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      Disparities in survival by stage after surgery between pancreatic head and body/tail in patients with nonmetastatic pancreatic cancer

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          Abstract

          Background

          The survival of pancreatic cancer patients with lesions in different locations is unclear. In addition, the different surgery types for nonmetastatic pancreatic head cancer (PHC) or body/tail cancer (PBTC) have different prognostic influences. We analyzed the association by stage between tumor location (head vs. body/tail) and survival of nonmetastatic pancreatic cancer patients who underwent surgery.

          Methods

          We identified stages I to III pancreatic cancer patients who underwent surgery from 2004 through 2015 by using the Surveillance, Epidemiology, and End Results (SEER) database. The adjusted hazard ratio (HR) and 95% confidence interval (CI) for cancer-specific survival (CSS) were obtained using Cox regression.

          Results

          A total of 13517 patients or 86.6% had PHC. PHC patients were more likely to have an advanced tumor stage, higher tumor grade, and more frequent and a higher number of positive lymph nodes compared with PBTC patients. The PHC patients had a worse CSS than PBTC patients (P<0.001) and were predominantly at stage I (P = 0.008) and II (P = 0.004). Multivariate Cox regression analysis showed that PHC was an independent prognostic factor associated with a worse CSS in pancreatic cancer patients (HR 1.132, 95% CI 1.042–1.228, P = 0.003), predominantly at stage II (HR 1.128, 95% CI 1.030–1.235, P = 0.009).

          Conclusion

          At a resectable early stage, the PHC patients had a worse CSS than PBTC patients after surgery. PHC was an independent prognostic factor associated with worse survival in pancreatic cancer patients, predominantly at stage II.

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          Most cited references21

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          Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators.

          This large-volume, single-institution review examines factors influencing long-term survival after resection in patients with adenocarcinoma of the head, neck, uncinate process, body, or tail of the pancreas. Between January 1984 and July 1999 inclusive, 616 patients with adenocarcinoma of the pancreas underwent surgical resection. A retrospective analysis of a prospectively collected database was performed. Both univariate and multivariate models were used to determine the factors influencing survival. Of the 616 patients, 526 (85%) underwent pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas, 52 (9%) underwent distal pancreatectomy for adenocarcinoma of the body or tail, and 38 (6%) underwent total pancreatectomy for adenocarcinoma extensively involving the gland. The mean age of the patients was 64.3 years, with 54% being male and 91% being white. The overall perioperative mortality rate was 2.3%, whereas the incidence of postoperative complications was 30%. The median postoperative length of stay was 11 days. The mean tumor diameter was 3.2 cm, with 72% of patients having positive lymph nodes, 30% having positive resection margins, and 36% having poorly differentiated tumors. Patients undergoing distal pancreatectomy for left-sided lesions had larger tumors (4.7 vs. 3.1 cm, P < 0.0001), but fewer node-positive resections (59% vs. 73%, P = 0.03) and fewer poorly differentiated tumors (29% vs. 36%, P < 0.001), as compared to those undergoing pancreaticoduodenectomy for right-sided lesions. The overall survival of the entire cohort was 63% at 1 year and 17% at 5 years, with a median survival of 17 months. For right-sided lesions the 1- and 5-year survival rates were 64% and 17%, respectively, compared to 50% and 15% for left-sided lesions. Factors shown to have favorable independent prognostic significance by multivariate analysis were negative resection margins (hazard ratio [HR] = 0.64, confidence interval [CI] = 0.50 to 0.82, P = 0.0004), tumor diameter less than 3 cm (HR = 0.72, CI = 0.57 to 0.90, P = 0.004), estimated blood loss less than 750 ml (HR = 0.75, CI = 0.58 to 0.96, P = 0.02), well/moderate tumor differentiation (HR = 0.71, CI = 0.56 to 0.90, P = 0.005), and postoperative chemoradiation (HR = 0.50, CI = 0.39 to 0.64, P < 0.0001). Tumor location in head, neck, or uncinate process approached significance in the final multivariate model (HR = 0.60, CI = 0.35 to 1.0, P = 0.06). Pancreatic resection remains the only hope for long-term survival in patients with adenocarcinoma of the pancreas. Completeness of resection and tumor characteristics including tumor size and degree of differentiation are important independent prognostic indicators. Adjuvant chemoradiation is a strong predictor of outcome and likely decreases the independent significance of tumor location and nodal status.
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            The anatomic location of pancreatic cancer is a prognostic factor for survival.

