through targeting miR-503/CCND1 axis. Transl Oncol 2024; 39:101810. [PMID: 37871516 PMCID: PMC10622713 DOI: 10.1016/j.tranon.2023.101810] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 09/16/2023] [Accepted: 10/16/2023] [Indexed: 10/25/2023] Open
Abstract
PURPOSE The present study aimed to reveal the function and underlying molecular mechanism of circRNA NIMA related kinase 6 (circNEK6) in promoting the progression of pancreatic ductal adenocarcinoma (PDAC). METHODS The differentially expressed circRNAs in three paired PDAC tissues and adjacent tissues were identified by RNA sequencing. CircNEK6 was screened out to further explore its relationship with the prognosis of PDAC patients. The target microRNAs and mRNAs of circNEK6 were analyzed through online databases and detected by quantitative real-time polymerase chain reaction. Cell counting kit-8 assay, clone formation assay, transwell assay, flow cytometry and western blot were used to explore the function of circNEK6 on the biological behaviors of PDAC cells. The in vivo antitumor effect of circNEK6 silencing on PDAC was investigated by nude mouse xenograft models. RESULTS 203 differentially expressed circRNAs including circNEK6 were identified between paired PDAC tissues and adjacent tissues, and the expression level of circNEK6 was negatively correlated with the prognosis of PDAC patients. The results of in vitro experiments showed that knockdown of circNEK6 repressed the proliferation, migration and invasion, but induced the apoptosis of PDAC cells. Moreover, circNEK6 silencing inhibited tumor growth and prolonged the survival time of PDAC-bearing mice. Mechanistically, miR-503/cyclin D1 (CCND1) axis was predicted and confirmed as the target of circNEK6. CONCLUSIONS CircNEK6 serves as a competing endogenous RNA of CCND1 by absorbing miR-503, which might be treated as a novel and potential target for PDAC treatment.
Collapse
Affiliation(s)
- Zhiying Shao
- Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Xueting Chen
- Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Hui Qiu
- Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, No. 9 Kunpeng North Road, Xuzhou, Jiangsu 221000, China
| | - Muchen Xu
- Department of Radiation Oncology, Dushu Lake Hospital Affilated to Soochow University, Medical Center of Soochow University, Suzhou, Jiangsu 215000, China
| | - Xin Wen
- Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, No. 9 Kunpeng North Road, Xuzhou, Jiangsu 221000, China
| | - Ziqin Chen
- Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Zhengyang Liu
- Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
| | - Xin Ding
- Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, No. 9 Kunpeng North Road, Xuzhou, Jiangsu 221000, China.
| | - Longzhen Zhang
- Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221000, China; Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, No. 9 Kunpeng North Road, Xuzhou, Jiangsu 221000, China.
| |
Collapse
|
|
35
|
Katz MHG, Petroni GR, Bauer T, Reilley MJ, Wolpin BM, Stucky CC, Bekaii-Saab TS, Elias R, Merchant N, Dias Costa A, Lenehan P, Cardot-Ruffino V, Rodig S, Pfaff K, Dougan SK, Nowak JA, Varadhachary GR, Slingluff CL, Rahma O. Multicenter randomized controlled trial of neoadjuvant chemoradiotherapy alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic adenocarcinoma. J Immunother Cancer 2023; 11:e007586. [PMID: 38040420 PMCID: PMC10693876 DOI: 10.1136/jitc-2023-007586] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2023] [Indexed: 12/03/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a challenging target for immunotherapy because it has an immunosuppressive tumor microenvironment. Neoadjuvant chemoradiotherapy can increase tumor-infiltrating lymphocyte (TIL) density, which may predict overall survival (OS). We hypothesized that adding programmed cell death protein 1 (PD-1) blockade to chemoradiotherapy would be well tolerated and increase TILs among patients with localized PDAC. METHODS Patients were randomized 2:1 to Arm A (receiving pembrolizumab plus chemoradiotherapy (capecitabine and external beam radiation)) or Arm B (receiving chemoradiotherapy alone) before anticipated pancreatectomy. Primary endpoints were (1) incidence and severity of adverse events during neoadjuvant therapy and (2) density of TILs in resected tumor specimens. TIL density was assessed using multiplexed immunofluorescence histologic examination. RESULTS Thirty-seven patients were randomized to Arms A (n=24) and B (n=13). Grade ≥3 adverse events related to neoadjuvant treatment were experienced by 9 (38%) and 4 (31%) patients in Arms A and B, respectively, with one patient experiencing dose-limiting toxicity in Arm A. Seventeen (71%) and 7 (54%) patients in Arms A and B, respectively, underwent pancreatectomy. Median CD8+ T-cell densities in Arms A and B were 67.4 (IQR: 39.2-141.8) and 37.9 (IQR: 22.9-173.4) cells/mm2, respectively. Arms showed no noticeable differences in density of CD8+Ki67+, CD4+, or CD4+FOXP3+ regulatory T cells; M1-like and M2-like macrophages; or granulocytes. Median OS durations were 27.8 (95% CI: 17.1 to NR) and 24.3 (95% CI: 12.6 to NR) months for Arms A and B, respectively. CONCLUSIONS Adding pembrolizumab to neoadjuvant chemoradiotherapy was safe. However, no convincing effect on CD8+ TILs was observed.
