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Jaiswal S, Cox KE, Amirfakhri S, Din Parast Saleh A, Kobayashi K, Lwin TM, Talib S, Aithal A, Mallya K, Jain M, Mohs AM, Hoffman RM, Batra SK, Bouvet M. Targeting Human Pancreatic Cancer with a Fluorophore-Conjugated Mucin 4 (MUC4) Antibody: Initial Characterization in Orthotopic Cell Line Mouse Models. J Clin Med 2024; 13:6211. [PMID: 39458160 PMCID: PMC11508345 DOI: 10.3390/jcm13206211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 10/13/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
Background/Objectives: Pancreatic cancer is the third leading cause of death related to cancer. The only possible cure presently is complete surgical resection; however, this is limited by difficulty in clearly defining tumor margins. Enhancement of the visualization of pancreatic ductal adenocarcinoma (PDAC) tumor margins using near-infrared dye-conjugated tumor-specific antibodies was pioneered by using anti-CEA, anti-CA19.9, and anti-MUC5AC in orthotopic mouse models of pancreatic cancer. Recently, an antibody to Mucin 4 (MUC4) conjugated to a fluorescent probe has shown promise in targeting colon tumors in orthotopic mouse models. Methods: In the present study, we targeted pancreatic cancer using an anti-MUC4 antibody conjugated to IRDye800 (anti-MUC4-IR800) in orthotopic mouse models. Two pancreatic cancer human cell lines were used, SW1990 and CD18/HPAF. Results: Anti-MUC4-IR800 targeted the two pancreatic cancer cell line tumors in orthotopic mouse models with high tumor-to-pancreas ratios and high tumor-to-liver ratios, with greater targeting seen in SW1990. Conclusions: The present results suggest anti-MUC4-IR800's potential to be used in fluorescence-guided surgical resection of pancreatic cancer.
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Affiliation(s)
- Sunidhi Jaiswal
- Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (S.J.); (S.A.); (A.D.P.S.); (K.K.); (R.M.H.)
- VA San Diego Healthcare System, La Jolla, CA 92161, USA
| | - Kristin E. Cox
- Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (S.J.); (S.A.); (A.D.P.S.); (K.K.); (R.M.H.)
- VA San Diego Healthcare System, La Jolla, CA 92161, USA
| | - Siamak Amirfakhri
- Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (S.J.); (S.A.); (A.D.P.S.); (K.K.); (R.M.H.)
- VA San Diego Healthcare System, La Jolla, CA 92161, USA
| | - Aylin Din Parast Saleh
- Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (S.J.); (S.A.); (A.D.P.S.); (K.K.); (R.M.H.)
| | - Keita Kobayashi
- Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (S.J.); (S.A.); (A.D.P.S.); (K.K.); (R.M.H.)
| | - Thinzar M. Lwin
- Department of Surgical Oncology, City of Hope, Duarte, CA 91010, USA;
| | - Sumbal Talib
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA; (S.T.); (A.M.M.)
| | - Abhijit Aithal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA; (A.A.); (K.M.); (M.J.); (S.K.B.)
| | - Kavita Mallya
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA; (A.A.); (K.M.); (M.J.); (S.K.B.)
| | - Maneesh Jain
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA; (A.A.); (K.M.); (M.J.); (S.K.B.)
| | - Aaron M. Mohs
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA; (S.T.); (A.M.M.)
| | - Robert M. Hoffman
- Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (S.J.); (S.A.); (A.D.P.S.); (K.K.); (R.M.H.)
- VA San Diego Healthcare System, La Jolla, CA 92161, USA
- AntiCancer Inc., San Diego, CA 92111, USA
| | - Surinder K. Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA; (A.A.); (K.M.); (M.J.); (S.K.B.)
| | - Michael Bouvet
- Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA; (S.J.); (S.A.); (A.D.P.S.); (K.K.); (R.M.H.)
- VA San Diego Healthcare System, La Jolla, CA 92161, USA
- UCSD Moores UCSD Cancer Center, 3855 Health Sciences Drive #0987, La Jolla, CA 92093-0987, USA
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Muilenburg KM, Ehrhorn EG, Olson MT, Isder CC, Klute KA, Talmon GA, Carlson MA, Ly QP, Mohs AM. MUC16 Retention after Neoadjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2024; 16:3439. [PMID: 39456534 PMCID: PMC11506185 DOI: 10.3390/cancers16203439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/27/2024] [Accepted: 10/03/2024] [Indexed: 10/28/2024] Open
Abstract
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Currently, surgical resection is the only potentially curative treatment. Unfortunately, less than 20% of PDAC patients are eligible for surgical resection at diagnosis. In the past few decades, neoadjuvant chemotherapy treatment (NCT) has been investigated as a way to downstage PDAC tumors for surgical resection. Fluorescence-guided surgery (FGS) is a technique that can aid in increasing complete resection rates by enhancing the tumor through passive or active targeting of a contrast agent. In active targeting, a probe (e.g., antibody) binds a protein differentially upregulated in the tumor compared to normal tissue. Mucin 16 (MUC16), a transmembrane glycoprotein, has recently been explored as an FGS target in preclinical tumor models. However, the impact of chemotherapy on MUC16 expression is unknown. Methods: To investigate this issue, immunohistochemistry was performed on PDAC patient samples. Results: We found that MUC16 expression was retained after NCT in patient samples (mean expression = 5.7) with minimal change in expression between the matched diagnostic (mean expression = 3.66) and PDAC NCT patient samples (mean expression = 4.5). Conclusions: This study suggests that MUC16 is a promising target for FGS and other targeted therapies in PDAC patients treated with NCT.
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Affiliation(s)
- Kathryn M. Muilenburg
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (K.M.M.); (C.C.I.)
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (E.G.E.); (M.T.O.); (K.A.K.); (G.A.T.); (M.A.C.); (Q.P.L.)
| | - Evie G. Ehrhorn
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (E.G.E.); (M.T.O.); (K.A.K.); (G.A.T.); (M.A.C.); (Q.P.L.)
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA
| | - Madeline T. Olson
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (E.G.E.); (M.T.O.); (K.A.K.); (G.A.T.); (M.A.C.); (Q.P.L.)
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA
| | - Carly C. Isder
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (K.M.M.); (C.C.I.)
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (E.G.E.); (M.T.O.); (K.A.K.); (G.A.T.); (M.A.C.); (Q.P.L.)
| | - Kelsey A. Klute
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (E.G.E.); (M.T.O.); (K.A.K.); (G.A.T.); (M.A.C.); (Q.P.L.)
- Department of Internal Medicine, University of Nebraska Medical Center, 42nd and Emile, Omaha, NE 68198, USA
| | - Geoffrey A. Talmon
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (E.G.E.); (M.T.O.); (K.A.K.); (G.A.T.); (M.A.C.); (Q.P.L.)
- Department of Pathology and Microbiology, University of Nebraska Medical Center, 985900 Nebraska Medical Center, Omaha, NE 68198, USA
| | - Mark A. Carlson
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (E.G.E.); (M.T.O.); (K.A.K.); (G.A.T.); (M.A.C.); (Q.P.L.)
- Department of Surgery, University of Nebraska Medical Center, 983280 Nebraska Medical Center, Omaha, NE 68198, USA
| | - Quan P. Ly
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (E.G.E.); (M.T.O.); (K.A.K.); (G.A.T.); (M.A.C.); (Q.P.L.)
- Department of Surgery, University of Nebraska Medical Center, 983280 Nebraska Medical Center, Omaha, NE 68198, USA
| | - Aaron M. Mohs
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (K.M.M.); (C.C.I.)
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; (E.G.E.); (M.T.O.); (K.A.K.); (G.A.T.); (M.A.C.); (Q.P.L.)
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, S 45th St, Omaha, NE 68198, USA
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Matsui H, Ioka T, Takahashi T, Kawaoka T, Maeda Y, Yahara N, Kubo H, Nishimura T, Inokuchi T, Harada E, Shindo Y, Tokumitsu Y, Nakajima M, Takami T, Ito K, Tanaka H, Hamano K, Nagano H. Multicenter Prospective Cohort Study of Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer (YPB-001). Pancreas 2024; 53:e501-e512. [PMID: 38530956 DOI: 10.1097/mpa.0000000000002323] [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] [Indexed: 03/28/2024]
Abstract
OBJECTIVES The present multicenter prospective observational study investigated the effectiveness and safety of neoadjuvant chemotherapy (NAC) for patients with borderline resectable pancreatic cancer (BRPC) and those with RPC contacting major vessels, with respect to a historical control of upfront surgery. MATERIALS AND METHODS Patients with BRPC and RPC contacting major vessels were prospectively registered and administered NAC with durations and regimens determined by the corresponding treating physician. Our primary aim was to assess the R0 resection rate, and secondary aim was to evaluate safety, resection rate, time to treatment failure, overall survival, and response rate. RESULTS Fifty of 52 enrolled patients were analyzed; 2 with serious comorbidities died during treatment. Thirty-one patients underwent resection, with R0 resection being achieved in 26 (52% of total and 84% of all resected cases). Univariate and multivariate analyses indicated age (≥75 years) as the only independent predictor of nonresection. Median progression-free survival and median survival time were longer in the prospective cohort than in the historical cohort. CONCLUSIONS Overall, NAC for BRPC in real-world setting might yield R0 resection rates similar to those reported in previous clinical studies. Development of safe regimens and management strategies that can maintain treatment intensity in geriatric patients is warranted.
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Affiliation(s)
- Hiroto Matsui
- From the Department of Gastroenterological, Breast, and Endocrine Surgery, Yamaguchi University Graduate School of Medicine
| | - Tatsuya Ioka
- Yamaguchi University Hospital Cancer Center, Ube
| | | | - Toru Kawaoka
- Department of Surgery, Tokuyama Central Hospital, Yamaguchi
| | | | - Noboru Yahara
- Department of Surgery, Kanmon Medical Center, Shimonoseki
| | - Hidefumi Kubo
- Department of Surgery, Ube Industries Central Hospital, Ube
| | - Taku Nishimura
- Department of Gastroenterological Surgery, JCHO Shimonoseki Medical Center, Shimonoseki
| | | | | | - Yoshitaro Shindo
- From the Department of Gastroenterological, Breast, and Endocrine Surgery, Yamaguchi University Graduate School of Medicine
| | - Yukio Tokumitsu
- From the Department of Gastroenterological, Breast, and Endocrine Surgery, Yamaguchi University Graduate School of Medicine
| | - Masao Nakajima
- From the Department of Gastroenterological, Breast, and Endocrine Surgery, Yamaguchi University Graduate School of Medicine
| | | | | | - Hidekazu Tanaka
- Radiation Oncology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | | | - Hiroaki Nagano
- From the Department of Gastroenterological, Breast, and Endocrine Surgery, Yamaguchi University Graduate School of Medicine
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Cihangir Emral A, Dikmen K, Tahernejad M, Sardari K, Rahman Pour A, Ekinci Ö, Kerem M. Histopathological evaluation after pancreatic surgery: Comparison of the results of HPB-specific pathologists and non-specific pathologists. Turk J Surg 2023; 39:310-314. [PMID: 38694527 PMCID: PMC11057938 DOI: 10.47717/turkjsurg.2023.6286] [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: 11/29/2023] [Accepted: 12/16/2023] [Indexed: 05/04/2024]
Abstract
Objectives The aim of this study was to compare the results of the evaluation of HPB-specific pathologists and general pathologists on the specimens of patients who underwent pancreaticoduodenectomy by the same surgical team. Material and Methods The pathological results of 159 patients who underwent pancreaticoduodenectomy (PD) in the periampullary region was retrospectively examined. Histopathological evaluation results of HPB-specific pathologist (S group) and other pathologists (NS group) were compared. Tumor size (mm), total lymph nodes, metastatic lymph nodes, surgical margin positive/negative (RO/R1/R2 resection) and data of patients who underwent vascular resection were evaluated. Results The specimens of 91 patients were examined by a HPB-specific pathologist (S group), and the specimens of 68 patients were examined by non-specific pathologists (NS group). When compared in terms of the average total number of lymph nodes and metastatic lymph nodes dissected, a statistically significant result was observed (p= 0.04, p <0.01 respectively). Additionally, surgical margin positivity (R1) was found to be statistically higher in the S group (p= 0.02). Conclusion In order for the success of HPB surgery to be reflected in the clinic, it is of great importance that the specimens are examined by HPBspecific pathologists.
