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1
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Uijterwijk BA, Moekotte A, Boggi U, Mazzola M, Groot Koerkamp B, Dalle Valle R, Koek S, Bolm L, Mazzotta A, Luyer M, Goh BKP, Suarez Muñoz MA, Björnsson B, Kazemier G, Ielpo B, Pessaux P, Kleeff J, Ghorbani P, Mavroeidis VK, Fusai GK, Salvia R, Zerbi A, Roberts KJ, Alseidi A, Al-Sarireh B, Serradilla-Martín M, Vladimirov M, Korkolis D, Soonawalla Z, Gruppo M, Bouwense SAW, Vollmer CM, Behrman SW, Christein JD, Besselink MG, Abu Hilal M. Oncological resection and perioperative outcomes of robotic, laparoscopic and open pancreatoduodenectomy for ampullary adenocarcinoma: a propensity score matched international multicenter cohort study. HPB (Oxford) 2025; 27:318-329. [PMID: 39765373 DOI: 10.1016/j.hpb.2024.11.013] [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: 04/22/2024] [Revised: 07/28/2024] [Accepted: 11/28/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND Ampullary adenocarcinoma (AAC) typically presents at an early stage due to biliary obstruction and therefore might be specifically suitable for minimally invasive pancreatoduodenectomy (MIPD). However, studies assessing MIPD specifically for AAC, including the robotic and laparoscopic approach, are limited. The aim of this study is to compare short- and long-term oncological resection and perioperative outcomes of robotic (RPD), laparoscopic (LPD) and open pancreatoduodenectomy (OPD) performed specifically for AAC. METHODS In this multicenter international cohort study, encompassing 35 centers from 11 countries, MIPD versus OPD and subgroup analyses of LPD versus RPD were undertaken. The primary outcomes regarded the oncological resection (R1 resection rate, lymph node yield) and 5-years overall survival. Secondary outcomes were perioperative outcomes (including intra-operative variables, surgical complications and hospital stay). RESULTS In total, patients with AAC who underwent OPD (1721) or MIPD (141) were included. After propensity-score matching, 134 patients per cohort were included. The MIPD group consisted of 53 RPDs and 71 LPDs (50 per group after PSM). There was no difference in overall survival between MIPD and OPD (61.6 % vs 56.2 %, P = 0.215). In the MIPD group, operative time was longer (439 vs 360 min, P < 0.001). Between RPD and LPD, overall survival was not significantly different (75.8 % vs 47.4 %, P = 0.098) and lymph node yield was higher in RPD (21 vs 18, P = 0.014). CONCLUSION In conclusion, patients with AAC seem to have comparable oncological resection and perioperative outcomes from MIPD compared to the traditional OPD. Both RPD as LPD appear to be safe alternatives for patients with AAC, which warrants confirmation by future randomized studies.
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Affiliation(s)
- Bas A Uijterwijk
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands.
| | - Alma Moekotte
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Ugo Boggi
- Department of Surgery, Pisa University Hospital, Pisa, Italy
| | - Michele Mazzola
- Division of Oncologic and Mini-invasive General Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | | | - Sharnice Koek
- Fiona Stanley Hospital, Department of Surgery, Perth, Australia
| | - Louisa Bolm
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany
| | - Alessandro Mazzotta
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France
| | - Misha Luyer
- Catharina Hospital Eindhoven, Department of Surgery, the Netherlands
| | - Brian K P Goh
- Singapore General Hospital, Department of Hepatopancreatobiliary and Transplant Surgery, Duke-National University of Singapore, Singapore
| | | | - Bergthor Björnsson
- Department of Surgery in Linköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Geert Kazemier
- Department of Surgery, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands
| | | | - Patrick Pessaux
- Hepatobiliary and Pancreatic Surgical Unit, Nouvel Hôpital Civil (NHC), Strasbourg, France
| | - Jorg Kleeff
- Department of Surgery, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Poya Ghorbani
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - Vasileios K Mavroeidis
- Department of Academic Surgery, The Royal Marsden Hospital, London, UK; Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Giuseppe K Fusai
- Department of Surgery, Royal Free London NHS Foundation Trust, London, UK
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Keith J Roberts
- Faculty of Medicine, University of Birmingham, Birmingham, UK
| | | | | | - Mario Serradilla-Martín
- Instituto de Investigación Sanitaria Aragón, Department of Surgery, Miguel Servet University Hospital, Zaragoza, Spain
| | - Miljana Vladimirov
- Department of General Surgery, Paracelsus Medical University Nürnberg, 90419, Nürnberg, Germany; Department of Abdominal Surgery, University Hospital Lippe, University Bielefeld, Campus Detmold, Germany
| | - Dimitris Korkolis
- Department of Surgery, Hellenic Anticancer Hospital 'Saint Savvas', Athens, Greece
| | - Zahir Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Mario Gruppo
- Veneto Institute of Oncology IOV - IRCCS, Unit of Surgical Oncology of the Digestive Tract, Italy
| | - Stefan A W Bouwense
- Department of Surgery, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Charles M Vollmer
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA
| | - Stephen W Behrman
- Department of Surgery, University of Tennessee Health Science Center, Memphis, USA
| | - John D Christein
- Department of Surgery, University of Alabama School of Medicine, Birmingham, USA
| | - Marc G Besselink
- Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
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2
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Ecker BL, Seier K, Eckhoff AM, Tortorello GN, Allen PJ, Balachandran VP, Blackburn N, D’Angelica MI, DeMatteo RP, Blazer DG, Drebin JA, Fisher WE, Fortuna D, Gill AJ, Gingras MC, Kingham TP, Lee MK, Lidsky ME, Nussbaum DP, Overman MJ, Samra JS, Shen R, Sigel CS, Soares KC, Vollmer CM, Wei AC, Zani S, Roses RE, Gonen M, Jarnagin WR. Genome-Derived Ampullary Adenocarcinoma Classifier and Postresection Prognostication. JAMA Surg 2024; 159:1365-1373. [PMID: 39259526 PMCID: PMC11391358 DOI: 10.1001/jamasurg.2024.3588] [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: 03/08/2024] [Accepted: 06/28/2024] [Indexed: 09/13/2024]
Abstract
Importance Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use. Objective To test external validity of the prognostic value of the hidden genome classifier of AA. Design, Setting, and Participants This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020. Exposures The multilevel meta-feature regression model previously trained on a prospectively sequenced cohort of 3411 patients (1001 pancreatic adenocarcinoma, 165 distal bile duct adenocarcinoma, and 2245 colorectal adenocarcinoma) was applied to AA sequencing data to quantify the relative proportions of parental cell of origin. Main Outcome and Measures Genomic classification was correlated with immunohistologic subtype (intestinal [INT] or pancreatobiliary [PB]) and with overall survival (OS), using the log-rank test and Cox proportional hazard models. Results Among 192 patients with AA (median age, 69.0 [IQR, 60.0-74.0] years and 134 were male [64%]), concordance between immunohistologic and genomic subtypes was 55%. Most INT subtype tumors were categorized into the colorectal genomic subtype (43 of 57 [72.9%]). Of the 114 PB subtype tumors, 29 had a pancreatic genomic profile (25.4%) and 24 had a distal bile duct genomic profile (21.1%). Whereas the standard immunohistologic subtypes were not associated with survival (log rank P = .26), predicted genomic probabilities were correlated with survival probability. Genomic scores with higher colorectal probability were associated with higher survival probability; higher pancreatic and distal bile duct probabilities were associated with lower survival probability. Conclusions and Relevance The AA genomic classifier is reproducible with available molecular testing in a diverse international cohort of patients and improves stratification of the divergent clinical outcomes beyond standard immunohistologic classification. These data provide a molecular classification that may be incorporated into clinical trials for prospective validation.
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Affiliation(s)
- Brett L. Ecker
- Division of Surgical Oncology, Rutgers Cancer Institute, New Brunswick, New Jersey
| | - Kenneth Seier
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Austin M. Eckhoff
- Department of Surgery, Duke University School of Medicine, Durham, North Carolina
| | - Gabriella N. Tortorello
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Peter J. Allen
- Department of Surgery, Duke University School of Medicine, Durham, North Carolina
| | - Vinod P. Balachandran
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Nicola Blackburn
- The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, Sydney, New South Wales, Australia
| | - Michael I. D’Angelica
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ronald P. DeMatteo
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Daniel G. Blazer
- Department of Surgery, Duke University School of Medicine, Durham, North Carolina
| | - Jeffrey A. Drebin
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - Danielle Fortuna
- Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Anthony J. Gill
- The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, Sydney, New South Wales, Australia
- Royal North Shore Hospital, Westbourne Street, St Leonards, New South Wales, Australia
| | - Marie-Claude Gingras
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
| | - T. Peter Kingham
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Major K. Lee
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Michael E. Lidsky
- Department of Surgery, Duke University School of Medicine, Durham, North Carolina
| | - Daniel P. Nussbaum
- Department of Surgery, Duke University School of Medicine, Durham, North Carolina
| | - Michael J. Overman
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jaswinder S. Samra
- Royal North Shore Hospital, Westbourne Street, St Leonards, New South Wales, Australia
| | - Ronglai Shen
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Carlie S. Sigel
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Kevin C. Soares
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Charles M. Vollmer
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Alice C. Wei
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Sabino Zani
- Department of Surgery, Duke University School of Medicine, Durham, North Carolina
| | - Robert E. Roses
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Mithat Gonen
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - William R. Jarnagin
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
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Hasegawa S, Wada H, Kubo M, Mukai Y, Mikamori M, Akita H, Matsuura N, Kitakaze M, Masuike Y, Sugase T, Shinno N, Kanemura T, Hara H, Sueda T, Nishimura J, Yasui M, Omori T, Miyata H, Ohue M. The clinical significance of the lymph node ratio as a recurrence indicator in ampullary cancer after curative pancreaticoduodenectomy. Langenbecks Arch Surg 2024; 409:302. [PMID: 39377937 DOI: 10.1007/s00423-024-03481-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: 02/10/2024] [Accepted: 09/16/2024] [Indexed: 10/09/2024]
Abstract
BACKGROUND The clinical significance of the lymph node ratio (LNR), the number of metastatic lymph nodes per dissected lymph node, has not been sufficiently clarified in ampullary cancer. METHODS Among patients diagnosed histopathologically with ampullary cancer between 1980 and 2018, the study included 106 who underwent pathological radical resection by pancreaticoduodenectomy. The relationships between the LNR and metastatic lymph node sites and prognosis were examined. RESULTS Multivariate analysis revealed that sex and lymph node metastasis were independent prognostic factors. In the 46 patients (43%) with metastatic lymph nodes, the LNR in the recurrence group was significantly higher than that in the non-recurrence group (0.15 ± 0.11 vs. 0.089 ± 0.071, p = 0.025). The receiver operating characteristic curve demonstrated that the LNR cut-off value, 0.07 (area under the curve = 0.70, sensitivity 81%, specificity 56%), was a significant indicator for recurrence (22% vs. 61%, p = 0.016) and prognosis (5-year survival: 48% vs. 83%, p = 0.028). Among the metastatic lymph node sites in the 46 positive cases, lymph node metastases developed from the peripancreatic head region (80%, 37/46) to the superior mesenteric artery (33%, 15/46) and para-aortic (11%, 5/46) regions. CONCLUSION Lymph node metastasis is an independent prognostic factor, and the LNR is a significant indicator for recurrence and prognosis in patients with ampullary cancer.