Collapse
Affiliation(s)
- Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Gina R Petroni
- Division of Translational Research and Applied Statistics, Department of Public Health Sciences, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Todd Bauer
- Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Matthew J Reilley
- Division of Hematology and Oncology, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Brian M Wolpin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | | | - Tanios S Bekaii-Saab
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Mayo Clin, Phoenix, Arizona, USA
| | - Rawad Elias
- Hartford HealthCare Cancer Institute, Plainville, Connecticut, USA
| | - Nipun Merchant
- Department of Surgery, University of Miami, Coral Gables, Florida, USA
| | - Andressa Dias Costa
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
| | - Patrick Lenehan
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA
| | - Victoire Cardot-Ruffino
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA
| | - Scott Rodig
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA
| | - Kathleen Pfaff
- Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Stephanie K Dougan
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA
| | - Jonathan Andrew Nowak
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA
| | - Gauri R Varadhachary
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Craig L Slingluff
- Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Osama Rahma
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
|
36
|
Wu VS, Elshami M, Stitzel HJ, Lee JJ, Hue JJ, Kyasaram RK, Hardacre JM, Ammori JB, Winter JM, Selfridge JE, Mohamed A, Chakrabarti S, Bajor D, Mahipal A, Ocuin LM. Why the Treatment Sequence Matters: Interplay Between Chemotherapy Cycles Received, Cumulative Dose Intensity, and Survival in Resected Early-stage Pancreas Cancer. Ann Surg 2023; 278:e677-e684. [PMID: 37071769 DOI: 10.1097/sla.0000000000005830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2023]
Abstract
OBJECTIVE To define the optimal threshold of perioperative chemotherapy completion and relative dose intensity (RDI) for patients with resected pancreatic ductal adenocarcinoma (PDAC). BACKGROUND Many patients who undergo pancreatectomy for PDAC fail to initiate or complete recommended perioperative chemotherapy. The association between the amount of perioperative chemotherapy received and overall survival (OS) is not well-defined. METHODS Single-institution analysis of 225 patients who underwent pancreatectomy for stage I/II PDAC (2010-2021). Associations between OS, chemotherapy cycles completed, and RDI were analyzed. RESULTS Regardless of treatment sequence, completion of ≥67% of recommended cycles was associated with improved OS compared with no chemotherapy [median OS: 34.5 vs 18.1 months; hazard ratio (HR): 0.43; 95% CI: 0.25-0.74] and <67% of cycles (median OS: 17.9 months; HR: 0.39; 95% CI: 0.24-0.64). A near-linear relationship existed between cycles completed and the RDI received (β = 0.82). A median RDI of 56% corresponded to the completion of 67% of cycles. Receipt of ≥56% RDI was associated with improved OS compared with no chemotherapy (median OS: 35.5 vs 18.1 months; HR: 0.44; 95% CI: 0.23-0.84) and <56% RDI (median OS: 27.2 months; HR: 0.44; 95% CI: 0.20-0.96). Neoadjuvant chemotherapy is associated with increased odds of receiving ≥67% of recommended cycles (odds ratio: 2.94; 95% CI: 1.45-6.26) and ≥56% RDI (odds ratio: 4.47; 95% CI: 1.72-12.50). CONCLUSIONS Patients with PDAC who received ≥67% of recommended chemotherapy cycles or ≥56% cumulative RDI had improved OS. Neoadjuvant therapy was associated with increased odds of receiving ≥67% of cycles and ≥56% cumulative RDI and should be considered in all patients with resectable PDAC.
Collapse
Affiliation(s)
- Victoria S Wu
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Mohamedraed Elshami
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Henry J Stitzel
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Jonathan J Lee
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Jonathan J Hue
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Ravi K Kyasaram
- Department of Cancer Informatics, University Hospitals Cleveland Medical Center/Seidman Cancer Center, Cleveland, OH
| | - Jeffrey M Hardacre
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - John B Ammori
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Jordan M Winter
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Jennifer Eva Selfridge
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
| | - Amr Mohamed
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
| | - Sakti Chakrabarti
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
| | - David Bajor
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
| | - Amit Mahipal
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
| | - Lee M Ocuin
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| |
Collapse
|
|
37
|
Spitzer HV, Kemp Bohan PM, Carpenter EL, Adams AM, Chang SC, Grunkemeier G, Vreeland TJ, Tzeng CWD, Katz MHG, Nelson DW. Impact of Adherence to Operative Standards and Stage-Specific Guideline-Recommended Therapy in Nonmetastatic Pancreatic Adenocarcinoma. Ann Surg Oncol 2023; 30:6662-6670. [PMID: 37330447 DOI: 10.1245/s10434-023-13758-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/29/2023] [Indexed: 06/19/2023]
Abstract
BACKGROUND Achieving optimal surgical outcomes in pancreatic adenocarcinoma requires a combination of both curative-intent resection to oncologic standards and stage-specific neoadjuvant or adjuvant therapy. This investigation sought to examine factors associated with receipt of standard-adherent surgery (SAS) and guideline-recommended therapy (GRT) and determine the impact of compliance on patient survival. PATIENTS AND METHODS From the 2006-2016 National Cancer Database, 21,304 patients underwent resection for nonmetastatic pancreatic adenocarcinoma. SAS was defined as pancreatic resection with negative margins and ≥ 15 lymph nodes examined. Stage-specific GRT was defined by current National Comprehensive Cancer Network guidelines. Multivariable models were used to determine predictors of adherence to SAS and GRT and prognostic impact on overall survival. RESULTS Overall, SAS was achieved in 39% and GRT in 65% of patients, but only 30% received both SAS and GRT. Increasing age, minority race, uninsured status, and greater comorbidities were associated with a decreased odds of receiving both SAS and GRT (all p < 0.05). SAS (HR 0.79; CI 0.76-0.81; p < 0.001) and GRT (HR 0.67; CI 0.65-0.69; p < 0.001) were each independently associated with a survival advantage. Receipt of both SAS and GRT was associated with significant improvement in median OS compared with receiving neither (2.2 years vs 1.1 years; p < 0.001) which was independently associated with a 78% increased risk of death (HR 1.78; CI 1.70-1.86; p < 0.001). CONCLUSIONS Despite survival benefits associated with adherence to operative standards and receipt of guideline-recommended therapy, compliance remains poor. Future efforts must be directed toward improved education and implementation efforts around both operative standards and therapy guidelines.