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Affiliation(s)
- Ahmet Cihangir Emral
- Department of General Surgery, Atılım University Faculty of Medicine, Ankara, Türkiye
| | - Kürşat Dikmen
- Department of General Surgery, Gazi University Faculty of Medicine, Ankara, Türkiye
| | | | | | | | - Özgür Ekinci
- Department of Pathology, Gazi University Faculty of Medicine, Ankara, Türkiye
| | - Mustafa Kerem
- Department of General Surgery, Gazi University Faculty of Medicine, Ankara, Türkiye
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Mangieri CW, Valenzuela CD, Solsky IB, Erali RA, Pardee T, Lima CMSR, Howerton R, Clark CJ, Shen P. Comparison of survival for metastatic pancreatic cancer patients treated with CPI-613 versus resected borderline-resectable pancreatic cancer patients. J Surg Oncol 2023; 128:844-850. [PMID: 37341164 DOI: 10.1002/jso.27365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 04/25/2023] [Accepted: 05/08/2023] [Indexed: 06/22/2023]
Abstract
INTRODUCTION Treatment of advanced pancreatic adenocarcinoma remains suboptimal. Therapeutic agents with a novel mechanism of action are desperately needed; one such novel agent is CPI-613 targets. We here analyze the outcomes of 20 metastatic pancreatic cancer patients treated with CPI-613 and FOLFIRINOX in our institution and evaluate their outcomes to borderline-resectable patients treated with curative surgery. METHODS A post hoc analysis was performed of the phase I CPI-613 trial data (NCT03504423) comparing survival outcomes to borderline-resectable cases treated with curative resection at the same institution. Survival was measured by overall survival (OS) for all study cases and disease-free survival (DFS) for resected cases with progression-free survival for CPI-613 cases. RESULTS There were 20 patients in the CPI-613 cohort and 60 patients in the surgical cohort. Median follow-up times were 441 and 517 days for CPI-613 and resected cases, respectively. There was no difference in survival times between CPI-613 and resected cases with a mean OS of 1.8 versus 1.9 year (p = 0.779) and mean PFS/DFS of 1.4 versus 1.7 years (p = 0.512). There was also no difference in 3-year survival rates for OS (hazard ratio [HR] = 1.063, 95% confidence interval [CI] 0.302-3.744, p = 0.925) or DFS/PFS (HR = 1.462, 95% CI 0.285-7.505, p = 0.648). CONCLUSION The first study to evaluate the survival between metastatic patients treated with CPI-613 versus borderline-resectable cases undergoing curative resection. Analysis revealed no significant differences in survival outcomes between the cohorts. Study results are suggestive that there may be potential utility with the addition of CPI-613 to potentially resectable pancreatic adenocarcinoma, although additional research with more comparable study groups are required.
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Affiliation(s)
- Christopher W Mangieri
- Atrium Wake Forest Baptist Medical Center, Division of Surgical Oncology, Winston-Salem, North Carolina, USA
| | - Cristian D Valenzuela
- Atrium Wake Forest Baptist Medical Center, Division of Surgical Oncology, Winston-Salem, North Carolina, USA
| | - Ian B Solsky
- Atrium Wake Forest Baptist Medical Center, Division of Surgical Oncology, Winston-Salem, North Carolina, USA
| | - Richard A Erali
- Atrium Wake Forest Baptist Medical Center, Division of Surgical Oncology, Winston-Salem, North Carolina, USA
| | - Timothy Pardee
- Atrium Wake Forest Baptist Medical Center, Division of Hematology and Oncology, Winston-Salem, North Carolina, USA
| | - Caio Max S Rocha Lima
- Atrium Wake Forest Baptist Medical Center, Division of Hematology and Oncology, Winston-Salem, North Carolina, USA
| | - Russell Howerton
- Atrium Wake Forest Baptist Medical Center, Division of Surgical Oncology, Winston-Salem, North Carolina, USA
| | - Clancy J Clark
- Atrium Wake Forest Baptist Medical Center, Division of Surgical Oncology, Winston-Salem, North Carolina, USA
| | - Perry Shen
- Atrium Wake Forest Baptist Medical Center, Division of Surgical Oncology, Winston-Salem, North Carolina, USA
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Masuda S, Yamakawa K, Masuda A, Toyama H, Sofue K, Nanno Y, Komatsu S, Omiya S, Sakai A, Kobayashi T, Tanaka T, Tsujimae M, Ashina S, Gonda M, Abe S, Uemura H, Kohashi S, Inomata N, Nagao K, Harada Y, Miki M, Irie Y, Juri N, Kanzawa M, Itoh T, Fukumoto T, Kodama Y. Association of Sarcopenia with a Poor Prognosis and Decreased Tumor-Infiltrating CD8-Positive T Cells in Pancreatic Ductal Adenocarcinoma: A Retrospective Analysis. Ann Surg Oncol 2023; 30:5776-5787. [PMID: 37191859 PMCID: PMC10409680 DOI: 10.1245/s10434-023-13569-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 02/27/2023] [Indexed: 05/17/2023]
Abstract
BACKGROUND Sarcopenia, defined as a loss of skeletal muscle mass and quality, is found in 30-65% of patients with pancreatic ductal adenocarcinoma (PDAC) at diagnosis, and is a poor prognostic factor. However, it is yet to be evaluated why sarcopenia is associated with poor prognosis. Therefore, this study elucidated the tumor characteristics of PDAC with sarcopenia, including driver gene alterations and tumor microenvironment. PATIENTS AND METHODS We retrospectively analyzed 162 patients with PDAC who underwent pancreatic surgery between 2008 and 2017. We defined sarcopenia by measuring the skeletal muscle mass at the L3 level using preoperative computed tomography images and evaluated driver gene alteration (KRAS, TP53, CDKN2A/p16, and SMAD4) and tumor immune (CD4+, CD8+, and FOXP3+) and fibrosis status (stromal collagen). RESULTS In localized-stage PDAC (stage ≤ IIa), overall survival (OS) and recurrence-free survival were significantly shorter in the sarcopenia group than in the non-sarcopenia group (2-year OS 89.7% versus 59.1%, P = 0.03; 2-year RFS 74.9% versus 50.0%, P = 0.02). Multivariate analysis revealed that sarcopenia was an independent poor prognostic factor in localized-stage PDAC. Additionally, tumor-infiltrating CD8+ T cells in the sarcopenia group were significantly less than in the non-sarcopenia group (P = 0.02). However, no difference was observed in driver gene alteration and fib.rotic status. These findings were not observed in advanced-stage PDAC (stage ≥ IIb). CONCLUSIONS Sarcopenia was associated with a worse prognosis and decreased tumor-infiltrating CD8+ T cells in localized-stage PDAC. Sarcopenia may worsen a patient's prognosis by suppressing local tumor immunity.
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Affiliation(s)
- Shigeto Masuda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Kohei Yamakawa
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Atsuhiro Masuda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
| | - Hirochika Toyama
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Keitaro Sofue
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Yoshihide Nanno
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Shohei Komatsu
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Satoshi Omiya
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Arata Sakai
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takeshi Tanaka
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Masahiro Tsujimae
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Shigeto Ashina
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Masanori Gonda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Shohei Abe
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Hisahiro Uemura
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Shinya Kohashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Noriko Inomata
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Kae Nagao
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Yoshiyuki Harada
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Mika Miki
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Yosuke Irie
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Noriko Juri
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Maki Kanzawa
- Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoo Itoh
- Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takumi Fukumoto
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
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Sina N, Olkhov-Mitsel E, Chen L, Karanicolas P, Sun L, Roopchand P, Rowsell C, Truong T. Utility of intraoperative pathology consultations of whipple resection specimens and their impact on final margin status. Heliyon 2023; 9:e20238. [PMID: 37810002 PMCID: PMC10560021 DOI: 10.1016/j.heliyon.2023.e20238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 09/06/2023] [Accepted: 09/14/2023] [Indexed: 10/10/2023] Open
Abstract
The resection margin status is a significant surgical prognostic factor for the long-term outcomes of patients undergoing pancreaticoduodenectomy (Whipple procedure). As a result, surgeons frequently rely on intraoperative consults (IOCs) involving frozen sections to evaluate margin clearance during these resections. Nevertheless, the impact of this practice on final margin status and long-term outcomes remains a topic of debate. This study aimed to assess the impact of IOCs on the clearance rate of resection margins following Whipple procedure and distal pancreatectomy. A retrospective database review of all patients who underwent Whipple procedure or distal pancreatectomy at our institution between 2018 and 2020 was performed to evaluate the utility of IOCs by gastrointestinal surgeons and its correlation with final postoperative surgical margin status. A significant variation in the frequency of IOC requests for margins among surgeons was noted. However, the use of frozen section analysis for intraoperative margin assessment was not significantly associated with the clearance rate of final post-operative margins. More frequent use of IOC did not result in higher final margin clearance rate, an important prognostic factor following Whipple procedure.
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Affiliation(s)
- Niloofar Sina
- Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
| | - Ekaterina Olkhov-Mitsel
- Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
| | - Lina Chen
- Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
| | - Paul Karanicolas
- Department of Surgery, Sunnybrook Health Science Center, Toronto, Ontario, M4N 3M5, Canada
| | - Laibao Sun
- Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
| | - Preeya Roopchand
- Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
| | - Corwyn Rowsell
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
- Department of Laboratory Medicine & Pathobiology, St. Michael's Hospital, Toronto, Ontario, M5B 1W8, Canada
| | - Tra Truong
- Division of Anatomic Pathology, Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, ON, M4N 3M5, Canada
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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8
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Charalampopoulou A, Barcellini A, Frittitta GE, Fulgini G, Ivaldi GB, Magro G, Liotta M, Orlandi E, Pullia MG, Tabarelli de Fatis P, Facoetti A. In Vitro Effects of Photon Beam and Carbon Ion Radiotherapy on the Perineural Invasion of Two Cell Lines of Neurotropic Tumours. Life (Basel) 2023; 13:794. [PMID: 36983949 PMCID: PMC10056732 DOI: 10.3390/life13030794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 02/16/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023] Open
Abstract
Primary mucosal melanoma (PMM) and pancreatic ductal adenocarcinoma (PDAC) are two aggressive malignancies, characterized by intrinsic radio-chemoresistance and neurotropism, a histological feature resulting in frequent perineural invasion (PNI), supported by neurotrophic factors secreted in the tumour microenvironment (TME), such as neurotrophin-3 (NT-3). Carbon-ion radiotherapy (CIRT) could represent an effective option in unresectable PMM and PDAC. Only a few data about the effects of CIRT on PNI in relation to NT-3 are available in the literature, despite the numerous pieces of evidence revealing the peculiar effects of this type of radiation on tumour cell migration. This in vitro study investigated for the first time the response of PMM and PDAC cells to NT-3 and evaluated the effects of conventional photon beam radiotherapy (XRT) and CIRT on cell viability, proliferation, and migration. Our results demonstrated the greater capacity of C-ions to generally decrease cell viability, proliferation, and migration, while the addition of NT-3 after both types of irradiation determined an increase in these features, maintaining a dose-dependent trend and acting more effectively as a chemoattractant than inductor in the case of migration.
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Affiliation(s)
- Alexandra Charalampopoulou
- Radiobiology Unit, Research and Development Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
- Hadron Academy PhD Course, Istituto Universitario di STUDI Superiori (IUSS), 27100 Pavia, Italy
| | - Amelia Barcellini
- Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapy, University of Pavia, 27100 Pavia, Italy
| | - Giuseppe Emanuele Frittitta
- Radiobiology Unit, Research and Development Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
- Biology and Biotechnology Department, University of Pavia, 27100 Pavia, Italy
| | - Giorgia Fulgini
- Radiobiology Unit, Research and Development Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
- Biology and Biotechnology Department, University of Pavia, 27100 Pavia, Italy
| | | | - Giuseppe Magro
- Medical Physics Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
| | - Marco Liotta
- Medical Physics Unit, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy
| | - Ester Orlandi
- Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
| | - Marco Giuseppe Pullia
- Physics Unit, Research and Development Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
| | | | - Angelica Facoetti
- Radiobiology Unit, Research and Development Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy
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9
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Chang J, Liu Y, Saey SA, Chang KC, Shrader HR, Steckly KL, Rajput M, Sonka M, Chan CHF. Machine-learning based investigation of prognostic indicators for oncological outcome of pancreatic ductal adenocarcinoma. Front Oncol 2022; 12:895515. [PMID: 36568148 PMCID: PMC9773248 DOI: 10.3389/fonc.2022.895515] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 11/09/2022] [Indexed: 12/13/2022] Open
Abstract
Introduction Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Surgical resection remains the only potential curative treatment option for early-stage resectable PDAC. Patients with locally advanced or micrometastatic disease should ideally undergo neoadjuvant therapy prior to surgical resection for an optimal treatment outcome. Computerized tomography (CT) scan is the most common imaging modality obtained prior to surgery. However, the ability of CT scans to assess the nodal status and resectability remains suboptimal and depends heavily on physician experience. Improved preoperative radiographic tumor staging with the prediction of postoperative margin and the lymph node status could have important implications in treatment sequencing. This paper proposes a novel machine learning predictive model, utilizing a three-dimensional convoluted neural network (3D-CNN), to reliably predict the presence of lymph node metastasis and the postoperative positive margin status based on preoperative CT scans. Methods A total of 881 CT scans were obtained from 110 patients with PDAC. Patients and images were separated into training and validation groups for both lymph node and margin prediction studies. Per-scan analysis and per-patient analysis (utilizing majority voting method) were performed. Results For a lymph node prediction 3D-CNN model, accuracy was 90% for per-patient analysis and 75% for per-scan analysis. For a postoperative margin prediction 3D-CNN model, accuracy was 81% for per-patient analysis and 76% for per-scan analysis. Discussion This paper provides a proof of concept that utilizing radiomics and the 3D-CNN deep learning framework may be used preoperatively to improve the prediction of positive resection margins as well as the presence of lymph node metastatic disease. Further investigations should be performed with larger cohorts to increase the generalizability of this model; however, there is a great promise in the use of convoluted neural networks to assist clinicians with treatment selection for patients with PDAC.
