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Kim MK, Choi JH, Cho IR, Lee SH, Ryu JK, Kim YT, Paik WH. Survival benefit of adjuvant treatment for ampullary cancer with lymph nodal involvement: A systematic review and meta-analysis. Hepatobiliary Pancreat Dis Int 2024; 23:559-565. [PMID: 38997856 DOI: 10.1016/j.hbpd.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 07/01/2024] [Indexed: 07/14/2024]
Abstract
BACKGROUND The efficacy of adjuvant treatment (AT) in ampullary cancer (AmC) remains controversial. This systematic review and meta-analysis aimed to evaluate the role of AT for AmC. DATA SOURCES A comprehensive systematic search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science databases. Studies comparing overall survival (OS) and recurrence-free survival (RFS) of patients who underwent AT or not following AmC resection were included. RESULTS A total of 3971 patients in 21 studies were analyzed. Overall pooled data showed no significant difference in effect on the OS by AT [hazard ratio (HR) = 0.998, 95% confidence interval (CI): 0.768-1.297]. No significant difference in recurrence between the AT and non-AT (nAT) groups was noted (HR = 1.158, 95% CI: 0.764-1.755). In subgroup analysis, patients who received AT showed favorable outcomes in the OS compared with those who received nAT in nodal-positive AmC (HR = 0.627, 95% CI: 0.451-0.870). Neither AT consisted of adjuvant chemotherapy with radiotherapy (HR = 0.804, 95% CI: 0.563-1.149) nor AT with adjuvant chemotherapy (HR = 0.883, 95% CI: 0.642-1.214) showed any significant effect on the OS. CONCLUSIONS The effect of AT in AmC on survival and recurrence did not show a significant benefit. Furthermore, effectiveness according to AT strategies did not show enhancement in survival. AT had an advantage in survival compared with nAT strategy in nodal-positive AmC. In cases of AmC with positive lymph nodal involvement, AT may be warranted regardless of detailed strategies.
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Affiliation(s)
- Min Kyu Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Ho Choi
- Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - In Rae Cho
- Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Kon Ryu
- Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Yong-Tae Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Woo Hyun Paik
- Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
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Ni R, Zhang T, Mou Y, Hu Z, Gu Z. Accurate prediction of the lymph node status in ampullary duodenal carcinoma: potential guidance for clinical management. BMC Cancer 2024; 24:1363. [PMID: 39511526 PMCID: PMC11542209 DOI: 10.1186/s12885-024-13119-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 10/28/2024] [Indexed: 11/15/2024] Open
Abstract
PURPOSE This study aimed to identify the risk factors associated with ampullary duodenal carcinoma (a-DC) and develop a clinical model to dynamically and accurately predict the risk of lymph node metastasis (LNM) in a-DC patients. METHODS Data from 4077 patients (2004-2020) were extracted from the Surveillance, Epidemiology, and End Results database to form a training cohort, while 173 cases (2010-2020) from Zhejiang Provincial People's Hospital in China were used as an external validation cohort. A reliable LASSO-logistic method was employed to identify independent risk factors for a-DC LNM, and a nomogram was developed based on these factors to assess the risk of a-DC LNM. The nomogram was evaluated using the Akaike information criterion, misclassification error, area under the curve, and likelihood ratio test. Finally, the nomogram's accuracy and generalizability were externally validated.. RESULTS After screening using LASSO and logistic regression four variables were identified as independent risk factors for a-DC LNM: sex (P < 0.001), tumor size (P < 0.001), grade (P < 0.001), and tumor extension (P < 0.001). The area under the curve of the nomogram was 74.8% in the training group and 88.9% in the external validation group. The calibration curves demonstrated that the LNM predictions made by the nomogram were in satisfactory agreement with the actual observed LNM. Additionally, the decision curve analysis curves indicated effective clinical utility of the nomogram. CONCLUSIONS A nomogram based on the LASSO-logistic analysis was constructed to predict a-DC LNM, demonstrating good performance and clinical application value.
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Affiliation(s)
- Ran Ni
- Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, 310004, China
- Tongde Hospital of Zhejiang province, Zhejiang Chinese Medical University, Hangzhou, 310012, China
| | - Tianpeng Zhang
- Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, 310004, China
| | - Yixuan Mou
- Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, 310004, China
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhiming Hu
- Tongde Hospital of Zhejiang province, Zhejiang Chinese Medical University, Hangzhou, 310012, China.
| | - Zongting Gu
- Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, 310004, China.
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Zhang ZY, Guan J, Wang XP, Hao DS, Zhou ZQ. Analysis of lymph node spread and its prognostic significance in ampullary adenocarcinoma: A retrospective study. Front Surg 2022; 9:901615. [PMID: 36090320 PMCID: PMC9458928 DOI: 10.3389/fsurg.2022.901615] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 07/21/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundNodal status is a vital prognostic factor for ampullary adenocarcinoma. This study was designed to evaluate the clinical significance of the positive nodes in this disease.MethodsData from 110 patients who underwent curative pancreatoduodenectomy for ampullary adenocarcinoma between January 2007 and December 2018 were retrospectively collected and analyzed.ResultsThe median number of lymph nodes per patient was 32 (20–46). Metastatic lymph nodes were found in 84 (76.4%) patients. In patients with positive nodules, the most commonly involved nodes were the #13 (80.1%) and #17 (78.6%) nodes, followed by #12 (69.0%) and #8 nodes (57.1%). Patients with 3–4 positive nodes among #13, #17, #12, and #8 had lower survival rates than those with 0 or 1–2 nodes.ConclusionAmpullary adenocarcinoma commonly spreads to #13, #17, #12, and #8 lymph nodes. These nodes affected the patients' survival rates dramatically.
