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Boubaddi M, Rossi J, Marichez A, Marty M, Amintas S, Laurent C, Dabernat S. Preoperative Prognostic Factors in Resectable Pancreatic Cancer: State of the Art and Prospects. Ann Surg Oncol 2025; 32:4117-4127. [PMID: 40095311 DOI: 10.1245/s10434-025-17062-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: 12/20/2024] [Accepted: 02/09/2025] [Indexed: 03/19/2025]
Abstract
BACKGROUND Only 15% to 20% of patients with pancreatic ductal adenocarcinoma (PDAC) have access to surgical resection, which represents the only chance of curative treatment. Current resection classifications are almost exclusively anatomic and do not correlate sufficiently with patient survival. It is essential to develop preoperative prognostic factors to distinguish patients at high risk of early postoperative recurrence from those who will have prolonged survival after surgery. In some cases, PDACs may present biomolecular differences reflecting their aggressiveness that are not yet assessable by the current clinical-biologic assessment. This study aimed to assess the preoperative prognostic factors that are already available and the future perspectives being developed. METHOD This study reviewed the literature using the PubMed public database for preoperative prognostic factors for resectable PDAC. CONCLUSION Validated preoperative prognostic factors, whether clinical, biologic, radiologic, or histologic, are very important in anticipating the course of each patient's disease. The identification of potential new prognostic biomarkers such as genomic, transcriptomic, and proteomic analyses and the dosage of circulating tumor DNA are very serious avenues to be developed, but the extraction and analysis techniques as well as the interpretation of their results need to be standardized in prospective studies.
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Affiliation(s)
- Mehdi Boubaddi
- Colorectal Unit, Department of Digestive Surgery, Bordeaux University Hospital, Bordeaux, France.
- BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, Bordeaux, France.
- Hepatobiliary and Pancreatic Surgery Department, Bordeaux University Hospital, Bordeaux, France.
| | - Julia Rossi
- BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, Bordeaux, France
| | - Arthur Marichez
- Colorectal Unit, Department of Digestive Surgery, Bordeaux University Hospital, Bordeaux, France
- BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, Bordeaux, France
| | - Marion Marty
- Tumor Biology and Tumor Bank Laboratory, CHU Bordeaux, Bordeaux, France
| | - Samuel Amintas
- BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, Bordeaux, France
| | - Christophe Laurent
- Colorectal Unit, Department of Digestive Surgery, Bordeaux University Hospital, Bordeaux, France
| | - Sandrine Dabernat
- BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, Bordeaux, France
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2
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Murata Y, Mizuno S, Kishiwada M, Hayasaki A, Nagata M, Noguchi D, Gyoten K, Ito T, Fujii T, Iizawa Y, Tanemura A, Kuriyama N. Prognostic impacts of biological and conditional factors in patients with anatomically resectable pancreatic adenocarcinoma treated with preoperative chemoradiotherapy. Medicine (Baltimore) 2025; 104:e42441. [PMID: 40388783 PMCID: PMC12091679 DOI: 10.1097/md.0000000000042441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 04/25/2025] [Indexed: 05/21/2025] Open
Abstract
The efficacy of preoperative chemoradiotherapy (CRT) for anatomically resectable pancreatic adenocarcinoma (R-PDAC) remains contentious. This study aims to elucidate the treatment outcomes of preoperative CRT for R-PDAC and to identify prognostic factors. This retrospective study included 109 R-PDAC patients treated with gemcitabine- or S-1 plus gemcitabine-based preoperative CRT from February 2005 to April 2023. Cox proportional hazards regression was employed to identify factors associated with worse overall survival (OS). Among the 109 cases, 90 patients (82.6%) underwent curative-intent resection following CRT. The median OS for the entire cohort was 36.5 months, significantly longer in resected cases than in unresected cases (40.6 vs 11.4 months). Multivariate analysis identified pretreatment serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) and the Eastern Cooperative Oncology Group performance status ≥1 as independent prognostic factors. When these factors were scored (risk score 0-3) using pre-CRT serum CA19-9 level (≥640 U/mL) and CEA (≥6.1 ng/mL), OS for risk scores 1 (n = 41), 2 (n = 20) or 3 (n = 6) was significantly shorter than for risk score 0 (n = 42) (score 0 vs 1 vs 2 vs 3: 49.1 vs 33.8 vs 16.1 vs 16.8 months). The presence of portal vein invasion on imaging and post-CRT serum CA 19-9 level (≥111 U/mL) were independent prognostic factors in resected cases. Biological factors, including serum levels of CA19-9 and CEA, along with conditional factor of Eastern Cooperative Oncology Group performance status ≥1, were identified as independent prognostic factors for R-PDAC patients treated with preoperative CRT. Preoperative CRT is considered effective for cases lacking these risk factors.
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Affiliation(s)
- Yasuhiro Murata
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Shugo Mizuno
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Masashi Kishiwada
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Aoi Hayasaki
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Motonori Nagata
- Department of the Radiology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Daisuke Noguchi
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Kazuyuki Gyoten
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Takahiro Ito
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Takehiro Fujii
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Yusuke Iizawa
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Akihiro Tanemura
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Naohisa Kuriyama
- Department of the Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
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Maggino L. Purely resectable versus biological borderline resectable pancreatic cancer: closely related or worlds apart? BJS Open 2025; 9:zraf054. [PMID: 40392527 PMCID: PMC12090763 DOI: 10.1093/bjsopen/zraf054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Accepted: 03/16/2025] [Indexed: 05/22/2025] Open
Affiliation(s)
- Laura Maggino
- Unit of General Surgery, Mater Salutis Hospital, Verona, Italy
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Rompen IF, Sereni E, Habib JR, Garnier J, Galimberti V, Perez Rivera LR, Vatti D, Lafaro KJ, Hewitt DB, Sacks GD, Burns WR, Cohen S, Kaplan B, Burkhart RA, Turrini O, Wolfgang CL, He J, Javed AA. Development of a Composite Score Based on Carbohydrate Antigen 19-9 Dynamics to Predict Survival in Carbohydrate Antigen 19-9-Producing Patients With Pancreatic Ductal Adenocarcinoma After Neoadjuvant Treatment. JCO Precis Oncol 2024; 8:e2400193. [PMID: 39565977 DOI: 10.1200/po.24.00193] [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: 03/29/2024] [Revised: 09/05/2024] [Accepted: 10/11/2024] [Indexed: 11/22/2024] Open
Abstract
PURPOSE Dynamics of carbohydrate antigen 19-9 (CA19-9) often inform treatment decisions during and after neoadjuvant chemotherapy (NAT) of patients with pancreatic ductal adenocarcinoma (PDAC). However, considerable dispute persists regarding the clinical relevance of specific CA19-9 thresholds and dynamics. Therefore, we aimed to define optimal thresholds for CA19-9 values and create a biochemically driven composite score to predict survival in CA19-9-producing patients with PDAC after NAT. METHODS Patients with PDAC who underwent NAT and surgical resection from 2012 to 2022 were retrospectively identified from three high-volume centers. CA19-9 nonproducers and patients with 90-day mortality, and macroscopically incomplete resections were excluded. A composite score was created on the basis of relative CA19-9 change and newly defined optimal thresholds of pre- and postneoadjuvant values for overall survival (OS) using patients from two centers and validated using data from the third center. RESULTS A total of 492 patients met inclusion criteria in the development cohort. Optimal CA19-9 cutoff values for predicting a difference in OS were 202 U/mL for preneoadjuvant and 78 U/mL for postneoadjuvant levels. Furthermore, increase in CA19-9 during neoadjuvant treatment was associated with worse OS (median-OS, 17.5 months v 26.0 months; P = .008). Not surpassing any or only one of these thresholds (composite score of 0-1) was associated with improved OS compared with patients with 2-3 points (median-OS, 29.9 months v 15.8 months; P < .001). Major serological response (90% decrease of CA19-9) had a positive and negative predictive value of 32% and 88%, respectively. CONCLUSION The composite score consisting of CA19-9 levels at diagnosis, after neoadjuvant treatment, and its dynamics demonstrates prognostic discrimination between low and high scores. However, better predictive biomarkers are needed to facilitate treatment decisions during neoadjuvant treatment.