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Affiliation(s)
- Jeremy Chang
- Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
| | - Yanan Liu
- Iowa Initiative for Artificial Intelligence, University of Iowa, Iowa City, IA, United States
| | - Stephanie A. Saey
- Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
| | - Kevin C. Chang
- Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
| | - Hannah R. Shrader
- Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States,Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
| | - Kelsey L. Steckly
- Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
| | - Maheen Rajput
- Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
| | - Milan Sonka
- Iowa Initiative for Artificial Intelligence, University of Iowa, Iowa City, IA, United States,Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, United States
| | - Carlos H. F. Chan
- Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States,Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States,*Correspondence: Carlos H. F. Chan,
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10
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Wu Z, Zhao P, Wang Z, Huang X, Wu C, Li M, Wang L, Tian B. Adjusting CA19-9 values with clinical stage and bilirubin to better predict survival of resectable pancreatic cancer patients: 5-year-follow-up of a single center. Front Oncol 2022; 12:966256. [PMID: 35965560 PMCID: PMC9372400 DOI: 10.3389/fonc.2022.966256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 07/11/2022] [Indexed: 11/16/2022] Open
Abstract
Background Pancreatic cancer mortality is growing every year, and radical resection is the most essential therapy strategy. It is critical to evaluate the long-term prognosis of individuals receiving radical surgery. CA19-9 is a biomarker for patient recurrence and survival, however obstructive jaundice has a significant impact on this index. Researchers have attempted to modify the index using various modification methods, but the results have been unsatisfactory. In this study, we adjusted CA19-9 values based on clinical stage and bilirubin and found that it provided better prediction than CA19-9 alone in assessing patients. Methods We analyzed over 5 years follow-up records of patients who underwent radical pancreatic cancer surgery between August 2009 and May 2017 in a single center. We investigated the association of risk factors with overall survival (OS) as well as disease-free survival (DFS) after surgery. Threshold values for high-risk features associated with poor prognosis in resectable pancreatic cancer were determined. The hazard ratios of the indicators were eventually examined under the stratification of patients’ clinical stages. Results A total of 202 patients were involved in the study. The optimum cut-off values for CA19-9 and CA19-9/TB for predicting overall survival were 219.4 (p = 0.0075) and 18.8 (p = 0.0353), respectively. CA19-9>219.4 increased the risk of patient mortality by 1.70 times (95% CI 1.217-2.377, p = 0.002), and tumor poor differentiation raised the risk by 1.66 times (95% CI 1.083-2.553, P = 0.02). Based on clinical stage stratification, we found discrepancies in the predictive efficacy of CA19-9 and CA19-9/TB. CA19-9 was a better predictor in clinical stage 1 (HR = 2.056[CI 95%1.169-3.616], P = 0.012), whereas CA19-9/TB indications were better in stages 2 (HR = 1.650[CI 95%1.023-2.662], P = 0.040) and 3 (HR = 3.989[CI95%1.145-13.896], P = 0.030). Conclusions CA19-9, CEA, and tumor differentiation are predictors for patients with resectable PDAC. CA19-9 values can be adjusted based on clinical stage and bilirubin levels to better predict overall survival in patients with resectable PDAC. CA19-9>219.4 predicted poor survival in individuals in clinical stage 1, whereas CA19-9/TB>18.8 predicted poor survival for individuals in stages 2 and 3.
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11
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Ko SW, Kim TH, Song TJ, Kim SH, Seo DW, Yoon JH, Cho CM, Cho JH, Choi JH, Lee DW, Lee SH, Yoon SB, Lee TH, Kim GH, Chun HJ. Prognosis and Clinical Characteristics of Patients with Pancreatic Ductal Adenocarcinoma Diagnosed by Endoscopic Ultrasonography but Indeterminate on Computed Tomography. Gut Liver 2022; 16:474-482. [PMID: 34615770 PMCID: PMC9099379 DOI: 10.5009/gnl210123] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 07/01/2021] [Accepted: 07/13/2021] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND/AIMS Endoscopic ultrasonography (EUS) provides high-resolution images and is superior to computed tomography (CT) scan in diagnosing small pancreatic ductal adenocarcinoma (PDAC). As a result, the use of EUS for early detection of PDAC has attracted attention. This study aimed to identify the clinical and radiological characteristics of patients with PDAC diagnosed by EUS but not found on CT scan. METHODS The medical records of patients diagnosed with PDAC at 12 tertiary referral centers in Korea from January 2003 to April 2019 were reviewed. This study included patients with pancreatic masses not clearly observed on CT scan but identified on EUS. The clinical characteristics and radiological features of the patients were analyzed, and survival analysis was performed. RESULTS A total of 83 patients were enrolled. The most common abnormal CT findings other than a definite mass was pancreatic duct dilatation, which was identified in 61 patients (73.5%). All but four patients underwent surgery. The final pathologic stages were as follows: IA (n=31, 39.2%), IB (n=8, 10.1%), IIA (n=20, 25.3%), IIB (n=17, 21.5%), III (n=2, 2.5%), and IV (n=1, 1.4%). The 5-year survival rate of these patients was 50.6% (95% confidence interval, 38.8% to 66.7%). Elevated liver function testing and R1 resection emerged as significant predictors of mortality in the multivariable Cox regression analysis. CONCLUSIONS This multicenter study demonstrated favorable long-term prognosis in patients with PDAC diagnosed by EUS but indeterminate on CT scan. EUS should be considered for patients with suspected PDAC but indeterminate on CT scan.
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Affiliation(s)
- Sung Woo Ko
- Department of Gastroenterology, Asan Medical Center, Seoul, Korea
| | - Tae Hyeon Kim
- Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Korea
| | - Tae Jun Song
- Department of Gastroenterology, Asan Medical Center, Seoul, Korea
| | - Seong-Hun Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Dong-Wan Seo
- Department of Gastroenterology, Asan Medical Center, Seoul, Korea
| | - Jai Hoon Yoon
- Division of Gastroenterology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Chang Min Cho
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jae Hee Cho
- Department of Internal Medicine, Gachon University College of Medicine, Incheon, Korea
| | - Jun-Ho Choi
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Dong Wook Lee
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Seung Bae Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Tae Hoon Lee
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University School of Medicine, Cheonan, Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Hoon Jai Chun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, Seoul, Korea
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12
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Park JH, Yoon YS, Lee S, Kim HY, Han HS, Lee JS, Chang W, Kim H, Na HY, Han S, Lee KH. Diagnostic Accuracy of CT for Evaluating Circumferential Resection Margin Status in Resectable or Borderline Resectable Pancreatic Head Cancer: A Prospective Study Using Axially Sliced Surgical Pathologic Correlation. Korean J Radiol 2022; 23:322-332. [PMID: 35029083 PMCID: PMC8876654 DOI: 10.3348/kjr.2021.0483] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 10/06/2021] [Accepted: 10/07/2021] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE CT plays a central role in determining the resectability of pancreatic cancer, which directs the use of neoadjuvant therapy. This study aimed to assess the diagnostic accuracy of CT in predicting circumferential resection margin (CRM) involvement in patients with resectable or borderline resectable pancreatic head cancer. MATERIALS AND METHODS Seventy-seven patients who were scheduled for upfront surgery for resectable or borderline resectable pancreatic head cancer were prospectively enrolled, and 75 patients (38 male and 37 female; mean age ± standard deviation, 68 ± 11 years) were finally analyzed. The CRM status was evaluated separately for the superior mesenteric artery (SMA) and posterior and superior mesenteric vein/portal vein (SMV/PV) margins. Three independent radiologists reviewed the preoperative CT images and evaluated the resection margin status. The reference standard for CRM status was pathologic examination of pancreaticoduodenectomy specimens in an axial plane perpendicular to the axis of the second portion of the duodenum. The diagnostic accuracy of CT was assessed for overall CRM involvement, defined as involvement of the SMA or posterior margins (per-patient analysis), and involvement of each of the three resection margins (per-margin analysis). The data were pooled using a crossed random effects model. RESULTS Forty patients had pathologically confirmed overall CRM involvement in pancreatic cancer, while CRM involvement was not seen in 35 patients. For overall CRM involvement, the pooled sensitivity and specificity were 15% (95% confidence interval: 7%-49%) and 99% (96%-100%), respectively. For each of the resection margins, the pooled sensitivity and specificity were 14% (9%-54%) and 99% (38%-100%) for the SMA margin, 12% (8%-46%) and 99% (97%-100%) for the posterior margin; and 37% (29%-53%) and 96% (31%-100%) for the SMV/PV margin, respectively. CONCLUSION CT showed very high specificity but low sensitivity in predicting pathological CRM involvement in pancreatic cancer.
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Affiliation(s)
- Ji Hoon Park
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
| | - Seungjae Lee
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
| | - Hae Young Kim
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Won Chang
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Young Na
- Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Seungyeob Han
- Department of Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Kyoung Ho Lee
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
- Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, Korea
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13
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Feng P, Cheng B, Wang ZD, Liu JG, Fan W, Liu H, Qi CY, Pan JJ. Application and progress of medical imaging in total mesopancreas excision for pancreatic head carcinoma. World J Gastrointest Surg 2021; 13:1315-1326. [PMID: 34950422 PMCID: PMC8649561 DOI: 10.4240/wjgs.v13.i11.1315] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 05/11/2021] [Accepted: 08/19/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic head carcinoma (PHC) is one of the common gastrointestinal malignancies with a high morbidity and poor prognosis. At present, radical surgery is still the curative treatment for PHC. However, in clinical practice, the actual R0 resection rate, the local recurrence rate, and the prognosis of PHC are unsatisfactory. Therefore, the concept of total mesopancreas excision (TMpE) is proposed to achieve R0 resection. Although there have various controversies and discussions on the definition, the range of excision, and clinical prognosis of TMpE, the concept of TMpE can effectively increase the R0 resection rate, reduce the local recurrence rate, and improve the prognosis of PHC. Imaging is of importance in preoperative examination for PHC; however, traditional imaging assessment of PHC does not focus on mesopancreas. This review discusses the application of medical imaging in TMpE for PHC, to provide more accurate preoperative evaluation, range of excision, and more valuable postoperative follow-up evaluation for TMpE through imaging. It is believed that with further extensive research and exploratory application of TMpE for PHC, large-sample and multicenter studies will be realized, thus providing reliable evidence for imaging evaluation.
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Affiliation(s)
- Pei Feng
- Department of Radiology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China
| | - Bo Cheng
- Department of Pathology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China
| | - Zhen-Dong Wang
- Department of Ultrasound, Beijing Sihui Hospital of Traditional Chinese Medicine, Beijing 100022, China
| | - Jun-Gui Liu
- Department of Hepatobiliary Surgery, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China
| | - Wei Fan
- Department of Radiology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China
| | - Heng Liu
- Department of Radiology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China
| | - Chao-Ying Qi
- Department of Radiology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China
| | - Jing-Jing Pan
- Department of Radiology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, China
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Dhall D, Shi J, Allende DS, Jang KT, Basturk O, Adsay NV, Kim GE. Towards a More Standardized Approach to Pathologic Reporting of Pancreatoduodenectomy Specimens for Pancreatic Ductal Adenocarcinoma: Cross-continental and Cross-specialty Survey From the Pancreatobiliary Pathology Society Grossing Working Group. Am J Surg Pathol 2021; 45:1364-1373. [PMID: 33899790 PMCID: PMC8446290 DOI: 10.1097/pas.0000000000001723] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
In recent literature and international meetings held, it has become clear that there are significant differences regarding the definition of what constitutes as margins and how best to document the pathologic findings in pancreatic ductal adenocarcinoma. To capture the current practice, Pancreatobiliary Pathology Society (PBPS) Grossing Working Group conducted an international multispecialty survey encompassing 25 statements, regarding pathologic examination and reporting of pancreatic ductal adenocarcinoma, particularly in pancreatoduodenectomy specimens. The survey results highlighted several discordances; however, consensus/high concordance was reached for the following: (1) the pancreatic neck margin should be entirely submitted en face, and if tumor on the slide, then it is considered equivalent to R1; (2) uncinate margin should be submitted entirely and perpendicularly sectioned, and tumor distance from the uncinate margin should be reported; (3) all other surfaces (including vascular groove, posterior surface, and anterior surface) should be examined and documented; (4) carcinoma involving separately submitted celiac axis specimen should be staged as pT4. Although no consensus was achieved regarding what constitutes R1 versus R0, most participants agreed that ink on tumor or at and within 1 mm to the tumor is equivalent to R1 only in areas designated as a margin, not surface. In conclusion, this survey raises the awareness of the discordances and serves as a starting point towards further standardization of the pancreatoduodenectomy grossing and reporting protocols.