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Affiliation(s)
- Zheng-Yun Zhang
- Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Jiao Guan
- Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Xin-Ping Wang
- Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Di-Si Hao
- Department of Surgery, Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology, Harbin, China
- Correspondence: Di-Si Hao Zun-Qiang Zhou
| | - Zun-Qiang Zhou
- Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Correspondence: Di-Si Hao Zun-Qiang Zhou
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Min EK, Hong SS, Kim JS, Choi M, Hwang HS, Kang CM, Lee WJ, Yoon DS, Hwang HK. Surgical Outcomes and Comparative Analysis of Transduodenal Ampullectomy and Pancreaticoduodenectomy: A Single-Center Study. Ann Surg Oncol 2021; 29:2429-2440. [PMID: 34931288 PMCID: PMC8933369 DOI: 10.1245/s10434-021-11190-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 11/26/2021] [Indexed: 11/18/2022]
Abstract
Background Transduodenal ampullectomy (TDA) is performed for adenoma or early cancer of the ampulla of Vater (AoV). This study aimed to analyze the short- and long-term outcomes of TDA (TDA group) when compared with conventional pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PD group). Methods Patients who underwent TDA between January 2006 and December 2019, and PD cases performed for AoV malignancy with carcinoma in-situ (Tis) (high-grade dysplasia, HGD) and T1 and T2 stage from January 2010 to December 2019 were reviewed.
Results Forty-six patients underwent TDA; 21 had a benign tumor, and 25 cases with malignant tumors were compared with PD cases (n = 133). Operation time (p < 0.001), estimated blood loss (p < 0.001), length of hospital stays (p = 0.003), and overall complication rate (p < 0.001) were lower in the TDA group than in the PD group. Lymph node metastasis rates were 14.6% in pT1 and 28.9% in pT2 patients. The 5-year disease-free survival and 5-year overall survival rates for HGD/Tis and T1 tumor between the two groups were similar (TDA group vs PD group, 72.2% vs 77.7%, p = 0.550; 85.6% vs 79.2%, p = 0.816, respectively). Conclusion TDA accompanied with lymph node dissection is advisable in HGD/Tis and T1 AoV cancers in view of superior perioperative outcomes and similar long-term survival rates compared with PD.
Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-11190-9.
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Affiliation(s)
- Eun-Ki Min
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Onsei University College of Medicine, Seodaemun-gu, Seoul, 03722, South Korea
| | - Seung Soo Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Onsei University College of Medicine, Seodaemun-gu, Seoul, 03722, South Korea
| | - Ji Su Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Onsei University College of Medicine, Seodaemun-gu, Seoul, 03722, South Korea
| | - Munseok Choi
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyeo Seong Hwang
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Ilsan, South Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Onsei University College of Medicine, Seodaemun-gu, Seoul, 03722, South Korea
| | - Woo Jung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Onsei University College of Medicine, Seodaemun-gu, Seoul, 03722, South Korea
| | - Dong Sup Yoon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Onsei University College of Medicine, Seodaemun-gu, Seoul, 03722, South Korea
| | - Ho Kyoung Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Onsei University College of Medicine, Seodaemun-gu, Seoul, 03722, South Korea.
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Efficacy and safety of adjuvant therapy after curative surgery for ampullary carcinoma: A systematic review and meta-analysis. Surgery 2021; 170:1205-1214. [PMID: 33902926 DOI: 10.1016/j.surg.2021.03.046] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/16/2021] [Accepted: 03/16/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND Ampullary carcinoma patients require radical resection for optimal survival; however, the outcomes are often unsatisfactory. The utility of adjuvant therapy among such patients is unclear, probably owing to its potential side effects. Therefore, this study investigated the benefits and safety of adjuvant therapy in resected ampullary carcinoma. METHODS Cochrane, Embase, Medline, and PubMed databases were systematically searched for eligible studies, and those comparing adjuvant therapy and surgical treatment alone were included. Hazard ratios for survival outcomes and the number of adverse events for safety endpoints were extracted and subjected to pooled analyses through a random-effects model. RESULTS In total, 27 studies involving 3,538 patients were included. Adjuvant therapy was significantly associated with decreased mortality risk (hazard ratio, 0.58; 95% confidence interval 0.40-0.84), especially for chemoradiotherapy (hazard ratio, 0.42; 95% confidence interval 0.28-0.62). Furthermore, adjuvant therapy was significantly associated with increased overall survival among high-risk patients (hazard ratio, 0.63; 95% confidence interval 0.48-0.82) or those with the pancreaticobiliary subtype (hazard ratio, 0.53; 95% confidence interval 0.32-0.85). By contrast, adjuvant therapy was not associated with improved overall survival among low-risk patients (hazard ratio, 0.93; 95% confidence interval 0.52-1.68) or those with the intestinal subtype (hazard ratio, 1.06; 95% confidence interval 0.57-1.95). Regarding the safety of adjuvant therapy, no intervention-related mortality occurred, and severe adverse events were within the acceptable range (risk difference, 0.04; 95% confidence interval 0.01-0.08). CONCLUSION The present results suggest that adjuvant therapy is safe and extends survival in high-risk patients or those with the pancreaticobiliary subtype of ampullary carcinoma.
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Chuang PJ, Wang HP, Lin YJ, Chen CC, Tien YW, Hsieh MS, Yang SH, Yen RF, Ko CL, Wu YW, Cheng MF. Preoperative 2-[ 18F]FDG PET-CT aids in the prognostic stratification for patients with primary ampullary carcinoma. Eur Radiol 2021; 31:8040-8049. [PMID: 33864503 DOI: 10.1007/s00330-021-07923-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 03/01/2021] [Accepted: 03/22/2021] [Indexed: 11/24/2022]
Abstract
OBJECTIVES We sought to investigate whether preoperative dual-phase 2-[18F]FDG PET-CT identify predictors for poor survival in patients with ampullary carcinoma receiving pancreaticoduodenectomy. METHODS The preoperative PET-CT images of patients with resected ampullary carcinoma from June 2007 to July 2017 were analyzed. Survival curves were analyzed using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard model was used to identify potential prognostic factors associated with disease-free survival (DFS) and overall survival (OS). RESULTS Fifty-four subjects (26 men, 28 women) were enrolled with a median tumor size of 20 mm. All patients were followed for a median period of 36.9 months with 3- and 5-year DFS of 50.3% and 44.2%, and OS of 77.0% and 68.2%, respectively. Parameters associated with DFS in multivariate analysis were lymphovascular invasion (hazard ratio [HR]: 9.45, p < 0.001), involved margin in pathology (HR: 7.67, p < 0.001), and tumor retention index (RI) from the dual-phase PET (HR: 2.41, p = 0.03), whereas involved margin (HR: 13.14, p < 0.001), post-recurrence chemotherapy (HR: 0.10, p < 0.001), and metabolic tumor volume (MTV) (HR: 4.62, p = 0.009) emerged as independent prognostic factors for OS. CONCLUSIONS Preoperative 2-[18F]FDG PET-CT offered independent prognostic biomarkers in patients with ampullary carcinoma receiving standard surgical resection. KEY POINTS • 2-[18F]FDG PET-CT offers good survival prediction before operation in primary malignant neoplasms at ampulla of Vater. • Dual-phase PET scan with bowel distention can better delineate Ampulla of Vater and characterize tumor physiology. • Preoperative risk stratification might aid in better treatment planning.