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Affiliation(s)
- Ingmar F Rompen
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Elisabetta Sereni
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Joseph R Habib
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Jonathan Garnier
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
- Department of Surgical Oncology, Aix-Marseille University, CRCM, Institut Paoli-Calmettes, Marseille, France
| | - Veronica Galimberti
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Lucas R Perez Rivera
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Deepa Vatti
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Kelly J Lafaro
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - D Brock Hewitt
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Greg D Sacks
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - William R Burns
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Steven Cohen
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Brian Kaplan
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Richard A Burkhart
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Olivier Turrini
- Department of Surgical Oncology, Aix-Marseille University, CRCM, Institut Paoli-Calmettes, Marseille, France
| | - Christopher L Wolfgang
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ammar A Javed
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY
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Bhandare MS, Gupta V, Chaudhari V, Nandy K, Ostwal V, Ramaswamy A, Nashikkar C, Engineer R, Krishnatry R, Shrikhande SV. Differential impact of incrementally elevated CA 19-9 levels on prognosis of resected pancreatic ductal adenocarcinoma. HPB (Oxford) 2024; 26:1237-1247. [PMID: 38944571 DOI: 10.1016/j.hpb.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/11/2024] [Accepted: 06/12/2024] [Indexed: 07/01/2024]
Abstract
BACKGROUND CA 19-9 is an extremely useful biomarker for pancreatic ductal adenocarcinomas (PDACs). However, the optimal cut-off and prognostic significance at higher cut-offs are yet to be determined. METHODS Retrospective analysis included patients with PDAC who underwent curative resection from January 2010 to May 2020 at Tata Memorial Centre, Mumbai. The pretherapy CA 19-9 was dichotomized using various cut-off levels and analysed. RESULTS In 244 included patients, the median overall survival (OS) for those with CA19-9 level (IU/ml) < or >78, 200, 500, 1000, and 2000 was 27, 24, 23, 22, 21 months versus 18, 16, 15, 14, 13 months; respectively, and was statistically significant (p-value- 0.002, 0.001, 0.002, 0.002 and 0.004, respectively). The number of recurrences and mortality had significant correlation with CA 19-9 cut-offs. On multivariate analysis, adjuvant treatment completion (p-0.004) and decreasing or stable CA19-9 after Neoadjuvant therapy (NAT) (p- 0.031) were associated with improved OS. CONCLUSION The prognostic significance of CA 19-9 was observed at all the cut-off levels examined, beyond mere elevated value as per the standard cut-off level. In patients with high CA19-9 level, surgery should be offered if technically and conditionally feasible, only when a response in CA19-9 level to NAT is achieved.
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Affiliation(s)
- Manish S Bhandare
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India.
| | - Vikas Gupta
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
| | - Vikram Chaudhari
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
| | - Kunal Nandy
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | | | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra, India
| | - Rahul Krishnatry
- Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra, India
| | - Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
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6
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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.
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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.
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7
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Gao X, In H. CA19-9 Benefits Prognostication of Pancreatic Cancer: Is It Time to Add CA19-9 to Its Staging Criteria? Ann Surg Oncol 2024; 31:4839-4840. [PMID: 38709364 DOI: 10.1245/s10434-024-15321-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 04/04/2024] [Indexed: 05/07/2024]
Affiliation(s)
- Xiang Gao
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Haejin In
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
- Department of Health, Behavior and Policy, Rutgers University, Piscataway, NJ, USA.
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8
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Murakami T, Kimura Y, Imamura M, Nagayama M, Kato T, Kukita K, Yoshida M, Masaki Y, Nakase H, Takemasa I. Predictors of occult metastases in potentially Resectable pancreatic ductal adenocarcinoma. Surg Open Sci 2024; 20:222-229. [PMID: 39156491 PMCID: PMC11327574 DOI: 10.1016/j.sopen.2024.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 07/09/2024] [Accepted: 07/19/2024] [Indexed: 08/20/2024] Open
Abstract
Background Patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) sometimes show unexpected liver, peritoneal, and para-aortic lymph node metastases intraoperatively. Despite radical pancreatectomy, a nonnegligible number of patients relapse within 6 months after surgery. The aim of this study was to identify the preoperative predictors of occult metastases (OM), defined as intraoperative distant metastases or within 6 months after pancreatectomy. Materials and methods This study included patients with R and BR PDAC who underwent curative-intent pancreatectomy or staging laparoscopy between 2006 and 2021. Multivariate logistic regression and Cox hazard analyses were performed to identify the preoperative predictors of OM and to assess the impact of these factors on prognosis after pancreatectomy. Results Of the 279 patients, OM was observed intraoperatively in 47 and postoperatively in 34. In the OM group, there were no differences in prognosis between patients who had intraoperative metastases and recurrence within 6 months (median survival time [MST], 18.1 vs. 12.9 months), and between patients who underwent pancreatectomy and those who did not (MST, 13.9 vs. 18.1 months). Preoperative tumor size ≥22 mm (odds ratio [OR], 2.03; 95 % confidence interval [CI], 1.16-3.53; p = 0.013) and preoperative CA19-9 level ≥ 118.8 U/mL (OR, 2.64; 95 % CI, 1.22-5.73; p = 0.014) were significant predictors of OM. Additionally, positive OM predictors were strong independent prognostic factors for overall survival after pancreatectomy (hazard ratio, 2.47; 95 % CI, 1.54-3.98; p < 0.001). Conclusion Multidisciplinary treatment strategies should be considered for patients with predictors of OM to avoid inappropriate surgical interventions.