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Affiliation(s)
- Deepti Dhall
- Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jiaqi Shi
- Department of Pathology, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
| | - Daniela S Allende
- Department of Pathology, Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Kee-Taek Jang
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nazmi Volkan Adsay
- Department of Pathology, Koç University and American Hospital, Istanbul, Turkey
| | - Grace E. Kim
- Department of Pathology, University of California San Francisco, San Francisco, CA
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15
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Garnier J, Ewald J, Poizat F, Traversari E, Marchese U, Palen A, Delpero JR, Turrini O. Prospective Evaluation of Resection Margins Using Standardized Specimen Protocol Analysis among Patients with Distal Cholangiocarcinoma and Pancreatic Ductal Adenocarcinoma. J Clin Med 2021; 10:jcm10153247. [PMID: 34362031 PMCID: PMC8348230 DOI: 10.3390/jcm10153247] [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: 06/05/2021] [Revised: 07/09/2021] [Accepted: 07/21/2021] [Indexed: 11/16/2022] Open
Abstract
PURPOSE Using a standardized specimen protocol analysis, this study aimed to evaluate the resection margin status of patients who underwent resection for either distal cholangiocarcinoma (DC) or pancreatic ductal adenocarcinoma (PDAC). This allowed a precise millimetric analysis of each inked margin. METHODS From 2010 to 2018, 355 consecutively inked specimens from patients with PDAC (n = 288) or DC (n = 67) were prospectively assessed. We assessed relationships between the tumor and the following margins: transection of the pancreatic neck, bile duct, posterior surface, margin toward superior mesenteric artery, and the surface of superior mesenteric vein/portal vein groove. Resection margins were evaluated using a predefined cut-off value of 1 mm; however, clearances of 0 and 1.5 mm were also evaluated. RESULTS Patients with DC were mostly men (64% vs. 49%, p = 0.028), of older age (68 yo vs. 65, p = 0.033), required biliary stenting more frequently (93% vs. 77%, p < 0.01), and received less neoadjuvant treatment (p < 0.001) than patients with PDAC. The venous resection rate was higher among patients with PDAC (p = 0.028). Postoperative and 90-day mortality rates were comparable. Patients with PDAC had greater tumor size (28.6 vs. 24 mm, p = 0.01) than those with DC. The R1 resection rate was comparable between the two groups, regardless of the clearance margin. Among the three types of resection margins, a venous groove was the most frequent in both entities. In multivariate analysis, the R1 resection margin did not influence patient survival in either PDAC or DC. CONCLUSION Our standardized specimen protocol analysis showed that the R1 resection rate was comparable in PDAC and DC.
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Affiliation(s)
- Jonathan Garnier
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
- Correspondence:
| | - Jacques Ewald
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Flora Poizat
- Department of Pathology, Institut Paoli-Calmettes, 13009 Marseille, France;
| | - Eddy Traversari
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Ugo Marchese
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Anais Palen
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Jean Robert Delpero
- Department of Surgical Oncology, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, 13009 Marseille, France; (J.R.D.); (O.T.)
| | - Olivier Turrini
- Department of Surgical Oncology, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, 13009 Marseille, France; (J.R.D.); (O.T.)
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Safi SA, Haeberle L, Fluegen G, Lehwald-Tywuschik N, Krieg A, Keitel V, Luedde T, Esposito I, Rehders A, Knoefel WT. Mesopancreatic excision for pancreatic ductal adenocarcinoma improves local disease control and survival. Pancreatology 2021; 21:787-795. [PMID: 33775563 DOI: 10.1016/j.pan.2021.02.024] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 02/11/2021] [Accepted: 02/25/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Survival in ductal adenocarcinoma of the pancreatic head (hPDAC) is poor. After implementation of the circumferential resection margin (CRM) into standard histopathological evaluation, the margin negative resection rate has drastically dropped. However, the impact of surgical radicality on survival and the influence of malignant infiltration of the mesopancreatic fat remains unclear. At our institution, a standardized dissection of the mesopancreatic lamina and peri-pancreatic vessels are obligatory components of radical pancreatoduodenectomy. The aim of our study was to histopathologically analyze mesopancreatic tumor infiltration and the influence of CRM-evaluated resection margin on relapse-free and overall survival. METHOD Clinicopathological and survival parameters of 264 consecutive patients who underwent surgery for hPDAC were evaluated. RESULTS The rate of R0 resection R0(CRM-) was 48.5%, after the implementation of CRM. Mesopancreatic fat infiltration was evident in 78.4% of all consecutively treated patients. Patients with mesopancreatic fat infiltration were prone to lymphatic metastases (N1 and N2) and had a higher rate of positive resection margin (R1/R0(CRM+)). In multivariate analysis, only R0 resection was shown to be an independent prognostic parameter. Local recurrence was diagnosed in only 21.1% and was significantly lower in patients with R0(CRM-) resected hPDACs (10.9%, p < 0.001). CONCLUSION Mesopancreatic excision is justified, since mesopancreatic fat invasion was evident in the majority of our patients. It is associated with a significantly improved local tumor control as well as longer relapse-free and overall survival.
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Affiliation(s)
- S-A Safi
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - L Haeberle
- Institute of Pathology, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - G Fluegen
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - N Lehwald-Tywuschik
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - A Krieg
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - V Keitel
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - T Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - I Esposito
- Institute of Pathology, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - A Rehders
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany
| | - W T Knoefel
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany.
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17
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Ge JC, Tao M, Li L, Ma ZL, Jiang B, Yuan CH, Wang HY, Peng Y, Xiu DR. Nomogram and competing risk model to predict recurrence after curative surgical resection of PDAC. Pancreatology 2021; 21:S1424-3903(21)00149-6. [PMID: 34001437 DOI: 10.1016/j.pan.2021.04.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 04/25/2021] [Accepted: 04/28/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Surgical resection remains the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC). However, a number of patients get disease recurred in a short time post-operation. Few studies have focused on the predictors of different recurrence patterns of PDAC. OBJECTIVE To try to establish and verify a nomogram to predict recurrence free survival (RFS) in PDAC patients, and to distinguish the risk factors of local recurrence first and distant metastasis first via competing risk model. METHODS Patients who underwent radical pancreatectomy for PDAC in our center from 2010 to 2018 were reviewed retrospectively. Kaplan-Meier methods and multivariate Cox regression analyses were used to identify the clinicopathological predictors of recurrence post-operation. And then, a nomogram was constructed and validated. Competing risk regression model was used to compare the predictors between local recurrence group and distant metastasis group. RESULTS A total of 200 patients were included into the final analysis, and 153 patients got disease relapsed post-operation. CA19-9 level, vascular resection, tumor differentiation, lymph node ratio (LNR) and adjuvant chemotherapy were identified as independent risk factors for recurrence free survival (RFS) and incorporated into the nomogram. The C-index of the nomogram was 0.650. Competing risk model indicated that the status of lymph-node metastasis was significantly associated the patterns of first relapse. CONCLUSIONS Nomogram and competing risk model were constructed to quantify the risk of recurrence following surgery for PDAC. Our findings may be useful for predicting RFS and recurrence pattern in clinical work.
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Affiliation(s)
- Jia-Chen Ge
- Department of General Surgery, Peking University Third Hospital, Beijing, People's Republic of China
| | - Ming Tao
- Department of General Surgery, Peking University Third Hospital, Beijing, People's Republic of China
| | - Lei Li
- Department of General Surgery, Peking University Third Hospital, Beijing, People's Republic of China
| | - Zhao-Lai Ma
- Department of General Surgery, Peking University Third Hospital, Beijing, People's Republic of China
| | - Bin Jiang
- Department of General Surgery, Peking University Third Hospital, Beijing, People's Republic of China
| | - Chun-Hui Yuan
- Department of General Surgery, Peking University Third Hospital, Beijing, People's Republic of China
| | - Hang-Yan Wang
- Department of General Surgery, Peking University Third Hospital, Beijing, People's Republic of China
| | - Ying Peng
- Department of General Surgery, Peking University Third Hospital, Beijing, People's Republic of China
| | - Dian-Rong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing, People's Republic of China.
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18
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Nappo G, Borzomati D, Zerbi A, Spaggiari P, Boggi U, Campani D, Mrowiec S, Liszka Ł, Coppola A, Amato M, Petitti T, Vistoli F, Montorsi M, Perrone G, Coppola R, Caputo D. The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial. Cancers (Basel) 2021; 13:2097. [PMID: 33926138 PMCID: PMC8123600 DOI: 10.3390/cancers13092097] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. METHODS PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. RESULTS One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. CONCLUSIONS The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis.
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Affiliation(s)
- Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (G.N.); (A.Z.)
| | - Domenico Borzomati
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (G.N.); (A.Z.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy;
| | - Paola Spaggiari
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (P.S.); (U.B.); (F.V.)
| | - Ugo Boggi
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (P.S.); (U.B.); (F.V.)
- Division of General and Transplant Surgery, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 56126 Pisa, Italy
| | - Daniela Campani
- Pathology Unit, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 56126 Pisa, Italy;
| | - Sławomir Mrowiec
- Department of Gastrointestinal Surgery, Medical University of Silesia, 40-055 Katowice, Poland;
| | - Łukasz Liszka
- Department of Pathomorphology and Molecular Diagnostics, Medical University of Silesia, 40-055 Katowice, Poland;
| | - Alessandro Coppola
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
| | - Michela Amato
- Pathology Unit, Campus Bio-Medico University of Rome, 00128 Rome, Italy; (M.A.); (G.P.)
| | - Tommasangelo Petitti
- Department of Public Health, Hygiene and Statistics, Campus Bio-Medico University of Rome, 00128 Rome, Italy;
| | - Fabio Vistoli
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (P.S.); (U.B.); (F.V.)
- Division of General and Transplant Surgery, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 56126 Pisa, Italy
| | - Marco Montorsi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy;
- Department of Surgery, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Giuseppe Perrone
- Pathology Unit, Campus Bio-Medico University of Rome, 00128 Rome, Italy; (M.A.); (G.P.)
| | - Roberto Coppola
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
| | - Damiano Caputo
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
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19
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Schmocker RK, Delitto D, Wright MJ, Ding D, Cameron JL, Lafaro KJ, Burns WR, Wolfgang CL, Burkhart RA, He J. Impact of Margin Status on Survival in Patients with Pancreatic Ductal Adenocarcinoma Receiving Neoadjuvant Chemotherapy. J Am Coll Surg 2021; 232:405-413. [PMID: 33338577 DOI: 10.1016/j.jamcollsurg.2020.11.018] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 11/25/2020] [Indexed: 01/04/2023]
Abstract
BACKGROUND Historically, a positive margin after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) was associated with decreased survival. In an era when neoadjuvant chemotherapy (NAC) is being used frequently, the prognostic significance of margin status is unclear. STUDY DESIGN Patients with localized PDAC who received NAC and underwent pancreatectomy from 2011 to 2018 were identified from a single-institution database. Patients with fewer than 2 months of NAC, R2 resection, or fewer than 90 days of follow-up were excluded. A positive margin included tumors within 1 mm of the surgical margin. RESULTS Four hundred and sixty-eight patients met inclusion criteria. Median age was 65 years and 53% were female. Preoperative clinical staging demonstrated that most had locally advanced (n = 222 [47%]) or borderline resectable (n = 172 [37%]) disease. Median follow-up was 18.5 months (interquartile range 10.6 to 30.0 months). Median duration of NAC was 119 days (interquartile range 87 to 168 days). FOLFIRINOX was first-line therapy for 67%, and 73% received neoadjuvant radiotherapy. Most underwent pancreaticoduodenectomy (69%). Forty percent were node-positive and 80% had an R0 resection. Fifty-six percent received at least 1 cycle of adjuvant therapy. Median overall survival and recurrence-free survival were 22.0 months (95% CI, 19.4 to 25.1 months) and 11.0 months (95% CI, 10.0 to 12.1 months). On multivariate analysis, margin status was not a significant predictor of overall survival or recurrence-free survival. Factors associated with overall survival included clinical stage, duration of NAC, nodal status, histopathologic treatment response score, and receipt of adjuvant chemotherapy. CONCLUSIONS Microscopic margin positivity is not associated with recurrence and survival in localized PDAC patients resected after treatment with NAC. Aggressive surgical extirpation in high-volume centers should be considered in selected patients after extensive NAC.
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Affiliation(s)
- Ryan K Schmocker
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD; Division of Surgical Oncology, Department of Surgery, The University of Tennessee Graduate School of Medicine, Knoxville, TN
| | - Daniel Delitto
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Michael J Wright
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ding Ding
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - John L Cameron
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Kelly J Lafaro
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - William R Burns
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Christopher L Wolfgang
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Richard A Burkhart
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Jin He
- Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
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20
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Weyhe D, Obonyo D, Uslar VN, Stricker I, Tannapfel A. Predictive factors for long-term survival after surgery for pancreatic ductal adenocarcinoma: Making a case for standardized reporting of the resection margin using certified cancer center data. PLoS One 2021; 16:e0248633. [PMID: 33735191 PMCID: PMC7971889 DOI: 10.1371/journal.pone.0248633] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 03/02/2021] [Indexed: 12/15/2022] Open
Abstract
Factors for overall survival after pancreatic ductal adenocarcinoma (PDAC) seem to be nodal status, chemotherapy administration, UICC staging, and resection margin. However, there is no consensus on the definition for tumor free resection margin. Therefore, univariate OS as well as multivariate long-term survival using cancer center data was analyzed with regards to two different resection margin definitions. Ninety-five patients met inclusion criteria (pancreatic head PDAC, R0/R1, no 30 days mortality). OS was analyzed in univariate analysis with respect to R-status, CRM (circumferential resection margin; positive: ≤1mm; negative: >1mm), nodal status, and chemotherapy administration. Long-term survival >36 months was modelled using multivariate logistic regression instead of Cox regression because the distribution function of the dependent data violated the requirements for the application of this test. Significant differences in OS were found regarding the R status (Median OS and 95%CI for R0: 29.8 months, 22.3–37.4; R1: 15.9 months, 9.2–22.7; p = 0.005), nodal status (pN0 = 34.7, 10.4–59.0; pN1 = 17.1, 11.5–22.8; p = 0.003), and chemotherapy (with CTx: 26.7, 20.4–33.0; without CTx: 9.7, 5.2–14.1; p < .001). OS according to CRM status differed on a clinically relevant level by about 12 months (CRM positive: 17.2 months, 11.5–23.0; CRM negative: 29.8 months, 18.6–41.1; p = 0.126). A multivariate model containing chemotherapy, nodal status, and CRM explained long-term survival (p = 0.008; correct prediction >70%). Chemotherapy, nodal status and resection margin according to UICC R status are univariate factors for OS after PDAC. In contrast, long-term survival seems to depend on wider resection margins than those used in UICC R classification. Therefore, standardized histopathological reporting (including resection margin size) should be agreed upon.