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Affiliation(s)
- Pei-Ju Chuang
- Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No.7, Chung-Shan South Road, Chung-Cheng District, Taipei, 100, Taiwan, Republic of China
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yu-Jen Lin
- Institute of Environmental and Occupational Health Sciences, National Taiwan University, Taipei, Taiwan
| | - Chieh-Chang Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Min-Shu Hsieh
- Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shih-Hung Yang
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ruoh-Fang Yen
- Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No.7, Chung-Shan South Road, Chung-Cheng District, Taipei, 100, Taiwan, Republic of China
| | - Chi-Lun Ko
- Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No.7, Chung-Shan South Road, Chung-Cheng District, Taipei, 100, Taiwan, Republic of China
| | - Yen-Wen Wu
- National Yang-Ming University School of Medicine, Taipei, Taiwan.,Department of Nuclear Medicine and Cardiovascular Medical Centre (Cardiology), Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Mei-Fang Cheng
- Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No.7, Chung-Shan South Road, Chung-Cheng District, Taipei, 100, Taiwan, Republic of China. .,Institute of Environmental and Occupational Health Sciences, National Taiwan University, Taipei, Taiwan.
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Lee JW, Choi SB, Lim TW, Kim WJ, Park P, Kim WB. Prognostic value of the lymph node metastasis in patients with ampulla of Vater cancer after surgical resection. Ann Hepatobiliary Pancreat Surg 2021; 25:90-96. [PMID: 33649260 PMCID: PMC7952676 DOI: 10.14701/ahbps.2021.25.1.90] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/12/2020] [Accepted: 10/12/2020] [Indexed: 12/19/2022] Open
Abstract
Backgrounds/Aims Patients with Ampulla of Vater cancer have a better prognosis than those with other periampullary cancers. This study aimed to determine the prognostic impact of lymph node metastasis on survival in patients with ampulla of Vater cancer after surgical resection. Methods From 1991 to 2016, we retrospectively reviewed data on 104 patients with ampulla of Vater cancer who had received pancreaticoduodenectomy. Clinicopathologic factors such as lymph node ratio (LNR) and number of metastatic lymph nodes that influence survival were statistically analyzed. Results 5-year survival rate after resection was 57.8%. Mean number of retrieved and metastatic lymph nodes was 13 and 0.95, respectively. In patients with lymph node metastasis, the median number of metastatic lymph nodes and was 1, and the mean LNR was 0.18. LNR >0.2 was a significant prognostic factor for overall survival. Patients with 0 or 1 metastatic lymph nodes had better survival than those with ≥2 metastatic lymph nodes. Univariate analysis revealed that histologic differentiation of tumor, lymph node metastasis, and T stage were significant prognostic factors for overall survival. Multivariate analysis revealed that tumor differentiation and number of metastatic lymph nodes were independent prognostic factors for survival. Conclusions Pancreaticoduodenectomy is an appropriate surgical procedure with acceptable long-term survival for ampulla of Vater cancer. Patients with LNR >0.2 and ≥2 positive lymph node metastasis had a poor survival. Tumor differentiation and ≥2 metastatic lymph nodes were independent significant prognostic factors for overall survival. Curative resection with lymph node dissection might control lymph node spread and enhance survival outcomes.
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Affiliation(s)
- Jeong Woo Lee
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Sae Byeol Choi
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Tae Wan Lim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Wan Joon Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Pyoungjae Park
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Wan Bae Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
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Survival Benefit of Adjuvant Chemotherapy After Pancreatoduodenectomy for Ampullary Adenocarcinoma: a Propensity-Matched National Cancer Database (NCDB) Analysis. J Gastrointest Surg 2021; 25:1805-1814. [PMID: 33230687 PMCID: PMC8275534 DOI: 10.1007/s11605-020-04879-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/10/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND The benefit of adjuvant chemotherapy (AC) after pancreatoduodenectomy (PD) for ampullary adenocarcinoma is uncertain. We aimed to evaluate the association of AC with survival in patients with resected ampullary adenocarcinoma. METHODS Using the National Cancer Database (NCDB) data from 2004 to 2016, patients with non-metastatic ampullary adenocarcinoma who underwent PD were identified. Patients with neoadjuvant radiotherapy and chemotherapy and survival < 6 months were excluded. Propensity score matching was used to account for treatment selection bias. A multivariable Cox proportional hazards model was then used to analyze the association of AC with survival. RESULTS Of 3186 (43%) AC and 4172 (57%) no AC (noAC) patients, 1720 AC and 1720 noAC patients remained in the cohort after matching. Clinicopathologic variables were well balanced after matching. After matching, AC was associated with improved survival (median 47.5 vs 39.6 months, p = 0.003), which remained after multivariable adjustment (HR: 0.83, CI95%: 0.76-0.91, p < 0.001). Multivariable interaction analyses showed that this benefit was seen irrespective of nodal status: N0 (HR: 0.81, CI95%: 0.68-0.97, p < 0.001), N1 (HR: 0.65, CI95%: 0.61-0.70, p < 0.001), N2 (HR: 0.73, CI95%: 0.59-0.90, p = 0.003), N3 (HR: 0.59, CI95%: 0.44-0.78, p < 0.001); and margin status: R0 (HR: 0.85, CI95%: 0.77-0.94, p < 0.001), R1 (HR: 0.69, CI95%: 0.48-1.00, p < 0.001). Stratified analyses by nodal and margin status demonstrated consistent results. CONCLUSION In this large retrospective cohort study, AC after resected ampullary adenocarcinoma was associated with a survival benefit in patients, including patients with node-negative and margin-negative disease.
