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Matsui Y, Hashimoto D, Nakagawa N, Yamaki S, Hayashi M, Takami H, Shibuya K, Yamada S, Satoi S, Fujii T. Long-term outcomes of prophylactic right-half dissection of the superior mesenteric artery nerve plexus in pancreatoduodenectomy for pancreatic ductal adenocarcinoma: five-year results from a randomized phase II trial. Surg Today 2025:10.1007/s00595-025-03062-6. [PMID: 40380996 DOI: 10.1007/s00595-025-03062-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Accepted: 04/23/2025] [Indexed: 05/19/2025]
Abstract
PURPOSES In pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC), Prophylactic right-half dissection of the superior mesenteric artery (SMA) nerve plexus has been attempted in pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. In this study, we evaluated the significance of prophylactic right-half dissection of the SMA nerve plexus by extending the observation period to 5 years. METHODS From April 2014 to June 2018, 74 patients with PDAC in the pancreatic head were randomly assigned to either the dissection group, in which the right half of the nerve plexus of the SMA was dissected (n = 37) or the preservation group, in which the nerve plexus of the SMA was completely preserved (n = 37). The 5-year relapse-free survival (RFS), overall survival (OS), and incidence of diarrhea were prospectively compared between groups. RESULTS The median RFS (20 vs. 16 months, P = 0.503) and OS (37.0 vs. 30.0 months, P = 0.582) did not differ significantly between the dissection and preservation groups. There was no significant difference in locoregional recurrence (27.0% vs. 37.8%, P = 0.320) or distant metastasis (64.9% vs. 83.0%, P = 0.451). Postoperative diarrhea occurred in 64.9% and 62.2% of the cases in the dissection and preservation groups, respectively (P = 0.809). CONCLUSION Prophylactic right half dissection of the SMA nerve plexus did not improve the RFS or OS.
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Affiliation(s)
- Yuki Matsui
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata, Osaka, 573-1010, Japan
| | - Daisuke Hashimoto
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata, Osaka, 573-1010, Japan
| | - Nobuhiko Nakagawa
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - So Yamaki
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata, Osaka, 573-1010, Japan
| | - Masamichi Hayashi
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hideki Takami
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kazuto Shibuya
- Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
| | - Suguru Yamada
- Department of Gastroenterological Surgery, Nagoya Central Hospital, Nagoya, Japan
| | - Sohei Satoi
- Department of Pancreatobiliary Surgery, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata, Osaka, 573-1010, Japan.
- Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
| | - Tsutomu Fujii
- Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan
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Keck T. [Evidence for the extent and oncological benefit of lymphadenectomy for pancreatic cancer]. CHIRURGIE (HEIDELBERG, GERMANY) 2025; 96:288-292. [PMID: 39820664 DOI: 10.1007/s00104-024-02219-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/27/2024] [Indexed: 01/19/2025]
Abstract
Pancreatic cancer is usually diagnosed at a late stage and is characterized by early systemic metastases, which can also be present in the form of micrometastases that are not primarily visible. Lymphatic metastases in pancreatic cancer are common. The extent of lymph node removal (lymphadenectomy, LAD) in pancreatic cancer is defined in the guidelines of the Association of the Scientific Medical Societies in Germany (AWMF) and according to currently available data has more diagnostic and prognostic relevance than therapeutic relevance; however, within the framework of modern multimodal treatment algorithms, radical surgery is the most relevant of all components of multimodal treatment with LAD playing an important role. According to current data, extended LAD without technical necessity in the surgery of the primary tumor brings no advantages for the patients but numerous limitations in the quality of life and should therefore not be performed as the standard. Important aspects of LAD for pancreatic cancer are the lymph node ratio, extended vs. standard LAD and innovations in LAD in the field of interaortocaval lymph nodes and the so-called triangle operation.
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Affiliation(s)
- Tobias Keck
- Direktor der Klinik für Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23568, Lübeck, Deutschland.
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Shyr BS, Wang SE, Chen SC, Shyr YM, Shyr BU. Mesopancreas dissection level 3 for pancreatic head cancer in combined robotic/open pancreatoduodenectomy: a propensity score-matched study. Surg Endosc 2025; 39:1191-1199. [PMID: 39739104 PMCID: PMC11794409 DOI: 10.1007/s00464-024-11475-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 12/04/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND Mesopancreas dissection (MPD) level 3 in combined robotic/open pancreatoduodenectomy (CR/OPD) is technique-demanding. This study aims to clarify the feasibility and justification of MPD level 3. METHODS Propensity score matching (PSM) analysis was conducted for 208 patients with pancreatic head cancer undergoing CR/OPD with or without MPD level 3. The comparison focused on surgical and oncological outcomes. RESULTS After PSM, each group comprised 86 patients. Surgical outcomes were comparable between these two groups, except longer operation time for MPD level 3 (+), median: 10.5 vs. 9.5 h, p = 0.002. MPD level 3 (+) group exhibited higher lymph node yield, median: 20 vs. 17, p < 0.001, and curative (R0) resection rate, 89.5% vs. 69.8%, p = 0.001, compared to MPD level 3 (-) group. Among the entire cohort, no significant survival difference was observed between the MPD Level 3 (+) and (-) groups. Survival outcome for R0 resection after CR/OPD was notably better than those for R2 resection, 5-year survival: 34.0% vs. 0, p = 0.038. However, within the curative (R0) resection cohort, no survival difference was observed between the MPD level 3 (+) and MPD level 3 (-) groups. CONCLUSION MPD level 3 in CR/OPD is technically feasible without increasing the surgical risks but takes one hour extra operating time. Incorporation of MPD level 3 does not confer a survival advantage within the curative (R0) resection cohort. The primary focus should continue to be on achieving curative (R0) resection to maximize the survival benefits for pancreatic head cancer.
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Affiliation(s)
- Bor-Shiuan Shyr
- Division of General Surgery, Department of Surgery and Therapeutic and Research Center of Pancreatic Cancer, Taipei Veterans General Hospital, Taipei Veterans General Hospital, National Yang Ming University, 201 Section 2 Shipai Road, Taipei, 112, Taiwan, ROC
- National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Shin-E Wang
- Division of General Surgery, Department of Surgery and Therapeutic and Research Center of Pancreatic Cancer, Taipei Veterans General Hospital, Taipei Veterans General Hospital, National Yang Ming University, 201 Section 2 Shipai Road, Taipei, 112, Taiwan, ROC
- National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Shih-Chin Chen
- Division of General Surgery, Department of Surgery and Therapeutic and Research Center of Pancreatic Cancer, Taipei Veterans General Hospital, Taipei Veterans General Hospital, National Yang Ming University, 201 Section 2 Shipai Road, Taipei, 112, Taiwan, ROC
- National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery and Therapeutic and Research Center of Pancreatic Cancer, Taipei Veterans General Hospital, Taipei Veterans General Hospital, National Yang Ming University, 201 Section 2 Shipai Road, Taipei, 112, Taiwan, ROC
- National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Bor-Uei Shyr
- Division of General Surgery, Department of Surgery and Therapeutic and Research Center of Pancreatic Cancer, Taipei Veterans General Hospital, Taipei Veterans General Hospital, National Yang Ming University, 201 Section 2 Shipai Road, Taipei, 112, Taiwan, ROC.
- National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
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4
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Messing EM. Standard vs extended lymphadenectomy for muscle invasive bladder cancer. Bladder Cancer 2025; 11:23523735251314984. [PMID: 40124790 PMCID: PMC11926826 DOI: 10.1177/23523735251314984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 12/10/2024] [Indexed: 03/25/2025]
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Nakane Y, Minami T, Kurumiya Y, Mizuno K, Sekoguchi E, Sugawara G, Inoue M, Kato T, Akita N. Pylorus-preserving pancreatoduodenectomy preserving blood supply for pancreatic cancer with a history of proximal gastrectomy and sigmoidectomy: a case report. Surg Case Rep 2024; 10:266. [PMID: 39570502 PMCID: PMC11582281 DOI: 10.1186/s40792-024-02063-w] [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: 08/05/2024] [Accepted: 11/06/2024] [Indexed: 11/22/2024] Open
Abstract
BACKGROUND Blood supply to the remnant stomach should be preserved during pancreatectomy in patients with a history of gastrectomy. Moreover, ischemic complications should be considered when performing pancreatoduodenectomy in patients with celiac axis and superior mesenteric artery (SMA) stenosis. However, whether these surgical procedures can be safely performed remains unclear. CASE PRESENTATION A 75-year-old man had a history of laparoscopic proximal gastrectomy (PG) with double-flap technique for gastric cancer and laparoscopic sigmoidectomy for sigmoid cancer treated 4 years ago. Follow-up computed tomography (CT) revealed an irregular nodular tumor measuring 13 mm in the pancreatic head. The patient was diagnosed with resectable pancreatic head cancer without lymph node metastasis (cT1cN0M0, cStageIA) according to the Union for International Cancer Control, 8th edition. As a standard pancreatic cancer treatment, two courses of preoperative chemotherapy with gemcitabine plus S-1 were administered. CT after preoperative chemotherapy identified no significant changes in tumor size but revealed SMA stenosis due to atherosclerosis. Blood flow to the left-sided colon was supplied from the middle colic artery via the SMA because of the past sigmoidectomy with inferior mesenteric artery detachment. Therefore, SMA stent placement was performed 1 day preoperatively. Subsequently, pylorus-preserving pancreatoduodenectomy (PPPD) was performed, preserving the remnant stomach with the right gastroepiploic (RGE) artery and vein. After resection, indocyanine green fluorescence imaging confirmed a good blood supply to the remnant stomach. The operation time was 467 min, and the blood lost was 442 mL. Histopathologically, the tumor was diagnosed as moderate adenocarcinoma and pT1cN0M0, Stage IA. The postoperative course was uneventful. The patient was discharged on postoperative day 23. S-1 as adjuvant chemotherapy was administered on postoperative day 63. The patient has been alive without recurrence for 7 months. CONCLUSIONS We performed PPPD preserving blood supply for pancreatic head cancer in a patient with benign SMA stenosis and a history of PG and sigmoidectomy. Blood supply was preserved through preoperative SMA stent placement and a surgical procedure preserving the RGE vessels. Furthermore, S-1 adjuvant chemotherapy was successfully initiated. These multimodal therapies contributed to a favorable clinical outcome.
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Affiliation(s)
- Yuto Nakane
- Department of Surgery, Toyota Kosei Hospital, 500-1 Josui-cho, Toyota, Aichi, 470-0396, Japan.