Collapse
Affiliation(s)
- Holly V Spitzer
- Department of Surgery, William Beaumont Army Medical Center, Uniformed Services University of the Health Sciences, Fort Bliss, TX, USA
| | | | | | - Alexandra M Adams
- Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, TX, USA
| | | | - Gary Grunkemeier
- Division of Cardiothoracic Surgery, Oregon Health and Science University, Portland, OR, USA
| | - Timothy J Vreeland
- Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, TX, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
| | - Daniel W Nelson
- Department of Surgery, William Beaumont Army Medical Center, Uniformed Services University of the Health Sciences, Fort Bliss, TX, USA.
| |
Collapse
|
|
38
|
Bohan RP, Riner AN, Herremans KM, George TJ, Hughes SJ, Solberg LB. Ethical Considerations of Biopsies in Early-Stage Pancreatic Cancer. JCO Oncol Pract 2023; 19:882-887. [PMID: 37647578 PMCID: PMC10615436 DOI: 10.1200/op.23.00044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 06/15/2023] [Accepted: 07/11/2023] [Indexed: 09/01/2023] Open
Abstract
PURPOSE The standard of care in resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC) has evolved to include neoadjuvant treatment before surgical resection. Current guidelines call for obtaining histologic tissue diagnosis via endoscopic ultrasound fine-needle aspiration before administration of neoadjuvant therapy, which differ from guidelines discouraging delay in surgical resection for a biopsy. MATERIALS AND METHODS Whether to proceed with treatment before a biopsy confirms that malignancy is a nuanced decision and includes considerations of physical and psychological risks entailed in both pursuing and forgoing a biopsy. RESULTS Accuracy of imaging and biopsy results, the presence of contributing clinical signs/symptoms, and the existing precedents of considering biopsies as waivable such as in scenarios with high clinical suspicion and primary surgical resection. CONCLUSION When considering the aspects of ethical medical practice including beneficence (doing good), nonmaleficence (avoiding harm), autonomy (allowing patients to make decisions about their care), and utilitarianism (doing the most good for the most people), analysis of whether guidelines guiding biopsies should continue to differ between resection and neoadjuvant treatments in PDAC is prudent.
Collapse
Affiliation(s)
- Riley P. Bohan
- University of Florida College of Medicine, Gainesville, FL
| | - Andrea N. Riner
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Kelly M. Herremans
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Thomas J. George
- Division of Hematology and Oncology, Department of Medicine, University of Florida College of Medicine, Gainesville, FL
| | - Steven J. Hughes
- Division of Surgical Oncology, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Lauren B. Solberg
- Program in Bioethics, Law and Medical Professionalism, Department of Community Health and Family Medicine, University of Florida College of Medicine, Gainesville, FL
| |
Collapse
|
|
39
|
Jain AJ, Maxwell JE, Katz MHG, Snyder RA. Surgical Considerations for Neoadjuvant Therapy for Pancreatic Adenocarcinoma. Cancers (Basel) 2023; 15:4174. [PMID: 37627202 PMCID: PMC10453019 DOI: 10.3390/cancers15164174] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 08/04/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of response to therapy. Herein, we review key surgical considerations when selecting patients for neoadjuvant therapy and curative-intent resection. Accurate determination of resectability at diagnosis is critical and should be based on not only anatomic criteria but also biologic and clinical criteria to determine optimal treatment sequencing. Borderline resectable or locally advanced pancreatic cancer is best treated with neoadjuvant therapy and resection, including vascular resection and reconstruction when appropriate. Lastly, providing nutritional, prehabilitation, and supportive care interventions to improve patient fitness prior to surgical intervention and adequately address the adverse effects of therapy is critical.
