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1
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Shin DW. [Treatment of Ampullary Adenocarcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:159-170. [PMID: 37876255 DOI: 10.4166/kjg.2023.110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 09/28/2023] [Accepted: 10/03/2023] [Indexed: 10/26/2023]
Abstract
The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary ampullary adenocarcinoma is a rare malignancy, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. Jaundice from a biliary obstruction is the most common symptom of ampullary adenocarcinoma. In the early stages, radical pancreatoduodenectomy is the standard surgical approach. On the other hand, no randomized controlled trial has provided evidence to guide physicians on the choice of adjuvant/palliative chemotherapy because of the rarity of the disease and the paucity of related research. This paper reports the biology, histology, current therapeutic strategies, and potential future therapies of ampullary adenocarcinoma.
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Affiliation(s)
- Dong Woo Shin
- Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
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2
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Iqbal H, Petrosyan A, Yoon J, Roytman M. A Complex Diagnosis of Ampullary Adenocarcinoma Presenting As Decompensated Cirrhosis. Cureus 2023; 15:e37566. [PMID: 37193458 PMCID: PMC10183155 DOI: 10.7759/cureus.37566] [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] [Accepted: 04/14/2023] [Indexed: 05/18/2023] Open
Abstract
Neoplasms arising from the ampulla of Vater are exceedingly rare, and there is a paucity of literature regarding their diagnosis and management. Ampullary cancer typically presents with jaundice and signs of biliary obstruction. We present a case of ampullary adenocarcinoma with concomitant choledocholithiasis that proved complex and diagnostically challenging.
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Affiliation(s)
- Humzah Iqbal
- Internal Medicine, University of California, San Francisco, Fresno, USA
| | - Arpine Petrosyan
- Internal Medicine, University of California, San Francisco, Fresno, USA
| | - Jennifer Yoon
- Gastroenterology and Hepatology, University of California, San Francisco, Fresno, USA
| | - Marina Roytman
- Gastroenterology and Hepatology, University of California, San Francisco, Fresno, USA
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3
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Verbeke C, Webster F, Brosens L, Campbell F, Del Chiaro M, Esposito I, Feakins RM, Fukushima N, Gill AJ, Kakar S, Kench JG, Krasinskas AM, van Laethem JL, Schaeffer DF, Washington K. Dataset for the reporting of carcinoma of the exocrine pancreas: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 2021; 79:902-912. [PMID: 34379823 DOI: 10.1111/his.14540] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 08/04/2021] [Accepted: 08/08/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVES Current guidelines for the pathology reporting on pancreatic cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with cancer of the exocrine pancreas (ductal adenocarcinoma and acinar cell carcinoma). The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations. METHODS AND RESULTS According to the ICCR's rigorous process for dataset development, an international expert panel consisting of pancreatic pathologists, a pancreatic surgeon and an oncologist produced a set of core and non-core data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or non-core element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalised and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website. CONCLUSIONS This first international dataset for cancer of the exocrine pancreas is intended to promote high quality, standardised pathology reporting. Its widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication and enhance comparability of data, all of which will help to improve the management of pancreatic cancer patients.