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Affiliation(s)
- Takeshi Murakami
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Yasutoshi Kimura
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Masafumi Imamura
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Minoru Nagayama
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Toru Kato
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Kazuharu Kukita
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Makoto Yoshida
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Yoshiharu Masaki
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
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9
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Waugh E, Glinka J, Breadner D, Liu R, Tang E, Allen L, Welch S, Leslie K, Skaro A. Survival benefit of neoadjuvant FOLFIRINOX for patients with borderline resectable pancreatic cancer. Ann Hepatobiliary Pancreat Surg 2024; 28:229-237. [PMID: 38296221 PMCID: PMC11128787 DOI: 10.14701/ahbps.23-107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 12/05/2023] [Accepted: 12/09/2023] [Indexed: 05/25/2024] Open
Abstract
Backgrounds/Aims While patients with borderline resectable pancreatic cancer (BRPC) are a target population for neoadjuvant chemotherapy (NAC), formal guidelines for neoadjuvant therapy are lacking. We assessed the perioperative and oncological outcomes in patients with BRPC undergoing NAC with FOLFIRINOX for patients undergoing upfront surgery (US). Methods The AHPBA criteria for borderline resectability and/or a CA19-9 level > 100 μ/mL defined borderline resectable tumors retrieved from a prospectively populated institutional registry from 2007 to 2020. The primary outcome was overall survival (OS) at 1 and 3 years. A Cox Proportional Hazard model based on intention to treat was used. A receiver-operator characteristics (ROC) curve was constructed to assess the discriminatory capability of the use of CA19-9 > 100 μ/mL to predict resectability and mortality. Results Forty BRPC patients underwent NAC, while 46 underwent US. The median OS with NAC was 19.8 months (interquartile range [IQR], 10.3-44.24) vs. 10.6 months (IQR, 6.37-17.6) with US. At 1 year, 70% of the NAC group and 41.3% of the US group survived (p = 0.008). At 3 years, 42.5 % of the NAC group and 10.9% of the US group survived (p = 0.001). NAC significantly reduced the hazard of death (adjusted hazard ratio, 0.20; 95% confidence interval, 0.07-0.54; p = 0.001). CA19-9 > 100 μ/mL showed poor discrimination in predicting mortality, but was a moderate predictor of resectability. Conclusions We found a survival benefit of NAC with FOLFIRINOX for BRPC. Greater pre-treatment of CA19-9 and multivessel involvement on initial imaging were associated with progression of the disease following NAC.
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Affiliation(s)
- Evelyn Waugh
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Juan Glinka
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Daniel Breadner
- Division of Medical Oncology, Department of Oncology, Western University, London, ON, Canada
| | - Rachel Liu
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Ephraim Tang
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Laura Allen
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Stephen Welch
- Division of Medical Oncology, Department of Oncology, Western University, London, ON, Canada
| | - Ken Leslie
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Anton Skaro
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
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10
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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.
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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
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11
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Kimura Y, Nakamura T, Imamura M, Nagayama M, Murakami T, Hayashi T, Kato T, Tanaka K, Yoshida M, Kukita K, Imai K, Yoshida M, Masaki Y, Motoya M, Kuwatani M, Koyama M, Ohnishi H, Takemasa I. Reconsidering resectable oncological conditions in pancreatic tail cancer: A multicenter retrospective study on prognostic factors in pancreatic tail cancer after resection (HOPS Pt-01). Pancreatology 2024; 24:109-118. [PMID: 38103948 DOI: 10.1016/j.pan.2023.12.004] [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: 07/24/2023] [Revised: 11/29/2023] [Accepted: 12/06/2023] [Indexed: 12/19/2023]
Abstract
BACKGROUND Pancreatic tail cancer (Pt-PC) is generally considered resectable when metastasis is absent, but doubts persist in clinical practice due to the variability in local tumor extent. We conducted a multicenter retrospective study to comprehensively identify prognostic factors associated with Pt-PC after resection. METHODS We enrolled 100 patients that underwent distal pancreatectomy. The optimal combination of factors influencing relapse-free survival (RFS) was determined using the maximum likelihood method (MLM) and corrected Akaike and Bayesian information criteria (AICc and BIC). Prognostic elements were then validated to predict oncological outcomes. RESULTS Therapeutic interventions included neoadjuvant treatment in 16 patients and concomitant visceral resection (CVR) in 37 patients; 89 patients achieved R0. Median RFS and OS after surgery were 23.1 and 37.1 months, respectively. AICc/BIC were minimized in the model with ASA-PS (≥2), CA19-9 (≥112 U/mL at baseline, non-normalized postoperatively), need for CVR, 6 pathological items (tumor diameter ≥19.5 mm, histology G1, invasion of the anterior pancreatic border, splenic vein invasion, splenic artery invasion, lymph node metastasis), and completed adjuvant treatment (cAT) for RFS. Regarding the predictive value of these 11 factors, area under the curve was 0.842 for 5-year RFS. Multivariate analysis of these 11 factors showed that predictors of RFS include CVR (hazard ratio, 2.13; 95 % confidence interval, 1.08-4.19; p = 0.028) and cAT (0.38, 0.19-0.76; p = 0.006). CONCLUSIONS The MLM identified certain Pt-PC cases warranting consideration beyond resectable during clinical management. Particular attention should be paid to conditions requiring CVR, even though immortal time bias remains unresolved with adjuvant treatment.
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Affiliation(s)
- Yasutoshi Kimura
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan.
| | - Toru Nakamura
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Masafumi Imamura
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Minoru Nagayama
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Takeshi Murakami
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tsuyoshi Hayashi
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan
| | - Toru Kato
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Kimitaka Tanaka
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Makoto Yoshida
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Gastroenterological Surgery, Kin-ikyo Chuo Hospital, Sapporo, Japan
| | - Kazuharu Kukita
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Koji Imai
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa, Japan
| | - Makoto Yoshida
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yoshiharu Masaki
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masayo Motoya
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan
| | - Masaki Kuwatani
- Hokkaido Pancreatic Cancer Study Group, HOPS, Sapporo, Japan; Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Masayuki Koyama
- Department of Public Health, Sapporo Medical University School of Medicine, Japan; Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hirofumi Ohnishi
- Department of Public Health, Sapporo Medical University School of Medicine, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
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12
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Rompen IF, Habib JR, Wolfgang CL, Javed AA. Anatomical and Biological Considerations to Determine Resectability in Pancreatic Cancer. Cancers (Basel) 2024; 16:489. [PMID: 38339242 PMCID: PMC10854859 DOI: 10.3390/cancers16030489] [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: 11/14/2023] [Revised: 01/11/2024] [Accepted: 01/19/2024] [Indexed: 02/12/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains associated with poor outcomes with a 5-year survival of 12% across all stages of the disease. These poor outcomes are driven by a delay in diagnosis and an early propensity for systemic dissemination of the disease. Recently, aggressive surgical approaches involving complex vascular resections and reconstructions have become more common, thus allowing more locally advanced tumors to be resected. Unfortunately, however, even after the completion of surgery and systemic therapy, approximately 40% of patients experience early recurrence of disease. To determine resectability, many institutions utilize anatomical staging systems based on the presence and extent of vascular involvement of major abdominal vessels around the pancreas. However, these classification systems are based on anatomical considerations only and do not factor in the burden of systemic disease. By integrating the biological criteria, we possibly could avoid futile resections often associated with significant morbidity. Especially patients with anatomically resectable disease who have a heavy burden of radiologically undetected systemic disease most likely do not derive a survival benefit from resection. On the contrary, we could offer complex resections to those who have locally advanced or oligometastatic disease but have favorable systemic biology and are most likely to benefit from resection. This review summarizes the current literature on defining anatomical and biological resectability in patients with pancreatic cancer.