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Affiliation(s)
- Shinichiro Hasegawa
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan.
| | - Masahiko Kubo
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Yosuke Mukai
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Manabu Mikamori
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Norihiro Matsuura
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Masatoshi Kitakaze
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Yasunori Masuike
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Takahito Sugase
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Naoki Shinno
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Takashi Kanemura
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Hisashi Hara
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Toshinori Sueda
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Junichi Nishimura
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Masayoshi Yasui
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Takeshi Omori
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Hiroshi Miyata
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Masayuki Ohue
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan
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Tarcan ZC, Esmer R, Akar KE, Bagci P, Bozkurtlar E, Saka B, Armutlu A, Sahin Ozkan H, Ozcan K, Taskin OC, Kapran Y, Aydin Mericoz C, Balci S, Yilmaz S, Cengiz D, Gurses B, Alper E, Tellioglu G, Bozkurt E, Bilge O, Cheng JD, Basturk O, Adsay NV. Intra-ampullary Papillary Tubular Neoplasm (IAPN): Clinicopathologic Analysis of 72 Cases Highlights the Distinctive Characteristics of a Poorly Recognized Entity. Am J Surg Pathol 2024; 48:1093-1107. [PMID: 38938087 DOI: 10.1097/pas.0000000000002275] [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: 06/29/2024]
Abstract
The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3 cm. Gross-microscopic correlation was crucial. From the duodenal perspective, the ampulla was typically raised symmetrically, with a patulous orifice, and was otherwise covered by stretched normal duodenal mucosa. However, in 6 cases, the protrusion of the intra-ampullary tumor to the duodenal surface gave the impression of an "ampullary-duodenal tumor," with the accurate diagnosis of IAPN established only by microscopic correlation illustrating the abrupt ending of the lesion at the edge of the ampulla. Microscopically, the preinvasive component often revealed mixed phenotypes (44.4% predominantly nonintestinal). The invasion was common (94%), typically small (mean=1.2 cm), primarily pancreatobiliary-type (75%), and showed aggressive features (lymphovascular invasion in 66%, perineural invasion in 41%, high budding in 30%). In 6 cases, the preinvasive component was pure intestinal, but the invasive component was pancreatobiliary. LN metastasis was identified in 42% (32% in those with ≤1 cm invasion). The prognosis was significantly better than ampullary-ductal carcinomas (median: 69 vs. 41 months; 3-year: 68% vs. 55%; and 5-year: 51% vs. 35%, P =0.047). In conclusion, unlike ampullary-duodenal carcinomas, IAPNs are often (44.4%) predominantly nonintestinal and commonly (94%) invasive, displaying aggressive features and LN metastasis even when minimally invasive, all of which render them less amenable to ampullectomy. However, their prognosis is still better than that of the "ampullary-ductal" carcinomas, with which IAPNs are currently grouped in CAP protocols (while IAPNs are kindreds of intraductal tumors of the pancreatobiliary tract, the latter represents the ampullary counterpart of pancreatic adenocarcinoma/cholangiocarcinoma).
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Affiliation(s)
- Zeynep C Tarcan
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | | | | | | | | | | | - Kerem Ozcan
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | | | - Serdar Balci
- Department of Pathology, Memorial Hospitals Group
| | | | | | | | | | | | | | - Orhan Bilge
- Department of Surgery, American Hospital, Istanbul, Turkey
| | | | - Olca Basturk
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
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5
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Srivastava A, Nekarakanti PK, Kanchodu S, Srivastava S, Mishra PK, Saluja SS. Role of adjuvant therapy in resected periampullary adenocarcinoma: A propensity matched case-control study. Ann Hepatobiliary Pancreat Surg 2024; 28:371-380. [PMID: 38600673 PMCID: PMC11341887 DOI: 10.14701/ahbps.24-032] [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: 02/02/2024] [Revised: 03/04/2024] [Accepted: 03/07/2024] [Indexed: 04/12/2024] Open
Abstract
Backgrounds/Aims The published data had contradictory information on the role of adjuvant therapy on resected periampullary carcinomas (PACA). The study was performed to evaluate the survival benefit of adjuvant treatment. Methods This was a propensity score matched case-control study from a prospectively maintained database from 2004-2019. The study included patients with nonpancreatic PACA who underwent curative resection. The patients (cases) who received adjuvant chemotherapy were compared with patients (controls) who were observed alone after surgery. Results Of 510 patients with PACA, 230 patients (cases = 107, controls = 123) formed the unmatched study cohort. After propensity score matching, 140 patients (cases = 70, controls = 70) formed the matched study cohort. The median overall survival (OS) was similar in cases than controls in the unmatched population but doubled non-significantly in cases after matching (unmatched population, 54 months vs. 54 months, p-value = 0.624; matched population, 71 months vs. 36 months, p-value = 0.087). However, the median recurrence-free survival (RFS) was non significantly higher in the control group (unmatched population, 59 months vs. 38 months, p-value = 0.195; matched population, 53 months vs. 40 months, p-value = 0.797). In cox regression analysis, age < 60 years, advanced T stage, and presence of perineural invasion were independent factors for worse RFS, while tumor recurrence was an independent factor for poor OS. Conclusions Patients with nonpancreatic PACA may have an OS benefit from adjuvant chemotherapy, and this needs to be validated with large prospective randomized studies.
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Affiliation(s)
- Anurita Srivastava
- Department of Radiotherapy, Maulana Azad Medical College (MAMC), New Delhi, India
| | - Phani Kumar Nekarakanti
- Department of GI Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research (GIPMER), New Delhi, India
| | - Sudheer Kanchodu
- Department of GI Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research (GIPMER), New Delhi, India
| | - Siddharth Srivastava
- Department of Gastro Medicine, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research (GIPMER), New Delhi, India
| | - Pramod Kumar Mishra
- Department of GI Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research (GIPMER), New Delhi, India
| | - Sundeep Singh Saluja
- Department of GI Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research (GIPMER), New Delhi, India
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6
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Demirci NS, Cavdar E, Ozdemir NY, Yuksel S, Iriagac Y, Erdem GU, Odabas H, Hacibekiroglu I, Karaagac M, Ucar M, Ozturk B, Bozkaya Y. Clinicopathologic Analysis and Prognostic Factors for Survival in Patients with Operable Ampullary Carcinoma: A Multi-Institutional Retrospective Experience. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:818. [PMID: 38793001 PMCID: PMC11122928 DOI: 10.3390/medicina60050818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 05/10/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024]
Abstract
Background and Objectives: In ampullary cancer, 5-year survival rates are 30-50%, even with optimal resection and perioperative systemic therapies. We sought to determine the important clinicopathological features and adjuvant treatments in terms of the prognosis of patients with operable-stage ampullary carcinomas. Materials and Methods: We included 197 patients who underwent pancreaticoduodenectomy to treat ampullary carcinomas between December 2003 and May 2019. Demographics, clinical features, treatments, and outcomes/survival were analyzed. Results: The median disease-free survival (mDFS) and median overall survival (mOS) were 40.9 vs. 63.4 months, respectively. The mDFS was significantly lower in patients with lymphovascular invasion (p < 0.001) and lymph node involvement (p = 0.027). Potential predictors of decreased OS on univariate analysis included age ≥ 50 years (p = 0.045), poor performance status (p = 0.048), weight loss (p = 0.045), T3-T4 tumors (p = 0.018), surgical margin positivity (p = 0.01), lymph node involvement (p = 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.007), and poor histological grade (p = 0.042). For the multivariate analysis, only nodal status (hazard ratio [HR]1.98; 95% confidence interval [CI], 1.08-3.65; p = 0.027) and surgical margin status (HR 2.61; 95% CI, 1.09-6.24; p = 0.03) were associated with OS. Conclusions: Nodal status and a positive surgical margin were independent predictors of a poor mOS for patients with ampullary carcinomas. Additional studies are required to explore the role of adjuvant therapy in patients with ampullary carcinomas.
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Affiliation(s)
- Nebi Serkan Demirci
- Department of Medical Oncology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098 Istanbul, Türkiye
| | - Eyyup Cavdar
- Department of Medical Oncology, Adiyaman Training and Research Hospital, Adiyaman University, 02000 Adiyaman, Türkiye
| | - Nuriye Yildirim Ozdemir
- Department of Medical Oncology, Faculty of Medicine, Yıldırım Beyazıt University, 06010 Ankara, Türkiye
| | - Sinemis Yuksel
- Department of Medical Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, 34865 Istanbul, Türkiye
| | - Yakup Iriagac
- Department of Medical Oncology, Balikesir Ataturk City Hospital, 10100 Balikesir, Türkiye
| | - Gokmen Umut Erdem
- Department of Medical Oncology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098 Istanbul, Türkiye
| | - Hatice Odabas
- Department of Medical Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, 34865 Istanbul, Türkiye
| | - Ilhan Hacibekiroglu
- Department of Medical Oncology, Faculty of Medicine, Sakarya University, 54050 Sakarya, Türkiye
| | - Mustafa Karaagac
- Department of Medical Oncology, Meram Medical Faculty, Necmettin Erbakan University, 42090 Konya, Türkiye;
| | - Mahmut Ucar
- Department of Medical Oncology, Faculty of Medicine, Erciyes University, 38039 Kayseri, Türkiye
| | - Banu Ozturk
- Department of Medical Oncology, Akdeniz University, 07058 Antalya, Türkiye;
| | - Yakup Bozkaya
- Department of Medical Oncology, Yeniyuzyil University-Gaziosmanpasa Hospital, 34098 Istanbul, Türkiye;
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7
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Sugiura R, Kuwatani M, Kin T, Matsumoto R, Ikeda Y, Sano I, Hirata K, Yoshida M, Masaki Y, Ono M, Hirata H, Yamato H, Onodera M, Nakamura H, Taya Y, Ehira N, Nakajima M, Kawabata H, Ihara H, Kudo T, Kato S, Katanuma A. Risk factors for recurrent biliary obstruction following endoscopic biliary stenting in patients with unresectable ampullary cancer: A multicenter retrospective study. J Dig Dis 2024; 25:310-317. [PMID: 38973135 DOI: 10.1111/1751-2980.13288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 04/25/2024] [Accepted: 05/14/2024] [Indexed: 07/09/2024]
Abstract
OBJECTIVES Unresectable ampullary cancer (AC) is a rare disease entity. The risk factors for recurrent biliary obstruction (RBO) following endoscopic biliary stenting (EBS) for unresectable AC remain unknown. In this study we aimed to evaluate the cumulative RBO rate and to identify risk factors for RBO following palliative EBS in patients with unresectable AC. METHODS This multicenter retrospective observational study enrolled consecutive patients with unresectable AC who had undergone palliative EBS between April 2011 and December 2021. The cumulative rate of and risk factors for RBO following palliative EBS were evaluated via multivariate analysis. RESULTS The study analysis comprised 107 patients with a median age of 84 years (interquartile range 79-88 years). Plastic stents (PSs) and self-expandable metal stents (SEMSs) were placed in 53 and 54 patients, respectively. Functional success was accomplished in 104 (97.2%) patients. Of these, RBO occurred in 62 (59.6%) patients, with obstruction and complete/partial migration occurring in 47 and 15 patients, respectively. The median time to RBO was 190 days. Multivariate analysis showed that PS was associated with a higher rate of RBO compared to SEMS (hazard ratio [HR] 2.48; P < 0.01) and that the presence of common bile duct stones/sludge immediately after EBS was an independent risk factor for RBO (HR 1.99; P = 0.04). CONCLUSIONS The use of SEMS compared to PS during EBS reduced the time to RBO in patients with unresectable AC. Common bile duct stones/sludge immediately after EBS was a risk factor for RBO.