Collapse
Affiliation(s)
| | | | | | - Rebecca A. Snyder
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (A.J.J.)
| |
Collapse
|
|
40
|
Xie N, Fan X, Chen D, Chen J, Yu H, He M, Liu H, Yin X, Li B, Wang H. Peritumoral and Intratumoral Texture Features Based on Multiparametric MRI and Multiple Machine Learning Methods to Preoperatively Evaluate the Pathological Outcomes of Pancreatic Cancer. J Magn Reson Imaging 2023; 58:379-391. [PMID: 36426965 DOI: 10.1002/jmri.28538] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/13/2022] [Accepted: 11/14/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Radiomics-based preoperative evaluation of lymph node metastasis (LNM) and histological grade (HG) might facilitate the decision-making for pancreatic cancer and further efforts are needed to develop effective models. PURPOSE To develop multiparametric MRI (MP-MRI)-based radiomics models to evaluate LNM and HG. STUDY TYPE Retrospective. POPULATION The pancreatic cancer patients from the main center (n = 126) were assigned to the training and validation sets at a 4:1 ratio. The patients from the other center (n = 40) served as external test sets. FIELD STRENGTH/SEQUENCE A 3.0 T and 1.5 T/T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement T1-weighted imaging. ASSESSMENT A total of 10,686 peritumoral and intratumoral radiomics features were extracted which contained first-order, shape-based, and texture features. The following three-step method was applied to reduce the feature dimensionality: SelectKBest (a function from scikit-learn package), least absolute shrinkage and selection operator (LASSO), and recursive feature elimination based on random forest (RFE-RF). Six classifiers (random forest, logistic regression, support vector machine, K-nearest neighbor, decision tree, and XGBOOST) were trained and selected based on their performance to construct the clinical, radiomics, and combination models. STATISTICAL TESTS Delong's test was used to compare the models' performance. P value less than 0.05 was considered significant. RESULTS Twelve significant features for LNM and 11 features for HG were obtained. Random forest and logistic regression performed better than the other classifiers in evaluating LNM and HG, respectively, according to the surgical pathological results. The best performance was obtained with the models that combined peritumoral and intratumoral features with area under curve (AUC) values of 0.944 and 0.892 in the validation and external test sets for HG and 0.924 and 0.875 for LNM. DATA CONCLUSION Radiomics holds the potential to evaluate LNM and HG of pancreatic cancer. The combination of peritumoral and intratumoral features will make models more accurate. EVIDENCE LEVEL 4. TECHNICAL EFFICACY Stage 2.
Collapse
Affiliation(s)
- Ni Xie
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuhui Fan
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
- National Center for Translational Medicine (Shanghai), Shanghai, China
| | - Desheng Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingwen Chen
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
- National Center for Translational Medicine (Shanghai), Shanghai, China
| | - Hongwei Yu
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
- National Center for Translational Medicine (Shanghai), Shanghai, China
| | - Meijuan He
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
- National Center for Translational Medicine (Shanghai), Shanghai, China
| | - Hao Liu
- Yizhun Medical AI Technology Co. Ltd., Beijing, China
| | - Xiaorui Yin
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
| | - Baiwen Li
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Han Wang
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
- National Center for Translational Medicine (Shanghai), Shanghai, China
- Jiading Branch of Shanghai General Hospital, Shanghai, China
| |
Collapse
|
|
41
|
Tan Q, Chen C, Wang Z, Zhang H, Liu X, Ke N. Prognostic role of radiological splenic vessel involvement in patients with resectable pancreatic ductal adenocarcinoma of the body and tail: A retrospective analysis based on a large population. Eur J Radiol 2023; 165:110952. [PMID: 37421772 DOI: 10.1016/j.ejrad.2023.110952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 06/24/2023] [Accepted: 06/27/2023] [Indexed: 07/10/2023]
Abstract
BACKGROUND Tumors located in the pancreatic body or tail are more likely to invade splenic vessels; however, splenic artery (SpA) or vein (SpV) involvement is not included in the criteria for resectability. We aimed to analyze the prognostic role of radiological splenic vessel involvement in patients with resectable pancreatic ductal adenocarcinoma (PDAC) of the body and tail. METHODS Patients with resetable PDAC were retrospectively reviewed and analyzed. SpA and SpV involvement were graded as clear, abutment and encasement. Multivariate Cox and logistic regression analyses were used to identify prognostic factors for overall survival (OS) and risk factors for early recurrence, respectively. RESULTS Of the 234 patients, 94 patients had radiologic SpA invasion, including abutment in 47 patients and encasement in 47 patients, while 123 patients had radiological SpV invasion, including abutment in 69 patients and encasement in 54 patients. Patients with SpA or SpV encasement showed a significantly worse OS and recurrence-free survival than those with SpA or SpV clear (P < 0.001, respectively). In multivariate analysis, both SpA and SpV encasement were independently associated with poor OS (SpA: hazard ratio [HR] 1.89, P = 0.010; SpV: HR 2.01, P = 0.001) and early recurrence (SpA: odds ratio [OR] 4.98, P < 0.001; SpV: OR 3.71, P = 0.002). CONCLUSION Radiological SpA or SpV encasement independently decreases OS, and is associated with early recurrence of resectable PDAC of the body/tail.