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Affiliation(s)
- Dirk Weyhe
- University Hospital for Visceral Surgery, Pius-Hospital, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Dennis Obonyo
- University Hospital for Visceral Surgery, Pius-Hospital, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Verena Nicole Uslar
- University Hospital for Visceral Surgery, Pius-Hospital, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
- * E-mail:
| | - Ingo Stricker
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
| | - Andrea Tannapfel
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
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21
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Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity. Cancers (Basel) 2021; 13:cancers13051090. [PMID: 33806316 PMCID: PMC7961597 DOI: 10.3390/cancers13051090] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 02/26/2021] [Accepted: 02/28/2021] [Indexed: 12/13/2022] Open
Abstract
Simple Summary Pancreatic cancer, in its most common manifestation pancreatic ductal adenocarcinoma (PDAC), is a uniquely lethal disease with very limited treatment options and few prognostic biomarkers. Tumor budding is a proven independent, adverse prognostic factor in many tumor types including PDAC. Tumor buds can be detected histologically as single cancer cells or clusters of up to four cancer cells at the tumor invasive front. Tumor budding is biologically correlated to the induction of epithelial-mesenchymal transitions (EMT) and disease progression. In this study, we sought to investigate the immunological composition of tumors with high levels of tumor budding. We show that PDAC cases with a high grade of tumor budding display notably diminished anti-tumor immunity. These findings were further validated by gene expression analysis of PDAC cases from The Cancer Genome Atlas (TCGA). Our results provide insight on the immune escape mechanisms of tumor cells undergoing EMT. This offers the potential of designing novel treatments combining immunotherapies with EMT-targeted drugs. Abstract Tumor budding is associated with epithelial-mesenchymal transition and diminished survival in a number of cancer types including pancreatic ductal adenocarcinoma (PDAC). In this study, we dissect the immune landscapes of patients with high grade versus low grade tumor budding to determine the features associated with immune escape and disease progression in pancreatic cancer. We performed immunohistochemistry-based quantification of tumor-infiltrating leukocytes and tumor bud assessment in a cohort of n = 111 PDAC patients in a tissue microarray (TMA) format. Patients were divided based on the ITBCC categories of tumor budding as Low Grade (LG: categories 1 and 2) and High Grade (HG: category 3). Tumor budding numbers and tumor budding grade demonstrated a significant association with diminished overall survival (OS). HG cases exhibit notably reduced densities of stromal (S) and intratumoral (IT) T cells. HG cases also display lower M1 macrophages (S) and increased M2 macrophages (IT). These findings were validated using gene expression data from TCGA. A published tumor budding gene signature demonstrated a significant association with diminished survival in PDAC patients in TCGA. Immune-related gene expression revealed an immunosuppressive TME in PDAC cases with high expression of the budding signature. Our findings highlight a number of immune features that permit an improved understanding of disease progression and EMT in pancreatic cancer.
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22
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Maximizing Tumor Control and Limiting Complications With Stereotactic Body Radiation Therapy for Pancreatic Cancer. Int J Radiat Oncol Biol Phys 2020; 110:206-216. [PMID: 33358561 DOI: 10.1016/j.ijrobp.2020.11.017] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/04/2020] [Accepted: 11/05/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE Stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiation therapy is being increasingly used for pancreatic cancer (PCa), particularly in patients with locally advanced and borderline resectable disease. A wide variety of dose fractionation schemes have been reported in the literature. This HyTEC review uses tumor control probability models to evaluate the comparative effectiveness of the various SBRT treatment regimens used in the treatment of patients with localized PCa. METHODS AND MATERIALS A PubMed search was performed to review the published literature on the use of hypofractionated SBRT (usually in 1-5 fractions) for PCa in various clinical scenarios (eg, preoperative [neoadjuvant], borderline resectable, and locally advanced PCa). The linear quadratic model with α/β= 10 Gy was used to address differences in fractionation. Logistic tumor control probability models were generated using maximum likelihood parameter fitting. RESULTS After converting to 3-fraction equivalent doses, the pooled reported data and associated models suggests that 1-year local control (LC) without surgery is ≈79% to 86% after the equivalent of 30 to 36 Gy in 3 fractions, showing a dose response in the range of 25 to 36 Gy, and decreasing to less than 70% 1-year LC at doses below 24 Gy in 3 fractions. The 33 Gy in 5 fraction regimen (Alliance A021501) corresponds to 28.2 Gy in 3 fractions, for which the HyTEC pooled model had 77% 1-year LC without surgery. Above an equivalent dose of 28 Gy in 3 fractions, with margin-negative resection the 1-year LC exceeded 90%. CONCLUSIONS Pooled analyses of reported tumor control probabilities for commonly used SBRT dose-fractionation schedules for PCa suggests a dose response. These findings should be viewed with caution given the challenges and limitations of this review. Additional data are needed to better understand the dose or fractionation-response of SBRT for PCa.
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23
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Birgin E, Rasbach E, Téoule P, Rückert F, Reissfelder C, Rahbari NN. Impact of intraoperative margin clearance on survival following pancreatoduodenectomy for pancreatic cancer: a systematic review and meta-analysis. Sci Rep 2020; 10:22178. [PMID: 33335201 PMCID: PMC7746710 DOI: 10.1038/s41598-020-79252-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 12/03/2020] [Indexed: 12/13/2022] Open
Abstract
The use of intraoperative margin revision to achieve margin clearance in patients undergoing pancreatoduodenectomy for pancreatic cancer is controversial. We performed a systematic review and meta-analysis to summarize the evidence of intraoperative margin revisions of the pancreatic neck and its impact on overall survival (OS). Nine studies with 4501 patients were included. Patient cohort was stratified in an R0R0-group (negative margin on frozen and permanent section), R1R0-group (revised positive margin on frozen section which turned negative on permanent section), and R1R1-group (positive margin on frozen and permanent section despite margin revision). OS was higher in the R1R0-group (HR 0.83, 95% CI 0.72-0.96, P = 0.01) compared to the R1R1-group but lower compared to the R0R0-group (HR 1.20; 95% CI 1.05-1.37, P = 0.008), respectively. Subgroup analyses on the use of different margin clearance definitions confirmed an OS benefit in the R1R0-group compared to the R1R1-group (HR 0.81; 95% CI 0.65-0.99, P = 0.04). In conclusion, intraoperative margin clearance of the pancreatic neck margin is associated with improved OS while residual tumor indicates aggressive tumor biology. Consensus definitions on margin terminologies, clearance, and surgical techniques are required.
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Affiliation(s)
- Emrullah Birgin
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Erik Rasbach
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Patrick Téoule
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Felix Rückert
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Christoph Reissfelder
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Nuh N Rahbari
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
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24
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Karamitopoulou E, Esposito I, Zlobec I, Insilla AC, Wartenberg M, Schaeffer DF, Kalloger S, La Rosa S, Sempoux C, Ramos Centeno I, Lohneis P. Reproducibility of tumor budding assessment in pancreatic cancer based on a multicenter interobserver study. Virchows Arch 2020; 478:719-726. [PMID: 33330964 PMCID: PMC7990816 DOI: 10.1007/s00428-020-02987-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 11/02/2020] [Accepted: 12/03/2020] [Indexed: 02/06/2023]
Abstract
Tumor budding has been reported to be an independent prognostic factor in pancreatic ductal adenocarcinoma (PDAC). Its use in daily diagnostics would improve the prognostic stratification of patients. We performed a multicenter interobserver study to test various budding assessment methods for their reproducibility. Two serial sections of 50 resected, treatment-naïve PDACs were stained for Hematoxylin and Eosin (H&E) and pancytokeratin. Tumor budding was scored by independent observers at five participating centers in Switzerland, Germany, and Canada. Pathologists assessed tumor budding on a digital platform comparing H&E with pancytokeratin staining in 10 high-power fields (10HPF) and one HPF hotspot (1HPF). Additionally, tumor budding was assessed in one H&E hotspot at × 20 magnification, as suggested by the International Tumor Budding Consensus Conference (ITBCC). Correlation coefficients for bud counts between centers ranged from r = 0.58648 to r = 0.78641 for H&E and from r = 0.69288 to r = 0.81764 for pancytokeratin. The highest interobserver agreement across all centers was observed for pancytokeratin 10HPFs (ICC = 0.6). ICC values were 0.49, 0.48, 0.41, and 0.4 for H&E in 1HPF hotspot, H&E in 10HPFs, pancytokeratin in 1HPF, and H&E in one hotspot at ×20, respectively (ITBCC method). This interobserver study reveals a range between moderately poor to moderate agreement levels between pathologists for the different tumor budding assessment methods in PDAC. Acceptable levels of agreement were reached with the pancytokeratin 10HPF method, which can thus be recommended for the assessment of tumor budding in PDAC resection specimens. To improve the levels of interobserver agreement, the implementation of machine learning applications should be considered.
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Affiliation(s)
- Eva Karamitopoulou
- Pancreatic Cancer Research Group, Institute of Pathology, University of Bern, Bern, Switzerland.
| | - Irene Esposito
- Institute of Pathology Heinrich-Heine University & University Hospital, Duesseldorf, Germany
| | - Inti Zlobec
- Pancreatic Cancer Research Group, Institute of Pathology, University of Bern, Bern, Switzerland
| | - Andrea Cacciato Insilla
- Institute of Pathology Heinrich-Heine University & University Hospital, Duesseldorf, Germany
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Martin Wartenberg
- Pancreatic Cancer Research Group, Institute of Pathology, University of Bern, Bern, Switzerland
| | - David F Schaeffer
- Department of Pathology & Laboratory Medicine, University of British Columbia and Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, Canada
| | - Steve Kalloger
- Department of Pathology & Laboratory Medicine, University of British Columbia and Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, Canada
| | - Stefano La Rosa
- Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Christine Sempoux
- Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Irene Ramos Centeno
- Pancreatic Cancer Research Group, Institute of Pathology, University of Bern, Bern, Switzerland
| | - Philipp Lohneis
- Faculty of Medicine and University Hospital Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
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Oshi M, Tokumaru Y, Patel A, Yan L, Matsuyama R, Endo I, Katz MH, Takabe K. A Novel Four-Gene Score to Predict Pathologically Complete (R0) Resection and Survival in Pancreatic Cancer. Cancers (Basel) 2020; 12:E3635. [PMID: 33291601 PMCID: PMC7761977 DOI: 10.3390/cancers12123635] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 11/24/2020] [Accepted: 12/02/2020] [Indexed: 12/17/2022] Open
Abstract
Pathologically complete (R0) resection is essential for prolonged survival in pancreatic cancer. Survival depends not only on surgical technique, but also on cancer biology. A biomarker to predict survival is a critical need in pancreatic treatment. We hypothesized that this 4-gene score, which was reported to reflect cell proliferation, is a translatable predictive biomarker for pancreatic cancer. A total of 954 pancreatic cancer patients from multiple cohorts were analyzed and validated. Pancreatic cancer had the 10th highest median score of 32 cancers in The Cancer Genome Atlas (TCGA) cohort. The four-gene score significantly correlated with pathological grade and MKI67 expression. The high four-gene score enriched cell proliferation-related and cancer aggressiveness-related gene sets. The high score was associated with activation of KRAS, p53, transforming growth factor (TGF)-β, and E2F pathways, and with high alteration rate of KRAS and CDKN2A genes. The high score was also significantly associated with reduced CD8+ T cell infiltration of tumors, but with high levels of interferon-γ and cytolytic activity in tumors. The four-gene score correlated with the area under the curve of irinotecan and sorafenib in primary pancreatic cancer, and with paclitaxel and doxorubicin in metastatic pancreatic cancer. The high four-gene score was associated with significantly fewer R0 resections and worse survival. The novelty of the study is in the application of the four-gene score to pancreatic cancer, rather than the bioinformatics technique itself. Future analyses of inoperable lesions are expected to clarify the utility of our score as a predictive biomarker of systemic treatments.
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Affiliation(s)
- Masanori Oshi
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (M.O.); (Y.T.); (A.P.)
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (R.M.); (I.E.)
| | - Yoshihisa Tokumaru
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (M.O.); (Y.T.); (A.P.)
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan
| | - Ankit Patel
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (M.O.); (Y.T.); (A.P.)
| | - Li Yan
- Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| | - Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (R.M.); (I.E.)
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (R.M.); (I.E.)
| | - Matthew H.G. Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Kazuaki Takabe
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (M.O.); (Y.T.); (A.P.)
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (R.M.); (I.E.)
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan
- Department of Breast Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
- Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14263, USA
- Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, Japan
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26
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Kang CM, Lee WJ. Is Laparoscopic Pancreaticoduodenectomy Feasible for Pancreatic Ductal Adenocarcinoma? Cancers (Basel) 2020; 12:3430. [PMID: 33218187 PMCID: PMC7699219 DOI: 10.3390/cancers12113430] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/11/2020] [Accepted: 11/14/2020] [Indexed: 02/08/2023] Open
Abstract
Margin-negative radical pancreatectomy is the essential condition to obtain long-term survival of patients with pancreatic cancer. With the investigation for early diagnosis, introduction of potent chemotherapeutic agents, application of neoadjuvnat chemotherapy, advancement of open and laparoscopic surgical techniques, mature perioperative management, and patients' improved general conditions, survival of the resected pancreatic cancer is expected to be further improved. According to the literatures, laparoscopic pancreaticoduodenectomy (LPD) is also thought to be good alternative strategy in managing well-selected resectable pancreatic cancer. LPD with combined vascular resection is also feasible, but only expert surgeons should handle these challenging cases. LPD for pancreatic cancer should be determined based on surgeons' proficiency to fulfil the goals of the patient's safety and oncologic principles.
