|
1
|
Ozyigit Buyuktalanci D, Gun E, Dilek ON, Dilek FH. Histopathological and prognostic variability of ampullary tumors: A comprehensive study on tumor location, histological subtypes, and survival outcomes. Ann Diagn Pathol 2025; 77:152476. [PMID: 40157155 DOI: 10.1016/j.anndiagpath.2025.152476] [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: 01/28/2025] [Revised: 03/17/2025] [Accepted: 03/21/2025] [Indexed: 04/01/2025]
Abstract
Ampullary tumors present diagnostic challenges due to the complex anatomical and histological structure of the ampullary region. They can be classified into four types based on location: Periampullary-duodenal, intra-ampullary, ampullary-ductal, and ampullary-NOS (not otherwise specified). Periampullary-duodenal tumors are exophytic, ulcerovegetative, and often intestinal-type adenocarcinomas with frequent lymph node metastasis. Intra-ampullary tumors are polypoid and confined to the ampullary canal. Ampullary-ductal tumors exhibit sclerotic thickening in the bile or pancreatic duct and are typically pancreatobiliary-type adenocarcinomas. Ampullary-NOS includes tumors that do not fit other classifications. This study aimed to classify ampullary tumors by their anatomical localization, compare histopathological features, and assess the prognostic outcomes for each group. A total of 111 ampullary tumors were selected from 229 pancreaticoduodenectomy specimens over 10 years at our hospital. Clinical, imaging, and macroscopic findings were re-evaluated microscopically. Tumors were classified into four anatomical groups, and their histopathological characteristics and prognosis were analyzed. The cohort had a mean age of 62 ± 10.49 years, with 69 (62.2 %) males and 42 (37.8 %) females. The median survival was 28.23 months. Tumor distribution was as follows: 14.4 % intra-ampullary, 25.2 % ampullary-ductal, 10.8 % periampullary-duodenal, and 49.5 % not otherwise specified (NOS). Pancreatobiliary-type adenocarcinoma (p = 0.003), perineural invasion (p < 0.0001), and lymphovascular invasion (p = 0.002) were significantly more frequent in the ampullary-ductal and NOS groups, which were associated with poorer overall survival (p = 0.011). In addition, lymphovascular invasion and surgical margin positivity were identified as independent prognostic markers. Classifying ampullary tumors based on anatomical location is crucial due to significant histopathological and prognostic differences between the groups.
Collapse
Affiliation(s)
| | - Eylul Gun
- Department of Pathology, Basildon University Hospital, Mid and South Essex NHS Foundation Trust, Basildon, GB, United Kingdom
| | - Osman Nuri Dilek
- Department of General Surgery, Izmir Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey
| | - Fatma Husniye Dilek
- Department of Pathology, Izmir Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey
| |
Collapse
|
|
2
|
Kim HS, Heo CM, Choi YS, Suh SW, Lee SE. Prognostic significance of histologic phenotype in periampullary adenocarcinomas. Front Oncol 2024; 14:1407828. [PMID: 39081711 PMCID: PMC11286735 DOI: 10.3389/fonc.2024.1407828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 07/02/2024] [Indexed: 08/02/2024] Open
Abstract
Background Periampullary adenocarcinomas typically exhibit either intestinal or pancreatobiliary (PB) differentiation, and the type of differentiation may be prognostically more important than the anatomic site of origin. This study aimed to evaluate prognostic significance of histological type of periampullary carcinomas. Methods Microscopic slides from 110 consecutive pancreatoduodenectomies performed between 2010 and 2020 were reviewed and classified as intestinal or PB type. Clinicopathological factors were compared between PB-(n=93) and intestinal-type (n=17) differentiation. Results The intestinal type included significantly more patients with well-differentiated histology (35.3% vs. 11.8%, p=0.001) and fewer patients with perineural invasion (41.2% vs. 76.4%, p=0.029), advanced T stage (> T3; 41.2% vs.74.2%, p=0.007), and systemic recurrence (71.4% vs. 92.9%, p=0.005) than PB type. The 5-year-overall survival rate of intestinal-type was significantly higher than that of PB-type (58.8% vs. 20.4%, p=0.003). When pancreatic cancer was separately analyzed, the intestinal type showed the best 5-year-overall survival rate, with no significant difference between the PB types excluding PDAC and PDAC (39.4% vs. 19.2%, p=0.148). In multivariate analysis, curative resection (hazard ratio, 0.417; 95% CI, 0.219-0.792, p=0.008) was the only significant prognostic factor. Conclusion Although intestinal histologic phenotype was not an independent prognostic factor on multivariate analysis, it showed pathologic features associated with better survival, while the PB type showed more aggressive tumor biology and consequently worse survival. Further studies are needed to demonstrate the prognostic significance of histologic phenotype.
Collapse
Affiliation(s)
- Hee-Sung Kim
- Department of Pathology, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Chang-Min Heo
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Yoo-Shin Choi
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Suk-Won Suh
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Seung Eun Lee
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
3
|
Nappo G, Funel N, Laurenti V, Stenner E, Carrara S, Bozzarelli S, Spaggiari P, Zerbi A. Ampullary Cancer: Histological Subtypes, Markers, and Clinical Behaviour-State of the Art and Perspectives. Curr Oncol 2023; 30:6996-7006. [PMID: 37504367 PMCID: PMC10378042 DOI: 10.3390/curroncol30070507] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/15/2023] [Accepted: 07/20/2023] [Indexed: 07/29/2023] Open
Abstract
There are different cancers in the peri-ampullary region, including pancreatic ductal adenocarcinoma (PDAC), duodenum cancers (DCs), and ampullary adenocarcinoma (AAC). Here, significant morphological-molecular characterizations should be necessary for the distinction of primary tumours and classifications of their subtypes of cancers. The sub classification of AACs might include up to five different variants, according to different points of view, concerning the prevalence of the two more-cellular components found in the ampulla. In particular, regarding the AACs, the most important subtypes are represented by the intestinal (INT) and the pancreato-biliary (PB) ones. The subtyping of AACs is essential for diagnosis, and their identifications have been impacting clinical management responses to treatments and overall survival (os) after surgery. Pb is associated with a worse clinical outcome. Otherwise, the criteria, through which are possible to attribute its subtype classification, are not well established. A triage of immune markers represented by CK7, CK20, and CDX-2 seem to represent the best compromise in order to split the cohort of AAC patients in the INT and PB groups. The test of choice for the sub-classification of AACs is represented by the immuno-histochemical approach, in which its molecular classification acquires its diagnostic, predictive, and prognostic value for both the INT and PB patients.
Collapse
Affiliation(s)
- Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy (A.Z.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy
| | - Niccola Funel
- USL Toscana Nordovest, Chemical-Clinical Analysis Laboratory, Department of Diagnostics, 56121 Pisa, Italy; (N.F.); (E.S.)
| | - Virginia Laurenti
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy (A.Z.)
| | - Elisabetta Stenner
- USL Toscana Nordovest, Chemical-Clinical Analysis Laboratory, Department of Diagnostics, 56121 Pisa, Italy; (N.F.); (E.S.)
| | - Silvia Carrara
- Endoscopic Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Silvia Bozzarelli
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Paola Spaggiari
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy;
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy (A.Z.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy
| |
Collapse
|
|
4
|
Shin DW, Kim S, Jung K, Jung JH, Kim B, Ahn J, Kim J, Hwang JH, Lee JC. Impact of histopathological type on the prognosis of ampullary carcinoma: A systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:306-315. [PMID: 36272870 DOI: 10.1016/j.ejso.2022.10.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 08/27/2022] [Accepted: 10/05/2022] [Indexed: 02/23/2023]
Abstract
Histologically, ampullary carcinomas (ACs) can be classified into intestinal (INT-AC) and pancreatobiliary (PB-AC) subtypes. However, the prognostic implications of these subtypes remain unclear. This study aimed to evaluate the impact of the histopathologic phenotype of ACs on survival following pancreaticoduodenectomy. We searched PubMed, Embase, and Medline for studies published in English from 1994 to 2021. A meta-analysis was performed using Review Manager 5.3. The primary endpoint was overall survival (OS). We identified 3,890 articles; of these, 37 articles involving 3,455 participants (1,659 INT-ACs and 1,796 PB-ACs) were included. Patients in the PB-ACs group had significantly shorter OS than those in the INT-ACs group (hazard ratio [HR]: 1.79, 95% confidence interval [95% CI]: 1.51-2.13, p < 0.001, I2 = 61%). A similar tendency was observed in the immunohistochemistry staining group (HR: 1.76, 95% CI: 1.33-2.33, p < 0.001, I2 = 67%), which included 24 studies and 1,638 patients, and the non-immunohistochemistry group (HR: 1.84, 95% CI: 1.53-2.22, p = 0.04, I2 = 46%), which included 13 studies and 1,817 patients. Subgroup analysis revealed that patients with PB-AC had higher frequencies of advanced (III, IV) and pT3-4 stage AC, lymph node metastasis, poorly differentiated tumor, positive surgical margins, lymphovascular invasion, and perineural invasion, than those with INT-AC. Patients with PB-AC had a significantly shorter OS than those with INT-AC due to a higher aggressiveness. Because the histopathologic subtype is a major prognostic factor in patients with resected AC, routine histopathologic classification should be considered even in clinical settings without immunohistochemistry.
Collapse
Affiliation(s)
- Dong Woo Shin
- Department of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Republic of Korea
| | - Sihyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Kwangrok Jung
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Jae Hyup Jung
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Bomi Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Jinwoo Ahn
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Jaihwan Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jong-Chan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
| |
Collapse
|
|
5
|
Dawande PP, Akhtar F, Wankhade RS, Bankar NJ. Signet Ring Cell Carcinoma at the Ampulla of Vater: A Very Rare Diagnosis. Cureus 2022; 14:e30403. [DOI: 10.7759/cureus.30403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 10/17/2022] [Indexed: 11/07/2022] Open
|
|
6
|
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.
Collapse
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
| |
Collapse
|
|
7
|
Zhang X, Sun C, Li Z, Wang T, Zhao L, Niu P, Guo C, Chen Y, Che X, Zhao D. Development and Validation of a New Lymph Node Ratio-Based Staging System for Ampullary Carcinoma After Curative Pancreaticoduodenectomy. Front Oncol 2022; 11:811595. [PMID: 35127524 PMCID: PMC8810493 DOI: 10.3389/fonc.2021.811595] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 12/15/2021] [Indexed: 01/03/2023] Open
Abstract
Background Lymph node metastasis (LNM) is closely associated with the prognosis of ampullary carcinoma (AC). The purpose of this study is to explore the relationship between lymph node ratio (LNR) and the prognosis of patients with AC after curative pancreaticoduodenectomy and to establish a new LNR-based staging system. Methods AC patients in the Cancer Hospital, Chinese Academy of Medical Sciences, between 1998 and 2020 were retrospectively reviewed as the training cohort; and AC patients in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018 were obtained as the validation cohort. Within the training group, Kaplan–Meier survival analyses and Cox proportional hazards regression were conducted to assess the prognostic value of LNR and establish a new LNR-based staging system. Then, the new staging system was compared with the 8th American Joint Committee on Cancer (AJCC) TNM staging system in both the training and validation cohorts. Results A total of 264 patients in the training cohort and 199 patients in the validation cohort were enrolled. Significant overall survival (OS) difference was observed between LNR-low stage and LNR-high stage in both training (p = 0.001) and validation cohorts (p < 0.001). Then a new LNR-based staging system was developed. Under the new system, the number of patients in the training cohort and validation cohort of stage I, stage II, and stage III was 30 (11%) vs. 18 (9%), 190 (72%) vs. 96 (48%), and 44 (17%) vs. 85 (43%), respectively. The new staging system classified patients with respect to survival better than did the 8th AJCC TNM staging system. Conclusions The new LNR-based staging system had better discriminability for predicting survival in AC patients after curative pancreaticoduodenectomy. More data are needed for further validation.