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Affiliation(s)
- Ryo Sugiura
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Masaki Kuwatani
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Toshifumi Kin
- Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Hokkaido, Japan
| | - Ryusuke Matsumoto
- Department of Gastroenterology, Obihiro Kosei Hospital, Obihiro, Hokkaido, Japan
| | - Yuki Ikeda
- Department of Gastroenterology, Oji General Hospital, Tomakomai, Hokkaido, Japan
| | - Itsuki Sano
- Department of Internal Medicine, Kushiro Rosai Hospital, Kushiro, Hokkaido, Japan
| | - Koji Hirata
- Department of Gastroenterology and Hepatology, Hakodate Municipal Hospital, Hakodate, Hokkaido, Japan
| | - Makoto Yoshida
- Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan
| | - Yoshiharu Masaki
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan
| | - Michihiro Ono
- Department of Gastroenterology, Steel Memorial Muroran Hospital, Muroran, Hokkaido, Japan
| | - Hajime Hirata
- Department of Gastroenterology, Tomakomai City Hospital, Tomakomai, Hokkaido, Japan
| | - Hiroaki Yamato
- Department of Gastroenterology, Iwamizawa Municipal General Hospital, Iwamizawa, Hokkaido, Japan
| | - Manabu Onodera
- Department of Gastroenterology, NTT East Sapporo Hospital, Sapporo, Hokkaido, Japan
| | - Hideaki Nakamura
- Department of Gastroenterology, Hokkaido Gastroenterology Hospital, Sapporo, Hokkaido, Japan
| | - Yoko Taya
- Department of Gastroenterology, Hokkaido Medical Center, Sapporo, Hokkaido, Japan
| | - Nobuyuki Ehira
- Department of Gastroenterology, Kitami Red Cross Hospital, Kitami, Hokkaido, Japan
| | - Masahito Nakajima
- Department of Gastroenterology, Aiiku Hospital, Sapporo, Hokkaido, Japan
| | - Hidemasa Kawabata
- Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Hideyuki Ihara
- Department of Gastroenterology, Tonan Hospital, Sapporo, Hokkaido, Japan
| | - Taiki Kudo
- Department of Gastroenterology, IMS Sapporo Digestive Disease Center General Hospital, Sapporo, Hokkaido, Japan
| | - Shin Kato
- Department of Gastroenterology, Sapporo City General Hospital, Sapporo, Hokkaido, Japan
| | - Akio Katanuma
- Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Hokkaido, Japan
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8
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Siddiqui SH, Kumari N, Mishra S, Radha P, Mohindra S, Singh RK, Krishnani N. PD-L1 Expression in Ampullary Adenocarcinoma. Int J Surg Pathol 2024; 32:263-272. [PMID: 37291997 DOI: 10.1177/10668969231177263] [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] [Indexed: 06/10/2023]
Abstract
INTRODUCTION Ampullary adenocarcinoma is a rare neoplasm often treated by the complex Whipple's procedure. Several histological factors predict poor prognosis including pancreatobiliary morphology, presence of lymphovascular, perineural invasion and local or distant metastasis. Systemic therapy with gemcitabine, 5-fluorouracil regimens are given with variable benefits. Immunotherapy checkpoint inhibitors have shown beneficial anti-tumor effects in several carcinomas, the most remarkable being in non-small cell lung cancer. Administration of these novel drugs is based on immunohistochemical expression (which may or may not be indicative of response to therapy) along with meticulous decision making by the multidisciplinary team. Immunohistochemistry (IHC) is an effective means of immune marker demonstration and has been used in various tumor types for predictive and prognostic purposes. METHODS PD-L1 IHC (clone E1L3N) was applied in 101 cases of ampullary adenocarcinoma. Tumor infiltrating lymphocytes were also evaluated. The immunoreactivity was assessed and categorized into following staining thresholds: <1%, <5%, <10% and ≥10% for tumor cells (membranous and/or cytoplasmic staining pattern), and 5% and 10% cut-offs for immune cells. RESULTS We found that at a 10% cut-off, 73.3% (74/101) patients were men (P = .006) older than 50 years of age (P < .001) presenting with a tumor measuring <3 cm (P = .001). It was significantly associated with intestinal differentiation (P = .004) and grade 1 tumors (P = .001). Twelve patients presented with recurrence as well (P = .03). CONCLUSION In the context of ampullary adenocarcinoma, this study highlights the positivity observed with the PD-L1 IHC clone E1L3N at different thresholds, with the particularly stronger associations being evident at a 10% cut-off.
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Affiliation(s)
- Saima Haleem Siddiqui
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Niraj Kumari
- Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India
| | - Shravan Mishra
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Paturu Radha
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Samir Mohindra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Rajneesh K Singh
- Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Narendra Krishnani
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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9
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Tewari M, Swain JR, Mishra RR, Dixit VK, Shukla HS. Expression Profile of KRAS and p16 in Periampullary Cancer. Indian J Surg Oncol 2024; 15:25-34. [PMID: 38511045 PMCID: PMC10948726 DOI: 10.1007/s13193-023-01819-4] [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: 04/03/2023] [Accepted: 09/06/2023] [Indexed: 03/22/2024] Open
Abstract
Activating point mutations in codons 12, 13, and 61 of the KRAS gene and loss of p16 expression, a tumor suppressor gene, are common genetic alterations in periampullary cancer (PAC). The present study explores expression profile of KRAS and p16 genes in PAC and its prognostic relevance. A total of 50 patients with PAC who underwent potentially curative pancreaticoduodenectomy were included in the study. Formalin-fixed, paraffin-embedded tissue samples were analyzed for point mutations in codons 12 and 13 of KRAS and codon 9 of p16 using polymerase chain reaction. KRAS mutation in codon 12/13 was found in 32 (64%) and loss of p16 expression in 36 (72%) cases. KRAS mutation was significantly associated with higher grade, higher pathological tumor (pT) stage, lymphovascular invasion (LVI), perineural invasion (PNI), and pathological lymph nodes (pN) involvement on univariate analysis. On multivariate analysis, significant association of KRAS remained with higher grade (p = 0.031), pT stage (p = 0.09), and LVI (p = 0.028). On univariate analysis, loss of p16 expression was significantly associated with higher grade, pN involvement, LVI, PNI, and pT stage whereas on multivariate analysis, statistical significant association of p16 was found with higher grade of tumor only (p = 0.04). Patients with KRAS mutation had significantly (p = 0.018) worse disease-free survival (DFS) whereas no significant association was found in overall survival (OS). Loss of p16 expression had no association with either DFS or OS. The presence of p16 and KRAS alterations in patients with PAC suggests aggressive tumor biology. KRAS mutations confer a significantly poor DFS in PAC.
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Affiliation(s)
- Mallika Tewari
- Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, U.P. 221005 India
| | - Jyoti R. Swain
- Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, U.P. 221005 India
| | - Raghvendra R. Mishra
- Medical Lab Technology, DDU Kaushal Kendra, Institute of Medical Sciences, Banaras Hindu University, Varanasi, U.P. 221005 India
| | - Vinod K. Dixit
- Department Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, U.P. 221005 India
| | - H. S. Shukla
- Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, U.P. 221005 India
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10
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Aaquist T, Fristrup CW, Hasselby JP, Hamilton-Dutoit S, Eld M, Pfeiffer P, Mortensen MB, Detlefsen S. Prognostic importance of margin clearance in ampullary adenocarcinoma following pancreaticoduodenectomy in a Danish population-based nationwide study. HPB (Oxford) 2024; 26:241-250. [PMID: 37996299 DOI: 10.1016/j.hpb.2023.10.009] [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: 09/11/2022] [Revised: 04/01/2023] [Accepted: 10/07/2023] [Indexed: 11/25/2023]
Abstract
BACKGROUND In this Danish nationwide population-based study, we evaluated the prognostically relevant minimum tumour-free margin width following pancreaticoduodenectomy (PD) for ampullary adenocarcinoma (AAC) and evaluated whether certain margins hold independent prognostic information. METHODS We included 128 patients who underwent PD for AAC from 2015 to 2019. Clinical and pathological data including well-known prognostic factors were retrieved from the Danish Pancreatic Cancer Database. Missing data were obtained by review of pathology reports and re-microscopy of resection specimens. All PD specimens were examined using a standardised pathological protocol including multicolour inking, axial slicing and exact reporting of margin widths. The cohort was dichotomised into involved and uninvolved groups, using different margin clearance definitions (0.5-≥3.0 mm). RESULTS Following PD for AAC, margin clearance of ≥1 mm was independently associated with improved chance of survival compared with <1 mm (HR: 0.30, 95 % CI: 0.14-0.64 (p = 0.002)). Posterior and anterior margin widths were narrower compared with superior mesenteric artery and vein margins. Posterior margin and anterior surface had isolated prognostic significance in multivariable analysis. CONCLUSION Following PD for AAC, margin clearance of at least 1 mm is independently associated with improved survival. Our data further indicate that anterior surface and posterior margin hold particular prognostic value.
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Affiliation(s)
- Trine Aaquist
- Department of Pathology, Odense University Hospital, Odense, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Odense Patient Data Exploratory Network-OPEN, Odense University Hospital, Odense, Denmark
| | - Claus W Fristrup
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Odense Patient Data Exploratory Network-OPEN, Odense University Hospital, Odense, Denmark; Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Jane P Hasselby
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | | | - Mikkel Eld
- Department of Pathology, Aalborg University Hospital, Aalborg, Denmark
| | - Per Pfeiffer
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Michael B Mortensen
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Sönke Detlefsen
- Department of Pathology, Odense University Hospital, Odense, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Odense Patient Data Exploratory Network-OPEN, Odense University Hospital, Odense, Denmark.
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11
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Kwon CH, Ahn JH, Seo HI, Kim DU, Han SY, Kim S, Lee NK, Hong SB, Park YM, Noh BG. Clinical impact of ampulla of Vater cancer subtype classification based on immunohistochemical staining. World J Surg Oncol 2024; 22:5. [PMID: 38167037 PMCID: PMC10763163 DOI: 10.1186/s12957-023-03289-y] [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: 10/20/2023] [Accepted: 12/26/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND The histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance. METHODS Seventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors. RESULTS Classifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI. CONCLUSIONS Classification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.
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Affiliation(s)
- Chae Hwa Kwon
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Ji Hyun Ahn
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Pathology, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Hyung Il Seo
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.
- Department of Surgery, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-Ro, Seo-Gu, Busan, 49241, South Korea.
| | - Dong Uk Kim
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Sung Yong Han
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Suk Kim
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Radiology, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Nam Kyung Lee
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Radiology, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Seung Baek Hong
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Radiology, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Young Mok Park
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Surgery, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-Ro, Seo-Gu, Busan, 49241, South Korea
| | - Byeong Gwan Noh
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Surgery, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-Ro, Seo-Gu, Busan, 49241, South Korea
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Tsagkalidis V, Langan RC, Ecker BL. Ampullary Adenocarcinoma: A Review of the Mutational Landscape and Implications for Treatment. Cancers (Basel) 2023; 15:5772. [PMID: 38136318 PMCID: PMC10741460 DOI: 10.3390/cancers15245772] [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: 11/09/2023] [Revised: 12/01/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
Ampullary carcinomas represent less than 1% of all gastrointestinal malignancies with an incidence of approximately 6 cases per 1 million. Histologic examination and immunohistochemistry have been traditionally used to categorize ampullary tumors into intestinal, pancreatobiliary or mixed subtypes. Intestinal-subtype tumors may exhibit improved survival versus the pancreatobiliary subtype, although studies on the prognostic value of immunomorphologic classification have been inconsistent. Genomic classifiers hold the promise of greater reliability, while providing potential targets for precision oncology. Multi-institutional collaboration will be necessary to better understand how molecular classification can guide type and sequencing of multimodality therapy.
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Affiliation(s)
- Vasileios Tsagkalidis
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; (V.T.); (R.C.L.)
| | - Russell C. Langan
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; (V.T.); (R.C.L.)
- Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA
| | - Brett L. Ecker
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; (V.T.); (R.C.L.)
- Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA
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13
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Shin DW. [Treatment of Ampullary Adenocarcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:159-170. [PMID: 37876255 DOI: 10.4166/kjg.2023.110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 09/28/2023] [Accepted: 10/03/2023] [Indexed: 10/26/2023]
Abstract
The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary ampullary adenocarcinoma is a rare malignancy, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. Jaundice from a biliary obstruction is the most common symptom of ampullary adenocarcinoma. In the early stages, radical pancreatoduodenectomy is the standard surgical approach. On the other hand, no randomized controlled trial has provided evidence to guide physicians on the choice of adjuvant/palliative chemotherapy because of the rarity of the disease and the paucity of related research. This paper reports the biology, histology, current therapeutic strategies, and potential future therapies of ampullary adenocarcinoma.
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Affiliation(s)
- Dong Woo Shin
- Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
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14
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Miyamoto R, Takahashi A, Ogura T, Kitamura K, Ishida H, Matsudaira S, Kihara A, Kanda H, Kawashima Y. Transduodenal ampullectomy for early ampullary cancer: Clinical management, histopathological findings and long-term outcomes at a single center. Surgery 2023; 173:912-919. [PMID: 36697354 DOI: 10.1016/j.surg.2022.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 12/01/2022] [Accepted: 12/06/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND Transduodenal ampullectomy has been attempted in ampullary tumors, including early ampullary cancer. However, the indication and extent of transduodenal ampullectomy with curative intent remain controversial. Herein, we address the perioperative and long-term outcomes of patients with early ampullary cancer who underwent transduodenal ampullectomy at a single center. METHODS We retrospectively enrolled 10 early ampullary cancer patients who underwent transduodenal ampullectomy and 11 early ampullary cancer patients who underwent subtotal stomach-preserving pancreatoduodenectomy at Saitama Cancer Center between October 2008 and May 2021. Among this cohort, we analyzed the perioperative outcomes and long-term outcomes. RESULTS In terms of the perioperative outcomes between the transduodenal ampullectomy and subtotal stomach-preserving pancreatoduodenectomy groups, the transduodenal ampullectomy group exhibited a shorter operating time (244 minutes vs 390 minutes, P = .003), less intraoperative blood loss (67.5 grams vs 774 grams, P = .006) and shorter length of postoperative hospital stay (15 days vs 33 days). With respect to the postoperative nutrition status, the transduodenal ampullectomy group exhibited less postoperative weight loss (0.67% vs 8.95%, P = .021), a better Controlling Nutritional Status score (1.0 vs 2.1, P = .011) and a better Prognostic Nutritional Index score (42.9 vs 40.9, P = .018). The 5-year survival in the adenoma with high-grade dysplasia and T1 ampullary cancer which invaded the mucosal layer groups was 100%, whereas the median survival time in the T1 ampullary cancer which invaded the sphincter of Oddi group was 20.7 months (P = .0028). CONCLUSION Transduodenal ampullectomy is assumed to be a feasible and effective surgical procedure for the treatment of selected patients with early ampullary cancer, including patients with adenoma with high-grade dysplasia or T1 ampullary cancer which invaded the mucosal layer ampullary cancer.