Collapse
Affiliation(s)
- Qingquan Tan
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Chen Chen
- Department of Radiology, The First People's Hospital of Chengdu, Chengdu, Sichuan Province, China; Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Ziyao Wang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Haoqi Zhang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xubao Liu
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Nengwen Ke
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
| |
Collapse
|
|
42
|
Ngo-Huang AT, Parker NH, Xiao L, Schadler KL, Petzel MQB, Prakash LR, Kim MP, Tzeng CWD, Lee JE, Ikoma N, Wolff RA, Javle MM, Koay EJ, Pant SD, Folloder JP, Wang X, Cotto AM, Ju YR, Garg N, Wang H, Bruera ED, Basen-Engquist KM, Katz MHG. Effects of a Pragmatic Home-based Exercise Program Concurrent With Neoadjuvant Therapy on Physical Function of Patients With Pancreatic Cancer: The PancFit Randomized Clinical Trial. Ann Surg 2023; 278:22-30. [PMID: 37026453 PMCID: PMC10330108 DOI: 10.1097/sla.0000000000005878] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
OBJECTIVE To determine the effects of a preoperative, home-based exercise program on fitness and physical function in patients with pancreatic cancer. BACKGROUND We previously established a well-tolerated preoperative exercise program after finding a high frequency of sarcopenia and frailty in patients with pancreatic cancer. METHODS In this randomized, controlled trial (NCT03187951), patients with pancreatic cancer were randomized to Arm A: enhanced usual care or Arm B: prescribed aerobic and resistance exercise during neoadjuvant therapy. Patients received nutrition counseling and activity trackers. The primary endpoint was a 6-minute walk distance (6MWD; ≥14 meters improvement was clinically meaningful). Secondary endpoints included additional physical function tests, health-related quality of life, and clinical outcomes. RESULTS One hundred fifty-one patients were randomized. Objectively measured weekly activity (153.2±135.6 and 159.8±122.8 min in Arm A and B, respectively, P =0.62) and self-reported weekly moderate-to-strenuous physical activity (107.4±160.4 and 129.6±161.6 min in Arm A and Arm B, respectively, P =0.49) were similar, but weekly strength training sessions increased more in Arm B (by 1.8±1.8 vs 0.1±2.4 sessions, P <0.001). 6MWD improved in both Arm A (mean change 18.6±56.8 m, P =0.01) and Arm B (27.3±68.1 m, P =0.002). Quality of life and clinical outcomes did not significantly differ between arms. Pooling patients in both study groups, exercise, and physical activity was favorably associated with physical performance and clinical outcomes. CONCLUSIONS In this randomized trial of prescribed exercise versus enhanced usual care during neoadjuvant therapy for pancreatic cancer, a high volume of physical activity and increased exercise capacity were observed in both arms, highlighting the importance of activity among patients preparing for surgery.
Collapse
Affiliation(s)
- An T Ngo-Huang
- Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Nathan H Parker
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL
| | - Lianchun Xiao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Keri L Schadler
- Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Maria Q B Petzel
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Laura R Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Michael P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Robert A Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Milind M Javle
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eugene J Koay
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Shubham D Pant
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Justin P Folloder
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Xuemei Wang
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Alicia M Cotto
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL
| | - Ye Rang Ju
- Department of Health Disparities Research, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Naveen Garg
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Huamin Wang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eduardo D Bruera
- Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Karen M Basen-Engquist
- Department of Health Disparities Research, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| |
Collapse
|
|
43
|
Tsunedomi R, Shindo Y, Nakajima M, Yoshimura K, Nagano H. The tumor immune microenvironment in pancreatic cancer and its potential in the identification of immunotherapy biomarkers. Expert Rev Mol Diagn 2023; 23:1121-1134. [PMID: 37947389 DOI: 10.1080/14737159.2023.2281482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 11/06/2023] [Indexed: 11/12/2023]
Abstract
INTRODUCTION Pancreatic cancer (PC) has an extremely poor prognosis, even with surgical resection and triplet chemotherapy treatment. Cancer immunotherapy has been recently approved for tumor-agnostic treatment with genome analysis, including in PC. However, it has limited efficacy. AREAS COVERED In addition to the low tumor mutation burden, one of the difficulties of immunotherapy in PC is the presence of abundant stromal cells in its microenvironment. Among stromal cells, cancer-associated fibroblasts (CAFs) play a major role in immunotherapy resistance, and CAF-targeted therapies are currently under development, including those in combination with immunotherapies. Meanwhile, microbiomes and tumor-derived exosomes (TDEs) have been shown to alter the behavior of distant receptor cells in PC. This review discusses the role of CAFs, microbiomes, and TDEs in PC tumor immunity. EXPERT OPINION Elucidating the mechanisms by which CAFs, microbiomes, and TDEs are involved in the tumorigenesis of PC will be helpful for developing novel immunotherapeutic strategies and identifying companion biomarkers for immunotherapy. Spatial single-cell analysis of the tumor microenvironment will be useful for identifying biomarkers of PC immunity. Furthermore, given the complexity of immune mechanisms, artificial intelligence models will be beneficial for predicting the efficacy of immunotherapy.