Collapse
Affiliation(s)
- Xiaojie Zhang
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chongyuan Sun
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zefeng Li
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tongbo Wang
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lulu Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Penghui Niu
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chunguang Guo
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yingtai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xu Che
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
- *Correspondence: Xu Che, ; Dongbing Zhao,
| | - Dongbing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Xu Che, ; Dongbing Zhao,
| |
Collapse
|
|
8
|
Dwertmann Rico S, Büscheck F, Dum D, Luebke AM, Kluth M, Hube-Magg C, Hinsch A, Höflmayer D, Perez D, Izbicki JR, Neipp M, Mofid H, Daniels T, Isbert C, Fraune C, Möller K, Menz A, Bernreuther C, Lebok P, Clauditz T, Sauter G, Uhlig R, Wilczak W, Simon R, Steurer S, Burandt E, Marx A, Krech T. Mucin 5AC expression is common but unrelated to tumor progression in pancreatic adenocarcinoma. Int J Immunopathol Pharmacol 2022; 36:3946320221106504. [PMID: 35764407 PMCID: PMC9247369 DOI: 10.1177/03946320221106504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Introduction: Mucin 5AC (MUC5AC) belongs to the family of secreted gel-forming mucins. It is physiologically expressed in some normal mucin producing epithelial cells but also in pancreatic, ovarian, and colon cancer cells. The role of MUC5AC expression in cancer is not fully understood. This study was designed to explore the role of MUC5AC for pancreatic cancer progression, its association to microsatellite instability, and its diagnostic utility. Methods: Mucin 5AC expression was studied immunohistochemically in a tissue microarray (TMA) from 532 pancreatic cancers, 61 cancers of the ampulla Vateri, six acinar cell carcinomas and 12 large sections of pancreatitis. Results: Mucin 5AC staining was interpretable in 476 of 599 (79%) arrayed cancers. Staining was completely absent in normal pancreas and pancreatitis, but frequent in pancreatic cancer. Membranous and cytoplasmic MUC5AC expression was most common in pancreatic adenocarcinomas (71% of 423), followed by carcinomas of the ampulla Vateri (43% of 47), and absent in six acinar cell carcinomas. Mucin 5AC expression was unrelated to tumor phenotype (tumor stage, tumor grade, lymph node, and distant metastasis), and microsatellite instability in ductal adenocarcinomas and carcinomas of the ampulla Vateri. Conclusion: Our study indicates that MUC5AC is an excellent biomarker for pancreatic cancer diagnosis, especially to support the sometimes-difficult diagnosis on small biopsies. Mucin 5AC expression is unrelated to pancreatic cancer aggressiveness.
Collapse
Affiliation(s)
| | - Franziska Büscheck
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - David Dum
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas M Luebke
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Martina Kluth
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Andrea Hinsch
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Doris Höflmayer
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Daniel Perez
- General, Visceral and Thoracic
Surgery Department and Clinic, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Jakob R Izbicki
- General, Visceral and Thoracic
Surgery Department and Clinic, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Michael Neipp
- General, Vascular and Visceral
Surgery Clinic, Itzehoe Medical Center, Itzehoe, Germany
| | - Hamid Mofid
- General, Visceral Thoracic and
Vascular Surgery Clinic, Regio Clinic Pinneberg, Pinneberg, Germany
| | - Thies Daniels
- General, Visceral and Tumor Surgery
Clinic, Albertinen Hospital, Hamburg, Germany
| | - Christoph Isbert
- Department of General,
Gastrointestinal and Colorectal Surgery, Amalie Sieveking
Hospital, Hamburg, Germany
| | - Christoph Fraune
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Katharina Möller
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Anne Menz
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Patrick Lebok
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Till Clauditz
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Ria Uhlig
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Waldemar Wilczak
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Eike Burandt
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas Marx
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
- Department of Pathology, Academic Hospital
Fuerth, Fuerth, Germany
| | - Till Krech
- Institute of Pathology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
- Institute of Pathology, Clinical Center
Osnabrueck, Osnabrueck, Germany
| |
Collapse
|
|
9
|
Nappo G, Galvanin J, Gentile D, Capretti G, Pulvirenti A, Bozzarelli S, Rimassa L, Spaggiari P, Carrara S, Petitti T, Gavazzi F, Zerbi A. Long-term outcomes after pancreatoduodenectomy for ampullary cancer: The influence of the histological subtypes and comparison with the other periampullary neoplasms. Pancreatology 2021; 21:950-956. [PMID: 33795194 DOI: 10.1016/j.pan.2021.03.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 03/08/2021] [Accepted: 03/11/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Ampullary carcinoma (AC) is histologically classified as intestinal (In-AC), pancreaticobiliary (Pb-AC) or mixed-AC. The prognostic role of AC subtypes has been debated and remains unclear. The aims of this study were to evaluate outcomes after pancreatoduodenectomy (PD) for each subtype of AC and to compare these with pancreatic ductal adenocarcinoma [PDAC] and distal cholangiocarcinoma [DCC]. METHODS PDs performed for AC between 2010 and 2018 were retrospectively evaluated. Histological subtype was obtained for all patients. One-year, 3-year and 5-year disease-free-survival (DFS) and overall survival (OS) rates were calculated. Kaplan-Meier survival analysis was performed to compare Pb-AC, In-AC and mixed-AC. Comparison with PDs performed for PDAC and DCC during the same period was also performed. RESULTS A total of 97 patients undergoing PD for AC were evaluated: 34 (35.1%) In-AC, 54 (55.7%) Pb-AC and 9 mixed-AC (9.3%). DFS and OS rates for Pb-AC were significantly lower compared to In-AC (p < 0.05 and p < 0.01), but similar to mixed-AC (p = 0.3 and p = 0.4). Adjuvant therapy was not associated with increased survival, regardless of the histological subtype (p > 0.05). During the same period, 337 and 53 PDs for PDAC and DCC, respectively, were performed. In-AC was associated with significantly better outcomes compared to PDAC and DCC (p < 0.001); DFS and OS rates for Pb-AC and mixed AC were significantly higher compared to PDAC (p < 0.001), but similar to DCC (p > 0.05). CONCLUSIONS Pb-AC has significantly worse survival compared to In-AC. Moreover, mixed-AC should be considered as Pb-AC. Pb-AC and mixed-AC seem to have better prognosis compared to PDAC, but similar to DCC.
Collapse
Affiliation(s)
- G Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Milan, Italy.
| | - J Galvanin
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - D Gentile
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - G Capretti
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - A Pulvirenti
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
| | - S Bozzarelli
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
| | - L Rimassa
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center - IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - P Spaggiari
- Pathology Unit, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
| | - S Carrara
- Endoscopic Unit, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
| | - T Petitti
- Public Health and Statistics, Campus Bio-Medico University of Rome, Italy
| | - F Gavazzi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
| | - A Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| |
Collapse
|
|
10
|
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.
Collapse
|
|
11
|
Novel method for evaluating the indication for endoscopic papillectomy in patients with ampullary adenocarcinoma. Sci Rep 2021; 11:600. [PMID: 33436750 PMCID: PMC7804087 DOI: 10.1038/s41598-020-79836-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 11/27/2020] [Indexed: 01/06/2023] Open
Abstract
This study aimed to determine the clinicopathological features of the subtypes of ampullary carcinoma (AC) to explore the indications for endoscopic papillectomy (EP) in early AC. Fifty-seven patients with AC who underwent curative resection were retrospectively reviewed. The 0/IA stages were significantly more common in the intestinal type (I-type) than in the mixed and pancreatobiliary type (M&PB-type) (90.7% vs 35.7%, P < 0.001). Tis/T1a tumors limited to the ampulla [Tis/T1a(ampulla)] were significantly more likely to be I-type than M&PB-type (74.4% vs 14.3%, P = 0.002). The tub1 rate was significantly higher in the I-type than in the M&PB-type (81.4% vs 35.7%, P = 0.001). In the I-type, the tub1 rate was significantly higher for Tis/T1a(ampulla) than for T1a tumors limited to the sphincter of Oddi (100% vs 42.9%, P = 0.004). These observations suggest that I-type AC with tub1 is an indication for EP. The concordance rate of pathological subtypes between endoscopic biopsy and resected specimens was high (κ = 0.8053, P < 0.001). Tis/T1a(ampulla) showed no lymphovascular or perineural invasion. An endoscopic imaging finding of early AC with I-type and tub1 on biopsy could be an indication for EP. Identifying the pathological subtype of AC by endoscopic biopsy could be a novel preoperative approach for evaluating the indications for EP.
Collapse
|
|
12
|
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.
Collapse
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
| |
Collapse
|
|
13
|
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.
Collapse
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
| |
Collapse
|
|
14
|
Prognostic factors and benefits of adjuvant therapy for ampullary cancer following pancreatoduodenectomy: A systematic review and meta-analysis. Asian J Surg 2020; 43:1133-1141. [PMID: 32249101 DOI: 10.1016/j.asjsur.2020.03.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 02/28/2020] [Accepted: 03/13/2020] [Indexed: 12/16/2022] Open
Abstract
Ampullary cancer is a relatively rare gastrointestinal malignancy. The purpose of this study was to evaluate prognostic factors for survival and assess the benefits of adjuvant therapy following pancreaticoduodenectomy for this entity. Medline and EMBASE databases were searched to identify eligible studies from January 2000 to August 2019. Review Manager 5.3 statistical software was used for meta-analysis. 71 studies met the inclusion criteria and were included in the analysis for a total of 8280 patients. The median (range) 5-year overall survival and disease-free survival rates were 58% (32-82%) and 51% (28-73%) respectively. In meta-analysis, age >65 years at diagnosis, tumor size >20 mm, poor differentiation, pancreaticobiliary histotype, pT3-4 stage disease, presence of metastatic lymph node, number of metastatic nodes, perineural invasion, lymphovascular invasion, vascular invasion, pancreatic invasion, and positive surgical margins were independently associated with worse overall survival, whereas adjuvant therapy was associated with improved overall survival. In summary, in patients with ampullary cancer undergoing pancreaticoduodenectomy, tumor factors are the main predictors of worse survival and adjuvant treatment confers a survival benefit.
Collapse
|
|
15
|
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.