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Affiliation(s)
- Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul 03772, Korea;
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul 03772, Korea
| | - Woo Jung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul 03772, Korea;
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul 03772, Korea
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27
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Drake JA, Stiles ZE, Behrman SW, Glazer ES, Deneve JL, Somer BG, Vanderwalde NA, Dickson PV. The utilization and impact of adjuvant therapy following neoadjuvant therapy and resection of pancreatic adenocarcinoma: does more really matter? HPB (Oxford) 2020; 22:1530-1541. [PMID: 32209323 DOI: 10.1016/j.hpb.2020.02.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 01/13/2020] [Accepted: 02/26/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although neoadjuvant therapy is increasingly administered to patients with pancreatic ductal adenocarcinoma (PDAC), the impact of additional adjuvant therapy (AT) following resection is not well defined. METHODS The National Cancer Database (NCDB) was queried for patients who received neoadjuvant therapy followed by R0 or R1 resection for PDAC. Factors influencing survival, including the receipt of AT were evaluated. RESULTS Of patients receiving neoadjuvant therapy and resection 680 (33.8%) received AT and 1331 (66.2%) did not. For R0 resected patients (n = 1800), lymphovascular invasion (HR 1.24, p = 0.034) and increasing N classification (N1: HR 1.27, p = 0.019; N2: HR 1.51, p = 0.004) were associated with increased risk of death while AT was not associated with improved overall survival (OS) (HR 0.88, p = 0.179). Following R1 resection (n = 211), AT was associated with reduced risk of death (HR 0.57, p = 0.038). Within propensity matched cohorts, median OS for patients receiving and not receiving AT was 32.1 and 30.0 months after R0 resection (p = 0.184), and 23.6 and 20.5 months after R1 resection (p = 0.005). CONCLUSION This analysis demonstrated that AT did not yield OS benefit for patients who had neoadjuvant therapy and R0 resection and a statistically significant, although relatively short, improvement in OS for patients who underwent R1 resection.
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Affiliation(s)
- Justin A Drake
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA
| | - Zachary E Stiles
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA
| | - Stephen W Behrman
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA
| | - Evan S Glazer
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA
| | - Jeremiah L Deneve
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA
| | - Bradley G Somer
- Medical Oncology, West Cancer Center and Research Institute, 7945 Wolf River Blvd, Germanton, TN 38138, USA
| | - Noam A Vanderwalde
- Radiation Oncology, West Cancer Center and Research Institute, 7945 Wolf River Blvd, Germanton, TN 38138, USA
| | - Paxton V Dickson
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA.
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28
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Oshi M, Newman S, Tokumaru Y, Yan L, Matsuyama R, Endo I, Katz MHG, Takabe K. High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection. Cancers (Basel) 2020; 12:E2871. [PMID: 33036243 PMCID: PMC7599494 DOI: 10.3390/cancers12102871] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 10/01/2020] [Accepted: 10/04/2020] [Indexed: 12/21/2022] Open
Abstract
Pancreatic cancer is highly mortal due to uncontrolled cell proliferation. The G2M checkpoint pathway is an essential part of the cell cycle. We hypothesized that a high G2M pathway score is associated with cell proliferation and worse survival in pancreatic cancer patients. Gene set variation analysis using the Hallmark G2M checkpoint gene set was used as a score to analyze a total of 390 human pancreatic cancer patients from 3 cohorts (TCGA, GSE62452, GSE57495). High G2M score tumors enriched other cell proliferation genes sets as well as MKI67 expression, pathological grade, and proliferation score. Independent of other prognostic factors, G2M score was predictive of disease-specific survival in pancreatic cancer. High G2M tumor was associated with high mutation rate of KRAS and TP53 and significantly enriched these pathway gene sets, as well as high infiltration of Th2 cells. High G2M score consistently associated with worse overall survival in 3 cohorts, particularly in R1/2 resection, but not in R0. High G2M tumor in R1/2 highly enriched metabolic and cellular components' gene sets compared to R0. To our knowledge, this is the first study to use gene set variation analysis as a score to examine the clinical relevancy of the G2M pathway in pancreatic cancer.
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Affiliation(s)
- Masanori Oshi
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (M.O.); (R.M.); (I.E.)
- Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (S.N.); (Y.T.)
| | - Stephanie Newman
- Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (S.N.); (Y.T.)
- Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14263, USA
| | - Yoshihisa Tokumaru
- Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (S.N.); (Y.T.)
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan
| | - Li Yan
- Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| | - Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (M.O.); (R.M.); (I.E.)
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (M.O.); (R.M.); (I.E.)
| | - Matthew H. G. Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Kazuaki Takabe
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (M.O.); (R.M.); (I.E.)
- Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (S.N.); (Y.T.)
- Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14263, USA
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan
- Department of Breast Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
- Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, Japan
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29
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Nuckles BW, Lam K, Young KA, Dove JT, Shabahang MM, Blansfield JA. Quality Improvement for Surgical Resection of Pancreatic Head Adenocarcinoma : Hospital and Surgeon Predictors of Higher Than Expected R1 Resection Using the National Cancer Database. Am Surg 2020; 87:396-403. [PMID: 32993353 DOI: 10.1177/0003134820950281] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The mainstay of treatment for pancreatic cancer is surgical resection; however, positive surgical margins remain commonplace. We identified hospitals with higher than predicted rates of positive margins and isolated factors that caused this discordance. METHODS This is a retrospective review of patients with head of the pancreas adenocarcinoma in the National Cancer Database between 2004 and 2015. A nomogram was used to calculate the observed to expected positive margin rates (O/E) for facilities. If the O/E differed significantly (P < .05), it was considered an outlier. RESULTS Among a total of 19 968 patients, 24.3% had positive margins. Among hospitals with lower than expected positive margin rates, 73.6% were academic or research programs, 17% were comprehensive community cancer programs, and none were community cancer programs (P = .0002). Within the group with higher than expected positive margin rates, 47% were comprehensive community cancer programs and 38.6% were academic or research programs (P = .0002). The mean hospital volume was higher in the low positive margin group (110.4 vs 48.8, P < .0001). CONCLUSIONS Facility type and hospital volume can predict improvement in the O/E ratio for margin positivity in pancreatic adenocarcinoma resection. Surgeons should consider referral to academic or research facilities with higher case volumes for improved surgical resection.
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30
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Zhu C, Ma L, Jia Z, Shi H, Jin J, Lou W, Qin X. Novel morphological classification of the normal pancreatic uncinate process based on computed tomography. J Int Med Res 2020; 48:300060520957453. [PMID: 32972276 PMCID: PMC7522846 DOI: 10.1177/0300060520957453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Objectives This study aimed to assess computed tomographic (CT) features of the normal pancreatic uncinate process (UP) and to classify UP types on the basis of morphological characteristics. Methods From November 2017 to December 2018, consecutive Han Chinese adults were enrolled in this retrospective study. Morphometric evaluation of the UP was performed using CT imaging, including assessment of the maximal transverse diameter of the UP (MTDUP) and pancreas head, and assessment of the relationship between the UP and superior mesenteric vessels. Results A total of 318 participants were studied. The mean MTDUP and maximal transverse diameter of the pancreas head were 15.89 ± 4.82 mm and 46.47 ± 7.18 mm, respectively. The mean MTDUP was 10.83 ± 2.59 mm for type I UP (21.70% of participants), 13.87 ± 2.35 mm for type II (13.21%), 17.08 ± 3.43 mm for type III (56.29%), and 23.74 ± 5.02 mm for type IV (8.81%). There was a significant difference among the UP types. Conclusions Four types of normal UP can be defined on the basis of morphological CT features. The length of the UP significantly increases from types I to IV, and type III accounts for > 50%.
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Affiliation(s)
- Chunfu Zhu
- Department of Pancreas Center, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China
| | - Le Ma
- Department of Pancreas Center, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China
| | - Zhongzhi Jia
- Department of Interventional and Vascular Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China
| | - Haifeng Shi
- Department of Radiology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China
| | - Jianliang Jin
- Department of Anatomy, Nanjing Medical University, Nanjing, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Xihu Qin
- Department of Pancreas Center, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China
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Safe exposure of the left renal vein during laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: anatomical variations and pitfalls. Surg Today 2020; 50:1664-1671. [DOI: 10.1007/s00595-020-02053-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 05/31/2020] [Indexed: 01/09/2023]
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32
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Swan RZ, Niemeyer DJ, Seshadri RM, Thompson KJ, Walters A, Martinie JB, Sindram D, Iannitti DA. The Impact of Regionalization of Pancreaticoduodenectomy for Pancreatic Cancer in North Carolina since 2004. Am Surg 2020. [DOI: 10.1177/000313481408000619] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Pancreaticoduodenectomy (PD) carries a significant risk. High-volume centers (HVCs) provide improved outcomes and regionalization is advocated. Rapid regionalization could, however, have detrimental effects. North Carolina has multiple HVCs, including an additional HVC added in late 2006. We investigated regionalization of PD and its effects before, and after, the establishment of this fourth HVC. The North Carolina Hospital Discharge Database was queried for all PDs performed during 2004 to 2006 and 2007 to 2009. Hospitals were categorized by PD volume as: low (one to nine/year), medium (10 to 19/year), and high (20/year or more). Mortality and major morbidity was assessed by comparing volume groups across time periods. Number of PDs for cancer increased 91 per cent (129 to 246 cases) at HVCs, whereas decreasing at low-volume (62 to 58 cases) and medium-volume (80 to 46 cases) centers. Percentage of PD for cancer performed at HVCs increased significantly (47.6 to 70.3%) while decreasing for low- and medium-volume centers ( P < 0.001). Mortality was significantly less at HVCs (2.8%) compared with low-volume centers (10.3%) for 2007 to 2009. Odds ratio for mortality was significantly lower at HVCs during 2004 to 2006 (0.31) and 2007 to 2009 (0.34). Mortality for PD performed for cancer decreased from 6.6 to 4.6 per cent ( P = 0.31). Major morbidity was not significantly different between groups within either time period; however, there was a significant increase in major morbidity at low-volume centers ( P = 0.018). Regionalization of PD for cancer is occurring in North Carolina. Mortality was significantly lower at HVCs, and rapid regionalization has not detracted from the superior outcomes at HVCs.
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Affiliation(s)
- Ryan Z. Swan
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - David J. Niemeyer
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - Ramanathan M. Seshadri
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - Kyle J. Thompson
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - Amanda Walters
- Division of GI and Minimally-Invasive Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - John B. Martinie
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - David Sindram
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - David A. Iannitti
- Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina
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Perri G, Prakash LR, Katz MHG. Response to Preoperative Therapy in Localized Pancreatic Cancer. Front Oncol 2020; 10:516. [PMID: 32351893 PMCID: PMC7174698 DOI: 10.3389/fonc.2020.00516] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 03/23/2020] [Indexed: 12/22/2022] Open
Abstract
Evaluation of response to preoperative therapy for patients with pancreatic adenocarcinoma has been historically difficult. Therefore, preoperative regimens have generally been selected on the basis of baseline data such as radiographic stage and serum CA 19-9 level and then typically administered for a pre-specified duration as long as 6 months or more. The decision to proceed with resection following preoperative therapy likewise has rested upon the absence of disease progression rather than evidence for tumor response. This article reviews the basis for the evaluation of therapeutic response after preoperative therapy for pancreatic cancer in the existing scientific literature, and providing updates and new perspectives.
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Affiliation(s)
- Giampaolo Perri
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Laura R Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Pine JK, Haugk B, Robinson SM, Darne A, Wilson C, Sen G, French JJ, White SA, Manas DM, Charnley RM. Prospective assessment of resection margin status following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma after standardisation of margin definitions. Pancreatology 2020; 20:537-544. [PMID: 31996296 DOI: 10.1016/j.pan.2020.01.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 12/21/2019] [Accepted: 01/06/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Surgical resection remains the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). The prognostic value of resection margin status following pancreatoduodenectomy (PD) remains controversial. Standardised pathological assessment increases positive margins but limited data is available on the significance of involved margins. We investigated the impact of resection margin status in PDAC on patient outcome. METHOD We identified all patients with PD for PDAC at one pancreatic cancer centre between August 2008 and December 2014. Demographic, operative, adjuvant therapeutic and survival data was obtained. Pathology data including resection margin status of specific anatomic margins was collected and analysed. RESULTS 107 patients were included, all pathologically staged as T3 with 102 N1. 87.9% of patients were R1 of which 53.3% showed direct extension to the resection margin. Median survival for R0 patients versus R1<1 mm and R1 = 0 mm was 28.4 versus 15.4 and 25.1 versus 13.4 months. R1 = 0 mm status remained a predictor of poor outcome on multivariate analysis. Evaluation of individual margins (R1<1 mm) showed the SMV and SMA margins were associated with poorer overall survival. Multiple involved margins impacted negatively on outcome. SMA margin patient outcome with R1 = 1-1.9 mm was similar to R1=>2 mm. CONCLUSION Using an R1 definition of <1 mm and standardised pathology we demonstrate that R1 rates in PDAC can approach 90%. R1 = 0 mm remained an independent prognostic factor for overall survival. Using R1<1 mm we have shown that involvement of medial margins and multiple margins has significant negative impact on overall survival. We conclude that not all margin positivity has the same prognostic significance.