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Moekotte AL, Lof S, Van Roessel S, Fontana M, Dreyer S, Shablak A, Casciani F, Mavroeidis VK, Robinson S, Khalil K, Gradinariu G, Mowbray N, Al-Sarireh B, Fusai GK, Roberts K, White S, Soonawalla Z, Jamieson NB, Salvia R, Besselink MG, Abu Hilal M. Histopathologic Predictors of Survival and Recurrence in Resected Ampullary Adenocarcinoma: International Multicenter Cohort Study. Ann Surg 2020; 272:1086-1093. [PMID: 30628913 DOI: 10.1097/sla.0000000000003177] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of the study was to define histopathologic characteristics that independently predict overall survival (OS) and disease-free survival (DFS), in patients who underwent resection of an ampullary adenocarcinoma with curative intent. SUMMARY BACKGROUND DATA A broad range of survival rates have been described for adenocarcinoma of the ampulla of Vater, presumably due to morphological heterogeneity which is a result of the different epitheliums ampullary adenocarcinoma can arise from (intestinal or pancreaticobiliary). Large series with homogenous patient selection are scarce. METHODS A retrospective multicenter cohort analysis of patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma in 9 European tertiary referral centers between February 2006 and December 2017 was performed. Collected data included demographics, histopathologic details, survival, and recurrence. OS and DFS analyses were performed using Kaplan-Meier curves and Cox proportional hazard models. RESULTS Overall, 887 patients were included, with a mean age of 66 ± 10 years. The median OS was 64 months with 1-, 3-, 5-, and 10-year OS rates of 89%, 63%, 52%, and 37%, respectively. Histopathologic subtype, differentiation grade, lymphovascular invasion, perineural invasion, T-stage, N-stage, resection margin, and adjuvant chemotherapy were correlated with OS and DFS. N-stage (HR = 3.30 [2.09-5.21]), perineural invasion (HR = 1.50 [1.01-2.23]), and adjuvant chemotherapy (HR = 0.69 [0.48-0.97]) were independent predictors of OS in multivariable analysis, whereas DFS was only adversely predicted by N-stage (HR = 2.65 [1.65-4.27]). CONCLUSIONS Independent predictors of OS in resected ampullary cancer were N-stage, perineural invasion, and adjuvant chemotherapy. N-stage was the only predictor of DFS. These findings improve predicting survival and recurrence after resection of ampullary adenocarcinoma.
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Affiliation(s)
- Alma L Moekotte
- Department of Surgery, University Hospital of Southampton NHS Foundation Trust, Southampton, UK
| | - Sanne Lof
- Department of Surgery, University Hospital of Southampton NHS Foundation Trust, Southampton, UK
| | - Stijn Van Roessel
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Martina Fontana
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - Stephan Dreyer
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - Alaaeldin Shablak
- Department of Oncology, University Hospital of Southampton NHS Foundation Trust, Southampton, UK
| | - Fabio Casciani
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - Vasileios K Mavroeidis
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Stuart Robinson
- Department of Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | - Khalid Khalil
- Faculty of Medicine, University of Birmingham, Birmingham, UK
| | - George Gradinariu
- Department of Surgery, Royal Free London NHS Foundation Trust, London, UK
| | | | | | | | - Keith Roberts
- Faculty of Medicine, University of Birmingham, Birmingham, UK
| | - Steve White
- Department of Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | - Zahir Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Nigel B Jamieson
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - Roberto Salvia
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Mohammed Abu Hilal
- Department of Surgery, University Hospital of Southampton NHS Foundation Trust, Southampton, UK
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Moekotte AL, van Roessel S, Malleo G, Rajak R, Ecker BL, Fontana M, Han HS, Rabie M, Roberts KJ, Khalil K, White SA, Robinson S, Halimi A, Zarantonello L, Fusai GK, Gradinariu G, Alseidi A, Bonds M, Dreyer S, Jamieson NB, Mowbray N, Al-Sarireh B, Mavroeidis VK, Soonawalla Z, Napoli N, Boggi U, Kent TS, Fisher WE, Tang CN, Bolm L, House MG, Dillhoff ME, Behrman SW, Nakamura M, Ball CG, Berger AC, Christein JD, Zureikat AH, Salem RR, Vollmer CM, Salvia R, Besselink MG, Abu Hilal M, Aljarrah R, Barrows C, Cagigas MN, Lai ECH, Wellner U, Aversa J, Dickson PV, Ohtsuka T, Dixon E, Zheng R, Kowalski S, Freedman-Weiss M. Development and external validation of a prediction model for survival in patients with resected ampullary adenocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1717-1726. [PMID: 32624291 DOI: 10.1016/j.ejso.2020.04.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/26/2020] [Accepted: 04/09/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC. MATERIALS AND METHODS An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006-2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score. RESULTS Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73-0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73-0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. CONCLUSION A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.
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Affiliation(s)
- Alma L Moekotte
- Department of Surgery, University Hospital of Southampton NHS Foundation Trust, Southampton, UK; Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands.