Collapse
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
| |
Collapse
|
|
16
|
Agalar C, Aysal A, Unek T, Egeli T, Ozbilgin M, Akturk N, Semiz HS, Unek T, Akarsu M, Soyturk M, Ellidokuz H, Sagol O, Astarcioglu I. The Role of Log Odds of Positive Lymph Nodes in Predicting the Survival after Resection for Ampullary Adenocarcinoma. Pathol Oncol Res 2020; 26:467-473. [PMID: 30693420 DOI: 10.1007/s12253-019-00584-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 01/15/2019] [Indexed: 12/13/2022]
Abstract
Lymph node metastasis is a important factor on survival in ampullary adenocarcinoma. Log odds of positive lymph nodes (LODDS) is a novel prognostic indicator on lymph node status. We aimed to evaluate the prognostic impact of LODDS for the patients with ampullary adenocarcinoma who underwent R0 pancreaticoduodenectomy. The study includes 42 patients.. LODDS was calculated as "log (number of metastatic lymph nodes+0.5)/(number of total harvested nodes - metastatic lymph nodes+0.5)". LODDS subgroups were created based on their LODDS value: LODDS1(LODDS≤ - 1.5), LODDS2(-1.5 < LODDS≤ - 1.0), LODDS3(-1.0 < LODDS≤ - 0.5), LODDS4(LODDS> - 0.5). The mean survival time was 72.7 ± 7.82 months. Survival rates for 1, 3 and 5 years were 93%, 65% and 45%, respectively. The mean LODDS value was -1.0466 ± 0.51. LODDS subgroups show strong correlation with Overall Survival(OS). The mean survival were 114.8, 81.8, 56.6 and 25.6 months in LODDS subgroups 1, 2, 3 and 4, respectively (Log-rank; p = 0.002), in addition LOODS values shows correlation with perineural invasion and micro vascular invasion (p = 0.015 and p = 0.001 respectively). Findings in our patient group support the hypothesis that LODDS subgroups correlate with OS, and that value of LODDS has considerable role in prediction of OS as well.
Collapse
Affiliation(s)
- Cihan Agalar
- The Department of General Surgery, Dokuz Eylul University School of Medicine, Balcova, İnciraltı, 35340, İzmir, Turkey.
| | - Anıl Aysal
- The Department of Pathology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Tarkan Unek
- The Department of General Surgery, Dokuz Eylul University School of Medicine, Balcova, İnciraltı, 35340, İzmir, Turkey
| | - Tufan Egeli
- The Department of General Surgery, Dokuz Eylul University School of Medicine, Balcova, İnciraltı, 35340, İzmir, Turkey
| | - Mucahit Ozbilgin
- The Department of General Surgery, Dokuz Eylul University School of Medicine, Balcova, İnciraltı, 35340, İzmir, Turkey
| | - Nesrin Akturk
- The Department of Radiation Oncology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Huseyin Salih Semiz
- The Department of Medical Oncology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Tugba Unek
- The Department of Medical Oncology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Mesut Akarsu
- The Department of Gastroenterology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Müjde Soyturk
- The Department of Gastroenterology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Hulya Ellidokuz
- The Department of Preventive Oncology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Ozgul Sagol
- The Department of Pathology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Ibrahim Astarcioglu
- The Department of General Surgery, Dokuz Eylul University School of Medicine, Balcova, İnciraltı, 35340, İzmir, Turkey
| |
Collapse
|
|
17
|
Kuzular H, Çallı Demirkan N, Özban M. Ampulla vaterinin primer taşlı yüzük hücreli karsinomu: Olgu sunumu ve literatür özeti. PAMUKKALE MEDICAL JOURNAL 2019. [DOI: 10.31362/patd.421184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
18
|
Sikdar N, Saha G, Dutta A, Ghosh S, Shrikhande SV, Banerjee S. Genetic Alterations of Periampullary and Pancreatic Ductal Adenocarcinoma: An Overview. Curr Genomics 2018; 19:444-463. [PMID: 30258276 PMCID: PMC6128383 DOI: 10.2174/1389202919666180221160753] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Revised: 01/31/2018] [Accepted: 02/01/2018] [Indexed: 02/06/2023] Open
Abstract
Pancreatic Ductal AdenoCarcinoma (PDAC) is one of the most lethal malignancies of all solid cancers. Precancerous lesions for PDAC include PanIN, IPMNs and MCNs. PDAC has a poor prognosis with a 5-year survival of approximately 6%. Whereas Periampulary AdenoCarcinoma (PAC) having four anatomic subtypes, pancreatic, Common Bile Duct (CBD), ampullary and duodenum shows relative better prognosis. The highest incidence of PDAC has been reported with black with respect to white population. Similarly, incidence rate of PAC also differs with different ethnic populations. Several lifestyle, environmental and occupational exposures including long-term diabetes, obesity, and smoking, have been linked to PDAC, however, for PAC the causal risk factors were poorly described. It is now clear that PDAC and PAC are a multi-stage process resulting from the accumulation of genomic alterations in the somatic DNA of normal cells as well as inherited mutations. Approximately 10% of PDAC have a familial inheritance. Germline mutations in CDKN2A, BRCA2, STK11, PALB2, PRSS1, etc., as well as certain syndromes have been well associated with predisposition to PDAC. KRAS, CDKN2A, TP53 and SMAD4 are the 4 "mountains" (high-frequency driver genes) which have been known to earliest somatic alterations for PDAC while relatively less frequent in PAC. Our understanding of the molecular carcinogenesis has improved in the last few years due to extensive research on PDAC which was not well explored in case of PAC. The genetic alterations that have been identified in PDAC and different subgroups of PAC are important implications for the development of genetic screening test, early diagnosis, and prognostic genetic markers. The present review will provide a brief overview of the incidence and prevalence of PDAC and PAC, mainly, increased risk in India, the several kinds of risk factors associated with the diseases as well as required genetic alterations for disease initiation and progression.
Collapse
Affiliation(s)
- Nilabja Sikdar
- Address correspondence to this author at the Human Genetics Unit, Indian Statistical Institute, 203, B.T. Road Kolkata 700108, India; Tel (1): +91-33
-25773240 (L); (2): +91-9830780397 (M); Fax: +91 33 35773049;, E-mail:
| | | | | | | | | | | |
Collapse
|
|
19
|
da Silveira Santos JPL, Machado CJ, Junior EP, Rodrigues JBSR, Vidigal PT, Resende V. Immunohistochemical Predictors for Intestinal and Pancreatobiliary Types of Adenocarcinoma of The Ampulla of Vater. J Gastrointest Surg 2018; 22:1171-1178. [PMID: 29736668 DOI: 10.1007/s11605-018-3797-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 04/24/2018] [Indexed: 01/31/2023]
Abstract
OBJECTIVES To investigate immunohistochemical predictors for intestinal and pancreatobiliary types of adenocarcinoma of ampulla of Vater and identify clinicopathological characteristics associated with the histological types and patient survival. METHODS Immunohistochemical markers included MUC1, MUC2, MUC5AC, CDX2, CK7, and CK20. The data were analyzed by univariate and multivariate methods. The two-step cluster method was used to determine the best immunohistochemical markers to discriminate the intestinal from the pancreatobiliary type. RESULTS This study identified 9 (33.3%) intestinal and 21 (66.7%) pancreatobiliary tumors. CK7 and CDX2 achieved the highest value (= 1) as predictor markers, while CK20, MUC1, and MUC2 showed degrees of importance equal to 0.77, 0.71, and 0.68, respectively. MUC5AC did not reach 0.50 of importance. In the univariate analysis, lymph node involvement, staging (TNM), and angiolymphatic and perineural invasions were associated with histological types. The independent clinicopathological variable in the multivariate model to predict the histological type was angiolymphatic invasion (p = 0.005), OR = 17 (95% CI 2.33 to 123.83). The final model showed positive nodes (N1) associated with shorter survival (HR = 9.5; p = 0.006). Overall survival at 12, 36, and 60 months was 88.5, 67.0, and 47.6%, respectively. CONCLUSIONS CDX2 and CK7 were the immunohistochemical markers that best discriminated the intestinal from the pancreatobiliary type. Lymph node involvement had a high impact on survival and proved to be more frequent in the pancreatobiliary type.
Collapse
Affiliation(s)
- João Paulo Lemos da Silveira Santos
- Department of Surgery, Medical School, UFMG, Belo Horizonte, Rua Sergipe, 67 apto 2401, Bairro Funcionários, Belo Horizonte, CEP 30130 170, Brazil
| | - Carla Jorge Machado
- Department of Epidemiology, Medical School, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - Eduardo Paulino Junior
- Department of Histopathology, Medical School, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - João Bernardo Sancio Rocha Rodrigues
- Department of Surgery, Medical School, UFMG, Belo Horizonte, Rua Sergipe, 67 apto 2401, Bairro Funcionários, Belo Horizonte, CEP 30130 170, Brazil
| | - Paula Teixeira Vidigal
- Department of Histopathology, Medical School, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - Vivian Resende
- Department of Surgery, Medical School, UFMG, Belo Horizonte, Rua Sergipe, 67 apto 2401, Bairro Funcionários, Belo Horizonte, CEP 30130 170, Brazil.
| |
Collapse
|
|
20
|
Validation of the eighth edition of the American Joint Committee on Cancer staging system for ampulla of Vater cancer. Surgery 2018; 163:1071-1079. [DOI: 10.1016/j.surg.2017.12.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 12/07/2017] [Accepted: 12/13/2017] [Indexed: 01/28/2023]
|
|
21
|
de Klein GW, van Baarlen J, Mekenkamp LJ, Liem MSL, Klaase JM. Signet Ring Cell Carcinoma of the Ampulla of Vater: A Rare Histopathological Variant. Case Rep Gastroenterol 2018; 12:194-201. [PMID: 29805366 PMCID: PMC5968303 DOI: 10.1159/000488903] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 03/01/2018] [Indexed: 11/19/2022] Open
Abstract
Signet ring cell carcinoma (SRCC) of the ampulla of Vater is an extremely rare tumor. Our case describes a 45-year-old female presenting with jaundice and pruritus. Computed tomography, endoscopy, and endoscopic retrograde cholangiopancreatography showed a tumor of the ampulla of Vater without distant metastasis. Histological biopsy confirmed a malignant tumor with SRCC characteristics and immunohistochemical staining revealed a mixed type profile (both intestinal and pancreatobiliary characteristics). A pylorus-preserving pancreatoduodenectomy was performed and the patient recovered without complications. Pathology results concluded a pT2N0 ampullary SRCC. SRCC of the ampulla of Vater is known to be highly malignant. After 13 months of follow-up, our patient showed no signs of recurrence.
Collapse
Affiliation(s)
- Guus W de Klein
- Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Joop van Baarlen
- Laboratorium Pathologie Oost-Nederland (LabPON), Hengelo, The Netherlands
| | - Leonie J Mekenkamp
- Department of Internal Medicine, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Mike S L Liem
- Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Joost M Klaase
- Department of Surgery, Universitair Medisch Centrum Groningen, Groningen, The Netherlands
| |
Collapse
|
|
22
|
Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience. Eur J Surg Oncol 2018; 44:677-683. [PMID: 29506768 DOI: 10.1016/j.ejso.2018.02.008] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 01/28/2018] [Accepted: 02/06/2018] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. METHODS A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. RESULTS Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. CONCLUSIONS Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma.