| | - Takayuki Minami
- Department of Surgery, Toyota Kosei Hospital, 500-1 Josui-cho, Toyota, Aichi, 470-0396, Japan
| | - Yasuhiro Kurumiya
- Department of Surgery, Toyota Kosei Hospital, 500-1 Josui-cho, Toyota, Aichi, 470-0396, Japan
| | - Keisuke Mizuno
- Department of Surgery, Toyota Kosei Hospital, 500-1 Josui-cho, Toyota, Aichi, 470-0396, Japan
| | - Ei Sekoguchi
- Department of Surgery, Toyota Kosei Hospital, 500-1 Josui-cho, Toyota, Aichi, 470-0396, Japan
| | - Gen Sugawara
- Department of Surgery, Toyota Kosei Hospital, 500-1 Josui-cho, Toyota, Aichi, 470-0396, Japan
| | - Masaya Inoue
- Department of Surgery, Toyota Kosei Hospital, 500-1 Josui-cho, Toyota, Aichi, 470-0396, Japan
| | - Takehiro Kato
- Department of Surgery, Toyota Kosei Hospital, 500-1 Josui-cho, Toyota, Aichi, 470-0396, Japan
| | - Naohiro Akita
- Department of Surgery, Toyota Kosei Hospital, 500-1 Josui-cho, Toyota, Aichi, 470-0396, Japan
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Lerner SP, Tangen C, Svatek RS, Daneshmand S, Pohar KS, Skinner E, Schuckman A, Sagalowsky AI, Smith ND, Kamat AM, Kassouf W, Plets M, Bangs R, Koppie TM, Alva A, La Rosa FG, Pal SK, Kibel AS, Canter DJ, Thompson IM. Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer. N Engl J Med 2024; 391:1206-1216. [PMID: 39589370 PMCID: PMC11599768 DOI: 10.1056/nejmoa2401497] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
BACKGROUND Whether extended lymphadenectomy is associated with improved disease-free and overall survival, as compared with standard lymphadenectomy, among patients with localized muscle-invasive bladder cancer undergoing radical cystectomy is unclear. METHODS We randomly assigned, in a 1:1 ratio, patients with localized muscle-invasive bladder cancer of clinical stage T2 (confined to muscle) to T4a (invading adjacent organs) with two or fewer positive nodes (N0, N1, or N2) to undergo bilateral standard lymphadenectomy (dissection of lymph nodes on both sides of the pelvis) or extended lymphadenectomy involving removal of common iliac, presciatic, and presacral nodes. Randomization was performed during surgery and stratified according to the receipt and type of neoadjuvant chemotherapy, tumor stage (T2 vs. T3 or T4a), and a Zubrod's performance-status score (0 or 1 vs. 2; assessed on a 5-point scale, with higher scores indicating greater disability). The primary outcome was disease-free survival. Overall survival and safety were also assessed. RESULTS Of 658 patients who were enrolled, 592 eligible patients were randomly assigned to undergo extended lymphadenectomy (292 patients) or standard lymphadenectomy (300). Surgery was performed by 36 surgeons at 27 sites in the United States and Canada. Neoadjuvant chemotherapy had been received by 57% of the patients. At a median follow-up of 6.1 years, recurrence or death had occurred in 130 patients (45%) in the extended-lymphadenectomy group and in 127 (42%) in the standard-lymphadenectomy group, and the estimated 5-year disease-free survival was 56% and 60%, respectively (hazard ratio for recurrence or death, 1.10; 95% confidence interval [CI], 0.86 to 1.40; P = 0.45). Overall survival at 5 years was 59% in the extended-lymphadenectomy group and 63% in the standard-lymphadenectomy group (hazard ratio for death, 1.13; 95% CI, 0.88 to 1.45). Adverse events of grade 3 to 5 occurred in 157 patients (54%) in the extended-lymphadenectomy group and in 132 (44%) in the standard-lymphadenectomy group; death within 90 days after surgery occurred in 19 patients (7%) and 7 patients (2%), respectively. CONCLUSIONS As compared with standard lymphadenectomy, extended lymphadenectomy did not result in improved disease-free or overall survival among patients with muscle-invasive bladder cancer undergoing radical cystectomy and was associated with higher perioperative morbidity and mortality. (Funded by the National Cancer Institute and the Canadian Cancer Society; SWOG S1011 ClinicalTrials.gov number, NCT01224665.).
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Affiliation(s)
| | - Catherine Tangen
- SWOG Statistics and Data Management Center, Seattle, WA
- Fred Hutchinson Cancer Center, Seattle, WA
| | | | - Siamak Daneshmand
- University of Southern California/Norris Comprehensive Cancer Center, CA, Los Angeles, CA
| | | | | | - Anne Schuckman
- University of Southern California/Norris Comprehensive Cancer Center, CA, Los Angeles, CA
| | | | | | | | | | - Melissa Plets
- SWOG Statistics and Data Management Center, Seattle, WA
- Fred Hutchinson Cancer Center, Seattle, WA
| | - Rick Bangs
- Bladder Cancer Advocacy Network/SWOG Advocates, Pittsford, NY
| | | | | | | | | | | | - Daniel J. Canter
- Fox Chase Cancer Center, Philadelphia, PA (former during conduct of trial)/Oschsner Medical Center, Jefferson, LA (current)
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1724-1785. [PMID: 39389105 DOI: 10.1055/a-2338-3716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e874-e995. [PMID: 39389103 DOI: 10.1055/a-2338-3533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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Kato T, Watanabe Y, Oshima Y, Takase K, Watanabe Y, Okada K, Aikawa M, Okamoto K, Koyama I. Long-term outcomes and risk factors of pancreatic insufficiency after a pancreatoduodenectomy: A retrospective study. Surgery 2024; 176:880-889. [PMID: 38879380 DOI: 10.1016/j.surg.2024.04.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 04/14/2024] [Accepted: 04/27/2024] [Indexed: 08/18/2024]
Abstract
BACKGROUND An increasing number of patients are achieving long-term survival after pancreatoduodenectomy, meaning that risk assessments of endocrine and exocrine pancreatic insufficiency are needed. Herein, we investigated the risk factors for pancreatic insufficiency after pancreatoduodenectomy by incorporating pancreatic morphologic changes and perioperative factors. METHODS Patients who underwent pancreatoduodenectomy between January 2015 and December 2020 were enrolled in this single-center retrospective study. Clinicopathologic, surgical, and pancreatic morphologic factors were collected, and risk factors for exocrine pancreatic insufficiency and endocrine pancreatic insufficiency were analyzed. Exocrine pancreatic insufficiency was defined as steatorrhea requiring pancreatic enzymes and new onset steatosis, and endocrine pancreatic insufficiency was defined as postoperative new-onset diabetes mellitus. Multivariate analysis was performed. RESULTS Among the 206 patients enrolled, 14% and 24% developed endocrine pancreatic insufficiency and exocrine pancreatic insufficiency, respectively. Multivariate analysis revealed residual pancreatic stent 1 year postoperatively, lymph node metastasis, and postoperative pancreatic atrophy (P-atrophy) as independent risk factors for exocrine pancreatic insufficiency, whereas preoperative glycated hemoglobin levels, residual pancreatic stent, and postoperative main pancreatic duct dilatation were risk factors for endocrine pancreatic insufficiency. Subgroup analysis of pancreatic ductal adenocarcinoma revealed that exocrine pancreatic insufficiency in patients with pancreatic ductal adenocarcinoma was caused by preoperative decreased pancreatic function (high glycated hemoglobin and a low postoperative pancreatic fistula rate), whereas the high incidence of POPF influenced the development of exocrine pancreatic insufficiency in patients without pancreatic ductal adenocarcinoma. CONCLUSION Postoperative pancreatic atrophy and main pancreatic duct dilatation are risk factors for exocrine pancreatic insufficiency I and endocrine pancreatic insufficiency, respectively, and residual pancreatic stent affects both types of pancreatic dysfunction. Improving the surgical approach and stent management may help prevent these late complications.
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Affiliation(s)
- Tomotaka Kato
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan
| | - Yukihiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan.
| | - Yuhei Oshima
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan
| | - Kenichiro Takase
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan
| | - Yuichiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan
| | - Katsuya Okada
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan
| | - Masayasu Aikawa
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan
| | - Kojun Okamoto
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan
| | - Isamu Koyama
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan
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10
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Umino R, Nara S, Mizui T, Takamoto T, Ban D, Esaki M, Hiraoka N, Shimada K. Impact of Surgical Margin Status on Survival and Recurrence After Pancreaticoduodenectomy for Distal Cholangiocarcinoma: Is Microscopic Residual Tumor (R1) Associated with Higher Rates of Local Recurrence? Ann Surg Oncol 2024; 31:4910-4921. [PMID: 38679686 DOI: 10.1245/s10434-024-15313-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 04/03/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND Patients undergoing macroscopically curative resection for distal cholangiocarcinoma (DCC) have high recurrence rates and poor prognoses. This study aimed to investigate the impact of surgical margin status on survival and recurrence after resection of DCC, specifically focusing on microscopic residual tumor (R1) and its relationship to local recurrence. PATIENTS AND METHODS This was a retrospective analysis of patients who had undergone pancreaticoduodenectomy (PD) for DCC between 2005 and 2021. Surgical margin was classified as R0, R1cis (positive bile duct margin with carcinoma in situ), and R1inv (positive bile duct margin with an invasive subepithelial component and/or positive radial margin). RESULTS In total, 29 of 133 patients (21.8%) had R1cis and 23 (17.3%) R1inv. The 5-year overall survival (OS) for R0 (55.7%) did not differ significantly from that for R1cis/R1inv (47.4%/33.6%, respectively). The 5-year recurrence-free survival (RFS) for R0 was significantly longer than that for R1inv (50.1% vs. 17.4%, p = 0.003), whereas RFS did not differ significantly between those with R0 and R1cis. R1cis/R1inv status was not an independent predictor of OS and RFS in multivariate analysis. Cumulative incidence of isolated distant recurrence was significantly higher for R1cis/R1inv than for R0 (p = 0.0343/p = 0.0226, respectively), whereas surgical margin status was not significantly associated with rates of local or local plus distant recurrence. CONCLUSIONS Surgical margin status does not significantly impact OS and RFS in patients undergoing PD for DCC following precise preoperative imaging evaluation. Additionally, R1 status is significantly linked to higher isolated distant recurrence rather than local recurrence, highlighting the importance of multidisciplinary therapy.
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Affiliation(s)
- Ryosuke Umino
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan.
| | - Takahiro Mizui
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Nobuyoshi Hiraoka
- Department of Molecular Pathology, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan
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11
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Rompen IF, Habib JR, Sereni E, Stoop TF, Musa J, Cohen SM, Berman RS, Kaplan B, Hewitt DB, Sacks GD, Wolfgang CL, Javed AA. What is the optimal surgical approach for ductal adenocarcinoma of the pancreatic neck? - a retrospective cohort study. Langenbecks Arch Surg 2024; 409:224. [PMID: 39028426 DOI: 10.1007/s00423-024-03417-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 07/13/2024] [Indexed: 07/20/2024]
Abstract
BACKGROUND The appropriate surgical approach for pancreatic ductal adenocarcinoma (PDAC) is determined by the tumor's relation to the porto-mesenteric axis. Although the extent and location of lymphadenectomy is dependent on the type of resection, a pancreatoduodenectomy (PD), distal pancreatectomy (DP), or total pancreatectomy (TP) are considered equivalent oncologic operations for pancreatic neck tumors. Therefore, we aimed to assess differences in histopathological and oncological outcomes for surgical approaches in the treatment of pancreatic neck tumors. METHODS Patients with resected PDAC located in the pancreatic neck were identified from the National Cancer Database (2004-2020). Patients with metastatic disease were excluded. Furthermore, patients with 90-day mortality and R2-resections were excluded from the multivariable Cox-regression analysis. RESULTS Among 846 patients, 58% underwent PD, 25% DP, and 17% TP with similar R0-resection rates (p = 0.722). Significant differences were observed in nodal positivity (PD:44%, DP:34%, TP:57%, p < 0.001) and mean-number of examined lymph nodes (PD:17.2 ± 10.4, DP:14.7 ± 10.5, TP:21.2 ± 11.0, p < 0.001). Furthermore, inadequate lymphadenectomy (< 12 nodes) was observed in 30%, 44%, and 19% of patients undergoing PD, DP, and TP, respectively (p < 0.001). Multivariable analysis yielded similar overall survival after DP (HR:0.83, 95%CI:0.63-1.11), while TP was associated with worse survival (HR:1.43, 95%CI:1.08-1.89) compared to PD. CONCLUSION While R0-rates are similar amongst all approaches, DP is associated with inadequate lymphadenectomy which may result in understaging disease. However, this had no negative influence on survival. In the premise that an oncological resection of the pancreatic neck tumor is feasible with a partial pancreatectomy, no benefit is observed by performing a TP.
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Affiliation(s)
- Ingmar F Rompen
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Joseph R Habib
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Elisabetta Sereni
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Thomas F Stoop
- Amsterdam UMC, Department of Surgery, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Julian Musa
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Steven M Cohen
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Russell S Berman
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Brian Kaplan
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - D Brock Hewitt
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Greg D Sacks
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Christopher L Wolfgang
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA
| | - Ammar A Javed
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA.