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Affiliation(s)
- Ingmar F. Rompen
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY 10016, USA
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Joseph R. Habib
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY 10016, USA
| | - Christopher L. Wolfgang
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY 10016, USA
| | - Ammar A. Javed
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY 10016, USA
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13
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Li Z, Zhuo Q, Li B, Liu M, Chen C, Shi Y, Xu W, Liu W, Ji S, Yu X, Xu X. Feasibility of laparoscopic versus open pancreatoduodenectomy following neoadjuvant chemotherapy for borderline resectable pancreatic cancer: a retrospective cohort study. World J Surg Oncol 2024; 22:1. [PMID: 38169384 PMCID: PMC10759588 DOI: 10.1186/s12957-023-03277-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 12/09/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND There is no evidence supporting the feasibility of laparoscopic pancreaticoduodenectomy (LPD) compared to open pancreatoduodenectomy (OPD) following neoadjuvant chemotherapy (NACT) for pancreatic ductal adenocarcinoma (PDAC). METHODS The clinical data of consecutive patients with borderline resectable PDAC who received NACT and underwent either LPD or OPD between January 2020 and December 2022 at Fudan University Shanghai Cancer Center was prospectively collected and retrospectively analyzed. RESULTS The analysis included 57 patients in the OPD group and 20 in the LPD group. Following NACT, the LPD group exhibited a higher median CA19-9 decrease rate compared to the OPD group (85.3% vs. 66.9%, P = 0.042). Furthermore, 3 anatomically borderline PDACs in the LPD group and 5 in the OPD group were downstaged into resectable status (30.0% vs. 12.3%, P = 0.069). According to RECIST criteria, 51 (66.2%) patients in the entire cohort were evaluated as having stable disease. The median operation time for the LPD group was longer than the OPD group (419 vs. 325 min, P < 0.001), while the venous resection rate was 35.0% vs. 43.9%, respectively (P = 0.489). There was no difference in the number of retrieved lymph nodes, with a median number of 18.5 in the LPD group and 22 in the OPD group, and the R1 margin rate (15.0% vs. 12.3%) was also comparable. The incidence of Clavien-Dindo complications (35.0% vs. 66.7%, P = 0.018) was lower in the LPD group compared to the OPD group. Multivariable regression analysis revealed that a tumor diameter > 3 cm before NACT (HR 2.185) and poor tumor differentiation (HR 1.805) were independent risk factors for recurrence-free survival, and a decrease rate of CA19-9 > 70% (OR 0.309) was a protective factor for early tumor recurrence and overall survival. CONCLUSIONS LPD for PDAC following NACT is feasible and oncologically equivalent to OPD. Effective control of CA19-9 levels is beneficial in reducing early tumor recurrence and improving overall survival.
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Affiliation(s)
- Zheng Li
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Qifeng Zhuo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Borui Li
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Mengqi Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Chen Chen
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Yihua Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Wenyan Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Wensheng Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Xiaowu Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
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14
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Napoli N, Kauffmann EF, Ginesini M, Lami L, Lombardo C, Vistoli F, Campani D, Boggi U. Ca 125 is an independent prognostic marker in resected pancreatic cancer of the head of the pancreas. Updates Surg 2023; 75:1481-1496. [PMID: 37535191 PMCID: PMC10435596 DOI: 10.1007/s13304-023-01587-4] [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: 06/02/2023] [Accepted: 07/05/2023] [Indexed: 08/04/2023]
Abstract
The prognostic value of carbohydrate antigen 125 (Ca 125) is emerging also in pancreatic cancer (PDAC). In this study, we aim to define the prognostic value of Ca 125 in resected PDAC of the head of the pancreas. This is a single-center, retrospective study. Data from patients with a pre-operative assay of Ca 125 who underwent a pancreatic resection for PDAC between 2010 and 2018 were analyzed. As per National Comprehensive Cancer Guidelines, tumors were classified in resectable (R-PDAC), borderline resectable (BR-PDAC), and locally advanced (LA-PDAC). The Kaplan-Meier method was used to evaluate the overall survival. Cox proportional hazard regression was used to evaluate the role of pre-operative Ca 125 in predicting survival (while adjusting for confounders). The maximally selected log-rank statistic was used to identify a Ca 125 cut-off defining two groups with different survival probability. Inclusion criteria were met by 207 patients (R-PDAC: 80, BR-PDAC: 91, and LA-PDAC: 36). Ca 125 predicted overall survival before and after adjusting for confounding factors in all categories of anatomic resectability (R-PDAC: HR = 4.3; p = 0.0249) (BR-PDAC: HR = 7.82; p = 0.0024) (LA-PDAC: HR = 11.4; p = 0.0043). In BR-PDAC and LA-PDAC (n = 127), the division in two groups (high vs. low Ca 125) correlated with T stage (p = 0.0317), N stage (p = 0.0083), mean LN ratio (p = 0.0292), and tumor grading (p = 0.0143). This study confirmed the prognostic value of Ca125 in resected pancreatic cancer and, therefore, the importance of biologic over anatomic resectability. Ca 125 should be routinely assayed in surgical candidates with PDAC.
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Affiliation(s)
- Niccolò Napoli
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy.
| | | | - Michael Ginesini
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - Lucrezia Lami
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - Carlo Lombardo
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - Fabio Vistoli
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | | | - Ugo Boggi
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
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15
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Kwaśniewska D, Fudalej M, Nurzyński P, Badowska-Kozakiewicz A, Czerw A, Cipora E, Sygit K, Bandurska E, Deptała A. How A Patient with Resectable or Borderline Resectable Pancreatic Cancer should Be Treated-A Comprehensive Review. Cancers (Basel) 2023; 15:4275. [PMID: 37686551 PMCID: PMC10487031 DOI: 10.3390/cancers15174275] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/22/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high morbidity and mortality in which long-term survival rates remain disastrous. Surgical resection is the only potentially curable treatment for early pancreatic cancer; however, the right patient qualification is crucial for optimizing treatment outcomes. With the rapid development of radiographic and surgical techniques, resectability decisions are made by a multidisciplinary team. Upfront surgery (Up-S) can improve the survival of patients with potentially resectable disease with the support of adjuvant therapy (AT). However, early recurrences are quite common due to the often-undetectable micrometastases occurring before surgery. Adopted by international consensus in 2017, the standardization of the definitions of resectable PDAC (R-PDAC) and borderline resectable PDAC (BR-PDAC) disease was necessary to enable accurate interpretation of study results and define which patients could benefit from neoadjuvant therapy (NAT). NAT is expected to improve the resection rate with a negative margin to provide significant local control and eliminate micrometastases to prolong survival. Providing information about optimal sequential multimodal NAT seems to be key for future studies. This article presents a multidisciplinary concept for the therapeutic management of patients with R-PDAC and BR-PDAC based on current knowledge and our own experience.