            Pancreatic cancers of the body and tail (BT) appear to have poorer survival compared with head (HD) lesions. We hypothesized that potential disparities in outcome may be related to tumor location. Our objective was to examine the relationship between tumor location and survival. The Surveillance, Epidemiology, and End Results registry identified 33,752 patients with pancreatic adenocarcinoma and 6443 patients who underwent cancer-directed surgery between 1988 and 2004. Differences in survival and relationships between tumor location and clinical factors were assessed. Multivariate analysis was performed to determine the prognostic significance of tumor location. Median survival for the entire cohort was five months and was significantly lower for BT compared to HD lesions (four vs. six months, p<0.001). Distant metastases (67% vs. 36%, p<0.001) were greater and cancer-directed surgery (16% vs. 30%, p<0.001) was lower for BT tumors. Of 6443 resected patients, HD patients (n=5118) were younger, had a greater number of harvested lymph nodes, were more likely to be lymph node-positive, and had a higher proportion of T3/T4 lesions. Significant univariate predictors of survival included age, T-stage, number of positive and harvested lymph nodes. On multivariate analysis, BT location was a significant prognostic factor for decreased survival (OR 1.11, 95% CI 1.00-1.23, p=0.05). Pancreatic BT cancers have a lower rate of resectability and poorer overall survival compared to HD lesions. Prospective large-cohort studies may definitively prove that tumor location is a prognostic factor for survival in patients with pancreatic cancer.
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              Radical antegrade modular pancreatosplenectomy.

              Retrograde distal pancreatectomy with splenectomy is the standard procedure for cancers of the body and tail of the pancreas. However, this procedure has limitations in terms of the posterior extent of resection and the ability to achieve a complete N1 node resection.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: MethodologyRole: Validation
                Role: InvestigationRole: Validation
                Role: Data curationRole: Methodology
                Role: MethodologyRole: Validation
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                19 December 2019
                2019
                : 14
                : 12
                : e0226726
                Affiliations
                [1 ] Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
                [2 ] Department of Gastrointestinal Surgery, Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
                [3 ] Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, United States of America
                [4 ] Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
                VA Boston Healthcare System, Harvard Medical School (Brigham and Women's Hospital), UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-1288-7089
                Article
                PONE-D-19-19763
                10.1371/journal.pone.0226726
                6922472
                31856205
                8c1a16dc-e894-4e02-8082-941ef72ceb81
                © 2019 Zheng et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 July 2019
                : 3 December 2019
                Page count
                Figures: 1, Tables: 5, Pages: 12
                Funding
                Funded by: The 1.3.5 project for disciplines of excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University
                Award Recipient :
                Funded by: National Health and Family Planning Commission of Chengdu
                Award ID: 2016002
                Award Recipient :
                Funded by: Key Research projects of Department of science and Technology of Sichuan Province
                Award ID: 2018SZ0403
                Award Recipient :
                Funded by: Popularization and Application Project of Sichuan Health and Family Planning Commission
                Award ID: 18PJ387
                Award Recipient :
                This work was supported by the 1.3.5 project for disciplines of excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University (Grant no. ZY2017302 1-3-5); National Health and Family Planning Commission of Chengdu (Grant no. 2016002); Key Research projects of Department of science and Technology of Sichuan Province, China (Grant no. 2018SZ0403); and Popularization and Application Project of Sichuan Health and Family Planning Commission (Grant no. 18PJ387). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Surgical Oncology
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Oncology
                Surgical Oncology
                Medicine and Health Sciences
                Oncology
                Clinical Oncology
                Surgical Oncology
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Pancreatic Cancer
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Surgical Oncology
                Tumor Resection
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Oncology
                Surgical Oncology
                Tumor Resection
                Medicine and Health Sciences
                Oncology
                Clinical Oncology
                Surgical Oncology
                Tumor Resection
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Surgical Resection
                Tumor Resection
                Medicine and Health Sciences
                Diagnostic Medicine
                Prognosis
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Head and Neck Cancers
                Head and Neck Tumors
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Digestive System Procedures
                Pancreatectomy
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Endocrine System Procedures
                Pancreatectomy
                Custom metadata
                All files are available from the SEER database (accession number: 10457-Nov2017), which is a public use database ( https://seer.cancer.gov/).

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