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12
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Bhatti ABH, Dar FS, Ahmed IN. Pancreaticoduodenectomy with Para-aortic Lymph Node Dissection for Periampullary Cancer. Indian J Surg Oncol 2024; 15:338-343. [PMID: 38817990 PMCID: PMC11133244 DOI: 10.1007/s13193-023-01866-x] [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: 11/20/2023] [Accepted: 12/11/2023] [Indexed: 06/01/2024] Open
Abstract
There is no consensus on the utility of para-aortic lymph node dissection (PALND) in patients undergoing pancreaticoduodenectomy (PD) for periampullary cancer. The objective of this study was to assess survival in patients who underwent PD with PALND for pancreatic (PAC) and non-pancreatic (non-PAC) adenocarcinoma. All patients who underwent PD and PALND between 2011 and 2019 were reviewed (n = 114). We looked at the impact of tumor type (PAC versus non-PAC) and pathologically confirmed PALN metastasis (PALNM) on overall survival (OS). Out of 114 patients, PALNM were pathologically confirmed in 17(14.9%) patients. Without PALND, pathological staging would be pN0 in1(0.8%), pN1 in 3(2.5%), and pN2 in 13(11.2%) patients. The 30-day mortality was 3(2.6%) and 65(57%) patients received adjuvant treatment. The 4-year OS for PAC and non-PAC was 9% and 39% (P = 0.001). Advanced nodal involvement (pN2) was seen in 14/17(82.4%) and 21/97(21.6%) patients with and without PALNM, respectively (P < 0.001). For PAC, 4-year OS for patients with pN0-N1, pN2, and PALNM was 12%, 8%, and not reached (P = 0.067). For non-PAC, 4-year OS was 45%, 19%, and 12% (P = 0.006). In patients with non-PAC, despite metastatic involvement of PALN, acceptable long-term survival can be achieved with curative resection. For PAC, survival benefit with curative resection remains questionable.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Department of HPB Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
- Department of Pathology, Shifa International Hospital, Islamabad, Pakistan
| | - Faisal Saud Dar
- Department of HPB Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Imran Nazer Ahmed
- Department of Pathology, Shifa International Hospital, Islamabad, Pakistan
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13
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Turner KM, Wilson GC, Patel SH, Ahmad SA. ASO Practice Guidelines Series: Management of Resectable, Borderline Resectable, and Locally Advanced Pancreas Cancer. Ann Surg Oncol 2024; 31:1884-1897. [PMID: 37980709 DOI: 10.1245/s10434-023-14585-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 10/29/2023] [Indexed: 11/21/2023]
Abstract
Pancreatic adenocarcinoma is an aggressive disease marked by high rates of both local and distant failure. In the minority of patients with potentially resectable disease, multimodal treatment paradigms have allowed for prolonged survival in an increasingly larger pool of well-selected patients. Therefore, it is critical for surgical oncologists to be abreast of current guideline recommendations for both surgical management and multimodal therapy for pancreas cancer. We discuss these guidelines, as well as the underlying data supporting these positions, to offer surgical oncologists a framework for managing patients with pancreatic adenocarcinoma.
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Affiliation(s)
- Kevin M Turner
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Gregory C Wilson
- Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Sameer H Patel
- Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Syed A Ahmad
- Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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14
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Goess R, Jäger C, Perinel J, Pergolini I, Demir E, Safak O, Scheufele F, Schorn S, Muckenhuber A, Adham M, Novotny A, Ceyhan GO, Friess H, Demir IE. Lymph node examination and survival in resected pancreatic ductal adenocarcinoma: retrospective study. BJS Open 2024; 8:zrad125. [PMID: 38271272 PMCID: PMC10810280 DOI: 10.1093/bjsopen/zrad125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 09/12/2023] [Accepted: 10/01/2023] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND The minimum number of examined lymph nodes (ELN) required for adequate staging and best prediction of survival has not been established in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to investigate the influence of ELN on staging and survival in PDAC. METHODS Patients undergoing partial or total pancreatectomy for PDAC at two European university hospitals between 2007 and 2018 were retrospectively reviewed. Multivariate Cox regression model and survival analyses were performed to verify adequate staging. RESULTS Overall 341 (73 per cent) patients showed lymph node metastasis (N1/N2), whereas 125 (27 per cent) patients had no lymph node involvement (N0). With increasing number of ELN, the proportion of positive lymph nodes increased. The minimum number of ELN needed to detect lymph node involvement was 21. In multivariate analysis, examination of <21 lymph nodes was a significant negative predictor for survival. Examination of ≥21 ELN reversed this effect and ruled out possible misclassification. CONCLUSION The number of ELN affects survival in PDAC. Possible misclassification was identified when <21 lymph nodes were examined. Therefore, at least 21 lymph nodes must be examined to avoid false lymph node classification in all types of resection.
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Affiliation(s)
- Ruediger Goess
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany
| | - Carsten Jäger
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany
| | - Julie Perinel
- Department of Digestive Surgery, E. Herriot Hospital, Hospices civils de Lyon, Lyon, France
| | - Ilaria Pergolini
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany
| | - Elke Demir
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany
| | - Okan Safak
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany
| | - Florian Scheufele
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany
| | - Stephan Schorn
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany
| | - Alexander Muckenhuber
- Institute of Pathology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
| | - Mustapha Adham
- Department of Digestive Surgery, E. Herriot Hospital, Hospices civils de Lyon, Lyon, France
| | - Alexander Novotny
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
| | - Güralp O Ceyhan
- Department of General Surgery, HPB-Unit, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
| | - Helmut Friess
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany
| | - Ihsan Ekin Demir
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany
- Department of General Surgery, HPB-Unit, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
- Else Kröner Clinician Scientist Professorship for Translational Pancreatic Surgery, Munich, Germany
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15
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Miyazaki Y, Oda T, Shimomura O, Hashimoto S, Doi M, Takahashi K, Owada Y, Furuya K, Ogawa K, Ohara Y, Akashi Y, Enomoto T. Total Superior Mesenteric Artery Nerve Plexus Preservation During Pancreaticoduodenectomy for Pancreatic Cancer. World J Surg 2023; 47:2816-2824. [PMID: 37501009 DOI: 10.1007/s00268-023-07111-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/25/2023] [Indexed: 07/29/2023]
Abstract
BACKGROUND Superior mesenteric artery (SMA) nerve plexus (PLsma) dissection has been performed to achieve R0 resection in pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) in high-volume centers. However, full-extent PLsma preservation in PD is employed in our institution. The feasibility of the PLsma preservation strategy was investigated. METHODS Between January 2010 and December 2020, 156 patients underwent PLsma preservation PD for PDAC at our institution. Of these, 118 patients had resectable PDAC (R group) and 38 patients had borderline resectable artery (BR-A group). Clinical and oncological outcomes focusing on local recurrence, patient prognoses, and morbidities (including postoperative refractory diarrhea) were retrospectively analyzed and our postoperative outcomes were compared with those of other institutions. RESULTS Pathological R0 resection by PLsma preservation PD was achieved in 96 R group patients (81.4%) and 27 BR-A group patients (71.1%). The median postoperative hospital stay was 15.0 days in both groups. Local site-only recurrence was observed in 10.2% (12/118) of R-group and 10.5% (4/38) of BR-A-group patients, whereas distant site-only recurrence occurred in 21.2% (25/118) of R-group and 28.9% (11/38) of BR-A-group patients. Median survival times were 64.3 months (R group) and 35.4 months (BR-A group, p = 0.07). Median disease-free survival (DFS) times were 31.0 months (R group) and 12.0 months (BR-A group). No diarrhea requiring opioids was observed in either group. These results were equal or superior to those of PLsma dissection PD in other institutions. CONCLUSIONS PLsma preservation in PD was feasible compared to PLsma dissection in recurrence and overall survival.
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Affiliation(s)
- Yoshihiro Miyazaki
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Tatsuya Oda
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan.
| | - Osamu Shimomura
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Shinji Hashimoto
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Manami Doi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Kazuhiro Takahashi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yohei Owada
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Kinji Furuya
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Koichi Ogawa
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yusuke Ohara
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yoshimasa Akashi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Tsuyoshi Enomoto
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
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16
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Słodkowski M, Wroński M, Karkocha D, Kraj L, Śmigielska K, Jachnis A. Current Approaches for the Curative-Intent Surgical Treatment of Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2023; 15:cancers15092584. [PMID: 37174050 PMCID: PMC10177138 DOI: 10.3390/cancers15092584] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/24/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023] Open
Abstract
Radical resection is the only curative treatment for pancreatic cancer. However, only up to 20% of patients are considered eligible for surgical resection at the time of diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become the gold standard of treatment for resectable pancreatic cancer there are numerous ongoing trials aiming to compare the clinical outcomes of various surgical strategies (e.g., upfront surgery or neoadjuvant treatment with subsequent resection). Neoadjuvant treatment followed by surgery is considered the best approach in borderline resectable pancreatic tumors. Individuals with locally advanced disease are now candidates for palliative chemo- or chemoradiotherapy; however, some patients may become eligible for resection during the course of such treatment. When metastases are found, the cancer is qualified as unresectable. It is possible to perform radical pancreatic resection with metastasectomy in selected cases of oligometastatic disease. The role of multi-visceral resection, which involves reconstruction of major mesenteric veins, is well known. Nonetheless, there are some controversies in terms of arterial resection and reconstruction. Researchers are also trying to introduce personalized treatments. The careful, preliminary selection of patients eligible for surgery and other therapies should be based on tumor biology, among other factors. Such selection may play a key role in improving survival rates in patients with pancreatic cancer.
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Affiliation(s)
- Maciej Słodkowski
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrzębiec, Poland
| | - Marek Wroński
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Dominika Karkocha
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Leszek Kraj
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrzębiec, Poland
- Department of Oncology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Kaja Śmigielska
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Aneta Jachnis
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
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17
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Granieri S, Kersik A, Bonomi A, Frassini S, Bernasconi D, Paleino S, Germini A, Gjoni E, Cotsoglou C. The Role of Non-Peripancreatic Lymph Nodes in the Survival of Patients Suffering from Pancreatic Cancer of the Body and Tail: A Systematic Review and Meta-Analysis of High-Quality Studies. Cancers (Basel) 2023; 15:cancers15082322. [PMID: 37190250 DOI: 10.3390/cancers15082322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/12/2023] [Accepted: 04/13/2023] [Indexed: 05/17/2023] Open
Abstract
Lymph nodes (LNs)' metastases have a well-known detrimental impact on the survival outcomes of patients suffering from pancreatic cancer of the body and tail. However, the extent of the lymphadenectomy for this tumor location is still debated. The aim of this study was to systematically review the current literature to explore the incidence and the prognostic impact of non-peripancreatic lymph nodes (PLNs) in patients suffering from pancreatic cancer of the body and tail. A systematic review was conducted according to PRISMA and MOOSE guidelines. The primary endpoint was to assess the impact of non-PLNs on overall survival (OS). As a secondary endpoint, the pooled frequencies of different non-PLN stations' metastatic patterns according to tumor location were explored. Eight studies were included in data synthesis. An increased risk of death for patients with positive non-PLNs was detected (HR: 2.97; 95% CI: 1.81-4.91; p < 0.0001). Meta-analysis of proportions pointed out a 7.1% pooled proportion of nodal infiltration in stations 8-9. The pooled frequency for station 12 metastasis was 4.8%. LN stations 14-15 were involved in 11.4% of cases, whereas station 16 represented a site of metastasis in 11.5% of cases. Despite its potential beneficial effect on survival outcome, a systematic extended lymphadenectomy could not be recommended yet for patients suffering from PDAC of the body/tail.