Collapse
Affiliation(s)
- Ryouichi Tsunedomi
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Yoshitaro Shindo
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Masao Nakajima
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Kiyoshi Yoshimura
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan
- Department of Clinical Immuno-Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Setagaya, Tokyo, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| |
Collapse
|
|
44
|
Hackert T, Klaiber U, Hinz U, Strunk S, Loos M, Strobel O, Berchtold C, Kulu Y, Mehrabi A, Müller-Stich BP, Schneider M, Büchler MW. Portal Vein Resection in Pancreatic Cancer Surgery: Risk of Thrombosis and Radicality Determine Survival. Ann Surg 2023; 277:e1291-e1298. [PMID: 35793384 DOI: 10.1097/sla.0000000000005444] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To evaluate the outcomes of pancreatic cancer [pancreatic ductal adenocarcinoma (PDAC)] surgery with concomitant portal vein resection (PVR), focusing on the PVR type according to the International Study Group of Pancreatic Surgery (ISGPS). BACKGROUND Surgery offers the only chance for cure in PDAC. PVR is often performed for borderline or locally advanced tumors. METHODS Consecutive patients with PDAC operated between January 2006 and January 2018 were included. Clinicopathologic characteristics and outcomes were analyzed and tested for survival prediction. RESULTS Of 2265 PDAC resections, 1571 (69.4%) were standard resections and 694 (30.6%) were resections with PVR, including 149 (21.5%) tangential resections with venorrhaphy (ISGPS type 1), 21 (3.0%) resections with patch reconstruction (type 2), 491 (70.7%) end-to-end anastomoses (type 3), and 33 (4.8%) resections with graft interposition (type 4). The 90-day mortality rate was 2.6% after standard resection and 6.3% after resection with PVR ( P <0.0001). Postoperative portal vein thrombosis and pancreas-specific surgical complications most frequently occurred after PVR with graft interposition (21.2% and 48.5%, respectively). In multivariable analysis, age 70 years and above, ASA stages 3/4, increased preoperative serum carbohydrate antigen 19-9, neoadjuvant treatment, total pancreatectomy, PVR, higher UICC stage, and R+ resections were significant negative prognostic factors for overall survival. Radical R0 (>1 mm) resection resulted in 23.3 months of median survival. CONCLUSIONS This is the largest single-center, comparative cohort study of PVR in PDAC surgery, showing that postoperative morbidity correlates with the reconstruction type. When radical resection is achieved, thrombosis risk is outweighed by beneficial overall survival times of nearly 2 years.
Collapse
Affiliation(s)
- Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Yasuda S, Nagai M, Terai T, Kohara Y, Sho M. Essential updates 2021/2022: Surgical outcomes of oligometastasis in pancreatic ductal adenocarcinoma. Ann Gastroenterol Surg 2023; 7:358-366. [PMID: 37152775 PMCID: PMC10154895 DOI: 10.1002/ags3.12655] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/25/2022] [Accepted: 01/01/2023] [Indexed: 01/20/2023] Open
Abstract
Oligometastatic disease has been proposed as an intermediate state between localized and polymetastatic disease that can benefit from multimodal treatment, including surgery. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma, although there is still little evidence. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarized the current status of surgery in the multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives. In liver oligometastasis, multimodal treatment including surgery achieved favorable long-term survival, especially in patients with good responses to preoperative chemotherapy, with a median survival time from 25.5 to 54.6 months. In addition, the data from the National Cancer Database in the United States showed that patients who underwent surgery for oligometastatic liver metastases had a significantly longer overall survival than those who received chemotherapy alone. Prognostic biomarkers were identified, including carbohydrate antigen 19-9 (CA19-9) levels at diagnosis and preoperative chemotherapy with normalization of CA19-9 levels or favorable radiological response. Patients with lung oligometastasis had a more favorable long-term prognosis than those with other recurrence sites, and the updated literature further confirmed the previous studies. Overall survival was favorable, with 84 months after initial surgery and 29.2 months after metastasectomy, and a 5-year survival rate of 60.6% was also reported. In peritoneal oligometastasis, the results of conversion surgery after good responses to preoperative treatment with intraperitoneal therapy or systematic chemotherapy were reported, and the conversion rate and long-term prognosis were favorable. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarize the current status of surgery in multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives.
Collapse
Affiliation(s)
| | - Minako Nagai
- Department of SurgeryNara Medical UniversityNaraJapan
| | - Taichi Terai
- Department of SurgeryNara Medical UniversityNaraJapan
| | | | - Masayuki Sho
- Department of SurgeryNara Medical UniversityNaraJapan
| |
Collapse
|
|
46
|
de Scordilli M, Michelotti A, Zara D, Palmero L, Alberti M, Noto C, Totaro F, Foltran L, Guardascione M, Iacono D, Ongaro E, Fasola G, Puglisi F. Preoperative treatments in borderline resectable and locally advanced pancreatic cancer: current evidence and new perspectives. Crit Rev Oncol Hematol 2023; 186:104013. [PMID: 37116817 DOI: 10.1016/j.critrevonc.2023.104013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 04/10/2023] [Accepted: 04/24/2023] [Indexed: 04/30/2023] Open
Abstract
Surgery is the only curative treatment for non-metastatic pancreatic adenocarcinoma, but less than 20% of patients present a resectable disease at diagnosis. Treatment strategies and disease definition for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) vary in the different cancer centres. Preoperative chemotherapy (CT) is the standard of care for both BRPC and LAPC patients, however literature data are still controversial concerning the type, dose and duration of the different CT regimens, as well as regarding the integration of radiotherapy (RT) or chemoradiation (CRT) in the therapeutic algorithm. In this unsettled debate, we aimed at focusing on the therapeutic regimens currently in use and relative literature data, to report international trials comparing the available therapeutic options or explore the introduction of new pharmacological agents, and to analyse possible new scenarios in microenvironment evaluation before and after neoadjuvant therapies or in patients' selection at a molecular level.