Collapse
|
|
23
|
Abstract
OBJECTIVES The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival. METHODS Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1-2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses. RESULTS The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables. CONCLUSIONS Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting.
Collapse
|
|
24
|
Kagiya T, Shimoda H, Narita H, Odagiri T, Watanabe S, Ishido K, Kudo D, Kimura N, Wakiya T, Hakamada K. Microanatomical profiles on the lymphatic system in the human ampulla of Vater (immunohistochemistry and scanning electron microscopy). JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2017; 24:570-575. [PMID: 28846834 DOI: 10.1002/jhbp.499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Little information is available regarding microanatomy of lymphatic system in the ampulla of Vater, though it is of critical importance for an understanding of tumor progression via the lymphatics and determination of surgical strategy. The present study, therefore, aimed to demonstrate the distribution and microanatomical profiles on the lymphatic system in the ampulla. METHODS The fine distribution and structure of the lymphatic vessels were investigated in the ampulla and the stomach by immunohistochemistry for lymphatic- (D2-40) and blood vascular- (CD31) specific markers and scanning electron microscopy. The densities of lymphatic and blood vessels were also compared. RESULTS The duodenal papilla densely developed the lymphatics with distinct aspects of lymphatic capillaries, together with blood vessels. The density of lymphatic capillaries in the extramuscular layer in the ampulla was higher than those of both the other ampullary layers and the gastric extramuscular (subserosal) layer. CONCLUSIONS The ampulla of Vater showed widespread lymphatic capillaries throughout the entire wall. The specific vascular system is suited to produce lymph everywhere and drain without via such a large vessel as lymphatic collector. This suggests that tumor cells invade the lymphatics and metastasize more easily in the ampulla than in the other gastrointestinal regions.
Collapse
Affiliation(s)
- Takuji Kagiya
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Hiroshi Shimoda
- Department of Anatomical Science, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Hirokazu Narita
- Department of Anatomical Science, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Tadashi Odagiri
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Seiji Watanabe
- Department of Anatomical Science, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Keinosuke Ishido
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Daisuke Kudo
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Norihisa Kimura
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Taiichi Wakiya
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Kenichi Hakamada
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| |
Collapse
|
|
25
|
Zhou Y, Li D, Wu L, Si X. The histopathologic type predicts survival of patients with ampullary carcinoma after resection: A meta-analysis. Pancreatology 2017; 17:273-278. [PMID: 28131524 DOI: 10.1016/j.pan.2017.01.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 12/27/2016] [Accepted: 01/19/2017] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The results of studies on the prognostic value of histopathologic differentiation of the intestinal and pancreatobiliary types of ampullary carcinoma after resection are conflicting. A meta-analysis was undertaken to investigate this issue. METHODS A systematic literature search was performed to identify articles published from January 2000 to August 2016. Data were pooled for meta-analysis using Review Manager 5.3. RESULTS Twenty three retrospective studies involving a total of 2234 patients were identified for inclusion, of whom 1021 (45.7%) had intestinal type tumors and 899 (40.2%) had pancreaticobiliary type tumors. Patients with the pancreaticobiliary type had high rates of poor tumor differentiation (P < 0.001), lymph node metastasis (P < 0.001), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and positive resection margins (P = 0.004), as compared with those with the intestinal type. The pancreaticobiliary type predicted a worse overall survival (hazard ratio [HR] 1.84, 95% CI 1.49-2.27; P < 0.001) and disease-free survival (HR 1.93, 95% CI 1.23-3.01; P = 0.004). CONCLUSION The histopathologic type has major impact on survival in patients with ampullary carcinoma after resection, and the pancreaticobiliary type reflects a more aggressive tumor biology and is associated with worse survival.
Collapse
Affiliation(s)
- Yanming Zhou
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China.
| | - Dianqi Li
- Department of the First Surgery, Chinese PLA 413 Hospital, Zhoushan, China
| | - Lupeng Wu
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Xiaoying Si
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| |
Collapse
|
|
26
|
Alkhasawneh A, Duckworth LV, George TJ, Desai NV, Sommerfeld AJ, Lu X, Toro TZ. Clinical, morphologic, and immunophenotypic characteristics of ampullary carcinomas with an emphasis on SMAD4 expression. J Gastrointest Oncol 2016; 7:974-981. [PMID: 28078121 DOI: 10.21037/jgo.2016.06.14] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND The purpose of our study was to examine the relationship between clinicopathologic variables and morphologic subtypes in ampullary carcinoma, with an emphasis on the expression of SMAD4 tumor suppressor gene. METHODS Sixty-three cases of ampullary carcinomas resected between 2000-2011 were included in this study. Clinical characteristics and outcome data were recorded. Tumors were classified as pancreatobiliary or intestinal type based on morphology, and immunohistochemical (IHC) studies for cytokeratin 7 (CK7), cytokeratin 20 (CK20), cytokeratin 17 (CK17), and SMAD4 were performed. RESULTS Forty-nine percent of the ampullary tumors were pancreatobiliary, 29% were intestinal, and 22% were other variants. Tumors with pancreatobiliary morphology showed worse overall survival than those with intestinal morphology or other variants (P=0.03). A trend for higher stage, recurrence and less survival was seen in cases with negative SMAD4 expression. In multivariate analysis, age group (≤60 vs. >60 years) and expression of CK17 were the most prognostic of survival. CONCLUSIONS Ampullary tumors with pancreatobiliary morphology have a worse overall survival, while negative SMAD4 expression is associated with a trend of less survival.
Collapse
Affiliation(s)
- Ahmad Alkhasawneh
- Department of Pathology, University of Florida College of Medicine, Jacksonville, FL 32204, USA
| | - Lizette Vila Duckworth
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Thomas J George
- Department of Medicine, University of Florida, College of Medicine, Gainesville, FL 32610, USA
| | - Neelam V Desai
- Department of Medicine, University of Florida, College of Medicine, Gainesville, FL 32610, USA
| | - Alex J Sommerfeld
- Department of Medicine, University of Florida, College of Medicine, Gainesville, FL 32610, USA
| | - Xiaomin Lu
- Department of Biostatistics, University of Florida, Gainesville, FL 32610, USA
| | - Tania Zuluaga Toro
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA
| |
Collapse
|
|
27
|
Kim BJ, Jang HJ, Kim JH, Kim HS, Lee J. KRAS mutation as a prognostic factor in ampullary adenocarcinoma: a meta-analysis and review. Oncotarget 2016; 7:58001-58006. [PMID: 27517148 PMCID: PMC5295407 DOI: 10.18632/oncotarget.11156] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Accepted: 07/30/2016] [Indexed: 02/07/2023] Open
Abstract
Ampullary adenocarcinoma (A-AC) is a rare malignancy arising from the ampulla of Vater. KRAS mutation is detected in 30-40% of patients with A-AC, but its clinical implication and prognostic value are not well described. We conducted this meta-analysis to investigate the association between KRAS mutation and prognosis in patients with A-AC. We searched Pubmed, MEDLINE, EMBASE, and the Cochrane Library databases for articles including following terms in their titles, abstracts, or keywords: 'ampullary or periampullary or ampulla of vater', 'cancer or carcinoma', and 'KRAS'. There were five studies with survival data of patients. A total of 388 patients with A-AC from the 5 studies were included in the overall survival (OS) analysis, and 169 patients from 2 studies were eligible for the relapse-free-survival (RFS) analysis. Out of 388 patients, 175 (45%) had KRAS mutation. There was no association between KRAS mutation and OS (HR = 1.06, 95% CI: 0.87-1.29, P = 0.58). However, there was a significant correlation between KRAS mutation and worse RFS (HR = 2.74, 95% CI: 1.52-4.92, P = 0.0008). In conclusion, this meta-analysis indicates that KRAS mutation is associated with poor RFS, but not with OS in patients with A-AC.
Collapse
Affiliation(s)
- Bum Jun Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul 07441, Republic of Korea
| | - Hyun Joo Jang
- Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Hwasung 18450, Republic of Korea
| | - Jung Han Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul 07441, Republic of Korea
| | - Hyeong Su Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul 07441, Republic of Korea
| | - Jin Lee
- Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Hwasung 18450, Republic of Korea
| |
Collapse
|
|
28
|
Asano E, Okano K, Oshima M, Kagawa S, Kushida Y, Munekage M, Hanazaki K, Watanabe J, Takada Y, Ikemoto T, Shimada M, Suzuki Y. Phenotypic characterization and clinical outcome in ampullary adenocarcinoma. J Surg Oncol 2016; 114:119-27. [DOI: 10.1002/jso.24274] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 04/15/2016] [Indexed: 12/14/2022]
Affiliation(s)
- Eisuke Asano
- Department of Gastroenterological Surgery; Kagawa University; Kagawa Japan
| | - Keiichi Okano
- Department of Gastroenterological Surgery; Kagawa University; Kagawa Japan
| | - Minoru Oshima
- Department of Gastroenterological Surgery; Kagawa University; Kagawa Japan
| | - Seiko Kagawa
- Department of Pathology; Kagawa University; Kagawa Japan
| | - Yoshio Kushida
- Department of Pathology; Kagawa University; Kagawa Japan
| | - Masaya Munekage
- Department of First Surgery; Kochi University School of Medicine; Kochi Japan
| | - Kazuhiro Hanazaki
- Department of First Surgery; Kochi University School of Medicine; Kochi Japan
| | - Jota Watanabe
- Department of Hepato-Biliary-Pancreatic and Breast Surgery; Ehime University Graduate School of Medicine; Ehime Japan
| | - Yasutsugu Takada
- Department of Hepato-Biliary-Pancreatic and Breast Surgery; Ehime University Graduate School of Medicine; Ehime Japan
| | - Tetsuya Ikemoto
- Department of Digestive and Transplant Surgery; Tokushima University; Tokushima Japan
| | - Mitsuo Shimada
- Department of Digestive and Transplant Surgery; Tokushima University; Tokushima Japan
| | - Yasuyuki Suzuki
- Department of Gastroenterological Surgery; Kagawa University; Kagawa Japan
| | | |
Collapse
|
|
29
|
Ha HR, Oh DY, Kim TY, Lee K, Kim K, Lee KH, Han SW, Chie EK, Jang JY, Im SA, Kim TY, Kim SW, Bang YJ. Survival Outcomes According to Adjuvant Treatment and Prognostic Factors Including Host Immune Markers in Patients with Curatively Resected Ampulla of Vater Cancer. PLoS One 2016; 11:e0151406. [PMID: 26974670 PMCID: PMC4790941 DOI: 10.1371/journal.pone.0151406] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Accepted: 02/26/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Ampulla of Vater cancer (AoV Ca) is a rare tumor, and its adjuvant treatment has not been established. The purpose of this study was to find out prognostic factors including host immunity and role of adjuvant treatment in AoV Ca. METHODS AND FINDINGS We reviewed 227 AoV Ca patients with curative resection. Clinical characteristics, adjuvant treatment, disease-free survival (DFS) and overall survival (OS) were analyzed. Among all patients, 63.9, 36.1 and 33.9% had T1/T2, T3/T4 stage and lymph node-positive disease (LN+), respectively. OS of all patients was 90.9 months (95% CI: 52.9-129.0). OS was different according to neutrophil-to-lymphocyte ratio (HR 1.651, 95% CI: 1.11-2.47), platelet-to-lymphocyte ratio (HR 1.488, 95% CI: 1.00-2.21) and systemic inflammatory index (HR 1.669, 95% CI: 1.13-2.47). In multivariate analysis, adverse prognostic factors for OS included vascular invasion (HR 2.571, 95% CI: 1.20-5.53) and elevated CA 19-9 (HR 1.794, 95% CI: 1.07-3.05). A total of 104 patients (46.3%) received adjuvant treatment (25 out of 111of T1/T2 & LN (-), 79 out of 116 of T3/T4 or LN (+)). In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the longest OS (5-year OS rate: 47.0 vs. 41.4%). CONCLUSIONS Vascular invasion and elevated CA 19-9 were adverse prognostic factors in resected AoV Ca. In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the best survival outcome. Adjuvant treatment should be further defined in AoV Ca, especially with poor prognostic factors.