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Affiliation(s)
- Stefano Granieri
- General Surgery Unit, ASST-Brianza, Vimercate Hospital, Via Santi Cosma e Damiano, 10, 20871 Vimercate, Italy
| | - Alessia Kersik
- General Surgery Residency Program, University of Milan, Via Festa del Perdono, 7, 20122 Milan, Italy
| | - Alessandro Bonomi
- General Surgery Residency Program, University of Milan, Via Festa del Perdono, 7, 20122 Milan, Italy
| | - Simone Frassini
- General Surgery Residency Program, University of Pavia, Corso Str. Nuova, 65, 27100 Pavia, Italy
- General Surgery Unit, Department of Surgery, Fondazione I.R.C.C.S. Policlinico San Matteo, Viale Camillo Golgi, 19, 27100 Pavia, Italy
| | - Davide Bernasconi
- Center of Biostatistics for Clinical Epidemiology, University of Milan-Bicocca, Via Cadore, 48, 20854 Monza, Italy
| | - Sissi Paleino
- General Surgery Unit, ASST-Brianza, Vimercate Hospital, Via Santi Cosma e Damiano, 10, 20871 Vimercate, Italy
| | - Alessandro Germini
- General Surgery Unit, ASST-Brianza, Vimercate Hospital, Via Santi Cosma e Damiano, 10, 20871 Vimercate, Italy
| | - Elson Gjoni
- General Surgery Unit, ASST-Brianza, Vimercate Hospital, Via Santi Cosma e Damiano, 10, 20871 Vimercate, Italy
| | - Christian Cotsoglou
- General Surgery Unit, ASST-Brianza, Vimercate Hospital, Via Santi Cosma e Damiano, 10, 20871 Vimercate, Italy
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18
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de Geus SWL, Sachs TE. A Paradigm Shifts: Neoadjuvant Therapy for Clearly Resectable Pancreatic Cancer. Ann Surg Oncol 2023; 30:3427-3436. [PMID: 36869916 DOI: 10.1245/s10434-023-13281-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 02/12/2023] [Indexed: 03/05/2023]
Abstract
Over the past decade, neoadjuvant therapy has become the standard of care for patients with borderline resectable and locally advanced pancreatic cancer. The surgical community remains divided regarding the value of neoadjuvant therapy for patients who present with clearly resectable disease. Thus far, randomized controlled trials comparing neoadjuvant therapy with conventional upfront surgical strategies for patients with clearly resectable pancreatic cancer have been plagued by poor accrual, and are often underpowered. Nonetheless, meta-analyses of the results of these trials suggest that neoadjuvant therapy can be offered as an acceptable standard of care for patients with clearly resectable pancreatic cancer. Previous trials used neoadjuvant gemcitabine, but more recent studies have demonstrated superior survival for patients who were able to tolerate neoadjuvant FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan hydrochloride, and oxaliplatin). The increased utilization of FOLFIRINOX may be shifting the treatment paradigm in favor of neoadjuvant therapy among patients with clearly resectable disease. Randomized controlled trials assessing the value of neoadjuvant FOLFIRINOX in clearly resectable pancreatic cancer, which are expected to provide more conclusive recommendations, are still ongoing. This review outlines the rationale, considerations, and current level of evidence for the use of neoadjuvant therapy in patients with clearly resectable pancreatic cancer.
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Affiliation(s)
- Susanna W L de Geus
- Department of Surgical Oncology, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA
| | - Teviah E Sachs
- Department of Surgical Oncology, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
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19
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Lee KF, Lok HT, Fung AKY, Kung JWC, Lo EYJ, Chong CCN, Wong J, Ng KKC, Lai PBS. The Impact of Involved Resection Margin on Recurrence and Survival After Pancreaticoduodenectomy for Periampullary Carcinoma, with Emphasis on Pancreatic Head Carcinoma. World J Surg 2023; 47:717-728. [PMID: 36335279 DOI: 10.1007/s00268-022-06816-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2022] [Indexed: 11/08/2022]
Abstract
BACKGROUND The supposed adverse effect of involved resection margin during pancreaticoduodenectomy (PD) for periampullary carcinoma or pancreatic head carcinoma (CaP) on long-term oncological outcomes is still inconclusive. METHODS This is a retrospective study on periampullary carcinoma undergoing PD. Patients with R0 (margin clear) resection were compared to patients with R1 (microscopically directly involved margin) resection. Patients with gross involved margin (R2 resection) were excluded. Long-term oncological outcomes measured included incidence and site of recurrent disease, overall survival (OS) and disease-free survival (DFS). A subgroup analysis was made on patients with CaP. RESULTS Between January 2003 and December 2019, 203 PD were identified for present study. The incidence of R1 resection was common (12% in periampullary carcinoma and 20% in CaP). In periampullary carcinoma, R1 resection had greater proportion of CaP, lesser proportion of carcinoma of ampulla (CaA), more perineural invasion, more lymph node (LN) metastasis. R1 group had a shorter OS and DFS, but no difference in the incidence and site of recurrent disease. In the subgroup of CaP (91 patients), R1 group did not differ from R0 group except for more LN metastasis. There was no difference in incidence and site of recurrent disease, OS and DFS. On multivariable analysis, R1 resection was not an independent factor for OS and DFS for periampullary carcinoma or for CaP only. CONCLUSION Involved resection margin was not uncommon. It was not associated with higher incidence of recurrent disease including local recurrence, and was not an independent prognosticator for OS and DFS.
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Affiliation(s)
- Kit-Fai Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China.
| | - Hon-Ting Lok
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Andrew K Y Fung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Janet W C Kung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Eugene Y J Lo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Charing C N Chong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - John Wong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Kelvin K C Ng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Paul B S Lai
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
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20
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Ghukasyan R, Banerjee S, Childers C, Labora A, McClintick D, Girgis M, Varley P, Dann A, Donahue T. Higher Numbers of Examined Lymph Nodes Are Associated with Increased Survival in Resected, Treatment-Naïve, Node-Positive Esophageal, Gastric, Pancreatic, and Colon Cancers. J Gastrointest Surg 2023:10.1007/s11605-023-05617-9. [PMID: 36854990 DOI: 10.1007/s11605-023-05617-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 01/22/2023] [Indexed: 03/02/2023]
Abstract
BACKGROUND OR PURPOSE The role of extended lymphadenectomy as part of resection for lymph node (LN)-positive gastrointestinal (GI) malignancies remains controversial with no clear clinical guidance. The purpose of this retrospective study is to determine whether the number of LNs examined as part of GI malignancy resections affects overall survival (OS) among patients with node-positive esophageal, gastric, pancreatic, and colon cancers. METHODS Participants with LN-positive GI cancers who were diagnosed between 2004 and 2015 and underwent oncologic resections were selected from National Cancer Database (NCDB). The primary predictor was the number of examined LNs categorized in tertiles. The effect on OS was measured by hazard ratio (HR) derived from multivariate Cox regression analyses. RESULTS From 2004 to 2015, 1877, 10,086, 18,193, and 102,500 patients with LN-positive esophageal, gastric, pancreatic, and colon adenocarcinomas who did not receive neoadjuvant treatment and underwent oncologic tumor resection were registered in the NCDB. Using multivariate Cox proportional hazard modeling, greater LNs examined in surgically resected LN-positive GI cancers were found to be associated with increased OS for all histologies. This association was the strongest (as compared to the lowest tertile) for gastric cancer (middle tertile: HR = 0.91, 95% CI, 0.86-0.96, p = 0.001; highest tertile: HR = 0.73, 95% CI, 0.69-0.78, p < 0.001), followed by colon (highest tertile: HR = 0.86, 95% CI, 0.84-0.88, p < 0.001), esophageal (highest tertile: HR = 0.83, 95% CI, 0.72-0.95, p = 0.01), and pancreatic (highest tertile: HR = 0.93, 95% CI, 0.89-0.98, p = 0.002) cancers. DISCUSSION AND CONCLUSION In patients with surgically resected node-positive GI malignancies who did not receive neoadjuvant systemic therapy, a higher number of examined LNs is associated with increased OS. This association is the strongest for gastric cancer, followed by colon, esophageal, and pancreatic cancers respectively.
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Affiliation(s)
- Razmik Ghukasyan
- Department of Surgery, David Geffen School of Medicine, University of California, 54-117 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA
| | - Sudeep Banerjee
- Department of Surgery, David Geffen School of Medicine, University of California, 54-117 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA
- Division of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Christopher Childers
- Department of Surgery, David Geffen School of Medicine, University of California, 54-117 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA
- Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Amanda Labora
- Department of Surgery, David Geffen School of Medicine, University of California, 54-117 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA
| | - Daniel McClintick
- David Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Mark Girgis
- Department of Surgery, David Geffen School of Medicine, University of California, 54-117 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA
| | - Patrick Varley
- Department of Surgery, University of Wisconsin School of Medicine, Madison, WI, USA
| | - Amanda Dann
- Department of Surgery, David Geffen School of Medicine, University of California, 54-117 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA
- Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Timothy Donahue
- Department of Surgery, David Geffen School of Medicine, University of California, 54-117 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA.
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21
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Lin Q, Zheng S, Yu X, Chen M, Zhou Y, Zhou Q, Hu C, Gu J, Xu Z, Wang L, Liu Y, Liu Q, Wang M, Li G, Cheng H, Zhou D, Liu G, Fu Z, Long Y, Li Y, Wang W, Qin R, Li Z, Chen R. Standard pancreatoduodenectomy versus extended pancreatoduodenectomy with modified retroperitoneal nerve resection in patients with pancreatic head cancer: a multicenter randomized controlled trial. Cancer Commun (Lond) 2023; 43:257-275. [PMID: 36579790 PMCID: PMC9926959 DOI: 10.1002/cac2.12399] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 12/11/2022] [Accepted: 12/14/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The extent of pancreatoduodenectomy for pancreatic head cancer remains controversial, and more high-level clinical evidence is needed. This study aimed to evaluate the outcome of extended pancreatoduodenectomy (EPD) with retroperitoneal nerve resection in pancreatic head cancer. METHODS This multicenter randomized trial was performed at 6 Chinese high-volume hospitals that enrolled patients between October 3, 2012, and September 21, 2017. Four hundred patients with stage I or II pancreatic head cancer and without specific pancreatic cancer treatments (preoperative chemotherapy or chemoradiation) within three months were randomly assigned to undergo standard pancreatoduodenectomy (SPD) or EPD, with the latter followed by dissection of additional lymph nodes (LNs), nerves and soft tissues 270° on the right side surrounding the superior mesenteric artery and celiac axis. The primary endpoint was overall survival (OS) by intention-to-treat (ITT). The secondary endpoints were disease-free survival (DFS), mortality, morbidity, and postoperative pain intensity. RESULTS The R1 rate was slightly lower with EPD (8.46%) than with SPD (12.56%). The morbidity and mortality rates were similar between the two groups. The median OS was similar in the EPD and SPD groups by ITT in the whole study cohort (23.0 vs. 20.2 months, P = 0.100), while the median DFS was superior in the EPD group (16.1 vs. 13.2 months, P = 0.031). Patients with preoperative CA19-9 < 200.0 U/mL had significantly improved OS and DFS with EPD (EPD vs. SPD, 30.8 vs. 20.9 months, P = 0.009; 23.4 vs. 13.5 months, P < 0.001). The EPD group exhibited significantly lower locoregional (16.48% vs. 35.20%, P < 0.001) and mesenteric LN recurrence rates (3.98% vs. 10.06%, P = 0.022). The EPD group exhibited less back pain 6 months postoperation than the SPD group. CONCLUSIONS EPD for pancreatic head cancer did not significantly improve OS, but patients with EPD treatment had significantly improved DFS. In the subgroup analysis, improvements in both OS and DFS in the EPD arm were observed in patients with preoperative CA19-9 < 200.0 U/mL. EPD could be used as an effective surgical procedure for patients with pancreatic head cancer, especially those with preoperative CA19-9 < 200.0 U/mL.
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22
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James NE, Kalakouti E, Chidambaram S, Gall TMH, Sodergren MH. Patient-Reported Quality of Life After Pancreatic and Liver Surgery. PATIENT REPORTED OUTCOMES AND QUALITY OF LIFE IN SURGERY 2023:121-145. [DOI: 10.1007/978-3-031-27597-5_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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23
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Lyu SC, Wang HX, Liu ZP, Wang J, Huang JC, He Q, Lang R. Clinical value of extended lymphadenectomy in radical surgery for pancreatic head carcinoma at different T stages. World J Gastrointest Surg 2022; 14:1204-1218. [PMID: 36504521 PMCID: PMC9727567 DOI: 10.4240/wjgs.v14.i11.1204] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 08/27/2022] [Accepted: 10/12/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND As the lymph-node metastasis rate and sites vary among pancreatic head carcinomas (PHCs) of different T stages, selective extended lymphadenectomy (ELD) performance may improve the prognosis of patients with PHC.
AIM To investigate the effect of ELD on the long-term prognosis of patients with PHC of different T stages.
METHODS We analyzed data from 216 patients with PHC who underwent surgery at our hospital between January 2011 and December 2021. The patients were divided into extended and standard lymphadenectomy (SLD) groups according to extent of lymphadenectomy and into T1, T2, and T3 groups according to the 8th edition of the American Joint Committee on Cancer’s staging system. Perioperative data and prognoses were compared among groups. Risk factors associated with prognoses were identified through univariate and multivariate analyses.