Collapse
Affiliation(s)
- Marco de Scordilli
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
| | - Anna Michelotti
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy; Department of Oncology, ASUFC University Hospital of Udine, 33100 Udine, Italy.
| | - Diego Zara
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
| | - Lorenza Palmero
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
| | - Martina Alberti
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy; Department of Oncology, ASUFC University Hospital of Udine, 33100 Udine, Italy.
| | - Claudia Noto
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
| | - Fabiana Totaro
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
| | - Luisa Foltran
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
| | - Michela Guardascione
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
| | - Donatella Iacono
- Department of Oncology, ASUFC University Hospital of Udine, 33100 Udine, Italy.
| | - Elena Ongaro
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
| | - Gianpiero Fasola
- Department of Oncology, ASUFC University Hospital of Udine, 33100 Udine, Italy.
| | - Fabio Puglisi
- Department of Medicine (DAME), University of Udine, 33100 Udine, Italy; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
| |
Collapse
|
|
47
|
Smaglo BG. Role for Neoadjuvant Systemic Therapy for Potentially Resectable Pancreatic Cancer. Cancers (Basel) 2023; 15:2377. [PMID: 37190305 PMCID: PMC10136472 DOI: 10.3390/cancers15082377] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/10/2023] [Accepted: 04/18/2023] [Indexed: 05/17/2023] Open
Abstract
Despite aggressive adjuvant management, a high percentage of patients who undergo appropriate surgical resection for pancreatic cancer will see their cancer recur and thus will not be cured. An important paradigm shift to achieve better outcomes has been therapy sequence, with neoadjuvant chemotherapy preceding surgery. Patients with a borderline resectable cancer, or patients with a resectable cancer but who have other high-risk features, are ideal candidates to consider for neoadjuvant chemotherapy. Among the high-risk features, a baseline elevated CA 19-9 concentration can be particularly useful, as its response trend during neoadjuvant chemotherapy can offer important insights into the prognosis after surgery. When selecting a neoadjuvant chemotherapy regimen, response data available for the use of FOLFIRINOX and gemcitabine and nabpaclitaxel in the metastatic setting support their use in this space. FOLFIRINOX is perhaps the preferred regimen, given its proven adjuvant benefit and possibly its superior tumor response rate; still, patient tolerance and thus ability to complete recommended treatment must be carefully considered. This review presents the evidence supporting neoadjuvant chemotherapy for resectable pancreatic cancer, the factors to consider when making such a recommendation, the selection of specific regimens, and our institutional approach using these tools.
Collapse
Affiliation(s)
- Brandon G Smaglo
- Department of GastroIntestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA
| |
Collapse
|
|
48
|
de Geus SWL, Sachs TE. A Paradigm Shifts: Neoadjuvant Therapy for Clearly Resectable Pancreatic Cancer. Ann Surg Oncol 2023; 30:3427-3436. [PMID: 36869916 DOI: 10.1245/s10434-023-13281-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 02/12/2023] [Indexed: 03/05/2023]
Abstract
Over the past decade, neoadjuvant therapy has become the standard of care for patients with borderline resectable and locally advanced pancreatic cancer. The surgical community remains divided regarding the value of neoadjuvant therapy for patients who present with clearly resectable disease. Thus far, randomized controlled trials comparing neoadjuvant therapy with conventional upfront surgical strategies for patients with clearly resectable pancreatic cancer have been plagued by poor accrual, and are often underpowered. Nonetheless, meta-analyses of the results of these trials suggest that neoadjuvant therapy can be offered as an acceptable standard of care for patients with clearly resectable pancreatic cancer. Previous trials used neoadjuvant gemcitabine, but more recent studies have demonstrated superior survival for patients who were able to tolerate neoadjuvant FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan hydrochloride, and oxaliplatin). The increased utilization of FOLFIRINOX may be shifting the treatment paradigm in favor of neoadjuvant therapy among patients with clearly resectable disease. Randomized controlled trials assessing the value of neoadjuvant FOLFIRINOX in clearly resectable pancreatic cancer, which are expected to provide more conclusive recommendations, are still ongoing. This review outlines the rationale, considerations, and current level of evidence for the use of neoadjuvant therapy in patients with clearly resectable pancreatic cancer.
Collapse
Affiliation(s)
- Susanna W L de Geus
- Department of Surgical Oncology, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA
| | - Teviah E Sachs
- Department of Surgical Oncology, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
| |
Collapse
|
|
49
|
Takagi T, Nagai M, Nishiwada S, Terai T, Yasuda S, Matsuo Y, Doi S, Kohara Y, Sho M. Importance of triple tumor markers as biomarkers in patients with pancreatic ductal adenocarcinoma. Ann Gastroenterol Surg 2023; 7:326-335. [PMID: 36998299 PMCID: PMC10043775 DOI: 10.1002/ags3.12629] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 09/25/2022] [Indexed: 04/01/2023] Open
Abstract
Aim There is an urgent need to establish biomarkers for the treatment of pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the usefulness of the combined assessment of carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and duke pancreatic monoclonal antigen type 2 (DUPAN-2) in PDAC. Methods We retrospectively investigated the impact of three tumor markers on overall survival (OS) and recurrence-free survival (RFS). Patients were classified into two groups: upfront surgery (US) and neoadjuvant chemoradiation (NACRT) groups. Results In total, 310 patients were evaluated. In the US group, patients who had all three elevated markers showed a significantly worse prognosis than the others (median: 16.4 months, P = .005). In the NACRT group, patients who had elevated CA 19-9 and CEA levels after NACRT had significantly worse prognosis than the others (median: 26.2 months, P < .001). The elevated DUPAN-2 levels before NACRT were associated with significantly worse prognosis than normal levels (median: 44.0 vs 59.2 months, P = .030). Patients who had elevated DUPAN-2 levels before NACRT with elevated CA 19-9 and CEA levels after NACRT showed extremely poor RFS (median: 5.9 months). Multivariate analysis revealed that a modified triple-positive tumor marker indicating elevated DUPAN-2 levels before NACRT and elevated CA19-9 and CEA levels after NACRT was an independent prognostic factor of OS (hazard ratio: 2.49, P = .007) and RFS (hazard ration: 2.47, P = .007). Conclusions The combined evaluation of three tumor markers may provide useful information for the treatment of patients with PDAC.