| | - Stijn van Roessel
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Giuseppe Malleo
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - Rushda Rajak
- Department of Histopathology, University Hospital of Southampton NHS Foundation Trust, Southampton, UK
| | - Brett L Ecker
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA
| | - Martina Fontana
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, South Korea
| | - Mohamed Rabie
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, South Korea
| | - Keith J Roberts
- Faculty of Medicine, University of Birmingham, Birmingham, UK
| | - Khalid Khalil
- Faculty of Medicine, University of Birmingham, Birmingham, UK
| | - Steven A White
- Department of Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | - Stuart Robinson
- Department of Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | - Asif Halimi
- Pancreatic Surgery Unit, Division of Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Laura Zarantonello
- Pancreatic Surgery Unit, Division of Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Giuseppe K Fusai
- Department of Surgery, Royal Free Hospital NHS Foundation Trust, London, UK
| | - George Gradinariu
- Department of Surgery, Royal Free Hospital NHS Foundation Trust, London, UK
| | - Adnan Alseidi
- Department of Surgery, Virginia Mason Medical Center, Seattle, USA
| | - Morgan Bonds
- Department of Surgery, Virginia Mason Medical Center, Seattle, USA
| | - Stephan Dreyer
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - Nigel B Jamieson
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
| | | | | | - Vasileios K Mavroeidis
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Zahir Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Niccolò Napoli
- Department of Surgery, Pisa University Hospital, Pisa, Italy
| | - Ugo Boggi
- Department of Surgery, Pisa University Hospital, Pisa, Italy
| | - Tara S Kent
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | | | - Chung N Tang
- Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
| | - Louisa Bolm
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Michael G House
- Department of Surgery, Indiana University School of Medicine, Indianapolis, USA
| | - Mary E Dillhoff
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, USA
| | - Stephen W Behrman
- Department of Surgery, University of Tennessee Health Science Center, Memphis, USA
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Chad G Ball
- Department of Surgery, University of Calgary, Calgary, Alberta, Canada
| | - Adam C Berger
- Department of Surgery, Jefferson Medical College, Philadelphia, USA
| | - John D Christein
- Department of Surgery, University of Alabama School of Medicine, Birmingham, USA
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Ronald R Salem
- Department of Surgery, Yale School of Medicine, New Haven, USA
| | - Charles M Vollmer
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA
| | - Roberto Salvia
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Mohammed Abu Hilal
- Department of Surgery, University Hospital of Southampton NHS Foundation Trust, Southampton, UK; Department of Surgery, Istituto Fondazione Poliambulanza, Brescia, Italy.
| | - Ra'ed Aljarrah
- Department of Surgery, University Hospital of Southampton NHS Foundation Trust, Southampton, UK
| | - Courtney Barrows
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | | | - Eric C H Lai
- Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
| | - Ulrich Wellner
- Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
| | - John Aversa
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Paxton V Dickson
- Department of Surgery, University of Tennessee Health Science Center, Memphis, USA
| | - Takao Ohtsuka
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Elijah Dixon
- Department of Surgery, University of Calgary, Calgary, Alberta, Canada
| | - Richard Zheng
- Department of Surgery, Jefferson Medical College, Philadelphia, USA
| | - Stacy Kowalski
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA
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Prognostic factors and benefits of adjuvant therapy for ampullary cancer following pancreatoduodenectomy: A systematic review and meta-analysis. Asian J Surg 2020; 43:1133-1141. [PMID: 32249101 DOI: 10.1016/j.asjsur.2020.03.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 02/28/2020] [Accepted: 03/13/2020] [Indexed: 12/16/2022] Open
Abstract
Ampullary cancer is a relatively rare gastrointestinal malignancy. The purpose of this study was to evaluate prognostic factors for survival and assess the benefits of adjuvant therapy following pancreaticoduodenectomy for this entity. Medline and EMBASE databases were searched to identify eligible studies from January 2000 to August 2019. Review Manager 5.3 statistical software was used for meta-analysis. 71 studies met the inclusion criteria and were included in the analysis for a total of 8280 patients. The median (range) 5-year overall survival and disease-free survival rates were 58% (32-82%) and 51% (28-73%) respectively. In meta-analysis, age >65 years at diagnosis, tumor size >20 mm, poor differentiation, pancreaticobiliary histotype, pT3-4 stage disease, presence of metastatic lymph node, number of metastatic nodes, perineural invasion, lymphovascular invasion, vascular invasion, pancreatic invasion, and positive surgical margins were independently associated with worse overall survival, whereas adjuvant therapy was associated with improved overall survival. In summary, in patients with ampullary cancer undergoing pancreaticoduodenectomy, tumor factors are the main predictors of worse survival and adjuvant treatment confers a survival benefit.
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12
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Luchini C, Veronese N, Nottegar A, Riva G, Pilati C, Mafficini A, Stubbs B, Simbolo M, Mombello A, Corbo V, Cheng L, Yachida S, Wood LD, Lawlor RT, Salvia R, Scarpa A. Perineural Invasion is a Strong Prognostic Moderator in Ampulla of Vater Carcinoma: A Meta-analysis. Pancreas 2019; 48:70-76. [PMID: 30451797 DOI: 10.1097/mpa.0000000000001194] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Ampulla of Vater carcinoma (AVC) has a broad spectrum of different prognoses. As such, new moderators of survival are urgently needed. We aimed at clarifying the prognostic role of perineural invasion in AVC. METHODS Using PubMed and SCOPUS databases, we conducted the first systematic review and meta-analysis on this topic. RESULTS Analyzing 29 articles for a total of 2379 patients, we found that the presence of perineural invasion increased the risk of all-cause mortality more than 2 times (relative risk [RR], 2.07; 95% confidence interval [CI], 1.78-2.42 [P < 0.0001]; hazard ratio [HR], 2.72; 95% CI, 1.86-3.97 [P < 0.0001]), of cancer-specific mortality more than 6 times (RR, 6.12; 95% CI, 3.25-11.54 [P < 0.0001]; HR, 6.59; 95% CI, 2.29-3.49 [P < 0.0001]), and of recurrence more than 2 times (RR, 2.63; 95% CI, 1.89-3.67 [P < 0.0001]; HR, 2.54; 95% CI, 1.24-5.21 [P = 0.01]). CONCLUSIONS Perineural invasion is strongly associated with a poorer prognosis in AVC, influencing both survival and risk of recurrence. It should be reported in the final pathology report and should be taken into account by future oncologic staging systems, identifying a group of AVC with a more malignant biological behavior.
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Affiliation(s)
| | - Nicola Veronese
- National Institute of Gastroenterology-Research Hospital, IRCCS "S. de Bellis," Castellana Grotte, Bari
| | - Alessia Nottegar
- Department of Surgery, Section of Pathology, San Bortolo Hospital, Vicenza, Italy
| | | | - Camilla Pilati
- Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, Paris-Descartes University, Paris, France
| | | | - Brendon Stubbs
- Health Service and Population Research Department, King's College London, London, United Kingdom
| | - Michele Simbolo
- ARC-Net Research Center, University of Verona, Verona, Italy
| | | | - Vincenzo Corbo
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN
| | - Shinichi Yachida
- Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan
| | | | - Rita T Lawlor
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
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Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience. Eur J Surg Oncol 2018; 44:677-683. [PMID: 29506768 DOI: 10.1016/j.ejso.2018.02.008] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 01/28/2018] [Accepted: 02/06/2018] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. METHODS A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. RESULTS Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. CONCLUSIONS Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma.