RESULTS The 1-, 2- and 3-year overall survival (OS) rates in the extended and SLD groups were 69.0%, 39.5%, and 26.8% and 55.1%, 32.6%, and 22.1%, respectively (P = 0.073). The 1-, 2- and 3-year disease-free survival rates in the extended and SLD groups of patients with stage-T3 PHC were 50.3%, 25.1%, and 15.1% and 22.1%, 1.7%, and 0%, respectively (P = 0.025); the corresponding OS rates were 65.3%, 38.1%, and 21.8% and 36.1%, 7.5%, and 0%, respectively (P = 0.073). Multivariate analysis indicated that portal vein invasion and lymphadenectomy extent were risk factors for prognosis in patients with stage-T3 PHC.
CONCLUSION ELD may improve the prognosis of patients with stage-T3 PHC and may be of benefit if performed selectively.
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Affiliation(s)
- Shao-Cheng Lyu
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Han-Xuan Wang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Ze-Ping Liu
- School of Biomedicine, Bejing City University, Beijing 100084, China
| | - Jing Wang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Jin-Can Huang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Qiang He
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Ren Lang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
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24
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Konishi T, Takano S, Furukawa K, Takayashiki T, Kuboki S, Suzuki D, Sakai N, Hosokawa I, Mishima T, Ohtsuka M. Impact of resection margin status on survival after operation for pancreatic head cancer with extrapancreatic nerve plexus invasion. J Surg Oncol 2022; 126:1038-1047. [PMID: 35796724 DOI: 10.1002/jso.27003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 06/15/2022] [Accepted: 06/26/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Extrapancreatic nerve plexus (PL) invasion of pancreatic ductal adenocarcinoma (PDAC) is an important factor for determining resectability and surgical method. We sought to clarify the characteristics of PDAC with PL invasion and clinical impact of the resection margin status on prognosis for PDAC with PL invasion. METHODS A total of 242 patients with pancreatic head cancer who underwent pancreatectomy were evaluated. Clinicopathological data and patient survival were analyzed. RESULTS Pathological PL invasion was observed in 68 patients (28.1%). Patients with PL invasion had significantly shorter disease-free survival (DFS) and showed trends toward worse overall survival (OS) than those without PL invasion. While multivariate analysis revealed that PL invasion was not an independent prognostic factor, PL invasion was associated with extensive venous invasion and a high percentage of lymph node metastases, both of which were independent factors affecting DFS and OS. Among patients with PL invasion, there was no significant difference in DFS and OS between the R0 and R1 resection groups. CONCLUSIONS PL invasion is a common pathological feature of aggressive PDAC with high propensity for invasiveness and metastatic potential. The microscopic resection margin status may not affect the survival of pancreatic head cancer patients with PL invasion.
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Affiliation(s)
- Takanori Konishi
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Shigetsugu Takano
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Katsunori Furukawa
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Tsukasa Takayashiki
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Satoshi Kuboki
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Daisuke Suzuki
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Nozomu Sakai
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Isamu Hosokawa
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Takashi Mishima
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
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25
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Langversion 2.0 – Dezember 2021 – AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e812-e909. [PMID: 36368658 DOI: 10.1055/a-1856-7346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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26
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Malleo G, Maggino L, Qadan M, Marchegiani G, Ferrone CR, Paiella S, Luchini C, Mino-Kenudson M, Capelli P, Scarpa A, Lillemoe KD, Bassi C, Castillo CFD, Salvia R. Reassessment of the Optimal Number of Examined Lymph Nodes in Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma. Ann Surg 2022; 276:e518-e526. [PMID: 33177357 DOI: 10.1097/sla.0000000000004552] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The aim of this study was to reappraise the optimal number of examined lymph nodes (ELNs) in pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA The well-established threshold of 15 ELNs in PD for PDAC is optimized for detecting 1 positive node (PLN) per the previous 7th edition of the American Joint Committee on Cancer (AJCC) staging manual. In the framework of the 8th edition, where at least 4 PLN are needed for an N2 diagnosis, this threshold may be inadequate for accurate staging. METHODS Patients who underwent upfront PD at 2 academic institutions between 2000 and 2016 were analyzed. The optimal ELN threshold was defined as the cut-point associated with a 95% probability of identifying at least 4 PLNs in N2 patients. The results were validated addressing the N-status distribution and stage migration. RESULTS Overall, 1218 patients were included. The median number of ELN was 26 (IQR 17-37). ELN was independently associated with N2-status (OR 1.27, P < 0.001). The estimated optimal threshold of ELN was 28. This cut-point enabled improved detection of N2 patients and stage III disease (58% vs 37%, P = 0.001). The median survival was 28.6 months. There was an improved survival in N0/N1 patients when ELN exceeded 28, suggesting a stage migration effect (47 vs 29 months, adjusted HR 0.649, P < 0.001). In N2 patients, this threshold was not associated with survival on multivariable analysis. CONCLUSION Examining at least 28 LN in PD for PDAC ensures optimal staging through improved detection of N2/stage III disease. This may have relevant implications for benchmarking processes and quality implementation.
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Affiliation(s)
- Giuseppe Malleo
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Laura Maggino
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Giovanni Marchegiani
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Salvatore Paiella
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Luchini
- Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Paola Capelli
- Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
| | - Aldo Scarpa
- Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Claudio Bassi
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | | | - Roberto Salvia
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
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27
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Wang W, Lou W, Xu Z, Chen H, Shen Z, Deng X, Peng C, Liu Y, Shen B. Long-term outcomes of standard versus extended lymphadenectomy in pancreatoduodenectomy for pancreatic ductal adenocarcinoma: A Chinese multi-center prospective randomized controlled trial. J Adv Res 2022:S2090-1232(22)00213-2. [PMID: 36198383 DOI: 10.1016/j.jare.2022.09.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 08/30/2022] [Accepted: 09/25/2022] [Indexed: 10/06/2022] Open
Abstract
INTRODUCTION The value of extended lymphadenectomy in pancreatoduodenectomy (PD) has been discussed by five randomized controlled studies. However, the limitations in the studies made their conclusions not sufficiently reliable. OBJECTIVES This multi-center randomized controlled study was designed to clarify the efficacy of extended lymphadenectomy in PD for pancreatic ductal adenocarcinoma (PDAC). METHODS From December 2016 to October 2018, 170 consecutive patients undergoing PD were enrolled and randomized to standard or extended lymphadenectomy for the treatment of PDAC from three high-volume institutions in China. Demographic, pathological characteristics and survival data of these patients were collected and analyzed. No neoadjuvant treatment was performed. The primary endpoint was the 3-year overall survival. RESULTS For all patients, the 3-year survival rate was 25.88%. There was no between-group difference in 3-year survival rate (27.16% vs 24.72% p=0.717). The median survival time for the standard group was 18 months, while for the extended group it was 15 months. The demographic and pathological characteristics were similar between groups. More positive lymph nodes could be found in the extended group (2.34 ± 3.46 vs 1.41 ± 2.12, p=0.035), which led to nodule stage migration. All patients received chemotherapy. But patients in extended group were more likely to fail in completion of all-cycles chemotherapy before recurrence (31.46% vs 17.28%, p=0.032). Incomplete chemotherapy before recurrence, higher N status and abnormal CA125 were independent risk factors for 1-year survival (p<0.001, 95% CI 0.076-0.368; p=0.017, 95% CI 1.113-3.021; p=0.021, 95% CI 1.136-4.960, respectively), which was higher in the standard group (75.31% vs 58.43%, p=0.020). CONCLUSION The extended lymphadenectomy in PD did not improve the long-term survival in patients with PDAC. Patients with extended lymphadenectomy had a worse 1-year overall survival. However, the nodule stage migration facilitated by the extended lymphadenectomy contributed to the precise tumor staging.
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Affiliation(s)
- Weishen Wang
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes (Shanghai), China; Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhiwei Xu
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes (Shanghai), China; Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Haoda Chen
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes (Shanghai), China; Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ziyun Shen
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes (Shanghai), China; Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaxing Deng
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes (Shanghai), China; Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chenghong Peng
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes (Shanghai), China; Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Yingbin Liu
- Department of General Surgery, Renji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Baiyong Shen
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes (Shanghai), China; Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
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28
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Surgical treatment of pancreatic cancer: Currently debated topics on morbidity, mortality, and lymphadenectomy. Surg Oncol 2022; 45:101858. [DOI: 10.1016/j.suronc.2022.101858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 09/07/2022] [Accepted: 09/26/2022] [Indexed: 11/21/2022]
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Appropriate Lymph Node Dissection Sites for Cancer in the Body and Tail of the Pancreas: A Multicenter Retrospective Study. Cancers (Basel) 2022; 14:cancers14184409. [PMID: 36139569 PMCID: PMC9497245 DOI: 10.3390/cancers14184409] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/01/2022] [Accepted: 09/08/2022] [Indexed: 11/17/2022] Open
Abstract
Distal pancreatectomy (DP) with lymphadenectomy is the standard surgery for pancreatic body-tail cancer. However, the optimal lymph node (LN) dissection area for DP remains controversial. Thus, we evaluated the frequency and patterns of LN metastasis based on the tumor site. In this multicenter retrospective study, we examined 235 patients who underwent DP for pancreatic cancer. Tumor sites were classified as confined to the pancreatic body (Pb) or pancreatic tail (Pt). The efficacy index (EI) was calculated by multiplying the frequency of metastasis to each LN station by the five-year survival rate of patients with metastasis to that station. LN metastasis occurred in 132/235 (56.2%) of the patients. Patients with Pb tumors showed no metastasis to the splenic hilum LN. Distal splenic artery LNs and anterosuperior/posterior common hepatic artery LNs did not benefit from dissection for Pb and Pt tumors, respectively. In multivariate analysis, splenic artery LN metastasis was identified as an independent predictor of poor overall survival in patients with pancreatic body-tail cancer. In conclusion, differences in metastatic LN sites were evident in pancreatic body-tail cancers confined to the Pb or Pt. Spleen-preserving pancreatectomy might be feasible for Pb cancer.
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Barrak D, Villano AM, Moslim MA, Hopkins SE, Lefton MD, Ruth K, Reddy SS. Total Neoadjuvant Treatment for Pancreatic Ductal Adenocarcinoma Is Associated With Limited Lymph Node Yield but Improved Ratio. J Surg Res 2022; 280:543-550. [PMID: 36096019 DOI: 10.1016/j.jss.2022.08.002] [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: 08/26/2021] [Revised: 07/09/2022] [Accepted: 08/16/2022] [Indexed: 10/14/2022]
Abstract
INTRODUCTION The lymph node yield (LNY) and lymph node ratio (LNR) of nodal metastases following pancreatoduodenectomy (PD) have been reported as prognostic parameters in patients with pancreatic ductal adenocarcinoma (PDAC). However, they have not been compared in the setting of various neoadjuvant therapy modalities. METHODS A single institutional retrospective study identified 134 patients diagnosed with resectable, BLR- and LA-PDAC who underwent PD at Fox Chase Cancer Center between 2010 and 2019. Patients were categorized based on first-line treatment as follows: surgery first (SF), total neoadjuvant therapy (TNT), and single modality neoadjuvant therapy (SMNT). The histopathological reports of the surgical specimens were examined to obtain LNY and determine the counts of lymph nodes with metastases. Subsequently, LNR was calculated as the number of positive lymph nodes divided by the number of lymph nodes examined. RESULTS Overall, 49, 38, 27, 12, and 8 patients underwent SF approach, SMNT, incomplete TNT, induction TNT, and consolidation TNT, respectively. There was no difference in R0 resection and vascular resection between the groups (P = 0.096 and 0.794, respectively). The median counts of LNY were 22, 15, 21, 11.5, and 10, respectively (P < 0.001). The average LNR was 0.16, 0.07, 0.03, 0.02, and 0.02, respectively (P < 0.001). There were statistically significant differences in overall survival in the TNT groups (log-rank test P = 0.030). CONCLUSIONS PDAC patients who undergo the TNT modality exhibit lower LNY and improved LNR compared with the SF approach and SMNT neoadjuvant therapy groups. This is likely explained by the increased treatment response and lymph node obliteration associated with the TNT approach. Our results question the minimal requirement of 11-18 harvested lymph nodes for PD following TNT.