Collapse
Affiliation(s)
- Hye rim Ha
- Department of Internal medicine, Seoul National University Hospital, Seoul, South Korea
| | - Do-Youn Oh
- Department of Internal medicine, Seoul National University Hospital, Seoul, South Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Tae-Yong Kim
- Department of Internal medicine, Seoul National University Hospital, Seoul, South Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - KyoungBun Lee
- Department of Pathology, Seoul National University Hospital, Seoul, South Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Seoul National University Hospital, Seoul, South Korea
| | - Kyung-Hun Lee
- Department of Internal medicine, Seoul National University Hospital, Seoul, South Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sae-Won Han
- Department of Internal medicine, Seoul National University Hospital, Seoul, South Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University Hospital, Seoul, South Korea
| | - Jin-Young Jang
- Department of Surgery, Seoul National University Hospital, Seoul, South Korea
| | - Seock-Ah Im
- Department of Internal medicine, Seoul National University Hospital, Seoul, South Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Tae-You Kim
- Department of Internal medicine, Seoul National University Hospital, Seoul, South Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sun-Whe Kim
- Department of Surgery, Seoul National University Hospital, Seoul, South Korea
| | - Yung-Jue Bang
- Department of Internal medicine, Seoul National University Hospital, Seoul, South Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| |
Collapse
|
|
30
|
Balci S, Basturk O, Saka B, Bagci P, Postlewait LM, Tajiri T, Jang KT, Ohike N, Kim GE, Krasinskas A, Choi H, Sarmiento JM, Kooby DA, El-Rayes BF, Knight JH, Goodman M, Akkas G, Reid MD, Maithel SK, Adsay V. Substaging Nodal Status in Ampullary Carcinomas has Significant Prognostic Value: Proposed Revised Staging Based on an Analysis of 313 Well-Characterized Cases. Ann Surg Oncol 2015; 22:4392-401. [PMID: 25783680 PMCID: PMC4575255 DOI: 10.1245/s10434-015-4499-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Current nodal staging (N-staging) of ampullary carcinoma in the TNM staging system distinguishes between node-negative (N0) and node-positive (N1) disease but does not consider the metastatic lymph node (LN) number. METHODS Overall, 313 patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma were categorized as N0, N1 (1-2 metastatic LNs), or N2 (≥3 metastatic LNs), as proposed by Kang et al. Clinicopathological features and overall survival (OS) of the three groups were compared. RESULTS The median number of LNs examined was 11, and LN metastasis was present in 142 cases (45 %). When LN-positive cases were re-classified according to the proposed staging system, 82 were N1 (26 %) and 60 were N2 (19 %). There was a significant correlation between proposed N-stage and lymphovascular invasion, perineural invasion, increased tumor size (each p < 0.001), and surgical margin positivity (p = 0.001). The median OS in LN-negative cases was significantly longer than that in LN-positive cases (107.5 vs. 32 months; p < 0.001). Patients with N1 and N2 disease had median survivals of 40 and 24.5 months, respectively (p < 0.0001). In addition, 1-, 3-, and 5-year survivals were 88, 76, 62 %, respectively, for N0; 90, 55, 31.5 %, respectively, for N1; and 68, 34, 30 %, respectively for N2 (p < 0.001). Even with multivariate modeling, the association between higher proposed N stage and shorter survival persisted (hazard ratio 1.6 for N1 and 1.9 for N2; p = 0.018). CONCLUSIONS Classification of nodal status in ampullary carcinomas based on the number of metastatic LNs has a significant prognostic value. A revised N-staging classification system should be incorporated into the TNM staging of ampullary cancers.
Collapse
Affiliation(s)
- Serdar Balci
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Olca Basturk
- Department of Pathology, New York University, New York, NY, USA
| | - Burcu Saka
- Department of Pathology, İstanbul Medipol University, İstanbul, Turkey
| | - Pelin Bagci
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Lauren M Postlewait
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA
| | - Takuma Tajiri
- Department of Pathology, Tokai University Hachiouji Hospital, Tokyo, Japan
| | - Kee-Taek Jang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nobuyuki Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Tokyo, Japan
| | - Grace E Kim
- Department of Pathology, University of California San Francisco, San Francisco, CA, USA
| | - Alyssa Krasinskas
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Hyejeong Choi
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Juan M Sarmiento
- Division of General and Gastrointstinal Surgery, Emory University, Atlanta, GA, USA
| | - David A Kooby
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA
| | | | | | - Michael Goodman
- Department of Epidemiology, Emory University, Atlanta, GA, USA
| | - Gizem Akkas
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Michelle D Reid
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA
| | - Volkan Adsay
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
| |
Collapse
|
|
31
|
Kwon MJ, Kim JW, Jung JP, Cho JW, Nam ES, Cho SJ, Kim JS, Park HR, Min SK, Seo J, Min KW, Kim DH, Jeon JY. Low incidence of KRAS, BRAF, and PIK3CA mutations in adenocarcinomas of the ampulla of Vater and their prognostic value. Hum Pathol 2015; 50:90-100. [PMID: 26997442 DOI: 10.1016/j.humpath.2015.11.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 11/19/2015] [Accepted: 11/20/2015] [Indexed: 02/08/2023]
Abstract
Ampullary adenocarcinomas (A-ACs) are rare malignancies with considerable importance because of their high curable resection rate and improved survival rate among periampullary cancers. The RAS-RAF-MAPK pathway is involved in the development of A-ACs and is a potential therapeutic target. However, molecular profiles of A-ACs and their prognostic impact are poorly understood. Peptide nucleic acid-mediated polymerase chain reaction clamping and Mutyper were used to detect KRAS, BRAF, and PIK3CA mutations in 62 paraffinized samples of A-ACs. Of 62 A-ACs, 30.6% had KRAS mutations, but no BRAF mutations and low frequency (1.6%) of PIK3CA mutation were detected. KRAS mutation was correlated with poor tumor differentiation and was a predictor of shorter recurrence-free survival period in overall A-ACs, whereas the prognosis according to the histologic subtypes was not affected by KRAS mutation. Lymph node metastasis was an independent prognostic factor of poor overall survival. Intestinal- and pancreatobiliary-type A-ACs had similar prognosis. Intestinal- and pancreatobiliary-type A-ACs had different prognostic factors; tumor differentiation and lymph node metastasis strongly predicted overall survival and recurrence-free survival in pancreatobiliary-type tumors, respectively, whereas no independent prognostic factors were demonstrated for intestinal-type tumors. Low incidence of KRAS mutations and their strong prognostic value in A-ACs may suggest the potential of survival benefit depending on the epidermal growth factor receptor-targeted therapy. Much lower frequencies of BRAF and PIK3CA mutations may suggest that they do not play a major role in the tumorigenesis of A-ACs. Different therapeutic protocols should be considered for treating pancreatobiliary- and intestinal-type A-ACs.
Collapse
Affiliation(s)
- Mi Jung Kwon
- Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea
| | - Jeong Won Kim
- Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Yeongdeungpo-gu, Seoul 150-950, Republic of Korea
| | - Jae Pil Jung
- Department of Surgery, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Gangweon-do 200-704, Republic of Korea
| | - Ji Woong Cho
- Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea
| | - Eun Sook Nam
- Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 134-701, Republic of Korea
| | - Seong Jin Cho
- Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 134-701, Republic of Korea
| | - Joo Seop Kim
- Department of Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 134-701, Republic of Korea
| | - Hye-Rim Park
- Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea
| | - Soo Kee Min
- Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea
| | - Jinwon Seo
- Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea
| | - Kyueng-Whan Min
- Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea
| | - Dong Hoon Kim
- Department of Pathology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Gyeonggi-do 445-170, Republic of Korea.
| | - Jang Yong Jeon
- Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea.
| |
Collapse
|
|
32
|
Validation of histomolecular classification utilizing histological subtype, MUC1, and CDX2 for prognostication of resected ampullary adenocarcinoma. Br J Cancer 2015; 113:64-8. [PMID: 25989273 PMCID: PMC4647538 DOI: 10.1038/bjc.2015.172] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 03/02/2015] [Accepted: 04/21/2015] [Indexed: 12/18/2022] Open
Abstract
Background: Outcomes for ampullary adenocarcinomas are heterogeneous, and numerous methods of categorisation exist. A histomolecular phenotype based on histology, caudal-type homeodomain transcription factor 2 (CDX2) staining and Mucin 1 (MUC1) staining has recently been tested and validated in two cohorts. We attempt to validate this classification in a large patient population. Methods: Tissue samples from 163 patients with resected ampullary adenocarcinoma were classified based on histology and immunohistochemical expression of CDX2 and MUC1. A pancreaticobiliary histomolecular classification (PB) was defined as a sample with pancreaticobiliary histology, positive MUC1 and negative CDX2 expression. Results: There were 82 deaths; median follow-up of 32.4 months; and median overall survival of 87.7 (95% CI 42.9–109.5) months. PB comprised 28.2% of the cases. Factors associated with overall survival were histological subtype (P=0.0340); T1/2 vs T3/4 (P=0.001); perineural (P<0.0001) and lymphovascular (P=0.0203) invasion; and histomolecular intestinal histomolecular phenotype (INT) vs PB phenotype (106.4 vs 21.2 months, P<0.0001). Neither MUC1 nor CDX2 was statistically significant, although MUC1 positivity defined as ⩾10% staining was significant (P=0.0023). In multivariate analysis, age (HR 1.03), PB phenotype (HR 2.26) and perineural invasion (PNI; HR 2.26) were associated with poor survival. Conclusions: The prognostic ability of histomolecular phenotype has been validated in an independent cohort of ampullary adenocarcinoma patients.