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Affiliation(s)
- Daria Kwaśniewska
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
| | - Marta Fudalej
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Paweł Nurzyński
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
| | | | - Aleksandra Czerw
- Department of Health Economics and Medical Law, Medical University of Warsaw, 01-445 Warsaw, Poland
- Department of Economic and System Analyses, National Institute of Public Health NIH-National Research Institute, 00-791 Warsaw, Poland
| | - Elżbieta Cipora
- Medical Institute, Jan Grodek State University in Sanok, 38-500 Sanok, Poland
| | - Katarzyna Sygit
- Faculty of Health Sciences, Calisia University, 62-800 Kalisz, Poland
| | - Ewa Bandurska
- Centre for Competence Development, Integrated Care and e-Health, Medical University of Gdansk, 80-204 Gdansk, Poland
| | - Andrzej Deptała
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
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16
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Wu HY, Li JW, Li JZ, Zhai QL, Ye JY, Zheng SY, Fang K. Comprehensive multimodal management of borderline resectable pancreatic cancer: Current status and progress. World J Gastrointest Surg 2023; 15:142-162. [PMID: 36896309 PMCID: PMC9988647 DOI: 10.4240/wjgs.v15.i2.142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/23/2022] [Accepted: 01/12/2023] [Indexed: 02/27/2023] Open
Abstract
Borderline resectable pancreatic cancer (BRPC) is a complex clinical entity with specific biological features. Criteria for resectability need to be assessed in combination with tumor anatomy and oncology. Neoadjuvant therapy (NAT) for BRPC patients is associated with additional survival benefits. Research is currently focused on exploring the optimal NAT regimen and more reliable ways of assessing response to NAT. More attention to management standards during NAT, including biliary drainage and nutritional support, is needed. Surgery remains the cornerstone of BRPC treatment and multidisciplinary teams can help to evaluate whether patients are suitable for surgery and provide individualized management during the perioperative period, including NAT responsiveness and the selection of surgical timing.
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Affiliation(s)
- Hong-Yu Wu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Jin-Wei Li
- Department of Neurosurgery, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou 545000, Guangxi Province, China
| | - Jin-Zheng Li
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Qi-Long Zhai
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Jing-Yuan Ye
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Si-Yuan Zheng
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Kun Fang
- Department of Surgery, Yinchuan Maternal and Child Health Hospital, Yinchuan 750000, Ningxia, China
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17
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Lee B, Yoon YS, Kang M, Park Y, Lee E, Jo Y, Lee JS, Lee HW, Cho JY, Han HS. Validation of the Anatomical and Biological Definitions of Borderline Resectable Pancreatic Cancer According to the 2017 International Consensus for Survival and Recurrence in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Upfront Surgery. Ann Surg Oncol 2023; 30:3444-3454. [PMID: 36695994 DOI: 10.1245/s10434-022-13043-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 11/14/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND The International Consensus Criteria (ICC) (2017) redefined patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) according to anatomical, biological, and conditional aspects. However, these new criteria have not been validated comprehensively. The aim of this retrospective cohort study was to validate the anatomical and biological definitions of BR-PDAC for oncological outcomes in patients with resectable (R) and BR-PDAC undergoing upfront surgery. METHODS A total of 404 patients who underwent upfront surgery for R- and BR-PDAC from 2004 to 2020 were included. The patients were classified according to the ICC as follows: resectable (R) (n = 259), anatomical borderline (BR-A) (n = 43), biological borderline (BR-B) (n = 81), and anatomical and biologic borderline (BR-AB) (n = 21). RESULTS Compared with the R and BR-B groups, the BR-A and BR-AB groups had higher postoperative complication rates (16.5% and 27.2% vs 32.5% and 33.4%; P < 0.001) and significantly lower R0 resection rates (85.7% and 80.2% vs 65.1% and 61.9%; P = 0.003). In contrast, compared with the R and BR-A groups, the BR-B (32.1%) and BR-AB (57.1%) groups had higher early recurrence rates (within postoperative 6 months) (16.5% and 25.6% vs 32.1% and 57.1%; P < 0.001) and significantly lower 3-year recurrence-free survival rates (36.1% and 20.7% vs 12.1% and 7.8%; P < 0.001). CONCLUSION Anatomically defined BR-PDAC was associated with a higher risk of margin-positive resection and postoperative complication rates, while biologically defined BR-PDAC was associated with higher early recurrence rates and lower survival rates. Thus, the anatomical and biological definitions are useful in predicting the prognosis and determining the usefulness of neoadjuvant therapy.
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Affiliation(s)
- Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea.
| | - MeeYoung Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Yeshong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Eunhye Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Yeongsoo Jo
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
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18
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Fawaz A, Abdel-Rahman O. Borderline Resectable Pancreatic Cancer: Challenges for Clinical Management. Cancer Manag Res 2022; 14:3589-3598. [PMID: 36597515 PMCID: PMC9805723 DOI: 10.2147/cmar.s340719] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 12/07/2022] [Indexed: 12/29/2022] Open
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) remains a significant worldwide health problem with a poor prognosis. A borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) is a tumor with limited vascular involvement that is technically resectable but with a high risk of positive margins (R1 resection). Objective To identify the current challenges that exist in the management of BR-PDAC. Methods A review of the literature was conducted to identify articles discussing the definitions and management of BR-PDAC. Key Findings Several anatomic definitions of BR-PDAC exist, and there is significant heterogeneity in their utilization across published trials. To improve the odds of a margin negative (R0) resection, a neoadjuvant treatment approach involving chemotherapy with or without radiation is currently preferred. While supporting the efficacy of a neoadjuvant approach in BR-PDAC, the largest published randomized trials have utilized older gemcitabine-based regimens. Recently published Phase II evidence and meta-analyses have supported the use of modern multi-agent regimens such as FOLFIRINOX. The utility of adding radiation to a chemotherapy backbone remains in question. Due to remnant fibrosis and edema following neoadjuvant therapy, accurately selecting patients for resection based on a restaging CT scan is challenging. Furthermore, the role of adjuvant therapy in BR-PDAC patients receiving neoadjuvant therapy needs to be defined. Conclusion Though progress has been made, the optimal management of BR-PDAC is uncertain. Phase III trials utilizing modern chemotherapeutic regimens are needed to establish a standard of care.
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Affiliation(s)
- Ali Fawaz
- Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Omar Abdel-Rahman
- Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
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19
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Ono S, Adachi T, Ohtsuka T, Kimura R, Nishihara K, Watanabe Y, Nagano H, Tokumitsu Y, Nanashima A, Imamura N, Baba H, Chikamoto A, Inomata M, Hirashita T, Furukawa M, Idichi T, Shinchi H, Maruyama Y, Nakamura M, Eguchi S. Predictive factors for early recurrence after pancreaticoduodenectomy in patients with resectable pancreatic head cancer: A multicenter retrospective study. Surgery 2022; 172:1782-1790. [PMID: 36123175 DOI: 10.1016/j.surg.2022.08.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 08/03/2022] [Accepted: 08/08/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Patients diagnosed with resectable pancreatic ductal adenocarcinoma often experience early recurrence even after upfront R0 resection. This study aimed to define early recurrence and identify preoperative risk factors for early recurrence after upfront pancreaticoduodenectomy in patients with resectable pancreatic ductal adenocarcinoma of the pancreatic head. METHODS This multicenter, retrospective study involved 500 patients who underwent pancreaticoduodenectomy resectable pancreatic ductal adenocarcinoma of the pancreatic head at 10 institutions between 2007 and 2016. Preoperative, intraoperative, and postoperative clinicopathological results were compared between early and non-early recurrence groups. Predictors of early recurrence were determined using statistical analyses. RESULTS Log-rank tests revealed a significant difference (P < .001) between recurrence within 3 to 6 months and 6 to 9 months. Early recurrence was subsequently defined as recurrence within 6 months. Patients were categorized into early recurrence (n = 104) and non-early recurrence groups (n = 389). The median overall survival of the early and non-early recurrence groups was 8.6 months and 42.6 months (P < .001), respectively. Preoperatively, high carbohydrate antigen 19-9 levels ≥120 U/mL, retroperitoneal invasion, and diabetes mellitus were identified as independent predictive risk factors for early recurrence according to multivariate analysis. Comparing survival rates among patients with 3, 2, 1, or none of these factors, the median overall survival was 17.6 (n = 90), 21.2 (n = 184), 47 (n = 141), and 61.5 (n = 73) months, respectively. CONCLUSION The optimal period that defines the early recurrence for resectable pancreatic ductal adenocarcinoma of the pancreatic head is 6 months. Tumor size ≥20 mm, preoperative carbohydrate antigen 19-9 levels ≥120 U/mL, retroperitoneal invasion of the tumor, and the presence of diabetes mellitus are independently associated with early recurrence.