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Affiliation(s)
- Ryoichi Miyamoto
- Department of Gastroenterological Surgery, Saitama Cancer Center, Kita-Adachi-gun, Saitama, Japan.
| | - Amane Takahashi
- Department of Gastroenterological Surgery, Saitama Cancer Center, Kita-Adachi-gun, Saitama, Japan
| | - Toshiro Ogura
- Department of Gastroenterological Surgery, Saitama Cancer Center, Kita-Adachi-gun, Saitama, Japan
| | - Kei Kitamura
- Department of Gastroenterological Surgery, Saitama Cancer Center, Kita-Adachi-gun, Saitama, Japan
| | - Hiroyuki Ishida
- Department of Gastroenterological Surgery, Saitama Cancer Center, Kita-Adachi-gun, Saitama, Japan
| | - Shinichi Matsudaira
- Department of Gastroenterological Surgery, Saitama Cancer Center, Kita-Adachi-gun, Saitama, Japan
| | - Atsushi Kihara
- Department of Pathology, Jichi Medical University, Tochigi, Japan
| | - Hiroaki Kanda
- Department of Pathology, Saitama Cancer Center, Kita-Adachi-gun, Saitama, Japan
| | - Yoshiyuki Kawashima
- Department of Gastroenterological Surgery, Saitama Cancer Center, Kita-Adachi-gun, Saitama, Japan
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15
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de Jong E, Lemmers D, Benedetti Cacciaguerra A, Bouwense S, Geurts S, Tjan-Heijnen V, Valkenburg-van Iersel L, Wilmink J, Besselink M, Abu Hilal M, de Vos-Geelen J. Oncologic management of ampullary cancer: International survey among surgical and medical oncologists. Surg Oncol 2022; 44:101841. [DOI: 10.1016/j.suronc.2022.101841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 08/12/2022] [Accepted: 08/19/2022] [Indexed: 11/27/2022]
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16
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He R, Yin T, Pan S, Wang M, Zhang H, Qin R. One hundred most cited article related to pancreaticoduodenectomy surgery: A bibliometric analysis. Int J Surg 2022; 104:106775. [PMID: 35840048 DOI: 10.1016/j.ijsu.2022.106775] [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: 01/13/2022] [Revised: 06/30/2022] [Accepted: 07/07/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND In light of the challenges associated with pancreaticoduodenectomy (PD) and recent key improvements, this bibliometric analysis aimed to analyze the 100 top-cited (T100) articles related to PD surgery to widen the awareness of relevant research on this procedure. METHODS The term "pancreaticoduodenectomy" was used to retrieve articles from the Web of Science Core Collection database. The 100 most cited manuscripts in the English language were identified and further analyzed by their countries of origin, publication journals, authors, and themes. RESULTS A thorough literature search was performed on the Web of Science until April 2020. The total number of citations for the T100 articles ranged from 227 to 3029. The T100 articles came from 18 different countries, with the USA accounting for the plurality (n = 72). Professor J.L. Cameron from Johns Hopkins Medicine USA published the most articles (n = 22), including one as the first author and two as a co-author. Furthermore, Johns Hopkins Medicine, USA, published the most articles on PD surgery (n = 24), with a total citation count of 14,151. The journal Annals of Surgery published 40 of the T100 articles, with 15,847 citations and an average citation count of 396. Among the T100 articles, the citation frequency following the year of publication showed a parabolic trend, with citations peaking in the 9th year following publication. CONCLUSION Our study identified and analyzed the T100 articles in PD surgery. The USA was the dominant country regarding articles, researchers, and institutions. The citations of the articles peaked in the 9th year after publication.
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Affiliation(s)
- Ruizhi He
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Taoyuan Yin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Shutao Pan
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Min Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Hang Zhang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Renyi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
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17
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Jung D, Jung JE, Kang CM. Which one will you choose; open, laparoscopic, or robotic transduodenal ampullectomy?: a case report. JOURNAL OF MINIMALLY INVASIVE SURGERY 2022; 25:73-76. [PMID: 35821688 PMCID: PMC9218403 DOI: 10.7602/jmis.2022.25.2.73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/02/2022] [Accepted: 05/12/2022] [Indexed: 11/11/2022]
Abstract
Transduodenal ampullectomy (TDA) is the treatment of choice for large premalignant lesions of the ampulla of Vater (AoV). With the development of surgical techniques, various methods, including the open, laparoscopic, and robotic approaches, for performing TDA have emerged. Herein, we report four consecutive cases treated with open, laparoscopic, and robotic TDA, with technical pitfalls and future perspectives of TDA in treating premalignant lesions of the AoV. The surgical techniques and principles for TDA were the same regardless of the surgical approaches. After surgery, none of the patients showed any abnormal findings or complications, except for digestive problems. All these surgical approaches are appropriate for patients requiring TDA; however, minimally invasive TDA, particularly the robotic approach is ideal. Considering the surgical complexity of TDA, the robotic approach is considered to be effective.
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Affiliation(s)
- Dawn Jung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Ji Eun Jung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
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18
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Quero G, Laterza V, Fiorillo C, Menghi R, De Sio D, Schena CA, Rosa F, Tortorelli AP, Di Cesare L, Cina C, Bensi M, Salvatore L, Alfieri S. The impact of the histological classification of ampullary carcinomas on long-term outcomes after pancreaticoduodenectomy: a single tertiary referral center evaluation. Langenbecks Arch Surg 2022; 407:2811-2821. [PMID: 35670860 DOI: 10.1007/s00423-022-02563-z] [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: 01/26/2022] [Accepted: 05/18/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE Ampullary carcinomas (ACs) are classified as pancreatobiliary (Pb-AC), intestinal (Int-AC), or mixed (Mixed-AC). The influencing role of AC subtypes on long-term outcomes is still matter of debate. Aim of this study is to evaluate the prognostic role of the three histological variants on the overall (OS) and disease-free survival (DFS) after pancreaticoduodenectomy(PD). METHODS All PDs for AC between 2004 and 2020 were included. Patients were classified according to the histological feature in Pb-AC, Int-AC, and Mixed-AC. Five-year OS and DFS were compared among the subtypes. Additionally, the prognostic role of the histological classification on OS and DFS was evaluated. RESULTS Fifty-six (48.7%) Pb-ACs, 53 (46.1%) Int-ACs, and 6 (5.2%) Mixed-ACs were evaluated. A poorer 5-year OS was evidenced for the Pb-AC group (54.1%) as compared to the Int-AC cohort (80.7%) (p = 0.03), but similar to the Mixed-AC population (33%) (p = 0.45). Pb-AC presented a worse 5-year DFS (42.3%) in comparison to the Int-AC (74.8%) (p = 0.002), while no difference was evidenced in comparison to the Mixed-AC (16.7%) (p = 0.51). At the multivariate analysis, the Pb-/Mixed-AC histotype was recognized as negative prognostic factor for both OS (OR: 2.29, CI: 1.05-4.98; p = 0.04) and DFS (OR: 2.17, CI: 1-4.33; p = 0.02). CONCLUSION Histological subtypes of AC play a relevant role in long-term outcomes after PD. Pb-ACs and Mixed-ACs show a more aggressive tumor biology and a consequent worse survival as compared to the Int-AC subtype.
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Affiliation(s)
- Giuseppe Quero
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy.,Università Cattolica del Sacro Cuore Di Roma, Largo Francesco Vito 1, 00168, Rome, Italy
| | - Vito Laterza
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy
| | - Claudio Fiorillo
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy.
| | - Roberta Menghi
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy
| | - Davide De Sio
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy
| | - Carlo Alberto Schena
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy
| | - Fausto Rosa
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy.,Università Cattolica del Sacro Cuore Di Roma, Largo Francesco Vito 1, 00168, Rome, Italy
| | - Antonio Pio Tortorelli
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy
| | - Ludovica Di Cesare
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy
| | - Caterina Cina
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy
| | - Maria Bensi
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy
| | - Lisa Salvatore
- Università Cattolica del Sacro Cuore Di Roma, Largo Francesco Vito 1, 00168, Rome, Italy.,Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy
| | - Sergio Alfieri
- Pancreatic Surgery Unit, Department of Surgery, Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy.,Università Cattolica del Sacro Cuore Di Roma, Largo Francesco Vito 1, 00168, Rome, Italy
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19
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Lee DH, Kim HJ, Cho CW, Yun SS, Lee DS. Factors influencing patterns of recurrence following pancreaticoduodenectomy for patients with distal bile duct cancer and ampulla of Vater cancer. Ann Hepatobiliary Pancreat Surg 2022; 26:138-143. [PMID: 35013007 PMCID: PMC9136428 DOI: 10.14701/ahbps.21-129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/15/2021] [Accepted: 10/19/2021] [Indexed: 11/17/2022] Open
Abstract
Backgrounds/Aims Pancreaticoduodenectomy (PD) is a standard surgical procedure for patients with periampullary cancer. During the follow-up period after PD, recurrence can be observed in various places with different prognosis. The aim of this study was to clarify the pattern of recurrence and factors affecting the survival of patients with periampullary cancer. Methods Overall, 88 patients who received PD for distal common bile duct cancer or ampulla of Vater cancer were finally included and their clinical characteristics were analyzed. Patients were divided into three groups: recurrence-free (RF) group, an isolated locoregional recurrence (LR) group, and a distant metastasis (DM) group. Prognostic factors affecting recurrence in each group were analyzed and a survival analysis was performed. Results Perineural invasion (PNI), T stage, and lymphovascular invasion (LVI) were significant risk factors for LR and PNI, lymph node metastasis, LVI, and T stage were associated with DM group compared to RF group in univariate analysis, respectively. N stage and PNI were significant risk factors (p = 0.046, p = 0.041) in overall survival of the LR and the DM groups. There was no significant difference in 5-year overall survival between the LR and DM groups. Conclusions T stage was a significant risk factor of LR, while PNI was a significant risk factor of DM. There was no significant difference in overall survival depending on the site of recurrence.
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Affiliation(s)
- Do Hyeon Lee
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Hyoung Joo Kim
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Chan Woo Cho
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Sung Su Yun
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Dong-Shik Lee
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
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20
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Kang J, Lee W, Shin J, Park Y, Kwon JW, Jun E, Song KB, Lee JH, Hwang DW, Park SY, Kim SC. Controversial benefit of 5-fluorouracil/leucovorin-based adjuvant chemotherapy for ampullary cancer: a propensity score-matched analysis. Langenbecks Arch Surg 2022; 407:1091-1097. [PMID: 35013798 DOI: 10.1007/s00423-021-02414-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 12/14/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Although surgery is the primary treatment for ampullary cancer (AC), the benefit of adjuvant chemotherapy (CTx) has not yet been confirmed. METHODS AC patients who were administered 5-fluorouracil(FU)/leucovorin(LV)-based CTx after curative intent surgery between 2011 and 2019 were included. Prognosis was compared between the observation (OB) and CTx groups after propensity score matching (PSM) using perioperative variables to control differences in patient characteristics. RESULTS Before PSM, of 475 patients, those in the CTx group (n = 281) had worse 5-year overall survival (OS) (82.1% vs. 78.5%, p = 0.017) and worse 5-year recurrence-free survival (RFS) (54.9% vs. 75.7%, p < 0.001) than those in the OB group (n = 194). In addition, the CTx group had a higher rate of poor prognostic factors such as a high T stage (p < 0.001), node metastasis (p < 0.001), and poor differentiation (p < 0.001). After PSM, perioperative outcomes were comparable. In addition, there were no significant differences in OS (hazard ratio [HR], 1.085; 95% confidence interval [CI], 0.688-1.710; p = 0.726) or RFS (HR, 0.883; 95% CI, 0.613 1.272; p = 0.505) between the CTx (n = 123) and OB (n = 123) groups even after stratification by TNM stage. Intestinal subtype showed better 5-year OS (83.7% vs 33.2%, p = 0.015) and RFS (46.5% vs 24.9%, p = 0.035) rate compared with pancreatobiliary/mixed subtype. CONCLUSION Patients who received adjuvant chemotherapy based on 5-FU/LV showed comparable oncologic outcomes to patients in the OB group even after stratification by tumor stage. The patients with intestinal subtype showed oncologic benefit for adjuvant 5-FU/LV CTx compared with pancreatobiliary or mixed subtypes.