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Affiliation(s)
- J K Pine
- Department of HPB Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK.
| | - B Haugk
- Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
| | - S M Robinson
- Department of HPB Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK
| | - A Darne
- Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
| | - C Wilson
- Department of HPB Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK
| | - G Sen
- Department of HPB Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK
| | - J J French
- Department of HPB Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK
| | - S A White
- Department of HPB Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK
| | - D M Manas
- Department of HPB Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK
| | - R M Charnley
- Department of HPB Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK
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35
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Performance of CT-based radiomics in diagnosis of superior mesenteric vein resection margin in patients with pancreatic head cancer. Abdom Radiol (NY) 2020; 45:759-773. [PMID: 31932878 DOI: 10.1007/s00261-019-02401-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVES To accurately identify the relationship between a portal radiomics score (rad-score) and pathologic superior mesenteric vein (SMV) resection margin and to evaluate the diagnostic performance in patients with pancreatic head cancer. MATERIALS AND METHODS A total of 181 patients with postoperatively and pathologically confirmed pancreatic head cancer who underwent multislice computed tomography within one month of resection between January 2016 and December 2018 were retrospectively investigated. For each patient, 1029 radiomics features of the portal phase were extracted, which were reduced using the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm. Multivariate logistic regression models were used to analyze the association between the portal rad-score and SMV resection margin. RESULTS Patients with negative (R0) and positive (R1) margins accounted for 70.17% (127) and 29.83% (54) of the cohort, respectively. The rad-score was significantly associated with the SMV resection margin status (p < 0.05). Multivariate analyses confirmed a significant and independent association between the portal rad-score and SMV resection margin (OR 4.62; 95% CI 2.19-9.76; p < 0.0001). The portal rad-score had high accuracy (area under the curve = 0.750). The best cut point based on maximizing the sum of sensitivity and specificity was - 0.741 (sensitivity = 64.8%; specificity = 74.0%; accuracy = 71.3%). Decision curve analysis indicated the clinical usefulness of radiomics score. CONCLUSIONS The portal rad-score is significantly associated with the pathologic SMV resection margin, and it can accurately and noninvasively predict the SMV resection margin in patients with pancreatic cancer.
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Li CG, Zhou ZP, Tan XL, Gao YX, Wang ZZ, Liu Q, Zhao ZM. Impact of resection margins on long-term survival after pancreaticoduodenectomy for pancreatic head carcinoma. World J Clin Cases 2019; 7:4186-4195. [PMID: 31911899 PMCID: PMC6940347 DOI: 10.12998/wjcc.v7.i24.4186] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 10/31/2019] [Accepted: 11/19/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The impact of resection margin status on long-term survival after pancreaticoduodenectomy (PD) for patients with pancreatic head carcinoma remains controversial and depends on the method used in the histopathological study of the resected specimens. This study aimed to examine the impact of resection margin status on the long-term overall survival of patients with pancreatic head carcinoma after PD using the tumor node metastasis standard.
METHODS Consecutive patients with pancreatic head carcinoma who underwent PD at the Chinese People's Liberation Army General Hospital between May 2010 and May 2016 were included. The impact of resection margin status on long-term survival was retrospectively analyzed.
RESULTS Among the 124 patients, R0 resection was achieved in 85 patients (68.5%), R1 resection in 38 patients (30.7%) and R2 resection in 1 patient (0.8%). The 1- and 3-year overall survival (OS) rates were significantly higher for the patients who underwent R0 resection than the rates for those who underwent R1 resection (1-year OS rates: 69.4% vs 53.0%; 3-year OS rates: 26.9% vs 11.7%). Multivariate analysis showed that resection margin status and venous invasion were significant risk factors for OS.
CONCLUSION Resection margin was an independent risk factor for OS for patients with pancreatic head carcinoma after PD. R0 resection was associated with significantly better OS after surgery.
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Affiliation(s)
- Cheng-Gang Li
- Second Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Zhi-Peng Zhou
- Second Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Xiang-Long Tan
- Second Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Yuan-Xing Gao
- Second Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Zi-Zheng Wang
- Second Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Qu Liu
- Second Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Zhi-Ming Zhao
- Second Department of Hepatobiliary Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
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Di Martino M, Muñoz de Nova JL, Guijarro Rojas M, Alday Muñoz E, Martín-Pérez E. Positive Resection Margins Detected by Standardized Study of a Pancreaticoduodenectomy Sample: Is There Any Real Impact on Long-term Survival? Cir Esp 2019; 98:127-135. [PMID: 31784034 DOI: 10.1016/j.ciresp.2019.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 08/16/2019] [Accepted: 09/09/2019] [Indexed: 10/25/2022]
Abstract
INTRODUCTION The pathological evaluation of pancreaticoduodenectomy (PD) samples and the impact of R1 resections on survival has recently been questioned. This study evaluates the introduction of a standardized pathology study protocol (PSP) and the prognosis of R1 resections after long-term follow-up. METHODS We reviewed data from a prospectively maintained database regarding 109 periampullary tumors treated by PD from 2005 to 2013. The results of the introduction of a PSP were analysed, and the recurrence rate (RR), disease-free survival (DFS) and overall survival (OS) of the R1 resections were evaluated for each positive margin. RESULTS The PD specimens of periampullary tumors analyzed by PSP showed a higher rate of isolated lymph nodes (17 vs. 8; P=.003), N+ (60% vs. 31%; P<.001), microvascular invasion (67% vs. 34%; P=.001) and R1 resections (42% vs. 18%; P=.010). Pancreatic adenocarcinomas with R1 resection in the PSP group were compared with R0, presenting higher percentages of vascular resections (P=.033), N+ (P=.029), lymphatic and perineural invasion (P=.047; P=.029), higher RR (P=.026), lower DFS (P=.016) and lower OS (P=.025). Invasion of the medial margin correlated with a worse prognosis. CONCLUSIONS Our series shows an increase in R1 resection after the introduction of a PSP. Infiltration of the medial margin seems to be associated with a higher RR and a decrease in DFS and OS.
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Affiliation(s)
- Marcello Di Martino
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario La Princesa, Madrid, España.
| | - Jose Luis Muñoz de Nova
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario La Princesa, Madrid, España
| | | | - Enrique Alday Muñoz
- Servicio de Anestesiología y Reanimación, Hospital Universitario La Princesa, Madrid, España
| | - Elena Martín-Pérez
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario La Princesa, Madrid, España
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Clinical impact of additional therapy for residual pancreatic cancer. Surg Today 2019; 50:440-448. [PMID: 31650262 DOI: 10.1007/s00595-019-01900-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 10/10/2019] [Indexed: 12/15/2022]
Abstract
PURPOSE This study aimed to explore the prognostic significance of the resection margin (R) status of pancreatic ductal adenocarcinoma (PDAC) patients receiving neoadjuvant therapy (NAT) or adjuvant chemotherapy (AC). METHODS We retrospectively reviewed 427 consecutive patients, and the overall survival (OS) and disease-free survival (DFS) were analyzed based on the R status by a propensity score analysis (PSA). RESULTS The R0 ratio of the NAT (+) group was significantly higher than that of the NAT (-) group (97.2% vs. 69.6%, P < 0.0001). Local recurrence was well controlled in the NAT (+) group compared to the NAT (-) group (15.3% vs. 34.1%, P = 0.0013). The PSA revealed no significant survival difference between R0 and R1 resection among those treated with AC (median survival time [MST]: 43.0 vs. 33.3 months, matching hazard ratio [HR]: 1.212, P = 0.5708). Furthermore, the DFS in R0 and R1 resection followed by AC was identical (MST: 20.6 vs. 17.7 months, matching HR: 1.020, P = 0.9482). CONCLUSIONS NAT was a significant predictor of R0 resection. When patients completed AC, there were no marked differences in the OS or DFS between R0 and R1 resection. Our results demonstrated that the clinical impact of the R1 status has waned in the current era of PDAC management.
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Karmazanovsky GG. Differential diagnosis and analysis of pancreatic cancer resectability using CT and MRI. ANNALY KHIRURGICHESKOY GEPATOLOGII = ANNALS OF HPB SURGERY 2019; 24:22-35. [DOI: 10.16931/1995-5464.2019322-35] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
The purpose of this publication is to comprehend the modern achievements of radiological diagnosis in surgical oncopancreatology via a critical analysis of recent English-language publications. CT and MRI are essential diagnostic methods in surgical and oncological pancreatology. The possibilities of tomography examination regarding analysis of tumor dimension, CT criteria for pancreatic cancer diagnosis, assessment of vascular invasion, differential diagnosis of tumors, as well as estimation of possible early postoperative complications and radiological features of the region of interest after neoadjuvant and adjuvant therapy for pancreatic tumors are critically analyzed. The role of modern diagnostic methods in improvement of treatment directly related to the early staging of pancreatic tumors is negligible, since the factors affecting the phases of slow and rapid tumor growth are unclear. Most likely, cyclic clinical and radiological evaluation of the pancreas will not give the expected results and is associated with advanced financial and physical costs. Perhaps, one of the approaches for effective treatment of pancreatic cancer will be the recognition of the need for laboratory and instrumental examinations by each patient. Acceptable frequency of examinations and own funds are determined by a patients himself in this case.
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Affiliation(s)
- G. G. Karmazanovsky
- Vishnevsky National Medical Research Center of Surgery, Pirogov Russian National Research Medical University of the Ministry of Health of Russia
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Panaro F, Kellil T, Vendrell J, Sega V, Souche R, Piardi T, Leon P, Cassinotto C, Assenat E, Rosso E, Navarro F. Microvascular invasion is a major prognostic factor after pancreatico-duodenectomy for adenocarcinoma. J Surg Oncol 2019; 120:483-493. [PMID: 31197842 DOI: 10.1002/jso.25580] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 04/03/2019] [Accepted: 05/18/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND Microvascular invasion (MVI) has been proved to be poor prognostic factor in many cancers. To date, only one study published highlights the relationship between this factor and the natural history of pancreatic cancer. The aim of this study was to assess the impact of MVI, on disease-free survival (DFS) and overall survival (OS), after pancreatico-duodenectomy (PD) for pancreatic head adenocarcinoma. Secondarily, we aim to demonstrate that MVI is the most important factor to predict OS after surgery compared with resection margin (RM) and lymph node (LN) status. MATERIALS AND METHODS Between January 2015 and December 2017, 158 PD were performed in two hepato-bilio-pancreatic (HBP) centers. Among these, only 79 patients fulfilled the inclusion criteria of the study. Clinical-pathological data and outcomes were retrospectively analyzed from a prospectively maintained database. RESULTS Of the 79 patients in the cohort, MVI was identified in 35 (44.3%). In univariate analysis, MVI (P = .012 and P < .0001), RM (P = .023 and P = .021), and LN status (P < .0001 and P = .0001) were significantly associated with DFS and OS. A less than 1 mm margin clearance did not influence relapse (P = .72) or long-term survival (P = .48). LN ratio > 0.226 had a negative impact on OS (P = .044). In multivariate analysis, MVI and RM persisted as independent prognostic factors of DFS (P = .0075 and P = .0098, respectively) and OS (P < .0001 and P = .0194, respectively). Using the likelihood ratio test, MVI was identified as the best fit to predict OS after PD for ductal adenocarcinomas compared with the margin status model (R0 vs R1) (P = .0014). CONCLUSION The MVI represents another major prognostic factor determining long-term outcomes.