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Affiliation(s)
- Dany Barrak
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Anthony M Villano
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Maitham A Moslim
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Steven E Hopkins
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Max D Lefton
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Karen Ruth
- Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Sanjay S Reddy
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
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James NE, Chidambaram S, Gall TM, Sodergren MH. Quality of life after pancreatic surgery - A systematic review. HPB (Oxford) 2022; 24:1223-1237. [PMID: 35304039 DOI: 10.1016/j.hpb.2022.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/18/2022] [Accepted: 02/23/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Surgery for patients with pancreatic cancer carries a high risk of major post-operative complications and only marginally improves overall survival. This review aims to assess the impact of surgical resection on health-related quality of life (HRQOL) of pancreatic cancer patients. METHODS A systematic review of the literature was performed according to the PRISMA guidelines. All studies assessing QOL using validated questionnaires in pancreatic cancer patients undergoing surgical resection were included. RESULTS Twenty-two studies were assessed. Patients reported a decrease in physical, social and global scales within the first 3 months after surgery. These values showed improvement and were comparable to baseline values by 6 months. Recovery in emotional functioning towards baseline figures was demonstrated in the first 3 months post-operatively. Symptom scales including pain, fatigue and diarrhoea deteriorated after surgery, but reverted to baseline after 3-6 months. CONCLUSIONS Surgical resection for pancreatic cancer has short-term negative impact on QOL. In the longer term, this will improve and eventually recover to baseline values after 6 months. Knowledge on the impact of surgery on QOL of pancreatic cancer patients is necessary to facilitate decision-making and tailoring of surgical techniques to the individual patient.
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Affiliation(s)
- Nicole E James
- Imperial College London, Exhibition Road, South Kensington, London SWC2AZ, UK
| | - Swathikan Chidambaram
- Imperial College London, Exhibition Road, South Kensington, London SWC2AZ, UK; Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College, London W12 0HS, UK
| | - Tamara Mh Gall
- Imperial College London, Exhibition Road, South Kensington, London SWC2AZ, UK; Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College, London W12 0HS, UK
| | - Mikael H Sodergren
- Imperial College London, Exhibition Road, South Kensington, London SWC2AZ, UK; Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College, London W12 0HS, UK.
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Matsuki R, Okano N, Hasui N, Kawaguchi S, Momose H, Kogure M, Suzuki Y, Nagashima F, Sakamoto Y. Trends in the surgical treatment for pancreatic cancer in the last 30 years. Biosci Trends 2022; 16:198-206. [PMID: 35732435 DOI: 10.5582/bst.2022.01250] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Pancreatic cancer has the poorest prognosis among digestive cancers. During the 1990s, the 5-year survival rate of surgical patients with pancreatic cancer was 14% in Japan. However, survival rates have increased to 40% in the 2020s due to the refinement of surgical procedures and the introduction of perioperative chemotherapy. Several pivotal randomized controlled trials have played an indispensable role to establish each standard treatment strategy. Resectability of pancreatic cancer can be classified into resectable, borderline resectable, and unresectable based on the anatomic configuration, and multidisciplinary treatment strategies for each classification have been revised rapidly. Investigation of superior perioperative adjuvant treatments for resectable and borderline resectable pancreatic cancer and the establishment of optimal conversion surgery for unresectable pancreatic cancer are the progressive subjects.
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Affiliation(s)
- Ryota Matsuki
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Tokyo, Japan
| | - Naohiro Okano
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan
| | - Nobuhiro Hasui
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Tokyo, Japan
| | - Shohei Kawaguchi
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Tokyo, Japan
| | - Hirokazu Momose
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Tokyo, Japan
| | - Masaharu Kogure
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Tokyo, Japan
| | - Yutaka Suzuki
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Tokyo, Japan
| | - Fumio Nagashima
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan
| | - Yoshihiro Sakamoto
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Tokyo, Japan
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Pu N, Yin H, Chen Q, Zhang J, Wu W, Lou W. Current status and future perspectives of clinical research in pancreatic cancer: Establishment of evidence by science. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:741-757. [PMID: 34514722 DOI: 10.1002/jhbp.1045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 08/18/2021] [Accepted: 08/27/2021] [Indexed: 11/09/2022]
Abstract
Pancreatic cancer is one of the most aggressive diseases in the world due to a lack of early detection, leading to an overall 5-year survival of only 10%. In recent years, clinical trials targeted pancreatic cancer in efforts to improve survival. These studies introduce new technologies, concepts, and evidence which have instilled new optimism for improving prognosis. This review summarizes the current status of the recent (5-year) clinical trials and describes contemporary research on pancreatic cancer, including surgical technology, diagnostic skills, traditional chemoradiotherapy, neoadjuvant chemotherapy, immunotherapy, targeted therapy, and precision medicine. Then, the future trend and direction of clinical trials on pancreatic cancer are discussed.
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Affiliation(s)
- Ning Pu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hanlin Yin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qiangda Chen
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jicheng Zhang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenchuan Wu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
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Minagawa T, Sugiura T, Okamura Y, Ito T, Yamamoto Y, Ashida R, Ohgi K, Sasaki K, Uesaka K. Clinical implications of lymphadenectomy for invasive ductal carcinoma of the body or tail of the pancreas. Ann Gastroenterol Surg 2022; 6:531-542. [PMID: 35847444 PMCID: PMC9271019 DOI: 10.1002/ags3.12551] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 12/16/2021] [Accepted: 01/05/2022] [Indexed: 01/23/2023] Open
Abstract
Aim The appropriate extent of lymphadenectomy for pancreatic cancer of the body/tail has not been standardized worldwide. The present study evaluated the optimal extent of harvesting lymph nodes. Methods Patients who underwent distal pancreatectomy for invasive ductal carcinoma of the pancreas between 2007 and 2018 were retrospectively reviewed. Patients were subclassified into three groups depending on the tumor location: pancreatic body (Pb), proximal pancreatic tail (Ptp), and distal pancreatic tail (Ptd). The pancreatic tail was further divided into even sections of Ptp and Ptd. Patterns of lymph node metastasis and the impact of lymph node metastasis on the prognosis were examined. Results A total of 120 patients were evaluated. Fifty-eight patients had a tumor in the Pb, 38 in the Ptp, and 24 in the Ptd. No patients with a Ptd tumor had metastasis beyond the peripancreatic and splenic hilar lymph nodes (LN-PSH). All patients with metastasis to the lymph nodes along the common hepatic artery (LN-CHA) or along the left lateral superior mesenteric artery (LN-SMA) also had metastasis to the LN-PSH. Recurrence after surgery occurred significantly earlier in this population. In a multivariate analysis, metastasis to the LN-CHA or LN-SMA (hazard ratio [HR] 3.3; P = .04) was an independent risk factor for overall survival. Furthermore, high levels of preoperative serum CA19-9 (HR 10.9; P = .013) were a predictive factor for metastasis to the LN-CHA or LN-SMA. Conclusions Metastasis to the LN-CHA or LN-SMA was rare but a significant prognostic factor in patients with pancreatic body/tail cancer.
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Affiliation(s)
- Takuya Minagawa
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Teiichi Sugiura
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Yukiyasu Okamura
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Takaaki Ito
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Yusuke Yamamoto
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Ryo Ashida
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Katsuhisa Ohgi
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Keiko Sasaki
- Division of PathologyShizuoka Cancer CenterShizuokaJapan
| | - Katsuhiko Uesaka
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
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Hsu DS, Kumar NS, Le ST, Chang AL, Kazantsev G, Spitzer AL, Peng PD, Chang CK. Centralization of pancreatic cancer treatment within an integrated healthcare system improves overall survival. Am J Surg 2022; 223:1035-1039. [PMID: 34607651 DOI: 10.1016/j.amjsurg.2021.09.036] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 09/11/2021] [Accepted: 09/29/2021] [Indexed: 01/11/2023]
Abstract
BACKGROUND Higher-volume centers for pancreatic cancer surgeries have been shown to have improved outcomes such as length of stay. We examined how centralization of pancreatic cancer care within a regional integrated healthcare system improves overall survival. METHODS We conducted a retrospective study of 1621 patients treated for pancreatic cancer from February 2010 to December 2018. Care was consolidated into 4 Centers of Excellence (COE) in surgery, medical oncology, and other specialties. Descriptive statistics, bivariate analysis, Chi-square tests, and Kaplan-Meier analysis were performed. RESULTS Neoadjuvant chemotherapy use rose from 10% to 31% (p < .001). The median overall survival (OS) improved by 3 months after centralization (p < .001), but this did not reach significance on multivariate analysis. CONCLUSIONS Our results suggest that in a large integrated healthcare system, centralization improves overall survival and neoadjuvant therapy utilization for pancreatic cancer patients.
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Affiliation(s)
- Diana S Hsu
- University of California, San Francisco - East Bay Surgery, Highland Hospital, 1411 E 31st St, Q1C 22134, Oakland, CA, 94602, USA; Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA.
| | - Nikathan S Kumar
- University of California, San Francisco - East Bay Surgery, Highland Hospital, 1411 E 31st St, Q1C 22134, Oakland, CA, 94602, USA; Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - Sidney T Le
- University of California, San Francisco - East Bay Surgery, Highland Hospital, 1411 E 31st St, Q1C 22134, Oakland, CA, 94602, USA; Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - Alex L Chang
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - George Kazantsev
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - Austin L Spitzer
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - Peter D Peng
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
| | - Ching-Kuo Chang
- Department of Surgery, Kaiser Permanente-Oakland Medical Center, 3600 Broadway, Oakland, CA, 94611, USA
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36
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Pijnappel EN, Suurmeijer JA, Koerkamp BG, Kos M, Siveke JT, Salvia R, Ghaneh P, van Eijck CHJ, van Etten-Jamaludin FS, Abrams R, Brasiuniene B, Büchler MW, Casadei R, van Laethem JL, Berlin J, Boku N, Conroy T, Golcher H, Sinn M, Neoptolemos JP, van Tienhoven G, Besselink MG, Wilmink JW, van Laarhoven HWM. Consensus Statement on Mandatory Measurements for Pancreatic Cancer Trials for Patients With Resectable or Borderline Resectable Disease (COMM-PACT-RB): A Systematic Review and Delphi Consensus Statement. JAMA Oncol 2022; 8:929-937. [PMID: 35446336 DOI: 10.1001/jamaoncol.2022.0168] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Importance Pancreatic cancer is the third most common cause of cancer death; however, randomized clinical trials (RCTs) of survival in patients with resectable pancreatic cancer lack mandatory measures for reporting baseline and prognostic factors, which hampers comparisons between outcome measures. Objective To develop a consensus on baseline and prognostic factors to be used as mandatory measurements in RCTs of resectable and borderline resectable pancreatic cancer. Evidence Review We performed a systematic literature search of the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Embase for RCTs on resectable and borderline resectable pancreatic cancer with overall survival as the primary outcome. We produced a systematic summary of all baseline and prognostic factors identified in the RCTs. A Delphi panel that included 13 experts was surveyed to reach a consensus on mandatory and recommended baseline and prognostic factors. Findings The 42 RCTs that met inclusion criteria reported a total of 60 baseline and 19 prognostic factors. After 2 Delphi rounds, agreement was reached on 50 mandatory baseline and 20 mandatory prognostic factors for future RCTs, with a distinction between studies of neoadjuvant vs adjuvant treatment. Conclusion and Relevance This findings of this systematic review and international expert consensus have produced this Consensus Statement on Mandatory Measurements in Pancreatic Cancer Trials for Resectable and Borderline Resectable Disease (COMM-PACT-RB). The baseline and prognostic factors comprising the mandatory measures will facilitate better comparison across RCTs and eventually will enable improved clinical practice among patients with resectable and borderline resectable pancreatic cancer.