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Abstract
OBJECTIVES The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival. METHODS Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1-2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses. RESULTS The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables. CONCLUSIONS Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting.
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15
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Acharya A, Markar SR, Sodergren MH, Malietzis G, Darzi A, Athanasiou T, Khan AZ. Meta-analysis of adjuvant therapy following curative surgery for periampullary adenocarcinoma. Br J Surg 2017; 104:814-822. [PMID: 28518410 DOI: 10.1002/bjs.10563] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 12/24/2016] [Accepted: 03/16/2017] [Indexed: 12/24/2022]
Abstract
BACKGROUND Periampullary cancers are uncommon malignancies, often amenable to surgery. Several studies have suggested a role for adjuvant chemotherapy and chemoradiotherapy in improving survival of patients with periampullary cancers, with variable results. The aim of this meta-analysis was to determine the survival benefit of adjuvant therapy for periampullary cancers. METHODS A systematic review was undertaken of literature published between 1 January 2000 and 31 December 2015 to elicit and analyse the pooled overall survival associated with the use of either adjuvant chemotherapy or chemoradiotherapy versus observation in the treatment of surgically resected periampullary cancer. Included articles were also screened for information regarding stage, prognostic factors and toxicity-related events. RESULTS A total of 704 titles were screened, of which 93 full-text articles were retrieved. Fourteen full-text articles were included in the study, six of which were RCTs. A total of 1671 patients (904 in the control group and 767 who received adjuvant therapy) were included. The median 5-year overall survival rate was 37·5 per cent in the control group, compared with 40·0 per cent in the adjuvant group (hazard ratio 1·08, 95 per cent c.i. 0·91 to 1·28; P = 0·067). In 32·2 per cent of patients who had adjuvant therapy, one or more WHO grade 3 or 4 toxicity-related events were noted. Advanced T category was associated worse survival (regression coefficient -0·14, P = 0·040), whereas nodal status and grade of differentiation were not. CONCLUSION This systematic review found no associated survival benefit for adjuvant chemotherapy or chemoradiotherapy in the treatment of periampullary cancer.
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Affiliation(s)
- A Acharya
- Division of Surgery, Department of Surgery and Cancer, St Mary's Hospital, Imperial College, London, UK
| | - S R Markar
- Division of Surgery, Department of Surgery and Cancer, St Mary's Hospital, Imperial College, London, UK
| | - M H Sodergren
- Division of Surgery, Department of Surgery and Cancer, St Mary's Hospital, Imperial College, London, UK
| | - G Malietzis
- Division of Surgery, Department of Surgery and Cancer, St Mary's Hospital, Imperial College, London, UK
| | - A Darzi
- Division of Surgery, Department of Surgery and Cancer, St Mary's Hospital, Imperial College, London, UK
| | - T Athanasiou
- Division of Surgery, Department of Surgery and Cancer, St Mary's Hospital, Imperial College, London, UK
| | - A Z Khan
- Department of Hepatopancreatobiliary Surgery, Royal Marsden Hospital, London, UK
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Flis V, Potrc S, Kobilica N, Ivanecz A. Pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head with venous resection. Radiol Oncol 2016; 50:321-8. [PMID: 27679549 PMCID: PMC5024653 DOI: 10.1515/raon-2015-0017] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 03/26/2015] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Recent reports have shown that patients with vascular tumour invasion who undergo concurrent vascular resection can achieve long-term survival rates equivalent to those without vascular involvement requiring pancreaticoduodenectomy alone. There is no consensus about which patients benefit from the portal-superior mesenteric vein resection and there is no consensus about the best surgical technique of vessel reconstruction (resection with or without graft reconstruction). As published series are small the aim of this study was to evaluate our experience in pancreatectomies with en bloc vascular resection and reconstruction of vessels. METHODS Review of database at University Clinical Centre Maribor identified 133 patients (average age 65.4 ± 8.6 years, 69 female patients) who underwent pancreatoduodenectomy between January 2006 and August 2014. Clinical data, operative results, pathological findings and postoperative outcomes were collected prospectively and analyzed. Current literature and our experience in pancreatectomies with en bloc vascular resection and reconstruction of portal vein are reviewed. RESULTS Twenty-two patients out of 133 (16.5%) had portal vein-superior mesenteric vein resection and portal vein reconstruction (PVR) during pancreaticoduodenectomy. In fourteen patients portal vein was reconstructed without the use of synthetic vascular graft. In these series two types of venous reconstruction were performed. When tumour involvement was limited to the superior mesenteric vein (SPV) or portal vein (PV) such that the splenic vein could be preserved, and vessels could be approximated without tension a primary end-to-end anastomosis was performed. When tumour involved the SMV-splenic vein confluence, splenic vein ligation was necessary. In the remaining eight procedures interposition graft was needed. Dacron grafts with 10 mm diameter were used. There was no infection after dacron grafting. One patient had portal vein thrombosis after surgery: it was thrombosis after primary reconstruction. There were no thromboses in patients with synthetic graft interposition. There were no significant differences in postoperative morbidity, mortality or grades of complication between groups of patients with or without a PVR. Median survival time in months was in a group with vein resection 16.13 months and in a group without vein resection 15.17 months. Five year survival in the group without vein resection was 19.5%. Comparison of survival curves showed equal hazard rates with log-rank p = 0.090. CONCLUSIONS Survival of patients with pancreatic cancer who undergo an R0 resection with reconstruction was comparable to those who have a standard pancreaticoduodenectomy with no added mortality or morbidity. Synthetic graft appeared to be an effective and safe option as an interposition graft for portomesenteric venous reconstruction after pancreaticoduodenectomy.