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Affiliation(s)
- Jaecheol Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, Republic of Korea.
| | - Jaehoon Shin
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Jae Woo Kwon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Seo Young Park
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.,Department of Statistics and Data Science, Korea National Open University, Seoul, Republic of Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, Republic of Korea
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21
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Sekaran A, Dey D, Singh A, Das P. Pathology of Malignant Lesions of the Gastrointestinal Tract. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:699-782. [DOI: 10.1007/978-981-16-6395-6_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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22
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Akoum A, Radwan R, El Hage S, El Masri J, Ezzeddine S. Severe Symptomatic Hypochloremia Associated with Rare Signet Ring Cell Carcinoma of the Ampulla of Vater: A Case Report. Cureus 2021; 13:e19492. [PMID: 34912633 PMCID: PMC8664403 DOI: 10.7759/cureus.19492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 11/12/2021] [Indexed: 11/11/2022] Open
Abstract
Hypochloremia is an electrolyte disturbance characterized by low serum concentration of chloride ions, often occurring in acute illnesses and characterized by nonspecific signs and symptoms. It rarely results from decreased intake and is predominantly due to either renal or extra-renal losses. We report a case of severely worsening symptomatic hypochloremia resulting from an extra-renal loss of chloride ion in a 58-year-old female patient presenting for prolonged protracted vomiting. Chloremia reached a surprising level of 48 mEq/L, the lowest level reported in the literature. The patient was eventually diagnosed with a rare signet ring cell carcinoma that occurred in the ampulla of Vater, leading to a malignant gastric outlet obstruction and causing extra-renal loss of chloride.
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Affiliation(s)
- Atef Akoum
- Medicine, Lebanese University, Faculty of Medical Sciences, Hadath, LBN
| | - Rached Radwan
- Internal Medicine, Lebanese University, Faculty of Medical Sciences, Hadath, LBN
| | - Said El Hage
- General Medicine, Lebanese University, Faculty of Medical Sciences, Hadath, LBN
| | - Jad El Masri
- Neurosciences, Neuroscience Research Center, Lebanese University, Faculty of Medicine, Hadath, LBN
| | - Salah Ezzeddine
- Gastroenterology, Rafic Hariri University Hospital, Beirut, LBN
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23
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Chakraborty S, Ecker BL, Seier K, Aveson VG, Balachandran VP, Drebin JA, D'Angelica MI, Kingham TP, Sigel CS, Soares KC, Vakiani E, Wei AC, Chandwani R, Gonen M, Shen R, Jarnagin WR. Genome-Derived Classification Signature for Ampullary Adenocarcinoma to Improve Clinical Cancer Care. Clin Cancer Res 2021; 27:5891-5899. [PMID: 34433650 DOI: 10.1158/1078-0432.ccr-21-1906] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 07/19/2021] [Accepted: 08/19/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE The clinical behavior of ampullary adenocarcinoma varies widely. Targeted tumor sequencing may better define biologically distinct subtypes to improve diagnosis and management. EXPERIMENTAL DESIGN The hidden-genome algorithm, a multilevel meta-feature regression model, was trained on a prospectively sequenced cohort of 3,411 patients (1,001 pancreatic adenocarcinoma, 165 distal bile-duct adenocarcinoma, 2,245 colorectal adenocarcinoma) and subsequently applied to targeted panel DNA-sequencing data from ampullary adenocarcinomas. Genomic classification (i.e., colorectal vs. pancreatic) was correlated with standard histologic classification [i.e., intestinal (INT) vs. pancreatobiliary (PB)] and clinical outcome. RESULTS Colorectal genomic subtype prediction was primarily influenced by mutations in APC and PIK3CA, tumor mutational burden, and DNA mismatch repair (MMR)-deficiency signature. Pancreatic genomic-subtype prediction was dictated by KRAS gene alterations, particularly KRAS G12D, KRAS G12R, and KRAS G12V. Distal bile-duct adenocarcinoma genomic subtype was most influenced by copy-number gains in the MDM2 gene. Despite high (73%) concordance between immunomorphologic subtype and genomic category, there was significant genomic heterogeneity within both histologic subtypes. Genomic scores with higher colorectal probability were associated with greater survival compared with those with a higher pancreatic probability. CONCLUSIONS The genomic classifier provides insight into the heterogeneity of ampullary adenocarcinoma and improves stratification, which is dictated by the proportion of colorectal and pancreatic genomic alterations. This approach is reproducible with available molecular testing and obviates subjective histologic interpretation.
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Affiliation(s)
- Saptarshi Chakraborty
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Brett L Ecker
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ken Seier
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Victoria G Aveson
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Vinod P Balachandran
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.,Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jeffrey A Drebin
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Michael I D'Angelica
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - T Peter Kingham
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Carlie S Sigel
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Kevin C Soares
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Efsevia Vakiani
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.,Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Alice C Wei
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Rohit Chandwani
- Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, New York.,Department of Surgery, Weill Cornell Medicine, New York, New York
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ronglai Shen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - William R Jarnagin
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
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24
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Park YM, Seo HI. Predictive value of metabolic activity detected by pre-operative 18F FDG PET/CT in ampullary adenocarcinoma. Medicine (Baltimore) 2021; 100:e27561. [PMID: 34678895 PMCID: PMC8542133 DOI: 10.1097/md.0000000000027561] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 10/03/2021] [Indexed: 01/05/2023] Open
Abstract
In ampullary adenocarcinoma cases, the clinical effects of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) have not yet been well-studied, unlike other prognostic factors that have been reported till date. This study aimed to investigate the clinical impact of maximum standardized uptake value (SUVmax) in predicting the prognosis of ampullary adenocarcinoma.Thirty-eight patients who underwent pre-operative 18F-FDG PET/CT and curative-intent resection of ampullary adenocarcinoma at Pusan National University Hospital (Pusan, South Korea) between 2008 and 2017 were retrospectively analyzed in this study. We evaluated the clinicopathologic outcomes according to the SUVmax using univariate and multivariate Cox proportional hazard regression analyses and receiver operating characteristic analysis to arrive at a cutoff value.Lymph node metastasis was detected in 9 patients, and 15 patients experienced a recurrence during the follow-up period. Among 38 patients, 33 showed an increased FDG uptake by the main tumor. SUVmax of 4.55 was selected as a significant independent predictive factor for patient survival along with poor tumor differentiation and high neutrophil-to-lymphocyte ratio in multivariate analysis (P = .016, hazard ratio = 5.040). Patients with SUVmax under 4.55 exhibited significantly longer overall survival than the rest (<4.55 vs ≥4.55), and the 5-year overall survival was 82.8% versus 57.4% (P = .049).SUVmax of 4.55 on 18F-FDG PET/CT could be a predictive factor for tumor biology and long-term survival in patients with ampullary adenocarcinoma. Nevertheless, considering the cost aspect and its limited prognostic effect, this study seems to require more patient and multicenter studies.
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25
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Shimizu Y, Ashida R, Sugiura T, Okamura Y, Ito T, Yamamoto Y, Ohgi K, Otsuka S, Notsu A, Uesaka K. Prognostic Impact of Indicators of Systemic Inflammation and the Nutritional Status of Patients with Resected Carcinoma of the Ampulla of Vater: A Single-Center Retrospective Study. World J Surg 2021; 46:246-258. [PMID: 34661701 DOI: 10.1007/s00268-021-06346-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/02/2021] [Indexed: 01/04/2023]
Abstract
BACKGROUND Several indicators of systemic inflammation and nutritional status were recently shown to serve as novel prognostic factors for certain cancers. Here, we aimed to investigate the prognostic impact of preoperative indicators of systemic inflammation and nutritional status associated with the survival of patients with resected ampulla of Vater carcinoma (AC). METHODS We retrospectively analyzed the records of 91 patients who underwent pancreatoduodenectomy (PD) for AC from January 2002 through December 2018. Indices for systemic inflammation and nutritional status (Systemic immune-inflammation index [SII], Prognostic nutritional index [PNI], modified Glasgow prognostic score [mGPS], and Controlling nutritional status score [CONUT]) were determined using preoperative blood tests. Clinicopathological factors and these indices were analyzed to identify predictors of overall survival (OS). RESULTS The median preoperative SII and PNI values were 456.7 and 47.5, respectively, and their optimal cut-off values were 670.0 and 50.0, respectively. Univariate analysis revealed that high SII, low PNI, mGPS ≥ 1, and malnutrition, assessed using the CONUT, were significant predictors of shorter OS. Multivariate analysis revealed that high SII (HR = 2.71, p = 0.023) and malnutrition assessed using the CONUT (hazard ratio = 3.98, p = 0.006) were independent predictors of shorter OS. CONCLUSION SII and the CONUT predicted the survival of patients with AC after radical resection. These indicators are easily calculated using preoperative blood tests and may contribute to the development of improved strategies to treat AC.
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Affiliation(s)
- Yuji Shimizu
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Takaaki Ito
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Katsuhisa Ohgi
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Shimpei Otsuka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Akifumi Notsu
- Clinical Research Center, Shizuoka Cancer Center, Sunto-Nagaizumi, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
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Ampullary Carcinoma: An Overview of a Rare Entity and Discussion of Current and Future Therapeutic Challenges. Curr Oncol 2021; 28:3393-3402. [PMID: 34590592 PMCID: PMC8482111 DOI: 10.3390/curroncol28050293] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 08/27/2021] [Accepted: 08/30/2021] [Indexed: 12/29/2022] Open
Abstract
Ampullary carcinomas (ACs) represent a rare entity, accounting for approximately 0.2% of all gastrointestinal solid tumors and 20% of all periampullary cancers (PACs). Unfortunately, few data are available regarding the optimal therapeutic strategy for ACs due to their rarity, and physicians frequently encounter significant difficulties in the management of these malignancies. In this review, we will provide an overview of current evidence on AC, especially focusing on biological features, histological characteristics, and available data guiding present and future therapeutic strategies for these rare, and still barely known, tumors.
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Mishra SK, Kumari N, Krishnani N, Singh RK, Mohindra S. Identification and prevalence of potentially therapeutic targetable variants of major cancer driver genes in ampullary cancer patients in India through deep sequencing. Cancer Genet 2021; 258-259:41-48. [PMID: 34455261 DOI: 10.1016/j.cancergen.2021.08.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 07/19/2021] [Accepted: 08/13/2021] [Indexed: 12/26/2022]
Abstract
Ampulla is a complex region located at the confluence of pancreatic and common bile duct and intestinal epithelium. Tumors arising in this region are anatomically and morphologically heterogenous, however they show unique as well as overlapping molecular features. Cancers of both these anatomic sites share morphological as well as genetic profile despite having few unique differences. Targeted therapies are currently emerging as one of the demanding approaches for treatment in most cancer types especially for malignant epithelial tumors and therefore genetic profiling of cancers is the key for identification of potentially therapeutic targetable mutations to know their prevalence and prognostic impact. We studied 97 resected cases of formalin fixed paraffin-embedded AC by deep targeted sequencing using Ampliseq cancer hotspot panel comprising of 50 oncogenes and tumor suppressor genes. Potentially therapeutic targetable mutations were observed in 58/83 (70%) cases. Fourteen patients did not show any pathogenic mutation. TP53 (48.1%), KRAS (37.3%), APC (25.3%), SMAD4 (22.8%), MET (16.8%), CTNNB1 (15.6%) and PIK3CA (10.8%) were the major mutated potential therapeutic targets. KRAS mutation (43.2 Vs. 32.6%) was more prevalent in pancreatobiliary subtype, while TP53 (58.6 Vs 35.1), APC (36.9 Vs 10.8), SMAD4 (28.2 Vs 16.2), MET (21.7 Vs 10.8) and CTNNB1 (19.5 Vs 10.8) were more prevalent in intestinal subtype. WNT signaling pathway was the major altered pathway in intestinal subtype. These mutated genes and pathways may be targeted with currently available drugs and may be explored for future development of targetable agents to improve the disease course in patients of AC.