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Affiliation(s)
- Shinichiro Ono
- Department of Surgery, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan.
| | - Tomohiko Adachi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
| | - Takao Ohtsuka
- Department of Surgery and Oncology, Kyushu University, Fukuoka, Japan
| | - Ryuichiro Kimura
- Department of Surgery and Oncology, Kyushu University, Fukuoka, Japan
| | | | - Yusuke Watanabe
- Department of Surgery, Kitakyushu Municipal Medical Center, Fukuoka, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University, Yamaguchi, Japan
| | - Yukio Tokumitsu
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University, Yamaguchi, Japan
| | - Atsushi Nanashima
- Department of Hepato-Biliary-Pancreas Surgery, Miyazaki University, Miyazaki, Japan
| | - Naoya Imamura
- Department of Hepato-Biliary-Pancreas Surgery, Miyazaki University, Miyazaki, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Kumamoto University, Kyushu, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Kumamoto University, Kyushu, Japan
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric Surgery, Oita University, Oita, Japan
| | - Teijiro Hirashita
- Department of Gastroenterological and Pediatric Surgery, Oita University, Oita, Japan
| | - Masayuki Furukawa
- Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center
| | - Tetsuya Idichi
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Fukuoka, Japan
| | - Hiroyuki Shinchi
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Fukuoka, Japan
| | | | - Masafumi Nakamura
- Department of Surgery and Oncology, Kyushu University, Fukuoka, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
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20
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Huang B, Geng H, Jin Y, Zhang X, Qian H, Ye D, Wu J, Zhu H, Yu Y, Zhou D, Li J. Is it justified to assess the resectability of pancreatic cancer combined with biological and conditional factors? Transl Cancer Res 2022; 11:3458-3470. [PMID: 36388054 PMCID: PMC9641078 DOI: 10.21037/tcr-22-1258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/25/2022] [Indexed: 10/29/2023]
Abstract
BACKGROUND This study aimed to investigate the biological and conditional resectability criteria for pancreatic ductal adenocarcinoma (PDAC), as proposed by the International Association of Pancreatology (IAP), as well as to identify the role of biological and conditional factors in assessing the resectability of PDAC. METHODS The clinical data of PDAC patients who underwent upfront open/laparoscopic pancreaticoduodenectomy (PD/LPD) or distal pancreatectomy (DP/LDP) at our hospital between January 2013 to June 2019 were retrospectively analyzed. Patients who were diagnosed with anatomically resectable PDAC, as defined by National Comprehensive Cancer Network (NCCN) guideline of PDAC guideline Version 1.2020, were enrolled. Based on IAP-criteria, these patients were divided into two groups, including IAP-resectable (IAP-R) and IAP Borderline Resectable (IAP-BR). Clinical characteristics and outcomes were compared between the two groups. In order to identify independent biological and conditional predictors of recurrence-free survival (RFS) and overall survival (OS) of enrolled patients, an analysis was performed through the use of a Cox proportional-hazard model. RESULTS Overall, 97 patients were included in this study. Among them, 38 patients were IAP-R and 59 patients were IAP-BR. Compared to the IAP-R group, the IAP-BR group had a higher early recurrence rate (62.7% vs. 42.1%; P=0.047), and the median RFS (9.2 vs. 18.3 months, P<0.01) and OS (19.1 vs. 30.6 months, P<0.05) were also significantly worse. Preoperative CA19-9 serum levels that exceeded 500 U/mL and/or an imaging diagnosis of regional lymph nodes metastasis were independently associated with OS and RFS of anatomically resectable PDAC. CONCLUSIONS The prognosis of patients with PDAC that undergo resection can be predicted more accurately by assessing the resectability of pancreatic cancer combined with anatomical and biological factors according to IAP criteria. Whether conditional factors should be included in the resectability criteria needs to be validated by prospective and large cohorts.
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Affiliation(s)
- Bingying Huang
- Department of Nursing, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Hao Geng
- Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yun Jin
- Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoxiao Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Hai Qian
- Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dan Ye
- Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jinhong Wu
- Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Huanbing Zhu
- Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuanquan Yu
- Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Donger Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiangtao Li
- Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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21
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Anger F, Lock JF, Klein I, Hartlapp I, Wiegering A, Germer CT, Kunzmann V, Löb S. Does Concurrent Cholestasis Alter the Prognostic Value of Preoperatively Elevated CA19-9 Serum Levels in Patients with Pancreatic Head Adenocarcinoma? Ann Surg Oncol 2022; 29:8523-8533. [PMID: 36094690 PMCID: PMC9640457 DOI: 10.1245/s10434-022-12460-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 08/06/2022] [Indexed: 11/28/2022]
Abstract
Background Pancreatic adenocarcinoma (PDAC) patients with preoperative carbohydrate antigen 19-9 (CA19-9) serum levels higher than 500 U/ml are classified as biologically borderline resectable (BR-B). To date, the impact of cholestasis on preoperative CA19-9 serum levels in these patients has remained unquantified. Methods Data on 3079 oncologic pancreatic resections due to PDAC that were prospectively acquired by the German Study, Documentation and Quality (StuDoQ) registry were analyzed in relation to preoperative CA19-9 and bilirubin serum values. Preoperative CA19-9 values were adjusted according to the results of a multivariable linear regression analysis of pathologic parameters, bilirubin, and CA19-9 values. Results Of 1703 PDAC patients with tumor located in the pancreatic head, 420 (24.5 %) presented with a preoperative CA19-9 level higher than 500 U/ml. Although receiver operating characteristics (ROC) analysis failed to determine exact CA19-9 cut-off values for prognostic indicators (R and N status), the T, N, and G status; the UICC stage; and the number of simultaneous vein resections increased with the level of preoperative CA19-9, independently of concurrent cholestasis. After adjustment of preoperative CA19-9 values, 18.5 % of patients initially staged as BR-B showed CA19-9 values below 500 U/ml. However, the postoperative pathologic results for these patients did not change compared with the patients who had CA19-9 levels higher than 500 U/ml after bilirubin adjustment. Conclusions In this multicenter dataset of PDAC patients, elevation of preoperative CA19-9 correlated with well-defined prognostic pathologic parameters. Bilirubin adjustment of CA19-9 is feasible but does not affect the prognostic value of CA19-9 in jaundiced patients. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-022-12460-w.