Collapse
|
|
33
|
Prognostic score for recurrence after Whipple's pancreaticoduodenectomy for ampullary carcinomas; results of an AGEO retrospective multicenter cohort. Eur J Surg Oncol 2015; 41:520-6. [DOI: 10.1016/j.ejso.2015.01.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Revised: 11/07/2014] [Accepted: 01/10/2015] [Indexed: 12/18/2022] Open
|
|
34
|
Ahmad SR, Adler DG. Cancer of the ampulla of vater: current evaluation and therapy. Hosp Pract (1995) 2015; 42:45-61. [PMID: 25485917 DOI: 10.3810/hp.2014.12.1158] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Ampullary cancer is a relatively rare cancer of the digestive tract. In contrast to pancreatic cancer, ampullary cancer is often curable if detected at an early stage. The evaluation and management of ampullary cancer is similar to, but distinct from, that of other pancreaticobiliary tumors. This manuscript will review the current evaluation, diagnosis, and therapy of patients with ampullary cancer. The diagnosis of ampullary cancer is complicated by its similar clinical presentation to pancreatic cancer as well as its nonspecific laboratory findings. Diagnostic modalities such as ERCP, EUS, and biopsy are necessary for differentiating the 2 cancers, and noninvasive imaging techniques such as MRI and CT may be used for tumor staging. Although pancreaticoduodenectomy is considered the primary curative surgical option, consensus guidelines regarding adjuvant and neoadjuvant chemoradiation therapies are lacking.
Collapse
Affiliation(s)
- Sarah R Ahmad
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, UT
| | | |
Collapse
|
|
35
|
Wen X, Wu W, Wang B, Yao H, Teng X. Signet ring cell carcinoma of the ampulla of Vater: Immunophenotype and differentiation. Oncol Lett 2014; 8:1687-1692. [PMID: 25202392 PMCID: PMC4156204 DOI: 10.3892/ol.2014.2344] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2013] [Accepted: 05/07/2014] [Indexed: 11/13/2022] Open
Abstract
Signet ring cell carcinoma (SRC) of the ampulla of Vater is extremely rare and the histogenesis remains unknown. In the present study, to investigate the immunohistochemical phenotypes, discuss the histological origin and evaluate the correlation between the immunohistochemical phenotypes and survival of ampullary SRC patients, a retrospective review was conducted. This included all ampullary carcinoma patients treated at The First Affiliated Hospital, College of Medicine, Zhejiang University, and was performed over a five-year period between 2008 and 2012. Eight resected ampullary SRC specimens were examined histopathologically and immunohistochemically, using cytokeratin (CK) and mucin (MUC) immunohistochemical phenotypes. Of all 162 patients with ampullary lesions, eight cases (4.9%) of ampullary SRC were identified. Immunohistochemical analyses of the eight cases revealed the positive expression of CK7 in five, CK19 in seven, CK20 in one, MUC1 in five, MUC2 in three, caudal-related homeobox transcription factor 2 in one, MUC5AC in seven and MUC6 in four of the eight cases, while loss of E-cadherin and β-catenin was observed in four of the eight cases. According to immunohistochemical classification, ampullary SRC can be classified into four subtypes: Intestinal (I), pancreatobiliary (PB), gastric and mixed types (composed of I mucosa lining and PB epithelium). Patients with the I-type ampullary SRC demonstrated a more favorable prognosis than that of patients with the PB-type ampullary SRC. Additionally, patients with ampullary SRC of I or PB type with gastric differentiation may have a worse prognosis than others. The coexpression of the E-cadherin/β-catenin complex may also indicate poor prognosis in PB-type ampullary SRC. In conclusion, the clinical five-year follow-up of the patients with pure SRC was more positive than that of those with I-, PB-, gastric- or mixed-type ampullary SRC. The coexpression of the E-cadherin/β-catenin complex may present a poor prognosis in the PB type of ampullary SRC.
Collapse
Affiliation(s)
- Xue Wen
- Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Weiqiang Wu
- Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Bo Wang
- Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Hongtian Yao
- Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Xiaodong Teng
- Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| |
Collapse
|
|
36
|
Predictors of long-term survival following resection for ampullary carcinoma: a large retrospective French multicentric study. Pancreas 2014; 43:692-7. [PMID: 24713843 DOI: 10.1097/mpa.0000000000000112] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVES Ampullary carcinoma is a rare tumor. There are neither sufficient available data related to management after resection of the neoplasm of the ampulla of Vater, nor any international recommendations. The aim of this study was to identify factors associated with recurrence and survival after curative resection. METHODS A retrospective follow-up study was conducted including patients with ampullary carcinoma who underwent resection with curative intent in 12 French surgical centers between January 1990 and November 2011. RESULTS In this study, 319 patients underwent surgical resection for an ampullary neoplasm. Disease recurred in 120 patients (37.6%), and the 5- and 10-year disease-free survival rates were 48.9% and 40.4%, respectively. In multivariable Cox regression, preoperative bilirubin, T stage, pancreaticobiliary histology subtype, and lymph node involvement were each significantly associated with the risk of recurrence. CONCLUSIONS Ampullary carcinomas are a heterogeneous group that can be classified as intestinal and pancreaticobiliary subtypes. Our findings indicate that pancreaticobiliary differentiation, advanced stage, and lymph node involvement are predictors of both poor disease-free and poor overall survival. It is still unclear what adjuvant treatment after curative resection of ampullary carcinoma is optimal. It would be informative to evaluate adjuvant therapy according to histological subtype.
Collapse
|
|
37
|
Yamamoto Y, Nemoto T, Okubo Y, Nihonyanagi Y, Ishiwatari T, Takuma K, Tochigi N, Okano N, Wakayama M, Igarashi Y, Shibuya K. Comparison between the location and the histomorphological/immunohistochemical characteristics of noninvasive neoplasms of the ampulla of Vater. Hum Pathol 2014; 45:1910-7. [PMID: 25081540 DOI: 10.1016/j.humpath.2014.05.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2014] [Revised: 05/24/2014] [Accepted: 05/30/2014] [Indexed: 12/24/2022]
Abstract
To determine useful factors when selecting an appropriate procedure for noninvasive ampullary neoplasia, we investigated the relationship between the location and the histomorphological/immunohistochemical characteristics of 56 noninvasive ampullary neoplasms obtained by endoscopic papillectomy (EP). All subjects were classified according to histomorphology and location of neoplasms, and we evaluated the characteristics of each classified group using complementary immunohistochemical procedures. The CK20-positive rates of each location type were also evaluated. Subjects presented with 52 intestinal-type adenomas (low/high grade, 32:20) and 4 noninvasive pancreatobiliary papillary neoplasms (low/high grade, 1:3). Twenty-seven periampullary (peri-AMP)-type tumors and 23 extended-type tumors comprised the intestinal type, and the intra-ampullary (intra-AMP) type was composed of 4 pancreatobiliary and 2 intestinal histomorphological types. The CK20-positive rates of these 3 location types differed significantly (peri-AMP type, 50.6% ± 21.0%; extended type, 35.4% ± 18.6%; intra-AMP type, 6.9% ± 6.3%). The CK20-positive rate for intestinal-type tumors of the intra-AMP location type was lower than that of the peri-AMP location type. Intestinal-type tumors without CDX2 expression included extended and intra-AMP types, which are tumors that may show positive vertical margins when EP is performed. In this study, we found that an understanding of pancreatobiliary-type histology is an important aspect for the investigation of tumors involving the common channel of the ampulla. Furthermore, immunostaining of CDX2 and CK20 provides beneficial information if considering whether to perform an EP.
Collapse
Affiliation(s)
- Yoshiro Yamamoto
- Department of Surgical Pathology, Toho University School of Medicine, Ota-ku, Tokyo 143-8541, Japan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, Ota-ku, Tokyo 143-8541, Japan
| | - Tetsuo Nemoto
- Department of Surgical Pathology, Toho University School of Medicine, Ota-ku, Tokyo 143-8541, Japan.
| | - Yoichiro Okubo
- Department of Surgical Pathology, Toho University School of Medicine, Ota-ku, Tokyo 143-8541, Japan
| | - Yasuhiro Nihonyanagi
- Department of Surgical Pathology, Toho University School of Medicine, Ota-ku, Tokyo 143-8541, Japan
| | - Takao Ishiwatari
- Department of Surgical Pathology, Toho University School of Medicine, Ota-ku, Tokyo 143-8541, Japan
| | - Kensuke Takuma
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, Ota-ku, Tokyo 143-8541, Japan
| | - Naobumi Tochigi
- Department of Surgical Pathology, Toho University School of Medicine, Ota-ku, Tokyo 143-8541, Japan
| | - Naoki Okano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, Ota-ku, Tokyo 143-8541, Japan
| | - Megumi Wakayama
- Department of Surgical Pathology, Toho University School of Medicine, Ota-ku, Tokyo 143-8541, Japan
| | - Yoshinori Igarashi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, Ota-ku, Tokyo 143-8541, Japan
| | - Kazutoshi Shibuya
- Department of Surgical Pathology, Toho University School of Medicine, Ota-ku, Tokyo 143-8541, Japan
| |
Collapse
|
|
38
|
Mikhitarian K, Pollen M, Zhao Z, Shyr Y, Merchant N, Parikh A, Revetta F, Washington K, Vnencak-Jones C, Shi C. Epidermal growth factor receptor signaling pathway is frequently altered in ampullary carcinoma at protein and genetic levels. Mod Pathol 2014; 27:665-74. [PMID: 24186143 PMCID: PMC4007414 DOI: 10.1038/modpathol.2013.185] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Revised: 08/10/2013] [Accepted: 08/13/2013] [Indexed: 02/06/2023]
Abstract
Our objective was to explore alteration of the epidermal growth factor receptor (EGFR) signaling pathway in ampullary carcinoma. Immunohistochemical studies were employed to evaluate expression of amphiregulin as well as expression and activation of EGFR. A lab-developed assay was used to identify mutations in the EGFR pathway genes, including KRAS, BRAF, PIK3CA, PTEN, and AKT1. A total of 52 ampullary carcinomas were identified, including 25 intestinal-type and 24 pancreatobiliary-type tumors, with the intestinal type being associated with a younger age at diagnosis (P=0.03) and a better prognosis (P<0.01). Expression of amphiregulin correlated with better differentiation (P<0.01), but no difference was observed between two major histologic types. Expression and activation of EGFR was more commonly seen in the pancreatobiliary type (P<0.01). Mutations were detected in 50% of the pancreatobiliary type and 60% of the intestinal type. KRAS was the most common gene mutated in the pancreatobiliary type (42%) as well as the intestinal type (52%). Other mutations detected included PIK3CA, SMAD4 and BRAF. KRAS mutations at codons 12 and 13 did not adversely affect overall survival. In conclusion, EGFR expression and activation were different between intestinal- and pancreatobiliary-type ampullary carcinoma. KRAS mutation was common in both histologic types; however, the incidence appeared to be lower in the pancreatobiliary type compared with its pancreatic counterpart, pancreatic ductal adenocarcinoma. Mutational analysis of the EGFR pathway genes may provide important insights into personalized treatment for patients with ampullary carcinoma.