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Affiliation(s)
- Shravan Kumar Mishra
- Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India
| | - Niraj Kumari
- Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Raebareli, UP, India.
| | - Narendra Krishnani
- Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India
| | - Rajneesh Kumar Singh
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India
| | - Samir Mohindra
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India
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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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Ampullary carcinoma of the duodenum: current clinical issues and genomic overview. Surg Today 2021; 52:189-197. [PMID: 33797636 DOI: 10.1007/s00595-021-02270-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 01/17/2021] [Indexed: 02/07/2023]
Abstract
Ampullary carcinomas of the duodenum are uncommon. Moreover, the diversity in the clinical outcomes of these patients makes it difficult to interpret previous studies and clinical trial results. The difficulty in proper staging of ampullary carcinomas, especially with regard to the T category of the tumor in the TNM system, reflects the anatomic complexity and non-uniform histopathologic subtypes. One major reason for this difficulty in interpretation is that the tumors may arise from any of the three epithelia (duodenal, biliary, or pancreatic) that converge at this location. Generally, ampullary carcinomas are classified into intestinal and pancreaticobiliary types based on morphology and immunohistochemical features. While many studies have described their specific characteristics and clinical impact, the prognostic value of these subtypes is controversial. In recent years, whole-exome sequencing analyses have advanced our understanding of the genomic overview of ampullary carcinoma. Gene mutations serve as prognostic and predictive biomarkers for this disease. Therefore, basic knowledge of the genomic profile of ampullary carcinomas is required for surgeons to understand how best to apply precision medicine as well as surgery and adjuvant therapies. This review provides an overview of the current basic and clinical issues of ampullary carcinoma.
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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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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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Palmeri M, Funel N, Franco GD, Furbetta N, Gianardi D, Guadagni S, Bianchini M, Pollina LE, Ricci C, Chiaro MD, Candio GD, Morelli L. Tissue microarray-chip featuring computerized immunophenotypical characterization more accurately subtypes ampullary adenocarcinoma than routine histology. World J Gastroenterol 2020; 26:6822-6836. [PMID: 33268964 PMCID: PMC7684454 DOI: 10.3748/wjg.v26.i43.6822] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/24/2020] [Accepted: 08/27/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Ampullary adenocarcinomas (AACs) are heterogeneous tumors currently classified into three important sub-classes (SC): Intestinal (INT), Pancreato-Biliary (PB) and Mixed-Type (MT). The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent. However, they respond differently to chemotherapy and have different prognostic outcomes. The SC are often difficult to identify with conventional histology alone. The clinical outcome of all three remains unclear, particularly for MT. AIM To identify two main subtypes of AACs, using an immunohistochemical (IHC) score based on CDX2, CK7 and CK20. METHODS Tissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2, CK7 and CK 20. An IHC score was obtained for each marker by counting the number of positive cells (0 = no stained cells; 1 < 25%; 2 < 50% and 3 > 50%) and their intensity (1 = weak; 2 = moderate and 3 = strong). A global score (GS) was then obtained by summation of the IHC scores of each marker. The MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype, obtaining only two AACs subtypes. The overall survival in INT and PB patients was obtained by Kaplan-Meier methods. RESULTS Histological parameters defined the AACs subtypes as follows: 15% INT, 45% PB and 40% MT. Using IHC expression and the GS, 75% and 25% of MT samples were assigned to either the INT or the PB group. The mean value of the GS was 9.5 (range 4-16). All INT samples had a GS above the average, distinct from the PB samples which had a GS score significantly below the average (P = 0.0011). The INT samples were identified by high expression of CDX2 and CK20, whereas PB samples exhibited high expression of CK7 and no expression of CK20 (P = 0.0008). The INT group had a statistically significant higher overall survival than in the PB group (85.7 mo vs 20.3 mo, HR: 8.39; 95%CI: 1.38 to 18.90; P = 0.0152). CONCLUSION The combination of histopathological and molecular criteria enables the classification of AACs into two clinically relevant histo-molecular phenotypes, which appear to represent distinct disorders with potentially significant changes to the current therapeutic strategies.
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Affiliation(s)
- Matteo Palmeri
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Niccola Funel
- Division of Surgical Pathology, University-Hospital of Pisa, Pisa 56124, Italy
| | - Gregorio Di Franco
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Niccolò Furbetta
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Desirée Gianardi
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Simone Guadagni
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Matteo Bianchini
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Luca E Pollina
- Division of Surgical Pathology, University-Hospital of Pisa, Pisa 56124, Italy
| | - Claudio Ricci
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa 56124, Italy
| | - Marco Del Chiaro
- Department of Surgery, University of Colorado, Denver, CO 80045, United States
| | - Giulio Di Candio
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Luca Morelli
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
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Ma CH, Lee JH, Song KB, Hwang DW, Kim SC. Predictors of early recurrence following a curative resection in patients with a carcinoma of the ampulla of Vater. Ann Surg Treat Res 2020; 99:259-267. [PMID: 33163455 PMCID: PMC7606130 DOI: 10.4174/astr.2020.99.5.259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 07/13/2020] [Accepted: 07/29/2020] [Indexed: 11/30/2022] Open
Abstract
PURPOSE Ampulla of Vater (AoV) carcinoma has a relatively good prognosis. The 5-year recurrence rate for AoV is still around 40%-50% however, and most recurrences occur in the early period. The aim of this study was to identify predictors of an early recurrence in AoV patients following a curative resection. METHODS The clinicopathological data for 501 consecutive patients that underwent a resection for AoV in our institute between January 2000 and December 2015 were retrospectively reviewed. The characteristics of any recurrences and early recurrence patients were analyzed accordingly. Early recurrence was defined as occurring within one year of resection. RESULTS There were 170 diagnosed recurrences in our study population, 57.1% of whom were men, with a mean age of 60.1 years (range, 30-94 years). Almost all of the study patients underwent a pancreaticoduodenectomy, and 9% underwent minimally invasive surgery. Of the 170 recurrent cases, 107 were diagnosed with an early recurrence and had 1-, 3-, and 5-year overall survival rates of 77.7%, 18.4%, 10.5%, respectively. The factors that significantly influenced early recurrences, determined by multivariate analysis, lymphovascular invasion (LVI), lymph node ratio (LNR), and poor differentiation were found to be independent determinants of a recurrence within 1 year. CONCLUSION An early recurrence in AoV patients is ultimately lethal even though this cancer has a good prognosis. LVI, LNR, and poor differentiation are powerful predictors of an early recurrence in AoV. Hence, intensive surveillance and new therapeutic strategies should be considered for AoV patients with these predictors following a curative resection.
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Affiliation(s)
- Chung Hyeun Ma
- Department of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Han S, Jang KT, Choi DW, Choi SH, Heo JS, Han IW, Park D, Ryu Y. Prognostic Impact of Intra-Ampullary Papillary-Tubular Neoplasm versus Flat Dysplasia as Precursor Lesions of Ampullary Adenocarcinoma. Dig Surg 2020; 37:505-514. [PMID: 33080609 DOI: 10.1159/000510961] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 08/17/2020] [Indexed: 12/10/2022]
Abstract
BACKGROUND The aim of this study is to compare the prognostic impact of 2 precursor lesions of ampullary adenocarcinoma, intra-ampullary papillary-tubular neoplasm (IAPN) and flat dysplasia (FD). METHODS From December 1994 to December 2012, a total of 359 patients underwent curative surgery for ampullary adenocarcinoma. RESULTS The precursor lesions were IAPNs in 134 (37.3%) patients and FD in the other 225 (62.7%) patients. The FD group had more aggressive tumor biology with advanced T stage (p = 0.002), nodal involvement (p < 0.001), poor differentiation (p < 0.001), perineural and lymphovascular invasion (p < 0.001), and pancreatobiliary or mixed subtype (p < 0.001). Five-year overall survival rates were 71.1% in the IAPN group and 51.4% in the FD group (p = 0.002), respectively. Five-year disease-free survival rates were 69.7% in the IAPN group and 49.6% in the FD group (p < 0.001), respectively. The recurrence rate was also higher in the FD group (49.8 vs. 30.6%; p < 0.001). On multivariate analysis, higher levels of tumor markers including CEA and CA19-9, lymph node metastasis, poorly differentiated histology, and perineural invasion were negative predictive factors for survival. Higher levels of CEA and CA19-9, lymphovascular invasion, and FD were independent prognostic factors for recurrence. CONCLUSION FD was significantly associated with worse prognosis and a greater tendency toward advanced disease. Further studies are needed to clarify the impacts of these precursor lesions.
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Affiliation(s)
- Sunjong Han
- Department of Surgery, Chungnam National University Sejong Hospital, Sejong, Republic of Korea
| | - Kee-Taek Jang
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Wook Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea,
| | - Seong Ho Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jin Seok Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - In Woong Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - DaeJoon Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Youngju Ryu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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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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Manne A, Hatic H, Li P, Jacob R, Williams G, Paluri R. The Clinical Benefit of Adjuvant Therapy in Long-Term Survival of Early-Stage Ampullary Carcinoma: A Single Institutional Experience. J Clin Med Res 2020; 12:560-567. [PMID: 32849944 PMCID: PMC7430918 DOI: 10.14740/jocmr4267] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 07/15/2020] [Indexed: 12/13/2022] Open
Abstract
Background The role of adjuvant chemotherapy (CT) or combination chemoradiation (CRT) remains uncertain for ampullary carcinoma (AC). In this analysis, we reviewed our institution’s experience with early-stage AC. Methods AC patients who had definitive surgical intervention at the University of Alabama, Birmingham, between 2005 and 2015, were identified. Clinicopathologic factors and disease statuses were obtained from chart review. The univariate Cox proportional hazard model was conducted for evaluating the parameters associated with overall survival (OS). Kaplan-Meier method and log-rank method were used to compare the time-to-events. We estimated the survival for the patients who had definitive surgery (pancreaticoduodenectomy (PD) or ampullectomy), and followed them up with assessing the influence of adjuvant treatment (chemoradiotherapy or CT) alone on the survival in the early-stage (stage I/II) AC. Results A total of 63 patients had definitive surgery. The median OS and progression-free survival (PFS) for all the patients who had definitive surgery were 40.5 months and 28 months, respectively. Adjuvant treatment was administered in 60% of patients with early-stage (stage I/II) AC (CT 36% and CRT 24%), while 22% were on surveillance post surgery. The pathological stage ≥ 2, Lymph node (LN) metastasis, peri-nodal extension (PNE) and peri-pancreatic extension (PPE) were found to be the determinants for poor OS and PFS by univariate analysis. Multiple Cox regression of these variables showed a significant influence of PPE and pathological staging on the OS and PFS, respectively. In the early-stage AC with no high-risk features, adjuvant therapy did not improve the survival over surgery alone (40.5 vs. 51.7 months, P = 0.93). The addition of radiation to CT did not yield improved outcome in early-stage cancers. For CRT and CT, OS was 22.8 versus 65.7 months (P = 0.3975), and PFS was 25.3 versus 65.7 months (P = 0.4699). Conclusions In the early-stage AC, adjuvant therapy may not improve the outcome in the short term but may benefit over a long period. It should be considered, especially in patients with adverse risk factors. Radiation therapy may not be useful in managing AC in the adjuvant setting.
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Affiliation(s)
- Ashish Manne
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
| | - Haris Hatic
- Department of Hematology & Oncology, University of Alabama, Birmingham, AL, USA
| | - Peng Li
- Department of Hematology & Oncology, University of Alabama, Birmingham, AL, USA
| | - Rojymon Jacob
- Department of Radiation Oncology, University of Alabama, Birmingham, AL, USA
| | - Grant Williams
- Department of Hematology & Oncology, University of Alabama, Birmingham, AL, USA
| | - Ravi Paluri
- Department of Hematology & Oncology, University of Alabama, Birmingham, AL, USA
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Vilhordo DW, Gregório C, Valentini DF, Edelweiss MIA, Uchoa DM, Osvaldt AB. Prognostic Factors of Long-term Survival Following Radical Resection for Ampullary Carcinoma. J Gastrointest Cancer 2020; 52:872-881. [PMID: 32808236 DOI: 10.1007/s12029-020-00479-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The incidence of adenocarcinoma of the ampulla of Vater has been increasing over the past years. Nevertheless, it is still a rare disease and the prognostic factors predicting long-term survival are not sufficiently clarified. This study aims to evaluate the association between histopathological characteristics and long-term survival of patients with ampullary cancer after curative resection, as well as the efficiency of immunohistochemical expression of CK7, CK20, and CDX2 to distinguish the histopathological (intestinal or pancreaticobiliary) patterns. METHODS Demographic, histopathological data, pTNM stage, and immunohistochemical expression patterns were collected from 65 patients with adenocarcinoma of the ampulla of Vater. Five and 10-year overall and disease-free survival rates after curative resection were determined. RESULTS Of the 65 patients with ampullary carcinoma, 47 (72%) underwent radical resection. The 5- and 10-year overall survival rate was 46% and 37%, respectively. Our results demonstrate that the main prognostic factors were the presence and number of lymph node metastases, lymph node ratio (LNR), differentiation grade, and lymphovascular invasion. After multivariate analysis, only lymph node ratio ≥ 20% remained an independent prognostic factor of survival (HR: 2.63 95% CI: 1.05-6.61; p = 0.039). CONCLUSION Here, we demonstrated more evidence that the lymph node metastases are associated with poor prognosis in ampullary carcinoma. Particularly, the relation between the number of metastatic lymph nodes and the number of harvested lymph node (LNR) should be considered a major prognostic factor.