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Affiliation(s)
- Friedrich Anger
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany.
| | - Johan Friso Lock
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Ingo Klein
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Ingo Hartlapp
- Department of Internal Medicine II, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Armin Wiegering
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany.,Comprehensive Cancer Centre Mainfranken, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Christoph-Thomas Germer
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany.,Comprehensive Cancer Centre Mainfranken, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Volker Kunzmann
- Department of Internal Medicine II, Julius Maximilians University Wuerzburg, Wuerzburg, Germany.,Comprehensive Cancer Centre Mainfranken, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
| | - Stefan Löb
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Wuerzburg, Germany
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22
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Oba A, Del Chiaro M, Satoi S, Kim SW, Takahashi H, Yu J, Hioki M, Tanaka M, Kato Y, Ariake K, Wu YHA, Inoue Y, Takahashi Y, Hackert T, Wolfgang CL, Besselink MG, Schulick RD, Nagakawa Y, Isaji S, Tsuchida A, Endo I. New criteria of resectability for pancreatic cancer: A position paper by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:725-731. [PMID: 34581016 DOI: 10.1002/jhbp.1049] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 08/28/2021] [Accepted: 09/01/2021] [Indexed: 12/15/2022]
Abstract
The symposium "New criteria of resectability for pancreatic cancer" was held during the 33nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) in 2021 to discuss the potential modifications that could be made in the current resectability classification. The meeting focused on setting the foundation for developing a new prognosis-based resectability classification that is based on the tumor biology and the response to neoadjuvant treatment (NAT). The symposium included selected experts from Western and Eastern high-volume centers who have discussed their concept of resectability status through published literature. During the symposium, presenters reported new resectability classifications from their respective institutions based on tumor biology, conditional status, pathology, and genetics, in addition to anatomical tumor involvement. Interestingly, experts from all the centers reached the agreement that anatomy alone is insufficient to define resectability in the current era of effective NAT. On behalf of the JSHBPS, we would like to summarize the content of the conference in this position paper. We also invite global experts as internal reviewers of this paper for intercontinental cooperation in creating an up-to-date, prognosis-based resectability classification that reflects the trends of contemporary clinical practice.
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Affiliation(s)
- Atsushi Oba
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA
| | - Sohei Satoi
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA
- Department Surgery, Kansai Medical University, Osaka, Japan
| | - Sun-Whe Kim
- Department Surgery, Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Jun Yu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Masayoshi Hioki
- Department of Surgery, Fukuyama City Hospital, Hiroshima, Japan
| | - Masayuki Tanaka
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yoshiyasu Kato
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kyohei Ariake
- Department of Surgery, Tohoku University, Sendai, Japan
| | - Y H Andrew Wu
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Yosuke Inoue
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yu Takahashi
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany
| | | | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Richard D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA
| | - Yuichi Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Shuji Isaji
- Director of Mie University Graduate School of Medicine, Tsu, Japan
| | - Akihiko Tsuchida
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School Medicine, Yokohama, Japan
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23
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Nappo G, Donisi G, Zerbi A. Borderline resectable pancreatic cancer: Certainties and controversies. World J Gastrointest Surg 2021; 13:516-528. [PMID: 34194610 PMCID: PMC8223708 DOI: 10.4240/wjgs.v13.i6.516] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/09/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is currently a well-recognized entity, characterized by some specific anatomic, biological and conditional features: It includes patients with a stage of disease intermediate between the resectable and the locally advanced ones. The term BR identifies a tumour with an aggressive biological behaviour, on which a neoadjuvant approach instead of an upfront surgery one should be preferred, in order to obtain a radical resection (R0) and to avoid an early recurrence after surgery. Even if during the last decades several studies on this topic have been published, some aspects of BR-PDAC still represent a matter of debate. The aim of this review is to critically analyse the available literature on this topic, particularly focusing on: The problem of the heterogeneity of definition of BR-PDAC adopted, leading to a misinterpretation of published data; its current management (neoadjuvant vs upfront surgery); which neoadjuvant regimen should be preferably adopted; the problem of radiological restaging and the determination of resectability after neoadjuvant therapy; the post-operative outcomes after surgery; and the role and efficacy of adjuvant treatment for resected patients that already underwent neoadjuvant therapy.
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Affiliation(s)
- Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano 20089, Italy
| | - Greta Donisi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano 20089, Italy
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano 20089, Italy
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24
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Kato H, Horiguchi A, Ito M, Asano Y, Arakawa S. Essential updates 2019/2020: Multimodal treatment of localized pancreatic adenocarcinoma: Current topics and updates in survival outcomes and prognostic factors. Ann Gastroenterol Surg 2021; 5:132-151. [PMID: 33860134 PMCID: PMC8034700 DOI: 10.1002/ags3.12427] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 11/26/2020] [Accepted: 12/22/2020] [Indexed: 12/13/2022] Open
Abstract
Overall survival of patients with localized pancreatic ductal adenocarcinoma (PDAC) is extremely poor. Therefore, the establishment of multimodal treatment strategies is indispensable for PDAC patients because surgical treatment alone could not contribute to the improvement of survival. In this review article, we focus on the current topics and advancement of the treatments for localized PDAC including resectable, borderline resectable, and locally advanced PDAC in accordance with the articles mainly published from 2019 to 2020. Reviewing the articles, the recent progress of multimodal treatments notably improves the prognosis of patients with localized PDAC. For resectable PDAC, neoadjuvant chemo or chemoradiation therapy, rather than upfront surgery, plays a key role, especially in patients with a large tumor, poor performance status, high tumor marker levels, peripancreatic lymph nodes metastasis, or neural invasion suspected on preoperative imaging. For borderline resectable PDAC, neoadjuvant treatments followed by surgery is a desirable approach, and maintenance of immunonutritional status during the treatments are also important. For locally advanced disease, conversion surgery has a central role in improving a survival outcome; however, its indication should be standardized.