Collapse
Affiliation(s)
- Kaidi Mikhitarian
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN
| | - Maressa Pollen
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN
| | - Zhiguo Zhao
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
| | - Yu Shyr
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
| | - Nipun Merchant
- Department of Surgery, Surgical Oncology, Vanderbilt University Medical Center, Nashville, TN
| | - Alexander Parikh
- Department of Surgery, Surgical Oncology, Vanderbilt University Medical Center, Nashville, TN
| | - Frank Revetta
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN
| | - Kay Washington
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN
| | - Cindy Vnencak-Jones
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN
| | - Chanjuan Shi
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN
| |
Collapse
|
|
39
|
Okano K, Oshima M, Yachida S, Kushida Y, Kato K, Kamada H, Wato M, Nishihira T, Fukuda Y, Maeba T, Inoue H, Masaki T, Suzuki Y. Factors predicting survival and pathological subtype in patients with ampullary adenocarcinoma. J Surg Oncol 2014; 110:156-62. [PMID: 24619853 DOI: 10.1002/jso.23600] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Accepted: 02/17/2014] [Indexed: 12/22/2022]
Abstract
BACKGROUND Carcinoma of the ampulla of Vater is uncommon. This study aimed to clarify predictors of survival for ampullary adenocarcinoma and to identify characteristics of its two major pathological subtypes. METHODS Medical records were reviewed for 86 patients who underwent curative resection for ampullary adenocarcinoma between 2000 and 2012 at 12 principal hospitals in Kagawa, Japan. RESULTS Resection was most common among 75-79-year-old patients. Actuarial 1-, 3-, and 5-year postoperative survival rates for ampullary adenocarcinoma were 90%, 72.3%, and 69.1%, respectively. Preoperative biliary drainage; serum CA19-9 and total bilirubin levels; pathological grade; perineural, vascular, pancreatic, and duodenal invasion; nodal metastasis; UICC-T stage; and pancreatobiliary subtype were predictors of poor survival. An elevated serum CA19-9 level; an elevated total bilirubin level; lymphatic, vascular, perineural, and pancreatic invasion; and advanced overall tumor stage were more common in patients with pancreatobiliary-type tumors than in patients with intestinal-type tumors. Additionally, pathologic subtype analysis showed that each subtype had distinct prognostic factors. CONCLUSIONS Preoperative elevated serum CA19-9 and total bilirubin levels are prognostic factors for ampullary adenocarcinoma, and are both associated with pancreatobiliary-type tumors. Surgeons should be aware of these factors because pancreatobiliary-type adenocarcinoma is aggressively invasive and is associated with poor survival.
Collapse
Affiliation(s)
- Keiichi Okano
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Zhou J, Zhang Q, Li P, Shan Y, Zhao D, Cai J. Prognostic relevance of number and ratio of metastatic lymph nodes in resected carcinoma of the ampulla of Vater. Chin J Cancer Res 2014; 25:735-42. [PMID: 24385702 DOI: 10.3978/j.issn.1000-9604.2013.12.03] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Accepted: 12/04/2013] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVES To explore the prognostic relevance of the number and ratio of metastatic lymph nodes in resected Carcinoma of the ampulla of Vater (CAV). METHODS The clinical data of 155 patients who underwent pancreaticoduodenectomy (PD) for cancer of the ampulla of Vater between January 1990 and December 2010 were retrospectively analyzed. Kaplan-Meier method was used in survival analysis and Log rank method in comparison. Multivariate analysis was performed using Cox proportional hazards model. RESULTS Among these 155 patients, the in-hospital mortality rate was 4.5%, lymph node positive disease was 21.3%, and the 5-year survival rate was 51.6%. Patients with a lymph node ratio (LNR) >20% were more likely to have tumor differentiation, depth of duodenal involvement, depth of pancreatic invasion, T-stage and TNM-Stage. The number of the metastatic lymph nodes is important prognostic factors of the CAV. Univariate analysis showed that the factors associated with the prognosis included tumor size (P=0.036), tumor differentiation (P=0.019), LNR (P=0.032), number of metastatic lymph nodes (P=0.024), lymph node metastasis (P=0.03), depth of pancreatic invasion (P=0.001), T-stage (P=0.002), TNM stage (P=0.001), elevated CA 19-9 (P=0.000), and jaundice (P=0.021). Multivariate analysis showed that the factors associated with the prognosis were the number of metastatic lymph nodes (P=0.032; RR: 1.283; 95% CI: 1.022-1.611), tumor size (P=0.043; RR: 1.736; 95% CI: 1.017-2.963), and elevated CA 19-9 (P=0.003; RR: 3.247; 95% CI: 1.504-7.010). CONCLUSIONS LNR is a useful factor for predicting the prognosis of the radical treatment for CAV, whereas the number of metastatic lymph nodes is the most important factor. Further research on the locations, number, and LNR will be clinically meaningful to improve survival in patients with CAV.
Collapse
Affiliation(s)
- Jianguo Zhou
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
| | - Qian Zhang
- Department of General Surgery, Aerospace Central Hospital, Beijing 100049, China
| | - Peng Li
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
| | - Yi Shan
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
| | - Dongbing Zhao
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
| | - Jianqiang Cai
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
| |
Collapse
|
|
41
|
Increased number of metastatic lymph nodes in adenocarcinoma of the ampulla of Vater as a prognostic factor: A proposal of new nodal classification. Surgery 2014; 155:74-84. [DOI: 10.1016/j.surg.2013.08.004] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Accepted: 08/12/2013] [Indexed: 12/15/2022]
|
|
42
|
Sung R, Kang L, Han JH, Choi JW, Lee SH, Lee TH, Park SH, Kim HJ, Lee ES, Kim YS, Choi YW, Park SM. Differential expression of E-cadherin, β-catenin, and S100A4 in intestinal type and nonintestinal type ampulla of Vater cancers. Gut Liver 2013; 8:94-101. [PMID: 24516707 PMCID: PMC3916694 DOI: 10.5009/gnl.2014.8.1.94] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2013] [Revised: 03/05/2013] [Accepted: 04/04/2013] [Indexed: 12/18/2022] Open
Abstract
Background/Aims Epithelial-mesenchymal transition (EMT)-related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, β-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival. Methods A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin, β-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed. Results Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and β-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous β-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs. Conclusions Dysregulation of E-cadherin, β-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs.
Collapse
Affiliation(s)
- Rohyun Sung
- Department of Pathology, Medical Research Institute, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Li Kang
- Department of Internal Medicine, Medical Research Institute, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Joung-Ho Han
- Department of Internal Medicine, Medical Research Institute, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Jae-Woon Choi
- Department of Surgery, Medical Research Institute, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Sang Hwa Lee
- Department of Pathology, Research Center, Aerospace Medical Center, Cheongju, Korea
| | - Tae Hoon Lee
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Sang-Heum Park
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Hong Ja Kim
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Eaum Seok Lee
- Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea
| | - Young Suk Kim
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Young Woo Choi
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Seon Mee Park
- Department of Internal Medicine, Medical Research Institute, Chungbuk National University College of Medicine, Cheongju, Korea
| |
Collapse
|
|
43
|
Zhou J, Zhang Q, Li P, Shan Y, Zhao D, Cai J. Prognostic factors of carcinoma of the ampulla of Vater after surgery. Tumour Biol 2013; 35:1143-8. [PMID: 24026886 DOI: 10.1007/s13277-013-1153-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Accepted: 08/26/2013] [Indexed: 12/20/2022] Open
Abstract
The purpose of this study was to investigate the prognostic factors of carcinoma of the ampulla of Vater (CAV) after surgery. The clinicopathological factors related to the recurrence and prognosis of 162 CAV patients after surgical resection were retrospectively analyzed using univariate and multivariate methods. The in-hospital mortality rate was 4.32 % and the 5-year disease-free survival and overall survival of the 162 subjects were 55.1 and 51.7 %, respectively. Univariate analysis revealed that an advanced T stage (P = 0.002), lymph nodal metastasis (P = 0.002), poor differentiation (P = 0.006), tumor size (P = 0.033), tumor stage (P = 0.001), carbohydrate antigen (CA) 199 serum levels (P = 0.000), pancreatic invasion (P = 0.001), chemotherapy/radiation therapy (P = 0.006), and jaundice (P = 0.012) were factors that significantly affected the prognosis of CAV. Multivariate analysis showed that the pancreatic invasion (P = 0.009), lymph nodal metastasis (P = 0.009), and increased CA199 serum level (P = 0.001) were independent risk factors of recurrence. The pancreatic invasion, lymph nodal metastasis, and increased CA199 serum level are key prognostic factors of CAV after surgery.
Collapse
Affiliation(s)
- Jianguo Zhou
- Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, South Panjiayuan Rd, Beijing, 100021, China
| | | | | | | | | | | |
Collapse
|
|
44
|
Kumari N, Prabha K, Singh RK, Baitha DK, Krishnani N. Intestinal and pancreatobiliary differentiation in periampullary carcinoma: the role of immunohistochemistry. Hum Pathol 2013; 44:2213-9. [PMID: 23834763 DOI: 10.1016/j.humpath.2013.05.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Revised: 04/26/2013] [Accepted: 05/01/2013] [Indexed: 02/08/2023]
Abstract
Periampullary carcinoma (PC) is classified into intestinal and pancreatobiliary subtypes using morphology and immunohistochemistry (IHC). Different combinations of markers have been used in the literature. One hundred eight PCs were classified using morphology and IHC (CDX2, mucin [MUC] 2, cytokeratin [CK] 20, CK7, CK17, and MUC1). The expression of these markers was compared with different histologic subtypes, histopathologic prognostic parameters, and patients' survival. There were 38 intestinal and 53 pancreatobiliary subtypes classified on morphology alone. CDX2 showed high sensitivity (89.5%) and specificity (100%) for intestinal type. CK20 and MUC2 showed low sensitivity (50% and 39.5%) but high specificity (86.8% and 96.2%) for intestinal type. CK7 and CK17 showed a sensitivity of 90.5% and 32% and a specificity of 21% and 89.4%, respectively, for pancreatobiliary subtype. MUC1 was 100% sensitive but 0% specific in pancreatobiliary subtype. The overall median survival in morphologic and IHC intestinal type was 45 months versus 20 months in pancreatobiliary type (P = 0.01). Intestinal and pancreatobiliary types of PC were differentiated in 84.2% of cases by morphology alone and in 87.9% cases with IHC. CDX2-positive tumors had a median survival of 44 months versus 22 months in CDX2-negative tumors (P = .03). IHC helped in reclassifying an additional 4 cases of mixed and other types. Among the panel used, CDX2 showed a high sensitivity and specificity for intestinal subtype and was an independent prognostic marker for longer survival. Thus, CDX2 may be used routinely with morphology in subtyping of PC, and a panel of markers may be used in morphologically difficult cases.