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Affiliation(s)
- Esther N Pijnappel
- Department of Medical Oncology, Cancer Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - J Annelie Suurmeijer
- Department of Surgery, Cancer Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Milan Kos
- Department of Medical Oncology, Cancer Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Jens T Siveke
- Institute for Developmental Cancer Therapeutics, West German Cancer Center, University Medicine Essen, Essen, Germany
- Division of Solid Tumor Translational Oncology, German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany
| | | | - Paula Ghaneh
- Department of Molecular and Clinical Cancer Medicine University of Liverpool, Liverpool, UK
| | | | | | - Ross Abrams
- Sharett Institute of Oncology, Hadassah Medical Center, Jerusalem, Israel
| | - Birute Brasiuniene
- Department of Medical Oncology, National Cancer Institute, Faculty of Medicine, Vilnius University, Lithuania
| | - Markus W Büchler
- Department of General Surgery, University of Heidelberg, Heidelberg, Germany
| | | | - Jean-Luc van Laethem
- Department of Gastroenterology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Jordan Berlin
- Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, US
| | - Narikazu Boku
- Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Thierry Conroy
- Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy, France
| | - Henriette Golcher
- Department of Surgery, University Hospital Erlangen, Erlangen, Germany
| | - Marianne Sinn
- Charite-Universitatsmedizin Berlin, CONKO study group, Berlin, Germany
- University Medical Center of Hamburg-Eppendorf, Hamburg, Germany
| | - John P Neoptolemos
- Department of General Surgery, University of Heidelberg, Heidelberg, Germany
| | - Geertjan van Tienhoven
- Department of Radiation Oncology, Cancer Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Johanna W Wilmink
- Department of Medical Oncology, Cancer Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Hanneke W M van Laarhoven
- Department of Medical Oncology, Cancer Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Kurzversion 2.0 – Dezember 2021, AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:991-1037. [PMID: 35671996 DOI: 10.1055/a-1771-6811] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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38
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Brunner M, Krautz C, Weber GF, Grützmann R. [Better Therapy for Pancreatic Cancer through More Radical Surgery?]. Zentralbl Chir 2022; 147:173-187. [PMID: 35378558 DOI: 10.1055/a-1766-7643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Despite advances in the treatment of pancreatic cancer, the survival of affected patients remains limited. A more radical surgical therapy could help to improve the prognosis, in particular by reducing the local recurrence rate, which is around 45% in patients with resected pancreatic cancer. In addition, patients with oligometastatic pancreatic cancer could also benefit from a more radical indication for surgery.Based on an analysis of the literature, important principles of pancreatic cancer surgery were examined.Even if even more radical surgical approaches such as an "extended" lymphadenectomy or a standard complete pancreatectomy do not bring any survival advantage, complete resection of the tumour (R0), a thorough locoregional lymphadenectomy and an adequate radical dissection in the area of the peripancreatic vessels including periarterial nerve plexuses should be the standard of pancreatic carcinoma resections. Whenever necessary to achieve an R0 resection, resections of the pancreas have to be extended, as well as additional venous vascular resections and multivisceral resections had to be performed. Simultaneous arterial vascular resections as part of pancreatic resections as well as surgical resections in oligometastatic patients should, however, be reserved for selected patients. These aspects of the surgical technique in pancreatic carcinoma mentioned above must not be neglected from the point of view of an "existing limited prognosis". On the contrary, they form the absolutely necessary basis in order to achieve good survival results in combination with system therapy. However, it may always be necessary to adapt these standards according to the age, comorbidities and wishes of the patient.
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Affiliation(s)
- Maximilian Brunner
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - Christian Krautz
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - Georg F Weber
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - Robert Grützmann
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen, Erlangen, Deutschland
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39
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Lee SE, Han SS, Kang CM, Kwon W, Paik KY, Song KB, Yang JD, Chung JC, Jeong CY, Kim SW. Korean Surgical Practice Guideline for Pancreatic Cancer 2021: A summary of evidence-based surgical approaches. Ann Hepatobiliary Pancreat Surg 2022; 26:1-16. [PMID: 35220285 PMCID: PMC8901981 DOI: 10.14701/ahbps.22-009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 02/17/2022] [Accepted: 02/17/2022] [Indexed: 11/17/2022] Open
Abstract
Pancreatic cancer is the eighth most common cancer and the fifth most common cause of cancer-related deaths in Korea. Despite the increasing incidence and high mortality rate of pancreatic cancer, there are no appropriate surgical practice guidelines for the current domestic medical situation. To enable standardization of management and facilitate improvements in surgical outcome, a total of 10 pancreatic surgical experts who are members of Korean Association of Hepato-Biliary-Pancreatic Surgery have developed new recommendations that integrate the most up-to-date, evidence-based research findings and expert opinions. This is an English version of the Korean Surgical Practice Guideline for Pancreatic Cancer 2021. This guideline includes 13 surgical questions and 15 statements. Due to the lack of high-level evidence, strong recommendation is almost impossible. However, we believe that this guideline will help surgeons understand the current status of evidence and suggest what to investigate further to establish more solid recommendations in the future.
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Affiliation(s)
- Seung Eun Lee
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea
| | - Sung-Sik Han
- Department of Surgery, National Cancer Center, Goyang, Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang Yeol Paik
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Do Yang
- Department of Surgery, Jeonbuk National University Medical School, Jeonju, Korea
| | - Jun Chul Chung
- Department of Surgery, Soon Chun Hyang University School of Medicine, Cheonan, Korea
| | - Chi-Young Jeong
- Department of Surgery, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Sun-Whe Kim
- Department of Surgery, National Cancer Center, Goyang, Korea
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40
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Long-Term Outcome of Patients with Postoperative Refractory Diarrhea After Tailored Nerve Plexus Dissection Around the Major Visceral Arteries During Pancreatoduodenectomy for Pancreatic Cancer. World J Surg 2022; 46:1172-1182. [PMID: 35119513 DOI: 10.1007/s00268-022-06457-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND For pancreatic ductal adenocarcinoma (PDAC) surgery, extended dissection of the nerve plexus (pl) around the superior mesenteric artery (SMA) or celiac artery (CA) is sometimes necessary. This consequently results in postoperative refractory diarrhea. This study aimed to evaluate the clinical impact of extended nerve plexus dissection around major arteries on postoperative diarrhea. METHODS Patients who underwent pancreatoduodenectomy (PD) for PDAC between January 2013 and December 2016 were included. The frequency of diarrhea (defined as a condition requiring opioid antidiarrheal drug for at least 6 months after surgery) and its short- and long-term outcomes were reviewed. RESULTS Of 200 consecutive patients who underwent PD, 78 (39.0%) developed postoperative refractory diarrhea (diarrhea group), and 73 of them (93.6%) underwent hemi-circumferential or more nerve dissection for SMA or CA; both plSMA and plCA dissection were associated with diarrhea. Borderline resectable artery (BR-A) PDAC was included more in the diarrhea group (32.0% vs. 13.1%, P = 0.001); however, the local recurrence rate in the diarrhea group was significantly lower than that in the non-diarrhea group (14.1% vs. 26.2%, P = 0.036). The completion of adjuvant chemotherapy and overall survival were comparable between the two groups. The pre-albumin level improved in 2 years, and 61.3% of patients with diarrhea could stop opioid antidiarrheal drugs within 3 years of surgery. CONCLUSIONS Although the frequency of diarrhea increased following nerve plexus dissection around arteries, diarrhea was controllable and resulted in a reduced local recurrence rate. Aggressive dissection of the nerve plexus may be justified for local disease control in BR-A PDAC.
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Karunakaran M, Barreto SG. Surgery for pancreatic cancer: current controversies and challenges. Future Oncol 2021; 17:5135-5162. [PMID: 34747183 DOI: 10.2217/fon-2021-0533] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 09/17/2021] [Indexed: 02/07/2023] Open
Abstract
Two areas that remain the focus of improvement in pancreatic cancer include high post-operative morbidity and inability to uniformly translate surgical success into long-term survival. This narrative review addresses specific aspects of pancreatic cancer surgery, including neoadjuvant therapy, vascular resections, extended pancreatectomy, extent of lymphadenectomy and current status of minimally invasive surgery. R0 resection confers longer disease-free survival and overall survival. Vascular and adjacent organ resections should be undertaken after neoadjuvant therapy, only if R0 resection can be ensured based on high-quality preoperative imaging, and that too, with acceptable post-operative morbidity. Extended lymphadenectomy does not offer any advantage over standard lymphadenectomy. Although minimally invasive distal pancreatectomies offers some short-term benefits over open distal pancreatectomy, safety remains a concern with minimally invasive pancreatoduodenectomy. Strict adherence to principles and judicious utilization of surgery within a multimodality framework is the way forward.
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Affiliation(s)
- Monish Karunakaran
- Department of Gastrointestinal Surgery, Gastrointestinal Oncology & Bariatric Surgery, Medanta Institute of Digestive & Hepatobiliary Sciences, Medanta-The Medicity, Gurugram 122001, India
- Department of Liver Transplantation & Regenerative Medicine, Medanta-The Medicity, Gurugram 122001, India
| | - Savio George Barreto
- College of Medicine & Public Health, Flinders University, South Australia, Australia
- Division of Surgery & Perioperative Medicine, Flinders Medical Center, Bedford Park, Adelaide, South Australia, Australia
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Ishida H, Ogura T, Takahashi A, Miyamoto R, Matsudaira S, Amikura K, Tanabe M, Kawashima Y. Optimal Region of Lymph Node Dissection in Distal Pancreatectomy for Left-Sided Pancreatic Cancer Based on Tumor Location. Ann Surg Oncol 2021; 29:2414-2424. [PMID: 34837132 DOI: 10.1245/s10434-021-11108-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 10/05/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND The optimal lymph node (LN) dissection for left-sided pancreatic cancer based on tumor location has remained unknown. In particular, the efficacy of LN dissection around the common hepatic artery and the celiac axis for distal tumors has not been established. This study was designed to elucidate the frequency and prognostic impact of LN metastasis, focusing on tumor location. METHODS Data from 110 patients with invasive pancreatic cancer who underwent distal pancreatectomy between 2007 and 2020 were collected. We used a quantitative value-the distance between the left side of the portal vein and the right side of tumor (DPT)-to define the tumor location. LN stations were divided into two groups: peripancreatic lymph nodes (PLN) and non-PLN. We then analyzed the frequency of LN metastasis based on the tumor location and prognostic factors. RESULTS Non-PLN metastasis was observed in 7.3% of patients. Non-PLN metastasis was found only in patients with a DPT < 20 mm. Patients with non-PLN metastasis exhibited a significantly worse prognosis than those with only-PLN metastasis (median survival time: 20.3 vs. 42.5 months, p = 0.048). Multivariate analysis for survival indicated that tumor size > 4 cm (hazard ratio [HR]: 2.23, p = 0.012) and metastasis in the non-PLN region (HR: 3.02, p = 0.015), and inability to undergo adjuvant chemotherapy (HR: 2.81, p = 0.0018) were also associated with poor prognosis. CONCLUSIONS Dissection of the non-PLN region can be avoided in selected patients with DPT ≥ 20 mm.
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Affiliation(s)
- Hiroyuki Ishida
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan.,Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
| | - Toshiro Ogura
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan. .,Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan.
| | - Amane Takahashi
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
| | - Ryoichi Miyamoto
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
| | - Shinichi Matsudaira
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
| | - Katsumi Amikura
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
| | - Minoru Tanabe
- Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
| | - Yoshiyuki Kawashima
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
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Wang J, Lyu SC, Zhu JQ, Li XL, Lang R, He Q. Extended lymphadenectomy benefits patients with borderline resectable pancreatic head cancer-a single-center retrospective study. Gland Surg 2021; 10:2910-2924. [PMID: 34804879 PMCID: PMC8575711 DOI: 10.21037/gs-21-201] [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: 03/30/2021] [Accepted: 09/09/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND Whether standard lymphadenectomy or extended lymphadenectomy should be performed is still under debate during pancreaticoduodenectomy (PD). We aimed to compare their morbidity and mortality rates among patients with pancreatic head cancer (PHC). METHODS In this retrospective study, a total of 322 patients were enrolled. According to the scope of intraoperative lymph node dissection, patients were divided into extended lymphadenectomy group (n=120) and standard lymphadenectomy group (n=202). Based on the resectability of the tumor, there were 198 cases of resectable PHC and 124 cases of borderline resectable PHC, respectively, in which further stratified analysis was carried out according to the extent of lymph node dissection. RESULTS All patients completed the operation successfully, with a perioperative morbidity rate of 27.9% and mortality rate of 0.9%. As for the overall patients, patients in the extended lymphadenectomy group had higher neutrophil-to-lymphocyte ratio (NLR), longer operation time, more intraoperative blood loss, lymph node dissection and patients with borderline resectable pancreatic head cancer (BRPHC) (P<0.05). The 1-, 2- and 3-year overall survival rates of patients with extended lymphadenectomy and standard lymphadenectomy were 71.9%, 50.6%, 30.0% and 70.0%, 32.9%, 21.5%, respectively (P=0.068). With regards to patients with BRPHC, the number of lymph node dissection in the extended lymphadenectomy group was more (P<0.05), and the 1-, 2- and 3-year overall survival rates of patients with extended lymphadenectomy and standard lymphadenectomy were 60.7%, 43.3%, 27.4% and 43.2%, 17.7%, 17.7%, respectively (P=0.007). CONCLUSIONS Patients with BRPHC tended to have vast lymph node metastasis. Extended lymphadenectomy can improve their long-term survival.