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Affiliation(s)
- Hiroyuki Kato
- Department of Gastroenterological SurgeryBantane HospitalFujita Health University School of MedicineNagoyaAichiJapan
| | - Akihiko Horiguchi
- Department of Gastroenterological SurgeryBantane HospitalFujita Health University School of MedicineNagoyaAichiJapan
| | - Masahiro Ito
- Department of Gastroenterological SurgeryBantane HospitalFujita Health University School of MedicineNagoyaAichiJapan
| | - Yukio Asano
- Department of Gastroenterological SurgeryBantane HospitalFujita Health University School of MedicineNagoyaAichiJapan
| | - Satoshi Arakawa
- Department of Gastroenterological SurgeryBantane HospitalFujita Health University School of MedicineNagoyaAichiJapan
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25
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Anger F, Döring A, van Dam J, Lock JF, Klein I, Bittrich M, Germer CT, Wiegering A, Kunzmann V, van Eijck C, Löb S. Impact of Borderline Resectability in Pancreatic Head Cancer on Patient Survival: Biology Matters According to the New International Consensus Criteria. Ann Surg Oncol 2020; 28:2325-2336. [PMID: 32920720 PMCID: PMC7940298 DOI: 10.1245/s10434-020-09100-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 08/18/2020] [Indexed: 12/19/2022]
Abstract
Background International consensus criteria (ICC) have redefined borderline resectability for pancreatic ductal adenocarcinoma (PDAC) according to three dimensions: anatomical (BR-A), biological (BR-B), and conditional (BR-C). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumour and vessels but that biological and conditional dimensions also are important. Methods Patients’ tumours were retrospectively defined borderline resectable according to ICC. The study cohort was grouped into either BR-A or BR-B and compared with patients considered primarily resectable (R). Differences in postoperative complications, pathological reports, overall (OS), and disease-free survival were assessed. Results A total of 345 patients underwent resection for PDAC. By applying ICC in routine preoperative assessment, 30 patients were classified as stage BR-A and 62 patients as stage BR-B. In total, 253 patients were considered R. The cohort did not contain BR-C patients. No differences in postoperative complications were detected. Median OS was significantly shorter in BR-A (15 months) and BR-B (12 months) compared with R (20 months) patients (BR-A vs. R: p = 0.09 and BR-B vs. R: p < 0.001). CA19-9, as the determining factor of BR-B patients, turned out to be an independent prognostic risk factor for OS. Conclusions Preoperative staging defining surgical resectability in PDAC according to ICC is crucial for patient survival. Patients with PDAC BR-B should be considered for multimodal neoadjuvant therapy even if considered anatomically resectable.
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Affiliation(s)
- Friedrich Anger
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Würzburg, Germany
| | - Anna Döring
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Würzburg, Germany
| | - Jacob van Dam
- Department of Surgery, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Johan Friso Lock
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Würzburg, Germany
| | - Ingo Klein
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Würzburg, Germany
| | - Max Bittrich
- Department of Internal Medicine II, Julius Maximilians University Wuerzburg, Würzburg, Germany
| | - Christoph-Thomas Germer
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Würzburg, Germany.,Comprehensive Cancer Centre Mainfranken, Julius Maximilians University Wuerzburg, Würzburg, Germany
| | - Armin Wiegering
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Würzburg, Germany.,Comprehensive Cancer Centre Mainfranken, Julius Maximilians University Wuerzburg, Würzburg, Germany
| | - Volker Kunzmann
- Department of Internal Medicine II, Julius Maximilians University Wuerzburg, Würzburg, Germany.,Comprehensive Cancer Centre Mainfranken, Julius Maximilians University Wuerzburg, Würzburg, Germany
| | - Casper van Eijck
- Department of Surgery, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Stefan Löb
- Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, Julius Maximilians University Wuerzburg, Würzburg, Germany.
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Takahashi H, Yamada D, Asukai K, Wada H, Hasegawa S, Hara H, Shinno N, Ushigome H, Haraguchi N, Sugimura K, Yamamoto K, Nishimura J, Yasui M, Omori T, Miyata H, Ohue M, Yano M, Sakon M, Ishikawa O. Clinical implications of the serum CA19-9 level in "biological borderline resectability" and "biological downstaging" in the setting of preoperative chemoradiation therapy for pancreatic cancer. Pancreatology 2020; 20:919-928. [PMID: 32563596 DOI: 10.1016/j.pan.2020.05.020] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 05/18/2020] [Accepted: 05/27/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Biological factors are emphasized in borderline resectable pancreatic cancer (BRPC), and CA19-9 is an important factor for biological borderline resectability (b-BR). The aim of this study was to investigate the cut-off value of CA19-9 for biological borderline resectability and "biological downstaging" in chemoradiation therapy (CRT) for pancreatic cancer (PC). METHODS A total of 407 patients with anatomically resectable PC (a-R) and BRPC (a-BR) received preoperative gemcitabine-based CRT. The b-BR was determined, according to the CA19-9 value prior to preoperative CRT (pre-CA19-9), as the subgroup of a-R cases in which the survival was comparable with that in a-BR cases. "Biological downstaging" was determined based on prognostic analyses regarding the CA19-9 value after preoperative CRT (post-CA19-9) in association with the survival of R cases (a-R cases without the b-BR factor). RESULTS The 5-year survival of a-R patients with pre-CA19-9 > 120 U/mL was comparable with that of a-BR patients (44% vs 34%, p = 0.082). The survival of b-BR patients with post-CRT CA19-9 ≤ 37 U/mL (normalized) was comparably favorable with that of R patients (56% vs 65%, p = 0.369). The incidence of distant recurrence was higher in b-BR patients without post-CA19-9 normalization than in those with post-CA19-9 normalization (70% vs 50%, p = 0.003), while the incidence of local recurrence was comparable between these two groups (12% vs 13%, p = 0.986). CONCLUSIONS Biological BRPC was determined to be an anatomically resectable disease with pre-CA19-9 > 120 U/mL, and post-CA19-9 normalization indicated "biological downstaging" in b-BR in the preoperative CRT strategy.
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Affiliation(s)
| | - Daisaku Yamada
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Kei Asukai
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Wada
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | - Hisashi Hara
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Naoki Shinno
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hajime Ushigome
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | - Keijiro Sugimura
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | | | - Masayoshi Yasui
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takeshi Omori
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Miyata
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masayuki Ohue
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masahiko Yano
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masato Sakon
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Osamu Ishikawa
- Department of Surgery, Osaka International Cancer Institute, Japan
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Systematic Analysis of Accuracy in Predicting Complete Oncological Resection in Pancreatic Cancer Patients-Proposal of a New Simplified Borderline Resectability Definition. Cancers (Basel) 2020; 12:cancers12040882. [PMID: 32260453 PMCID: PMC7226508 DOI: 10.3390/cancers12040882] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 03/20/2020] [Accepted: 04/01/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Borderline resectability in pancreatic cancer (PDAC) is currently debated. Methods: Patients undergoing pancreatic resections for PDAC were identified from a prospectively maintained database. As new borderline criteria, the presence of any superior mesenterico-portal vein alteration (SMPV) and perivascular stranding of the superior mesenteric artery (SMA) was evaluated in preoperative imaging. The accuracy of established radiological borderline criteria as compared to the new borderline criteria in predicting R status (sensitivity/negative predictive value) and overall survival was assessed. (3) Results: 118 patients undergoing pancreatic resections for PDAC from 2013 to 2018 were identified. Forty-three (36.4%) had radiological perivascular SMA stranding and 55 (46.6%) had SMPV alterations. Interrater reliability was 90% for SMA stranding and 87% for SMPV alterations. The new borderline definition including SMPV alterations and perivascular SMA stranding was the best predictor of conventional R status (p = 0.040, sensitivity 53%, negative predictive value 81%) and Leeds/Wittekind circumferential margin status (p = 0.050, sensitivity 73%, negative predictive value 79%) as compared to established borderline resectability definition criteria. Perivascular SMA stranding qualified as an independent negative prognostic parameter (HR 3.066, 95% CI 1.078-5.716, p = 0.036). Conclusion: The radiological evaluation of any SMPV alteration and perivascular SMA stranding predicts R status and overall survival in PDAC patients, and may serve to identify potential candidates for neoadjuvant therapy.
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