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Affiliation(s)
- Daniel Weiss Vilhordo
- Postgraduate Program in Medicine: Surgical Sciences, Medical School of Universidade Federal do Rio Grande do Sul - (FAMED-UFRGS), Porto Alegre, RS, Brazil
| | - Cleandra Gregório
- Postgraduate Program in Genetics and Molecular Biology, Medical School of Universidade Federal do Rio Grande do Sul - (FAMED-UFRGS), Porto Alegre, RS, Brazil
| | - Dirceu Felipe Valentini
- Service of Digestive Surgery, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, 90035-903, Brazil.
| | - Maria Isabel Albano Edelweiss
- Service of Pathology, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Diego Mendonça Uchoa
- Service of Pathology, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Alessandro Bersch Osvaldt
- Postgraduate Program in Medicine: Surgical Sciences, Medical School of Universidade Federal do Rio Grande do Sul - (FAMED-UFRGS), Porto Alegre, RS, Brazil.,Service of Digestive Surgery, Group for Biliary Tract and Pancreas, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
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Moekotte AL, Malleo G, van Roessel S, Bonds M, Halimi A, Zarantonello L, Napoli N, Dreyer SB, Wellner UF, Bolm L, Mavroeidis VK, Robinson S, Khalil K, Ferraro D, Mortimer MC, Harris S, Al-Sarireh B, Fusai GK, Roberts KJ, Fontana M, White SA, Soonawalla Z, Jamieson NB, Boggi U, Alseidi A, Shablak A, Wilmink JW, Primrose JN, Salvia R, Bassi C, Besselink MG, Abu Hilal M. Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study. Br J Surg 2020; 107:1171-1182. [PMID: 32259295 DOI: 10.1002/bjs.11555] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 12/14/2019] [Accepted: 01/23/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. METHODS An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses. RESULTS Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. CONCLUSION Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.
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Affiliation(s)
- A L Moekotte
- Departments of Surgery, Southampton, UK
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - G Malleo
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - S van Roessel
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - M Bonds
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington, USA
| | - A Halimi
- Pancreatic Surgery Unit, Division of Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - L Zarantonello
- Pancreatic Surgery Unit, Division of Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - N Napoli
- Department of Surgery, Pisa University Hospital, Pisa, Italy
| | - S B Dreyer
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - U F Wellner
- Department of Surgery, University Medical Centre Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - L Bolm
- Department of Surgery, University Medical Centre Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - V K Mavroeidis
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - S Robinson
- Department of Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - K Khalil
- Faculty of Medicine, University of Birmingham, Birmingham, UK
| | - D Ferraro
- Department of Surgery, Royal Free London NHS Foundation Trust, London, UK
| | - M C Mortimer
- Department of Surgery, Morriston Hospital, Swansea, UK
| | - S Harris
- Medical Statistics, Faculty of Medicine, University of Southampton, Southampton, UK
| | - B Al-Sarireh
- Department of Surgery, Morriston Hospital, Swansea, UK
| | - G K Fusai
- Department of Surgery, Royal Free London NHS Foundation Trust, London, UK
| | - K J Roberts
- Faculty of Medicine, University of Birmingham, Birmingham, UK
| | - M Fontana
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - S A White
- Department of Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Z Soonawalla
- Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - N B Jamieson
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - U Boggi
- Department of Surgery, Pisa University Hospital, Pisa, Italy
| | - A Alseidi
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington, USA
| | - A Shablak
- Departments of Medical Oncology, University Hospital of Southampton NHS Foundation Trust, Southampton, UK
| | - J W Wilmink
- Department of Medical Oncology, Cancer Centre Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
| | | | - R Salvia
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - C Bassi
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - M G Besselink
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - M Abu Hilal
- Departments of Surgery, Southampton, UK
- Department of Surgery, Istituto Fondazione Poliambulanza, Brescia, Italy
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Tashiro K, Kuroki N, Einama T, Iwasaki T, Miyata Y, Aosasa S, Inoue Y, Takahashi Y, Ogata S, Ueno H, Hase K, Yamamoto J, Kishi Y. Prognostic significance of regional lymph node metastasis according to station in ampullary carcinoma. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 27:712-720. [PMID: 32578342 DOI: 10.1002/jhbp.791] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 06/08/2020] [Accepted: 06/18/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND The TNM (Tumor, Node, Metastasis) classification of the 8th Union for International Cancer Control and the 6th Japanese classification of biliary tract cancer were made on the premise that the prognostic effect of each regional lymph node station is similar. However, some studies have reported different effects of lymph node metastasis location on post-resection prognosis. This study aimed to investigate outcome following radical resection of ampullary carcinoma according to station of lymph node metastasis. METHODS Patients who underwent surgical resection for ampullary carcinoma between January 2007 and December 2017 at two separate Japanese institutions were included. Regional lymph nodes were subclassified as follows: Pancreatoduodenal lymph nodes (PD) and others (OT). RESULTS Of the 101 patients analyzed, 34 had regional lymph node metastasis. OT metastasis was found in eight patients. Significant differences were found in relapse-free survival (RFS) and overall survival (OS) between the three study groups (no nodal metastasis, only PD metastasis and OT metastasis; P < .001 for both). OT metastasis was an independent prognostic factor in the multivariate analysis for RFS (hazard ratio [HR] 17.14; 95% confidence interval [CI], 6.33-43.93) and OS (HR 11.06; 95% CI, 3.7-32.99). CONCLUSION The poor prognosis of ampullary carcinoma patients with OT metastasis suggests that regional lymph nodes should not be categorized equally into one group.
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Affiliation(s)
- Keita Tashiro
- Department of Surgery, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan
| | - Naomi Kuroki
- Department of Gastrointestinal Surgery, Cancer Institute Hospital, Koto, Tokyo, Japan
| | - Takahiro Einama
- Department of Surgery, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan
| | - Toshimitsu Iwasaki
- Department of Surgery, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan
| | - Yoichi Miyata
- Department of Surgery, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan
| | - Suefumi Aosasa
- Department of Surgery, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan.,Department of Surgery, Shin-Kuki General Hospital, Kuki, Saitama, Japan
| | - Yosuke Inoue
- Department of Gastrointestinal Surgery, Cancer Institute Hospital, Koto, Tokyo, Japan
| | - Yu Takahashi
- Department of Gastrointestinal Surgery, Cancer Institute Hospital, Koto, Tokyo, Japan
| | - Sho Ogata
- Department of Pathology and Laboratory Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan
| | - Kazuo Hase
- Department of Surgery, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan
| | - Junji Yamamoto
- Department of Surgery, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan.,Department of Gastrointestinal Surgery, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki, Japan
| | - Yoji Kishi
- Department of Surgery, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan
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Abstract
The ampulla of Vater gives rise to a versatile group of cancers of mixed/hybrid histologic phenotype. Ampullary carcinomas (ACs) are most frequently intestinal or pancreatobiliary adenocarcinomas but other subtypes, such as medullary, mucinous, or signet ring/poorly cohesive cell carcinoma, may be encountered. Ampullary cancer can also be subclassified based on immunohistochemical features, however these classification systems fail to show robust prognostic reliability. More recently, the molecular landscape of AC has been uncovered, and has been shown to have prognostic and predictive significance. In this article, the site-specific, histologic, and genetic characteristics of ampullary carcinoma and its precursor lesions are discussed.
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Affiliation(s)
- Yue Xue
- Department of Pathology and Laboratory Medicine, Northwestern University, 251 East Huron Street, Room 7332, Chicago, IL 60611, USA
| | - Michelle D Reid
- Department of Pathology and Laboratory Medicine, Emory University Hospital, 1364 Clifton Road Northeast, Room H 180A, Atlanta, GA 30322, USA.
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Mathur A, Paul H, Ross S, Luberice K, Hernandez J, Vice M, Rosemurgy AS. Transduodenal Ampullectomy for Ampullary Adenomas: A Safe and Effective Procedure with Long-term Salutary Outcomes. Am Surg 2020. [DOI: 10.1177/000313481408000229] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
With widespread use of endoscopy, ampullary adenomas are more frequently identified, many of which are not amenable to endoscopic resection. Pancreatoduodenctomy is curative for these lesions but carries high morbidity. The purpose of this study was to determine the safety and efficacy of transduodenal ampullectomy for these lesions. Data were collected on 32 patients who underwent transduodenal ampullectomy from 2002 to 2010. The median age of patients was 64 years. Adenomas were found because of abdominal pain in 34 per cent, jaundice in 22 per cent, and incidentally on endoscopic screening in 16 per cent and on computed tomography scan of the abdomen in 9 per cent. All patients had a preoperative diagnosis of premalignant disease; 6 per cent required intraoperative conversion to pancreaticoduodenectomy after frozen section evaluation documented carcinoma. Of ampullectomies, 97 per cent had clear margins. Follow-up was 28 months. Four (13%) patients developed recurrent disease at 4 years, 2 years, 1.5 years, and 4 months; all had clear margins at ampullectomy and underwent subsequent pancreaticoduodenectomy with invasive malignancy in a single patient. After preoperative biopsy documenting premalignant disease, malignancy at ampullectomy is unusual. Recurrence is uncommon but occurs even with clear margins necessitating diligent follow-up; even with diligent follow-up, recurrence can be malignant.
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Al Abbas AI, Falvello V, Zenati M, Mani A, Hogg ME, Zeh HJ, Singhi A, Bahary N, Zureikat AH. Impact of adjuvant chemotherapy regimen on survival outcomes in immunohistochemical subtypes of ampullary carcinoma. J Surg Oncol 2020; 121:322-329. [PMID: 31840257 DOI: 10.1002/jso.25808] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Accepted: 12/02/2019] [Indexed: 01/24/2023]
Abstract
BACKGROUND AND OBJECTIVES Ampullary adenocarcinoma (AA) is classified by immunohistochemical (IHC) subtypes into intestinal (IN), pancreatobiliary (PB), and ambiguous (AM). The impact of adjuvant therapy on IHC subtype and disease stage is unclear. We examined the effect of adjuvant chemotherapy regimen on survival of ampullary cancers by IHC subtype and disease stage. METHODS Review of pancreatoduodenectomy (PD) performed for AA between 2005 and 2013 at a single center. The impact of regimen on IHC subtype and stage was analyzed. RESULTS One hundred and twenty-one patients were subtyped: IN = 32%, PB = 48%, and AM = 20% with overall survival of 45.6, 31.3, and 46.9 months, respectively. PB had higher pathologic T-stage, positive lymph node disease, and perineural and lymphovascular invasion (P < .05). 5-Fluorouracil (FU)-based adjuvant therapy improved survival compared to no treatment (87.4 vs 32.1 months; P = .046), and receipt of 5-FU emerged as an independent predictor of improved survival (hazard ratio [HR] 0.244; P = .031) regardless of subtype. 5-FU was superior to Gemcitabine in advanced-stage disease (stage IIB and III vs I+IIA, HR: 0.35; P < .05). CONCLUSIONS Adjuvant therapy with 5-FU confers a survival benefit in patients with advanced-stage AA regardless of subtype. The impact of various chemotherapy regimens on subtypes of ampullary cancer warrants further investigation.
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Affiliation(s)
- Amr I Al Abbas
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.,University of Texas Southwestern, Dallas, Texas
| | | | - Mazen Zenati
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Ashika Mani
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | | | | | - Aatur Singhi
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Nathan Bahary
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Amer H Zureikat
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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Ikeda C, Makino N, Matsuda A, Kakizaki Y, Ishizawa T, Kobayashi T, Sugahara S, Nishiduka M, Tsunoda M, Haga J, Tsunoda R, Ueno Y. Signet-ring cell carcinoma of the ampulla of Vater: a case diagnosed via repeated biopsies. Clin J Gastroenterol 2020; 13:607-614. [PMID: 31981088 PMCID: PMC7395027 DOI: 10.1007/s12328-020-01097-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 01/17/2020] [Indexed: 02/06/2023]
Abstract
Signet-ring cell carcinoma of the ampulla of Vater is a rare tumor. A 74-year-old woman presented with epigastric pain and was diagnosed with cholangitis. Her liver enzyme levels were elevated. Computed tomography showed an enhanced area in the periampullary region and marked common bile duct dilatation. On endoscopic retrograde cholangiopancreatography (ERCP), the ampulla exhibited a normal appearance without ulcer or mass. Histological biopsy confirmed the absence of malignancy. During follow-up, the patient again presented with acute cholangitis multiple times and underwent ERCP each time. The ampulla had the appearance of a reddish and erosive mucosa. Although biopsy was repeated, histological examination did not show any malignancy. After a total of 13 biopsies, the patient was diagnosed with ampullary carcinoma of non-exposed protruded type following the third ERC-guided biopsy. Careful follow-up and frequent endoscopic biopsies are important in cases of papillary carcinoma of non-exposed protruded type with normal ampullary mucosa on initial endoscopy because this condition is challenging to diagnose with a single biopsy.