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Affiliation(s)
- Vojko Flis
- Department of Vascular Surgery, Surgical clinics, University Clinical Centre Maribor, Slovenia
| | - Stojan Potrc
- Department of Vascular Surgery, Surgical clinics, University Clinical Centre Maribor, Slovenia
| | - Nina Kobilica
- Department of Vascular Surgery, Surgical clinics, University Clinical Centre Maribor, Slovenia
| | - Arpad Ivanecz
- Department of Vascular Surgery, Surgical clinics, University Clinical Centre Maribor, Slovenia
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Doepker MP, Thompson ZJ, Centeno BA, Kim RD, Wong J, Hodul PJ. Clinicopathologic and survival analysis of resected ampullary adenocarcinoma. J Surg Oncol 2016; 114:170-5. [PMID: 27158031 DOI: 10.1002/jso.24281] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Accepted: 04/20/2016] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Ampullary adenocarcinoma (AAC) is a rare neoplasm. We sought to determine the clinicopathologic factors contributing to the overall survival (OS) and recurrence-free (RFS) survival. METHODS Patients (pts) with resected AAC were identified from 1996 to 2015 and reviewed for clinicopathologic factors and correlated with outcome. RESULTS We identified and evaluated 106 pts diagnosed with AAC. The median age was 70.2 years (range 41-86) and 60 (56.6%) were male. Overall, 105 pts (99.1%) had a pancreaticoduodenectomy. An R0 resection was achieved in 101 (95%) pts. Median follow-up was 19 months with a median OS of 49.3 months. Lymph node metastasis and poorly differentiated tumors adversely affected OS on multivariate analysis (MVA). Twenty patients (18.9%) developed recurrence. The median RFS was 27 months. RFS was adversely affected by lymph node count and metastasis, tumor differentiation, and histological subtype on MVA. Survival was not affected by the addition of adjuvant therapy. Retrieval of ≤12 lymph nodes and lymph node ratio ≥0.10 resulted in worse OS on Kaplan-Meier analysis. CONCLUSIONS Our data show retrieval of ≤12 nodes, involvement of nodes with AAC, moderately or poorly differentiated tumors, and pancreaticobiliary subtype adversely affected survival, while the use of adjuvant therapy demonstrated no significant benefit. J. Surg. Oncol. 2016;114:170-175. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Matthew P Doepker
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
| | | | | | - Richard D Kim
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Joyce Wong
- Department of Surgical Oncology, Penn State Hershey Medical Center, Hershey, Pennsylvania
| | - Pamela J Hodul
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
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Panzeri F, Crippa S, Castelli P, Aleotti F, Pucci A, Partelli S, Zamboni G, Falconi M. Management of ampullary neoplasms: A tailored approach between endoscopy and surgery. World J Gastroenterol 2015; 21:7970-7987. [PMID: 26185369 PMCID: PMC4499340 DOI: 10.3748/wjg.v21.i26.7970] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Revised: 03/27/2015] [Accepted: 05/04/2015] [Indexed: 02/07/2023] Open
Abstract
Ampullary neoplasms, although rare, present distinctive clinical and pathological features from other neoplastic lesions of the periampullary region. No specific guidelines about their management are available, and they are often assimilated either to biliary tract or to pancreatic carcinomas. Due to their location, they tend to become symptomatic at an earlier stage compared to pancreatic malignancies. This behaviour results in a higher resectability rate at diagnosis. From a pathological point of view they arise in a zone of transition between two different epithelia, and, according to their origin, may be divided into pancreatobiliary or intestinal type. This classification has a substantial impact on prognosis. In most cases, pancreaticoduodenectomy represents the treatment of choice when there is an overt or highly suspicious malignant behaviour. The rate of potentially curative resection is as high as 90% and in high-volume centres an acceptable rate of complications is reported. In selected situations less invasive approaches, such as ampullectomy, have been advocated, although there are some concerns mainly because of a higher recurrence rate associated with limited resections for invasive carcinomas. Importantly, these methods have the drawback of not including an appropriate lymphadenectomy, while nodal involvement has been shown to be frequently present also in apparently low-risk carcinomas. Endoscopic ampullectomy is now the procedure of choice in case of low up to high-grade dysplasia providing a proper assessment of the T status by endoscopic ultrasound. In the present paper the evidence currently available is reviewed, with the aim of offering an updated framework for diagnosis and management of this specific type of disease.
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Bourgouin S, Ewald J, Mancini J, Moutardier V, Delpero JR, Le Treut YP. Predictors of Survival in Ampullary, Bile Duct and Duodenal Cancers Following Pancreaticoduodenectomy: a 10-Year Multicentre Analysis. J Gastrointest Surg 2015; 19:1247-55. [PMID: 25947547 DOI: 10.1007/s11605-015-2833-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 04/20/2015] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Predictors of survival following pancreaticoduodenectomy (PD) are well described for pancreatic cancers but are less detailed in ampullary (AC), bile duct (BDC) and duodenal cancers (DC). We therefore sought to evaluate the long-term results of PD for AC, BDC and DC, and to determine for each tumour the predictive factors of survival. METHODS Medical charts of patients operated on between 2001 and 2011 were retrospectively reviewed. Univariate and multivariate analyses were performed to determine predictors of survival. RESULTS One hundred thirty-five patients were identified. Mean follow-up was 47 ± 33 months. Median survival was not reached for DC and was 66 and 24 months for AC and BDC, respectively. Two-year and five-year survival rates were 80 and 51% for DC and 69 and 51% for AC, respectively. BDC had a significantly poorer prognosis, with two-year and five-year survival rates of 51 and 34%, respectively. Predictors of survival were weight loss, N stage and International Union Against Cancer (UICC) stage for AC, T stage and resection margin status for BDC and N stage for DC. CONCLUSION AC, BDC and DC display distinctive predictors of survival related to the biological aggressiveness. Preoperative malnutrition worsens the prognosis. The effect of adapted nutritional management on the survival improvement has to be studied.