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Affiliation(s)
- Fabrizio Panaro
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Saint Eloi Hospital, School of Medicine, Montpellier University Hospital, Montpellier, France
| | - Tarek Kellil
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Saint Eloi Hospital, School of Medicine, Montpellier University Hospital, Montpellier, France
| | - Julie Vendrell
- Department of Pathology and Onco-Biology/Solid Tumors Biology Lab, Arnaud de Villeneuve Hospital, School of Medicine, Montpellier University Hospital, Montpellier, France
| | - Valentina Sega
- Division of Surgical Oncology, Department of Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Regis Souche
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Saint Eloi Hospital, School of Medicine, Montpellier University Hospital, Montpellier, France
| | - Tullio Piardi
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Reims University Hospital-School of Medicine, Reims, France
| | - Piera Leon
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Saint Eloi Hospital, School of Medicine, Montpellier University Hospital, Montpellier, France
| | - Christophe Cassinotto
- Department of Radiology, Saint Eloi Hospital, School of Medicine, Montpellier University Hospital, Montpellier, France
| | - Eric Assenat
- Division of Medical Oncology, Department of Medicine, Saint Eloi Hospital, School of Medicine, Montpellier University Hospital, Montpellier, France
| | - Edoardo Rosso
- Department of Pathology and Onco-Biology/Solid Tumors Biology Lab, Arnaud de Villeneuve Hospital, School of Medicine, Montpellier University Hospital, Montpellier, France
| | - Francis Navarro
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Saint Eloi Hospital, School of Medicine, Montpellier University Hospital, Montpellier, France
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Alexakis N, Bramis K, Toutouzas K, Zografos G, Konstadoulakis M. Variant hepatic arterial anatomy encountered during pancreatoduodenectomy does not influence postoperative outcomes or resection margin status: A matched pair analysis of 105 patients. J Surg Oncol 2019; 119:1122-1127. [DOI: 10.1002/jso.25461] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Accepted: 03/03/2019] [Indexed: 08/30/2023]
Affiliation(s)
- Nicholas Alexakis
- Department of SurgeryMedical School, National and Kapodistrian University of AthensAthens Greece
| | - Konstandinos Bramis
- Department of SurgeryMedical School, National and Kapodistrian University of AthensAthens Greece
| | - Konstandinos Toutouzas
- Department of SurgeryMedical School, National and Kapodistrian University of AthensAthens Greece
| | - George Zografos
- Department of SurgeryMedical School, National and Kapodistrian University of AthensAthens Greece
| | - Manoussos Konstadoulakis
- Department of SurgeryMedical School, National and Kapodistrian University of AthensAthens Greece
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Dolay K, Malya FU, Akbulut S. Management of pancreatic head adenocarcinoma: From where to where? World J Gastrointest Surg 2019; 11:143-154. [PMID: 31057699 PMCID: PMC6478601 DOI: 10.4240/wjgs.v11.i3.143] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/19/2019] [Accepted: 03/20/2019] [Indexed: 02/06/2023] Open
Abstract
Pancreatic head adenocarcinoma (PHAC) is one of the most aggressive malignancies, and it has low long-term survival rates. Surgery is the only option for long-term survival. The difficulties associated with PHAC include higher frequencies of regional or distant lymph node metastases and vascular involvement, and positive resection margins in pancreatic and retroperitoneal tissues. Radical resections increase margin negativity and life expectancy; however, the extend of the surgery applied is controversial. Thus, western and eastern centers may use different approaches. Multiorgan, peripancreatic nerve plexus, and vascular resections have been discussed in relation to radical surgery for pancreatic cancer as have the roles of neoadjuvant and adjuvant therapy regimens. Determining the appropriate limits for surgery, standardizing definitions and surgical techniques according to guidelines, and centralizing pancreatic surgery within high-volume institutions to reduce mortality and morbidity rates are among the most important issues to consider. In this review, we evaluate the basic concepts underlying and the roles of radical surgery for PHAC, and lymphadenectomy, nerve plexus, retroperitoneal tissue, vascular, and multivisceral resections, total pancreatectomy, and liver metastases are discussed.
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Affiliation(s)
- Kemal Dolay
- Department of Surgery, Division of Hepato-Pancreato-Biliary Surgery, Istinye University, Liv Hospital, Istanbul 34340, Turkey
| | - Fatma Umit Malya
- Department of Surgery, Bezmialem Vakif University Faculty of Medicine, Istanbul 34093, Turkey
| | - Sami Akbulut
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
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Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a dismal prognosis and surgery is the only chance for cure. However, only few of the patients have localized tumor eligible for curative complete resection. Preoperative management and well-staging of the disease are the cornerstone for appropriate surgery and major issues to define the best therapeutic strategy. This review focuses on the surgical and optimal perioperative management of PDAC and summarizes updates data on the subject.
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Silvanto A, Balamurugan T, Bagwan I. Histopathological assessment of prognostic factors in pancreatic resection specimens using a standardised protocol. Pathologica 2019; 111:24-30. [PMID: 31217619 PMCID: PMC8138538 DOI: 10.32074/1591-951x-41-17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Accepted: 11/24/2018] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND Adenocarcinoma involving the pancreas shows differences in prognostic parameters including resection margin status depending on subtype. AIM To assess the reported incidence of each type and the rate of R1 resection using detailed histopathological examination protocol. METHODS All pancreaticoduodenectomies between June 2011 and June 2013 at our institute were analysed. These were classified according to the site of origin, R1 status, size, stage at resection, lymph node status and the rate of lymphovascular and perineural invasion. RESULTS 58 adenocarcinomas included 23 ductal, 16 intraductal papillary mucinous neoplasm (IPMN) related, 8 duodenal, 7 ampullary and 4 distal common bile duct (CBD) tumours. The CBD, pancreatic ductal and IPMN-related adenocarcinomas had the highest rates of R1 resection, at 75%, 69.5 and 62.5%, with the posterior and SMV margins most frequently involved. Ampullary adenocarcinoma had lower rates of R1 resection (14%) as well as perineural invasion (0%). CONCLUSION Ampullary adenocarcinomas had a lower rate of R1 resection and perineural invasion, both of which are parameters associated with a poorer outcome. This correlates with literature indicating ampullary tumours have a better prognosis. Our study also highlights the high rate of detection of microscopic margin involvement when a detailed histopathological examination protocol is employed.
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Affiliation(s)
| | | | - I.N. Bagwan
- Departments of Histopathology, Surrey Pathology Services, Frimley Park and Royal Surrey County Hospitals, Guildford, UK
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Rowan DJ, Logunova V, Oshima K. Measured residual tumor cellularity correlates with survival in neoadjuvant treated pancreatic ductal adenocarcinomas. Ann Diagn Pathol 2019; 38:93-98. [DOI: 10.1016/j.anndiagpath.2018.10.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 10/23/2018] [Accepted: 10/25/2018] [Indexed: 12/22/2022]
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Laparoscopic Distal Pancreatectomy: Our Experience in a Tertiary Referral Center. Surg Laparosc Endosc Percutan Tech 2019; 29:285-289. [PMID: 30676539 DOI: 10.1097/sle.0000000000000634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Despite an increase in the number of laparoscopic distal pancreatectomy (LDP) procedures being performed, the long-term oncology and operative results are still unclear. The aim of this study was to present the surgical and long-term results of patients undergoing LDP for the treatment of distal pancreatic tumors. MATERIALS AND METHODS A retrospective review was made of patients who underwent LDP in our clinic, between 2006 and 2018, and who were diagnosed with pancreas tail, neck, and corpus tumors. For the purposes of this study, the data related to the preoperative, operative, and postoperative characteristics of the patients were determined. RESULTS A total of 46 patients were identified as suitable for inclusion in the study. Of these, 52.1% were female individuals, and the average age of the whole group was 63 years. Previous surgery for malignant diseases was recorded for 54.3% of the patients, due to premalignant diseases in 13% and benign diseases in 32.7%. On average, 10 lymph nodes were removed from patients diagnosed with malignant tumors. The conversion rate was found to be 2.1%. The postoperative pancreatic fistula rate was 26%, and there was 1 complication each of grades III and IV according to the Clavien-Dindo classification. The mortality rate was 0%. CONCLUSIONS It was concluded that LDP of distal pancreas tumors seems to be both safe and effective in respect of the long-term results in addition to the early results of the operation.
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Katsourakis A, Vrabas I, Papanikolaou V, Apostolidis S, Chatzis I, Noussios G. The Role of Exercise in the Quality of Life in Patients After Pancreatectomy: A Prospective Randomized Controlled Trial. J Clin Med Res 2019; 11:65-71. [PMID: 30627280 PMCID: PMC6306133 DOI: 10.14740/jocmr3675] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 11/16/2018] [Indexed: 12/14/2022] Open
Abstract
Background Pancreatic resection is still a challenging operation characterised by high morbidity. The quality of life in patients after pancreatectomy is a critical outcome. The aim of our trial is to prove whether or not exercise has any benefit to the life of these patients. Methods The study was an open-label, randomized clinical trial. The patients were selected according to the Consolidated Standard of Reporting Trials criteria. The study was registered at the International Standard Randomized Controlled Trial registry (ISRCTN) with the study ID ISRCTN1087174. The study was approved by the Bioethics and Deontology Committee, Medical School of Aristotle University, Thessaloniki (ref: 166/29.10.2015). Results Once the allocation and the follow-up were completed, 21 patients in the exercise group and 22 in the control group were analyzed. There was no statistical difference between the two groups regarding co-morbidities and disease characteristics; however, the quality of life and the total status of health were superior in the exercise group. Conclusions Exercise can improve the quality of life in patients after complex operations like pancreatectomy.
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Affiliation(s)
| | - Ioannis Vrabas
- School of Physical Education and Sports Sciences at Serres, "Aristotle" University, Thessaloniki, Greece
| | | | | | - Iosif Chatzis
- Department of Surgery, Agios Dimitrios General Hospital, Thessaloniki, Greece
| | - George Noussios
- School of Physical Education and Sports Sciences at Serres, "Aristotle" University, Thessaloniki, Greece
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Fluorescent humanized anti-CEA antibody specifically labels metastatic pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model. Oncotarget 2018; 9:37333-37342. [PMID: 30647873 PMCID: PMC6324662 DOI: 10.18632/oncotarget.26484] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 12/04/2018] [Indexed: 11/25/2022] Open
Abstract
Pancreatic cancer is a highly lethal disease in part due to incomplete tumor resection. Targeting by tumor-specific antibodies conjugated with a fluorescent label can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we describe a patient-derived orthotopic xenograft model of pancreatic cancer that recapitulated the disease on a gross and microscopic level, along with physiologic clinical manifestations. We additionally show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively highlight the pancreatic cancer and its metastases in this model with a tumor-to-background ratio of 3.5 (SEM 0.9). The present results demonstrate the clinical potential of this labeling technique for fluorescence-guided surgery of pancreatic cancer.
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Franck C, Hass P, Malfertheiner P, Ricke J, Seidensticker M, Venerito M. Combined Systemic Chemotherapy and CT-Guided High-Dose-Rate Brachytherapy for Isolated Local Manifestation of Pancreatic Cancer after Surgical Resection. Digestion 2018; 98:69-74. [PMID: 29698952 DOI: 10.1159/000487359] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 02/02/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND Prospective data on the optimal management of patients with pancreatic ductal adenocarcinoma (PDA) and isolated local manifestation (ILM) after surgery are lacking. Hence, no statements with respect to this entity have been released from most international guidelines including European Society for Medical Oncology, National Comprehensive Cancer Network, and American Society for Clinical Oncology. METHODS We report for the first time a case-series of 3 patients with PDA and ILM receiving combined systemic chemotherapy and CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT). RESULTS CT-HDRBT allowed in all patients with pronounced chemotherapy-induced side effects either a pause of cytostatic treatment or de-escalation to a "maintenance" therapy (dose reduction, interval prolongation, scheme modification with withdrawal of most toxic drugs). CONCLUSION Combining CT-HDRBT to systemic chemotherapy in patients with PDA and ILM is feasible and safe. As for patients with PDA and ILM no standard of care exists, designing an appropriate randomized prospective trial for this highly selected group of patients is challenging.
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Affiliation(s)
- Caspar Franck
- Otto-von-Guericke Universitätsklinikum, Klinik für Gastroenterologie, Hepatologie und Infektiologie, Magdeburg, Germany
| | - Peter Hass
- Otto-von-Guericke Universitätsklinikum, Klinik für Strahlentherapie, Magdeburg, Germany
| | - Peter Malfertheiner
- Otto-von-Guericke Universitätsklinikum, Klinik für Gastroenterologie, Hepatologie und Infektiologie, Magdeburg, Germany
| | - Jens Ricke
- Otto-von-Guericke Universitätsklinikum, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany.,Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany.,Deutsche Akademie für Mikrotherapie (DAfMT), International School for Image Guided Interventions, Magdeburg, Germany
| | - Max Seidensticker
- Otto-von-Guericke Universitätsklinikum, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany.,Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany.,Deutsche Akademie für Mikrotherapie (DAfMT), International School for Image Guided Interventions, Magdeburg, Germany
| | - Marino Venerito
- Otto-von-Guericke Universitätsklinikum, Klinik für Gastroenterologie, Hepatologie und Infektiologie, Magdeburg, Germany
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Predictors of long-term survival after pancreaticoduodenectomy for peri-ampullary adenocarcinoma: A retrospective study of 5-year survivors. Hepatobiliary Pancreat Dis Int 2018; 17:443-449. [PMID: 30126828 DOI: 10.1016/j.hbpd.2018.08.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 07/25/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND Pancreaticoduodenectomy (PD) is the standard curative treatment for periampullary tumors. The aim of this study is to report the incidence and predictors of long-term survival (≥ 5 years) after PD. METHODS This study included patients who underwent PD for pathologically proven periampullary adenocarcinomas. Patients were divided into 2 groups: group (I) patients who survived less than 5 years and group (II) patients who survived ≥ 5 years. RESULTS There were 47 (20.6%) long-term survivors (≥ 5 years) among 228 patients underwent PD for periampullary adenocarcinoma. Patients with ampullary adenocarcinoma represented 31 (66.0%) of the long-term survivors. Primary analysis showed that favourable factors for long-term survival include age < 60 years old, serum CEA < 5 ng/mL, serum CA 19-9 < 37 U/mL, non-cirrhotic liver, tumor size < 2 cm, site of primary tumor, postoperative pancreatic fistula, R0 resection, postoperative chemotherapy, and no recurrence. Multivariate analysis demonstrated that CA 19-9 < 37 U/mL [OR (95% CI) = 1.712 (1.248-2.348), P = 0.001], smaller tumor size [OR (95% CI )= 1.335 (1.032-1.726), P = 0.028] and Ro resection [OR (95% CI) = 3.098 (2.095-4.582), P < 0.001] were independent factors for survival ≥ 5 years. The prognosis was best for ampullary adenocarcinoma, for which the median survival was 54 months and 5-year survival rate was 39.0%, and the poorest was pancreatic head adenocarcinoma, for which the median survival was 27 months and 5-year survival rate was 7%. CONCLUSIONS The majority of long-term survivors after PD for periampullary adenocarcinoma are patients with ampullary tumor. CA 19-9 < 37 U/mL, smaller tumor size, and R0 resection were found to be independent factors for long-term survival ≥ 5 years.
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