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Affiliation(s)
- Chisaki Ikeda
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
| | - Naohiko Makino
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan
| | - Akiko Matsuda
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan
| | - Yasuharu Kakizaki
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan
| | - Tetsuya Ishizawa
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan
| | - Toshikazu Kobayashi
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan
| | - Shinpei Sugahara
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan
| | - Mayo Nishiduka
- Department of Gastroenterology, Yonezawa City Hospital, 6-36 Aioichou, Yonezawa, Yamagata, 992-8502, Japan
| | - Michihiko Tsunoda
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan
| | - Junichiroh Haga
- Department of Surgery, Yonezawa City Hospital, 6-36 Aioichou, Yonezawa, Yamagata, 992-8502, Japan
| | - Rikiya Tsunoda
- Department of Pathology, Yonezawa City Hospital, 6-36 Aioichou, Yonezawa, Yamagata, 992-8502, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan
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Adjuvant therapy for true ampullary cancer: a systematic review. Clin Transl Oncol 2020; 22:1407-1413. [PMID: 31927720 DOI: 10.1007/s12094-019-02278-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 12/19/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Given the lack of evidence on the best adjuvant approach, this review closely examines optimal adjuvant management for resected true ampullary cancer and its histological subtypes. MATERIALS AND METHODS A comprehensive literature search of PubMed was performed to identify studies on resected true ampullary cancers, published between January 2010 and December 2018. Data including the use of radiation, chemotherapy or chemoradiation and the outcomes were extracted. RESULTS A total of 116 records were identified, of which 65 screened were selected. Finally, nine studies were included. Only two of the studies reported separately the outcomes of pancreatobiliary and intestinal subtypes. Patients in the selected studies were treated with a pancreaticoduodenectomy with negative margins. Patients treated with adjuvant therapy were more likely to be pT3-4 and have positive nodes; median survival ranged from 30 to 47 months. A significant benefit for adjuvant treatment was observed in four of the studies, restricted to patients at stage IIB or higher. Likewise, patients with positive nodes may have a longer median survival with adjuvant chemoradiation compared to observation. CONCLUSIONS The present review suggests a benefit for adjuvant treatment for patients with locally advanced tumors. Randomized trials are needed to ascertain the topic, as well as studies reporting toxicity and quality of life of resected true ampullary cancer patients.
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Correlation between Immunohistochemical and Histomorphological Features of Ampullary Carcinomas: A Study on 72 Cases from a Tertiary Health Care Center. Gastroenterol Res Pract 2020; 2020:2080351. [PMID: 32148475 PMCID: PMC7057012 DOI: 10.1155/2020/2080351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Accepted: 10/22/2019] [Indexed: 12/21/2022] Open
Abstract
Tumors involving the ampulla could be arising primarily in the ampulla or extending from the adjacent. When a neoplasm is centered primarily in the ampulla with or without periampullary mucosal involvement, it is considered a primary ampullary carcinoma. These tumors generally have a better prognosis than duodenal and pancreaticobiliary neoplasms secondarily involving the ampulla. Distinguishing between the two primary types has prognostic implications, as the pancreaticobiliary-type ampullary carcinomas are said to have a poorer prognosis than the intestinal-type. Morphological analysis alone may not suffice in this context. The role of immunohistochemistry has therefore been explored by various groups of workers. The purpose of the present study was to determine the role of morphology and cytokeratin profile in accurate typing of ampullary carcinomas as intestinal and pancreaticobiliary.
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Taggart MW, Foo WC, Lee SM. Tumors of the Gastrointestinal System Including the Pancreas. ONCOLOGICAL SURGICAL PATHOLOGY 2020:691-870. [DOI: 10.1007/978-3-319-96681-6_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Kang JS, Kim H, Kim JR, Han Y, Kim E, Byun Y, Choi YJ, Kwon W, Jang JY, Kim SW. Short- and long-term outcomes of pancreaticoduodenectomy in elderly patients with periampullary cancer. Ann Surg Treat Res 2019; 98:7-14. [PMID: 31909045 PMCID: PMC6940429 DOI: 10.4174/astr.2020.98.1.7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Revised: 10/28/2019] [Accepted: 11/15/2019] [Indexed: 12/19/2022] Open
Abstract
Purpose Pancreaticoduodenectomy (PD) is recently performed in older cancer patients. The complication rate of PD is high. The present study was to compare the postoperative short- and long-term outcomes of PD in between older patients and younger patients. Methods Between 2000 and 2014, patients who underwent PD due to periampullary cancers were enrolled. Patients aged 75 years or over were included in the older group. Results Total 1,249 patients were enrolled in this study and 168 patients (13.5%) were included in the older group. Postoperative complication rates, duration of postoperative hospital stay, and 30-day mortality were comparable between the 2 groups, although the admission rate of intensive care unit postoperatively was higher in the older adult group (20.8% vs. 10.5%, P < 0.001). In terms of long-term outcomes, 5-year overall survival rate was lower in the older group (23.4% vs. 41.8%, P < 0.001), and 5-year cumulative recurrence rate was higher in the older group without statistical significance (63.9% vs. 57.9%, P = 0.095). However, there were no statistical differences of cumulative recurrence in pancreatic cancer patients (81.5% vs. 82.5%, P = 0.805). Conclusion PD for periampullary cancer is a safe and feasible treatment in the older patients. The treatment modality for obtaining better survival outcomes will be investigated.
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Affiliation(s)
- Jae Seung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Ri Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eunjung Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yoonhyeong Byun
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yoo Jin Choi
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sun-Whe Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
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Park HM, Park SJ, Han SS, Hong SK, Hong EK, Kim SW. Very early recurrence following pancreaticoduodenectomy in patients with ampullary cancer. Medicine (Baltimore) 2019; 98:e17711. [PMID: 31689805 PMCID: PMC6946574 DOI: 10.1097/md.0000000000017711] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
We aimed to identify the factors for very early recurrence (within 6 months) of ampullary cancer following curative resection and to compare the immunohistochemical expression rate of various antibodies between the 2 main histologic subtypes of ampullary adenocarcinoma.In this retrospective study, the postoperative outcomes and clinicopathologic factors for very early recurrence that occurred in 14 of 93 patients who underwent pancreaticoduodenectomy (PD) for ampullary adenocarcinoma between January 2002 and August 2014 were analyzed. Thereafter, we identified the factors associated with very early recurrence following surgery. Additionally, we compared the expression rates of CK7, CK20, MUC1, MUC2, MUC5AC, MUC6, S100P, and CDX2 between the 2 main histologic subtypes of ampullary adenocarcinoma (NCC2019-0138).The patients who underwent PD for ampullary cancer were divided into 2 groups: very early recurrence and others. Compared with the other patients, the 14 patients (32.6%) who developed very early recurrence had shorter median disease-free survival (4.2 vs 49.7 months, P = .001) and overall survival (18.2 vs 113.7 months, P < .001). Large tumor, lymph node metastasis, and pancreatobiliary type were independently associated with very early recurrence of ampullary cancer following PD.Large tumor, lymph node metastasis, and pancreatobiliary type were the independent risk factors for very early recurrence of ampullary cancer following curative resection. Therefore, ampullary cancer patients with these factors should be considered to receive aggressive adjuvant treatment and frequent post-operative follow-up.
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Affiliation(s)
- Hyeong Min Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang-Si, Gyeonggi-Do,
- Kangown National University Graduate School, Chuncheon-Si, Kangwond-Do,
| | - Sang-Jae Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang-Si, Gyeonggi-Do,
| | - Sung-Sik Han
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang-Si, Gyeonggi-Do,
| | - Seong Kweon Hong
- Department of Surgery, Kangwon National University Hospital, Chuncheon-Si, Kangwon-Do, South Korea
| | - Eun Kyung Hong
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang-Si, Gyeonggi-Do,
| | - Sun-Whe Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang-Si, Gyeonggi-Do,
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Zhao W, Wang B, Zhao A, Tian Q, Zhang L, Wang L, Zhao X, Yang J, Dong D. The role of radiotherapy in patients with resected ampullary carcinoma: findings based on the SEER database. HPB (Oxford) 2019; 21:1535-1540. [PMID: 31056288 DOI: 10.1016/j.hpb.2019.03.369] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Accepted: 03/20/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The role of adjuvant radiotherapy for resected ampullary carcinoma (AC) remains controversial. The aim of this study was to assess the effect of adjuvant radiotherapy on survival in patients who underwent resection for AC. METHODS The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients diagnosed with AC from 2004 to 2012. Kaplan-Meier survival curve and multivariable Cox proportional hazards analyses were conducted to determine the effect of adjuvant radiotherapy on overall survival (OS) and disease-specific survival (DSS). Propensity score matching (PSM) method was used to balance the differences of clinicopathological characteristics between groups. RESULTS A total of 1227 patients were included. Patients who received adjuvant radiotherapy were younger, had more advanced T stage and N stage tumors and were more likely to receive chemotherapy (p < 0.001). Adjuvant radiotherapy failed to improve either OS (p = 0.119) or DSS (p = 0.188) in PSM cohorts. In subgroup analysis, no subgroup benefited from adjuvant radiotherapy and in patients older than 70 years, radiotherapy was associated with a worse OS and DSS. CONCLUSION Patients with resected AC do not benefit from adjuvant radiotherapy.
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Affiliation(s)
- Wen Zhao
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China
| | - Biyuan Wang
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China
| | - Andi Zhao
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China
| | - Qi Tian
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China
| | - Lingxiao Zhang
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China
| | - Le Wang
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China
| | - Xiaoai Zhao
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China
| | - Jin Yang
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China.
| | - Danfeng Dong
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China.
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50
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Tuncel D, Basturk O, Bradley KT, Kim GE, Xue Y, Reid MD, Balci S, Erbarut I, Adsay V. Poorly Cohesive (Signet Ring Cell) Carcinoma of the Ampulla of Vater. Int J Surg Pathol 2019; 28:236-244. [PMID: 31612756 DOI: 10.1177/1066896919880968] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
In the ampulla of Vater, carcinomas with "diffuse-infiltrative"/"signet ring cell" morphology, designated as "poorly cohesive carcinoma" (PCC) in the WHO classification, are very rare and poorly characterized. Nine cases with a classical PCC morphology constituting >50% of the tumor were identified. Mean age was 64.8 years (vs 64.6 in ampullary carcinomas [ACs]) and 6 were males, 3 females. The mean invasive tumor size was 2.5 cm (vs 1.9 in ACs). Other morphologic patterns displayed included cord-like infiltration (n=2), plasmacytoid cells (n=2), and microglandular component (n=4), including goblet cell adenocarcinoma-like foci. None of the cases were associated with dysplasia. By immunohistochemistry, the carcinomas did not show intestinal differentiation (CDX2 0/9, CK20 1/9, MUC2 3/9), MUC1 was positive in 4/9, MUC5AC was positive in 7/8. E-cadherin loss was noted in 4/9. All cases were advanced stage (6/9-pT3, 3/9-pT4) (vs 43% in ACs). Lymph node metastases were identified in 44% (vs 45% in AC). Six patients (67%) died of disease at a median of 25 months, 3 were alive at 13, 15, and 60 months. Overall median survival was significantly worse than that of intestinal-type ACs (26 vs 122 months, P = .006) and trended toward worse than pancreatobiliary type (26 vs 42 months, P = .1). In conclusion, PCCs constitute 2.45% of all ACs. These present as advanced tumors and express upper-gastrointestinal immunoprofile with frequent MUC5AC labeling, which may be helpful in identifying subtle infiltration in the surface mucosa since MUC5AC is not expressed in the ampullary mucosa. Patients have poor prognosis.
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Affiliation(s)
| | - Olca Basturk
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Grace E Kim
- University of California San Francisco, CA, USA
| | - Yue Xue
- Emory University, Atlanta, GA, USA
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