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Affiliation(s)
- Stéphane Bourgouin
- APHM La Conception, Department of Surgery and Liver Transplantation, Aix-Marseille University, 147 Boulevard Baille, Marseille, France,
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Survival in ampullary cancer: potential role of different KRAS mutations. Surgery 2015; 157:260-8. [PMID: 25616942 DOI: 10.1016/j.surg.2014.08.092] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2012] [Accepted: 08/27/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The prognosis of ampullary adenocarcinoma (AA) usually is favorable; however, a subset of AA have poor biology and outcomes similar to pancreatic cancer. Patients in this subset will have early recurrence and death usually within 2 years. To date, there are no genetic markers to identify these patients. This study identifies the high-risk subset of AA and evaluates the mutational status of KRAS in predicting poor outcome. METHODS The tumor registry of an academic center was reviewed for data on patients managed operatively with AA. KRAS genotypes were determined for these patients using a polymerase chain reaction-based assay on clinical specimens. Analysis of variance and χ(2) tests was used to categorize continuous and categorical variables. Univariate and multivariate survival analyses were performed using Kaplan-Meier and Cox methods, respectively. RESULTS A total of 146 patients were identified with AA between 1982 and 2008. After stringent pathologic review, 97 patients were confirmed with AA, of whom 75 had tissue specimens available for analysis. Genotyping revealed 67% were wild-type (KRAS(WT)), and 33% were mutant for KRAS. Patients with KRAS(G12D) (n = 9), the most common mutational genotype, had poorer median survival (62 months) compared with those with KRAS(non-G12D) mutants (median survival not reached, mean 145 months) and KRAS(WT) patients (155 months, P = .05). Patients with survival ≤30 months were labeled "high-risk." Of the 9 patients with KRAS(G12D), 56% were in this high-risk subset, compared with 18% of KRAS(WT) (P = .02) and 31% of KRAS(non-G12D) (P > .05) populations. Patients with KRAS(G12D) also were more likely to present with advanced T stage. CONCLUSION The KRAS(G12D) mutation identifies a subset of AA patients with poor prognoses and may be used to identify patients at risk of early recurrence and poorer survival who may benefit from adjuvant therapy.
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Zhao X, Dong J, Huang X, Zhang W, Jiang K. Prognostic factors for survival of patients with ampullary carcinoma after local resection. ANZ J Surg 2014; 85:567-71. [PMID: 24735093 DOI: 10.1111/ans.12600] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/03/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Local resection (LR) is a potentially effective alternative to pancreaticoduodenectomy for treatment of ampullary cancer, but the prognostic factors remain undefined. The purpose of this study was to identify the prognostic factors for ampullary cancer patients who had undergone LR. METHODS We retrospectively reviewed the clinical, pathological data and surgical approach of 34 ampullary cancer patients who had undergone LR during 1996-2009 at People's Liberation Army General Hospital. Prognostic factors for survival and recurrence were analysed. RESULTS The 1-, 3- and 5-year survival rates of the patients were 97.1, 69.5 and 53.7%, respectively. The gender, age, preoperative bilirubin levels, CA19-9 levels and preoperative biopsy did not correlate with the survival rates. The survival rates of patient with T1 and T2 tumours were superior to that of patients with T3 tumours (P = 0.000). Tumour size, surgical margin status and the extent of differentiation had no effect on survival rates (P = 0.464, P = 0.601 and P = 0.121, respectively). The survival rate of patients who had extraduodenal LR (12 cases) was superior to that of patients who had transduodenal LR (22 cases) (P = 0.026). Tumour recurrence occurred in 14 (41.2%) patients. Tumour infiltration (P = 0.014) correlated with the recurrence. CONCLUSION The degree of tumour infiltration is the pathological factor that most affects the survival of ampullary cancer patients who undergo LR. Extraduodenal LR is a promising surgical procedure, the efficacy of which is superior to that of transduodenal LR. The depth of tumour invasion correlated with the recurrence.
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Affiliation(s)
- Xiangqian Zhao
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China
| | - Jiahong Dong
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China
| | - Xiaoqiang Huang
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China
| | - Wenzhi Zhang
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China
| | - Kai Jiang
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China
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Westgaard A, Pomianowska E, Clausen OPF, Gladhaug IP. Intestinal-type and pancreatobiliary-type adenocarcinomas: how does ampullary carcinoma differ from other periampullary malignancies? Ann Surg Oncol 2012; 20:430-9. [PMID: 22956064 DOI: 10.1245/s10434-012-2603-0] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2012] [Indexed: 12/19/2022]
Abstract
BACKGROUND Ampullary carcinomas typically have either intestinal or pancreatobiliary type of differentiation, histopathologically resembling carcinomas of its adjacent tissues (duodenum, bile duct, or pancreas). We evaluated whether the histologic type itself is more important for long-term survival than the fact that the tumor originated in the ampulla. METHODS Microscopic slides from 207 consecutive pancreatoduodenectomies were reviewed (72 pancreatic, 46 biliary, 61 ampullary, and 28 duodenal adenocarcinomas; 76 intestinal type, 131 pancreatobiliary type). Tumor size, nodal involvement, margin involvement, degree of differentiation, vascular involvement, and perineural growth, as well as overall survival, were compared between different origins of the same histologic type. RESULTS Intestinal-type ampullary adenocarcinomas had similar frequency of poor histopathologic factors compared to duodenal adenocarcinomas, and pancreatobiliary-type ampullary adenocarcinomas had similar frequency of poor histopathologic factors compared to pancreatobiliary-type biliary and pancreatic adenocarcinomas. Adjusting for tumor size and nodal involvement, there was no difference in long-term survival between patients with intestinal-type ampullary, duodenal, or biliary and pancreatic tumors (p = 0.79), and there was no difference in long-term survival between patients with pancreatobiliary-type ampullary, biliary, or pancreatic tumors (p = 0.41). CONCLUSIONS Long-term survival for patients with ampullary carcinomas equals pancreatic, biliary, and duodenal carcinomas when the same histologic type is compared. It can be questioned whether ampullary carcinomas should be regarded as a separate entity in classification of solid tumors. Clinical trials on adjuvant treatments for periampullary carcinomas should stratify by pancreatobiliary type versus intestinal type of histologic differentiation.
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Affiliation(s)
- Arne Westgaard
- Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
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