Collapse
Affiliation(s)
| | - Minako Nagai
- Department of SurgeryNara Medical UniversityKashiharaJapan
| | | | - Taichi Terai
- Department of SurgeryNara Medical UniversityKashiharaJapan
| | - Satoshi Yasuda
- Department of SurgeryNara Medical UniversityKashiharaJapan
| | - Yasuko Matsuo
- Department of SurgeryNara Medical UniversityKashiharaJapan
| | - Shunsuke Doi
- Department of SurgeryNara Medical UniversityKashiharaJapan
| | | | - Masayuki Sho
- Department of SurgeryNara Medical UniversityKashiharaJapan
| |
Collapse
|
|
50
|
Roberts DA, Watson E, Macdonald C, Khan Y, Prideaux S, Puthiyakunnel Saji A, Postaleniec E, Selvakumar J, Haghighat Ghahfarokhi M, Davidson B, Gurusamy K. Management of pain and cachexia in pancreatic cancer: Protocol for two systematic reviews, network meta-analysis, surveys and focus groups (Preprint). JMIR Res Protoc 2023; 12:e46335. [PMID: 37014692 PMCID: PMC10139686 DOI: 10.2196/46335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 02/26/2023] [Accepted: 02/26/2023] [Indexed: 03/01/2023] Open
Abstract
BACKGROUND Approximately 75% of people with pancreatic cancer experience pain, and >50% of them have cachexia (weakness and wasting of the body). However, there is considerable uncertainty regarding the management of these distressing symptoms. OBJECTIVE Our primary objectives are to compare the relative benefits and harms of different interventions for pain in people with unresectable pancreatic cancer and for prevention and treatment of cachexia due to pancreatic cancer, through systematic reviews and network meta-analysis. Our secondary objectives are to develop an evidence-based clinical care pathway to manage pain and prevent and treat cachexia in people with pancreatic cancer through surveys and focus groups involving patients, carers, and health care professionals. METHODS We will perform 2 systematic reviews of the literature related to pain and cachexia in people with pancreatic cancer using searches from Cochrane Library, MEDLINE, Embase, Science Citation Index, and trial registries. Two researchers will independently screen for eligibility and identify randomized controlled trials (no language or publication status restriction), comparing interventions for pain or cachexia based on full-texts for articles shortlisted during screening. We will assess risk of bias in the trials using the Cochrane risk of bias tool (version 2.0) and obtain data related to baseline prognostic characteristics, potential effect modifiers and outcome data related to overall survival, health-related quality of life, treatment-related complications, and resource utilisation. We aim to conduct network meta-analysis on outcomes with multiple treatment comparisons where possible, otherwise, meta-analysis with direct comparisons, or narrative synthesis. We will perform various subgroup and sensitivity analyses. Using information obtained from both systematic reviews, we will conduct 2 surveys: one directed to patients or carers to assess acceptability of interventions, and the other to health care professionals to assess feasibility of delivery in the National Health Service. Four mixed focus groups will be conducted to evaluate findings and foster consensus in the development of the care pathway. RESULTS Funding was awarded from April 2022 (NIHR202727). Both systematic review protocols were prospectively registered on PROSPERO in May 2022. Formal searches began thereafter. Approval by the University College London Research Ethics Committee (23563/001) was received in December 2022. Data collection began in January 2023; data analysis will begin in May 2023 (completion expected by October 2023). CONCLUSIONS This study will comprehensively encompass major interventions for management of pain in people with unresectable pancreatic cancer, and prevention and treatment of cachexia in people with pancreatic cancer. Key stakeholders will facilitate the development of an evidence-based care pathway, ensuring both acceptability and feasibility. The project ends in April 2024 and published results are expected within 12 months of completion. We aim to present the findings through patient group websites, conferences, and publications, irrespective of the findings, in a peer-reviewed journal. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/46335.
Collapse
Affiliation(s)
- Danielle Amanda Roberts
- Division of Surgery and Interventional Science, Hampstead Campus, University College London, London, United Kingdom
| | - Eila Watson
- Supportive Cancer Care Research Group, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, United Kingdom
| | | | | | - Sarah Prideaux
- Patient and Public Involvement Representative, England, United Kingdom
| | | | - Emilia Postaleniec
- Leicester Medical School, The University of Leicester, Leicester, United Kingdom
| | - Jashan Selvakumar
- St George's, University of London Medical School, London, United Kingdom
| | | | - Brian Davidson
- Division of Surgery and Interventional Science, Hampstead Campus, University College London, London, United Kingdom
| | - Kurinchi Gurusamy
- Division of Surgery and Interventional Science, Hampstead Campus, University College London, London, United Kingdom
| |
Collapse
|