Collapse
Affiliation(s)
- Niraj Kumari
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 266014, India.
| | | | | | | | | |
Collapse
|
|
45
|
Wang T, Liang YM, Hu P, Cheng YF. Mucins differently expressed in various ampullary adenocarcinomas. Diagn Pathol 2011; 6:102. [PMID: 22027009 PMCID: PMC3214147 DOI: 10.1186/1746-1596-6-102] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2011] [Accepted: 10/25/2011] [Indexed: 12/18/2022] Open
Abstract
Background We investigated the occurrence and clinical significance of mucin expression in ampullary adenocarcinoma. Methods We retrospectively analyzed clinical, pathological, and survival data from 74 ampullary adenocarcinoma patients who received radical operation from January 2004 to November 2006. Results The tumors were located in the lower end of the common bile duct (46%), papillary duodenum (42%), and ampullary duodenum (12%), and expressed MUC1 (72%), MUC2 (20%), MUC5AC (43%), and MUC6 (27%). Expression of MUC1 was associated with tumor differentiation (OR: 4.71, 95% CI: 1.26, 17.66, P = 0.021). Expression of MUC5AC was associated with age (OR: 1.07, 95% CI: 1.11, 1.14, P = 0.026) and less vessel invasion(OR: 0.14, 95% CI: 0.03, 0.72, P = 0.019). The survival rates were not significantly different when patients had or had no expression of MUC1, MUC2, MUC5AC, or MUC6 in tumor. Patients with tumors positive for MUC5AC in the papillary duodenum had worse survival than those with tumors negative for MUC5AC (P = 0.044). Conclusions Expression of MUC1 was high (72%) in ampullary adenocarcinoma, while expressions of MUC2, MUC5AC, and MUC6 were lower. Mucins are useful markers to diagnose and identify ampullary adenocarcinoma, particularly in determining the degree of malignancy of ampullary adenocarcinoma.
Collapse
Affiliation(s)
- Tao Wang
- Department of Radiation Oncology, QiLu Hospital of Shandong University, Shandong, China
| | | | | | | |
Collapse
|
|
46
|
Zhao XQ, Dong JH, Zhang WZ, Liu Z. Prognosis of ampullary cancer based on immunohistochemical type and expression of osteopontin. Diagn Pathol 2011; 6:98. [PMID: 21992455 PMCID: PMC3213044 DOI: 10.1186/1746-1596-6-98] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2011] [Accepted: 10/13/2011] [Indexed: 12/27/2022] Open
Abstract
Background Ampullary cancer (AC) was classified as pancreatobiliary, intestinal, or other subtype based on the expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20). We aimed to explore the association of AC subtype with patient prognosis. Methods The relationship of AC subtype and expression of Osteopontin (OPN) with the prognosis of 120 AC patients after pancreaticoduodenectomy was investigated. Results The patients had pancreatobiliary (CK7+/CK20-, n = 24, 20%), intestinal (CK7-/CK20+, n = 29, 24.2%) or other (CK7+/CK20+ or CK7-/CK20-, n = 67, 55.8%) subtypes of AC, and their median survival times were 23 ± 4.2, 38 ± 2.8 and 64 ± 16.8 months, respectively. The survival times of 64 OPN- patients (53.3%) and 56 OPN+ patients (46.7%) were 69 ± 18.4 and 36 ± 1.3 months, respectively. There was no significant effect of AC subtype on survival of OPN- patients. For OPN+ patients, those with pancreatobiliary AC had a shorter survival time (22 ± 6.6 months) than those with intestinal AC (37 ± 1.4 months, p = 0.041), and other AC subtype (36 ± 0.9 months, p = 0.010); intestinal and other AC subtypes had similar survival times. Conclusions The prognosis of AC patients can be estimated based on immunohistochemical classification and OPN status.
Collapse
Affiliation(s)
- Xiang-Qian Zhao
- Hospital & Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
| | | | | | | |
Collapse
|
|
47
|
Hornick JR, Johnston FM, Simon PO, Younkin M, Chamberlin M, Mitchem JB, Azar RR, Linehan DC, Strasberg SM, Edmundowicz SA, Hawkins WG. A single-institution review of 157 patients presenting with benign and malignant tumors of the ampulla of Vater: management and outcomes. Surgery 2011; 150:169-76. [PMID: 21801957 DOI: 10.1016/j.surg.2011.05.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2010] [Accepted: 05/13/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Although benign ampullary tumors are removed endoscopically, due to their potential to progress to malignant disease, the favored treatment for adenocarcinoma is pancreaticoduodenectomy. We reviewed our institution's experience in order to identify which patients were at highest risk of disease progression following surgical resection, as well as evaluate whether localized T1 tumors are best treated by pancreaticoduodenectomy. METHODS We retrospectively reviewed 157 patients who presented with an ampullary mass, from 2001 to 2010, and identified 51 with benign adenoma and 106 with adenocarcinoma. RESULTS Patients with malignant tumors most often presented with larger tumors and jaundice, which alone was predictive of survival (OR = 67). Forty-five percent of patients with pathologically confirmed T1 tumors had positive lymph nodes and median survival was modest at 60 months. Lymph node involvement was predictive of recurrence and decreased survival. CONCLUSION Patients with malignant tumors often present with jaundice and larger tumors. These findings should warrant suspicion for cancer and expedited preoperative workup. Based on our finding that nearly half the patients with T1 tumors had positive lymph nodes, we recommend pancreaticoduodenectomy for any patient with biopsy proven adenocarcinoma who is a suitable candidate for surgery.
Collapse
Affiliation(s)
- John R Hornick
- Division of Hepatobiliary, Pancreatic, and Gastrointestinal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Kim KJ, Choi DW, Kim WS, Kim MJ, Song SC, Heo JS, Choi SH. Adenocarcinoma of the ampulla of Vater: predictors of survival and recurrence after curative radical resection. KOREAN JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 2011; 15:171-8. [PMID: 26421035 PMCID: PMC4582543 DOI: 10.14701/kjhbps.2011.15.3.171] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2011] [Revised: 07/02/2011] [Accepted: 07/25/2011] [Indexed: 01/01/2023]
Abstract
Backgrounds/Aims Because of low incidence rates, there have been few reports on the patterns of and risk factors for recurrence after curative resection of the ampulla of Vater (AoV) cancer. The aim of this study was to characterize patterns of recurrence and to evaluate risk factors affecting survival rates and recurrence after curative resection. Methods Medical records of 181 patients who had undergone pancreaticoduodenectomy with curative intent for AoV adenocarcinoma between December 1994 and March 2010 at Samsung Medical Center were retrospectively reviewed. Factors influencing on overall survival rate, recurrence rates, and recurrence patterns were analyzed. Results Lymph node metastases and high preoperative serum carcinoembryonic antigen (CEA) level >5 ng/ml were identified as independent factors affecting overall survival (p=0.006, p<0.001, respectively). Among the 181 patients, 69 developed local or distant recurrence within 3 years after curative resection. Lymph node metastasis, preoperative serum CEA level >5 ng/ml, and total bilirubin level >1.5 mg/dl were identified as independent prognostic factors of recurrence after curative resection (p=0.008, p<0.001, p=0.003, respectively). Conclusions AoV adenocarcinoma has a better prognosis than other periampullary carcinomas, but still has a high recurrence rate, especially during the first three years after curative radical resection. Therefore, careful follow-up is needed during the first 3 years, especially for the higher risk group. Further study of adjuvant therapy to decrease recurrence after curative resection is now warranted.
Collapse
Affiliation(s)
- Kang Jae Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Wook Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Woo Seok Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min Jung Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sun Choon Song
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin Seok Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seong Ho Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
49
|
Kim WS, Choi DW, Choi SH, Heo JS, You DD, Lee HG. Clinical significance of pathologic subtype in curatively resected ampulla of vater cancer. J Surg Oncol 2011; 105:266-72. [PMID: 21882202 DOI: 10.1002/jso.22090] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2011] [Accepted: 08/15/2011] [Indexed: 12/25/2022]
Abstract
BACKGROUND Ampullary cancer is considered to have a better prognosis than cancers of the distal bile duct and pancreas, and recent publications emphasize the prognostic importance of the histologic differentiation of the intestinal and pancreatobiliary types of ampullary cancer. The aims of this study were to identify those factors that affect recurrence after curative resection and to investigate differences between the clinicopathologic features of these two pathologic subtypes. PATIENTS AND METHODS The medical records of patients that underwent pancreatoduodenectomy for ampullary carcinoma from February 1995 to March 2009 at our institute were retrospectively reviewed. One hundred and four patients that underwent curative resection for ampullary carcinoma were enrolled in this study. One pathologist reviewed all pathologic reports and histopathologic findings. Data on clinicopathologic factors and disease free and overall survival were analyzed. RESULTS The 3- and 5-year disease free survival rates of the 104 study subjects were 62.2% and 57.7%, respectively, and overall survival rates were 69.4% and 60.1%, respectively. Multivariate analysis showed that an advanced T stage (P = 0.049), the presence of lymph node metastasis (P = 0.003), poor differentiation (P = 0.039), and the pancreatobiliary type (P = 0.022) significantly increased the risk of recurrence. Furthermore, the pancreatobiliary type was found to be more associated with an advanced T stage (P = 0.009), regional lymph node metastasis (P = 0.007), and perineural invasion (P = 0.026) than the intestinal type. In addition, pathologic subtype analysis showed that Carcinoembryonic antigen (CEA) level and lymph node metastasis were important predictors of recurrence in patients with the intestinal (P = 0.013) and pancreatobiliary types, respectively (P = 0.003). CONCLUSIONS An advanced T stage, nodal metastasis, poor differentiation, and the pancreaticobiliary type were found to be independent predictors of recurrence after curative resection of ampullary carcinoma by multivariate analysis. In addition, the pancreatobiliary type tended to present in a more advanced T stage and more frequently with regional lymph node involvement and perineural invasion than the intestinal type. Furthermore, CEA level and lymph node metastasis were found to be independent predictors of recurrence for the intestinal and pancreatobiliary types, respectively.
Collapse
Affiliation(s)
- Woo Seok Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | | | | | | | | | | |
Collapse
|
|
50
|
Moriya T, Kimura W, Hirai I, Takasu N, Mizutani M. Expression of MUC1 and MUC2 in ampullary cancer. Int J Surg Pathol 2011; 19:441-7. [PMID: 21700631 DOI: 10.1177/1066896911405654] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Mucins are high-molecular-weight glycoproteins that play important roles in carcinogenesis or tumor invasion. The authors investigated the expression of mucins in ampullary cancer. METHODS MUC1 and MUC2 expressions were examined using immunohistochemistry. Tissue samples were obtained from 32 patients with ampullary cancer who underwent resection at Yamagata University Hospital, Japan. The authors classified the cases with ampullary cancer into 2 subtypes--pancreatobiliary type (PB type) and intestinal type (I type)--using H&E, MUC1, and MUC2 staining. Then, the authors made a comparison of the clinicopathologic data of the 2 subtypes. RESULTS Fourteen patients (44%) were classified as PB type and 18 patients (56%) as I type. The PB-type group had significantly worse histopathologic characteristics than the I-type group in nodal involvement (PB type 57% vs I type 22%; P = .04), perineural invasion (PB type 50% vs I type 17%; P = .04), duodenal invasion (PB type 100% vs I type 33%; P = .01), and pancreatic invasion (PB type 71% vs I type 33%; P = .03). The PB-type group had significantly worse outcome than the I-type group (5-year survival: PB type 40% vs I type 72%; P = .03). CONCLUSION PB-type ampullary cancers were more aggressive than I-type carcinomas. MUC1 and MUC2 expression was useful for classification as PB or I type.
Collapse
|