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Affiliation(s)
- Jing Wang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Shao-Cheng Lyu
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ji-Qiao Zhu
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xian-Liang Li
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ren Lang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Qiang He
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Organ Transplant Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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Korean clinical practice guideline for pancreatic cancer 2021: A summary of evidence-based, multi-disciplinary diagnostic and therapeutic approaches. Pancreatology 2021; 21:1326-1341. [PMID: 34148794 DOI: 10.1016/j.pan.2021.05.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/20/2021] [Accepted: 05/04/2021] [Indexed: 02/08/2023]
Abstract
Pancreatic cancer is the eighth most common cancer and the fifth most common cause of cancer-related death in Korea. To enable standardization of management and facilitate improvements in outcome, a total of 53 multi-disciplinary experts in gastroenterology, surgery, medical oncology, radiation oncology, radiology, nuclear medicine, and pathology in Korea developed new recommendations that integrate the most up-to-date, evidence-based research findings and expert opinions. Recommendations were made on imaging diagnosis, endoscopic management, surgery, radiotherapy, palliative chemotherapy, and specific management procedures, including neoadjuvant treatment or adjuvant treatment for patients with resectable, borderline resectable, and locally advanced unresectable pancreatic cancer. This is the English version of the Korean clinical practice guideline for pancreatic cancer 2021. This guideline includes 20 clinical questions and 32 statements. This guideline represents the most standard guideline for the diagnosis and treatment of patients with pancreatic ductal adenocarcinoma in adults at this time in Korea. The authors believe that this guideline will provide useful and informative advice.
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Wang Z, Ke N, Wang X, Wang X, Chen Y, Chen H, Liu J, He D, Tian B, Li A, Hu W, Li K, Liu X. Optimal extent of lymphadenectomy for radical surgery of pancreatic head adenocarcinoma: 2-year survival rate results of single-center, prospective, randomized controlled study. Medicine (Baltimore) 2021; 100:e26918. [PMID: 34477122 PMCID: PMC8415937 DOI: 10.1097/md.0000000000026918] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 07/15/2021] [Accepted: 07/23/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Radical pancreaticoduodenectomy is the only possible cure for pancreatic head adenocarcinoma, and although several RCT studies have suggested the extent of lymph node dissection, this issue remains controversial. This article wanted to evaluate the survival benefit of different lymph node dissection extent for radical surgical treatment of pancreatic head adenocarcinoma. METHODS A total of 240 patients were assessed for eligibility in the study, 212 of whom were randomly divided into standard lymphadenectomy group (SG) or extended lymphadenectomy group (EG), there were 97 patients in SG and 95 patients in EG receiving the radical pancreaticoduodenectomy. RESULT The demography, histopathology and clinical characteristics were similar between the 2 groups. The 2-year overall survival rate in the SG was higher than the EG (39.5% vs 25.3%; P = .034). The 2-year overall survival rate in the SG who received postoperative adjuvant chemotherapy was higher than the EG (60.7% vs 37.1%; P = .021). There was no significant difference in the overall incidence of complications between the 2 groups (P = .502). The overall recurrence rate in the SG and EG (70.7% vs 77.5%; P = .349), and the patterns of recurrence between 2 groups were no significant differences. CONCLUSION In multimodality therapy system, the efficacy of chemotherapy should be based on the appropriate lymphadenectomy extent, and the standard extent of lymphadenectomy is optimal for resectable pancreatic head adenocarcinoma. The postoperative slowing of peripheral blood lymphocyte recovery might be 1 of the reasons why extended lymphadenectomy did not result in survival benefits. CLINICAL TRIAL REGISTRATION This trial was registered at ClinicalTrials.gov (NCT02928081) in October 7, 2016. https://clinicaltrials.gov/.
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Affiliation(s)
- Ziyao Wang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Nengwen Ke
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Wang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xing Wang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yonghua Chen
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hongyu Chen
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jinheng Liu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Du He
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Bole Tian
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Ang Li
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Weiming Hu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Kezhou Li
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xubao Liu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
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Toms C, Steffens D, Yeo D, Pulitano C, Sandroussi C. Quality of Life Instruments and Trajectories After Pancreatic Cancer Resection: A Systematic Review. Pancreas 2021; 50:1137-1153. [PMID: 34714277 DOI: 10.1097/mpa.0000000000001896] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
ABSTRACT This systematic review aimed to investigate the instruments available to measure quality of life (QOL) after pancreatic cancer surgery and to describe short- and long-term QOL outcomes. A comprehensive literature search was completed using PubMed, Embase, and Medline from inception to March 2019. Studies investigating QOL outcomes in patients undergoing pancreatic cancer surgery who were 18 years or older were included. The main outcomes of interest were QOL instruments and short (≤6 months) and long term (>6 months) QOL outcomes. The overarching domains of physical, psychosocial, overall QOL, symptoms, and other were used to summarize QOL outcomes. Thirty-five studies reporting on 3573 patients were included. Fifteen unique QOL instruments were identified, of which 4 were disease-specific instruments. Most of the included studies reported no changes in QOL at short- and long-term follow-ups for the overarching domains. No difference in QOL outcomes was reported between different surgical approaches, except laparoscopic versus open distal pancreatectomy, and pancreaticoduodenectomy versus distal pancreatectomy. There are a wide range of instruments available to measure QOL outcomes in pancreatic cancer surgical patients, although only few are disease-specific. Most of the included studies reported no significant changes in QOL outcomes at short- or long-term follow-ups.
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Affiliation(s)
- Clare Toms
- From the Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney Local Health District
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47
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Miyata Y, Yonamine N, Fujinuma I, Tsunenari T, Takihata Y, Iwasaki T, Einama T, Tsujimoto H, Ueno H, Yamamoto J, Kishi Y. Impact of Lymph Node Metastases Around the Superior Mesenteric Artery on Postoperative Outcomes of Pancreatic Head Cancer. World J Surg 2021; 45:3668-3676. [PMID: 34406453 DOI: 10.1007/s00268-021-06276-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND The neural plexus and lymph nodes around the superior mesenteric artery (LN#14), are the most frequent sites involved by pancreatic head cancer. However the influence of metastases to LN#14 on patients' prognosis has rarely been evaluated. METHODS The patients who underwent pancreatectomy for pancreatic head cancer between January 2010 and December 2018 were selected. The patients with nodal metastases were classified into an LN#14 + or LN#14-group according to LN#14 metastasis. Clinical and pathological characteristics and prognosis were compared between the two groups. RESULTS In total, 99 patients underwent pancreatectomy. Ninety-four patients were positive for lymph node metastases and 14 and 80 were classified as LN#14 + and LN#14 - , respectively. Postoperative median overall survival (OS) of the LN#14 + and LN#14 - groups was 10.2 and 31.1 months, respectively (P < 0.001). Median OS of the LN#14 + group was worse than that of patients with ≥ 4 metastatic nodes in the LN#14 - group (n = 35, 24.7 months, P = 0.002). In multivariate analysis, LN#14 + (hazard ratio [HR] = 3.89, 95% confidence interval [CI], 1.64-8.86) was one of the independent predictors of worse OS. CONCLUSION It might be feasible to recognize LN#14 metastases as an important prognostic factor independently from other regional lymph node metastases.
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Affiliation(s)
- Yoichi Miyata
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Naoto Yonamine
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Ibuki Fujinuma
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Takazumi Tsunenari
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Yasuhiro Takihata
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Toshimitsu Iwasaki
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Takahiro Einama
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Hironori Tsujimoto
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Junji Yamamoto
- Department of Gastrointestinal Surgery, Ibaraki Prefectural Central Hospital, Ibaraki, 309-1793, Japan
| | - Yoji Kishi
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
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Pancreatectomy Combined with Arterial Resection for Pancreatic Carcinoma with Arterial Infiltration: A Meta-analysis. Indian J Surg 2021. [DOI: 10.1007/s12262-020-02552-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Reconsideration of the Appropriate Dissection Range Based on Japanese Anatomical Classification for Resectable Pancreatic Head Cancer in the Era of Multimodal Treatment. Cancers (Basel) 2021; 13:cancers13143605. [PMID: 34298818 PMCID: PMC8303207 DOI: 10.3390/cancers13143605] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/06/2021] [Accepted: 07/15/2021] [Indexed: 12/11/2022] Open
Abstract
Patients with resectable pancreatic cancer are considered to already have micro-distant metastasis, because most of the recurrence patterns postoperatively are distant metastases. Multimodal treatment dramatically improves prognosis; thus, micro-distant metastasis is considered to be controlled by chemotherapy. The survival benefit of "regional lymph node dissection" for pancreatic head cancer remains unclear. We reviewed the literature that could be helpful in determining the appropriate resection range. Regional lymph nodes with no suspected metastases on preoperative imaging may become areas treated with preoperative and postoperative adjuvant chemotherapy. Many studies have reported that the R0 resection rate is associated with prognosis. Thus, "dissection to achieve R0 resection" is required. The recent development of high-quality computed tomography has made it possible to evaluate the extent of cancer infiltration. Therefore, it is possible to simulate the dissection range to achieve R0 resection preoperatively. However, it is often difficult to distinguish between areas of inflammatory changes and cancer infiltration during resection. Even if the "dissection to achieve R0 resection" range is simulated based on the computed tomography evaluation, it is difficult to identify the range intraoperatively. It is necessary to be aware of anatomical landmarks to determine the appropriate dissection range during surgery.
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Principe DR, Underwood PW, Korc M, Trevino JG, Munshi HG, Rana A. The Current Treatment Paradigm for Pancreatic Ductal Adenocarcinoma and Barriers to Therapeutic Efficacy. Front Oncol 2021; 11:688377. [PMID: 34336673 PMCID: PMC8319847 DOI: 10.3389/fonc.2021.688377] [Citation(s) in RCA: 121] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 06/29/2021] [Indexed: 12/15/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, with a median survival time of 10-12 months. Clinically, these poor outcomes are attributed to several factors, including late stage at the time of diagnosis impeding resectability, as well as multi-drug resistance. Despite the high prevalence of drug-resistant phenotypes, nearly all patients are offered chemotherapy leading to modest improvements in postoperative survival. However, chemotherapy is all too often associated with toxicity, and many patients elect for palliative care. In cases of inoperable disease, cytotoxic therapies are less efficacious but still carry the same risk of serious adverse effects, and clinical outcomes remain particularly poor. Here we discuss the current state of pancreatic cancer therapy, both surgical and medical, and emerging factors limiting the efficacy of both. Combined, this review highlights an unmet clinical need to improve our understanding of the mechanisms underlying the poor therapeutic responses seen in patients with PDAC, in hopes of increasing drug efficacy, extending patient survival, and improving quality of life.
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Affiliation(s)
- Daniel R. Principe
- Medical Scientist Training Program, University of Illinois College of Medicine, Chicago, IL, United States
- Department of Surgery, University of Illinois at Chicago, Chicago, IL, United States
| | | | - Murray Korc
- Department of Developmental and Cell Biology, University of California, Irvine, CA, United States
| | - Jose G. Trevino
- Department of Surgery, Division of Surgical Oncology, Virginia Commonwealth University, Richmond, VA, United States
| | - Hidayatullah G. Munshi
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
- Jesse Brown VA Medical Center, Chicago, IL, United States
| | - Ajay Rana
- Department of Surgery, University of Illinois at Chicago, Chicago, IL, United States
- Jesse Brown VA Medical Center, Chicago, IL, United States
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