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Affiliation(s)
- Caroline Verbeke
- Department of Pathology, University of Oslo, Oslo University Hospital, Oslo, Norway
| | - Fleur Webster
- International Collaboration on Cancer Reporting, Sydney, Australia
| | - Lodewijk Brosens
- Department of Pathology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands and Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Fiona Campbell
- Department of Pathology, Royal Liverpool University Hospital, Liverpool, United Kingdom
| | - Marco Del Chiaro
- Department of Surgery, University of Colorado Denver - Anschutz Medical Campus, Aurora, 80045, Colorado, United States
| | - Irene Esposito
- Institute of Pathology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Roger M Feakins
- Department of Histopathology, Royal Free Hospital, London, United Kingdom
| | | | - Anthony J Gill
- Sydney Medical School, The University of Sydney, Sydney, Australia.,Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, Australia.,NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, Australia
| | - Sanjay Kakar
- Department of Pathology, University of California, M590 San Francisco, United States
| | - James G Kench
- Sydney Medical School, The University of Sydney, Sydney, Australia.,Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, New South Wales Health Pathology, Camperdown, Australia
| | - Alyssa M Krasinskas
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, United States
| | - Jean-Luc van Laethem
- Department of Gastroenterology and Medical Oncology, Hôpital Erasme and Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - David F Schaeffer
- Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Kay Washington
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Centre, Nashville, Tennessee, United States
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Pothuri V, Herndon J, Ballentine SJ, Lim KH, Fields RC. A Case of a Pathological Complete Response to Neoadjuvant Nivolumab plus Ipilimumab in Periampullary Adenocarcinoma. Oncologist 2021; 26:722-726. [PMID: 33982365 DOI: 10.1002/onco.13821] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 04/30/2021] [Indexed: 12/16/2022] Open
Abstract
Herein, we report on a patient with known Lynch syndrome and periampullary adenocarcinoma that exhibited a pathological complete response to neoadjuvant nivolumab plus ipilimumab. Two MSH2 mutations, high microsatellite instability, high tumor mutational burden, and elevated PD-L1 expression were identified by next-generation sequencing and immunohistochemistry. Following FOLFIRINOX (Fluorouracil/Leucovorin/Irinotecan/Oxaliplatin) administration and disease progression, nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) were administered every 3 weeks for four total cycles. The patient responded well with minimal adverse effects and significant improvement in epigastric pain, appetite, and body weight. She then underwent resection consisting of pancreaticoduodenectomy, which demonstrated pathological complete response. Complete genomic profiling of periampullary carcinomas is crucial for optimal treatment selection as true ampullary masses and pancreatic ductal adenocarcinoma have different genetic profiles. This case provides an example of a patient who may have further benefited from first-line nivolumab plus ipilimumab to avoid the reduced efficacy and significant side effects associated with chemotherapy. KEY POINTS: A patient with known Lynch syndrome and ampullary adenocarcinoma harboring two MSH2 mutations, high microsatellite instability (MSI-high), high tumor mutational burden (TMB), and elevated PD-L1 expression achieved pathological complete response with neoadjuvant nivolumab plus ipilimumab. The combination of nivolumab plus ipilimumab may be a better first-line option for patients with ampullary adenocarcinomas harboring deficient mismatch repair, MSI-high, and high TMB. Complete genomic profiling of periampullary adenocarcinomas is crucial for optimal treatment selection as true ampullary masses and pancreatic ductal adenocarcinoma have different genetic profiles. The presence of either MSI-high or high TMB could be an appropriate predictive biomarker for response to nivolumab plus ipilimumab in the context of Lynch syndrome.
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Affiliation(s)
- Vikram Pothuri
- Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri, USA
| | - John Herndon
- Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri, USA
| | - Samuel J Ballentine
- Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri, USA
| | - Kian-Huat Lim
- Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri, USA
| | - Ryan C Fields
- Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri, USA
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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.
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6
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Lwin KM, Linn YH, Dee YKS. Ampullary Adenocarcinoma: a Mini-Review and a Case Report of a Clinically Stable Disease Patient Treated with Herbal Supplements. J Gastrointest Cancer 2020; 52:750-758. [PMID: 32860204 DOI: 10.1007/s12029-020-00501-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- Khin Maung Lwin
- FAME Pharmaceuticals Industry Co., Ltd., FAME Clinic, Yangon, Myanmar
| | - Ye Htut Linn
- Research and Development Department, FAME Pharmaceuticals Industry Co., Ltd., Yangon, Myanmar.
| | - Yamin Kyaw Swar Dee
- Research and Development Department, FAME Pharmaceuticals Industry Co., Ltd., Yangon, Myanmar
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7
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Krishnamurthy K, Sriganeshan V. Pancreatic Intraepithelial Neoplasia (PanIN) as a Morphologic Marker of Pancreatobiliary Type of Ampullary Carcinoma. Pathol Oncol Res 2020; 26:1735-1739. [PMID: 31642034 DOI: 10.1007/s12253-019-00754-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 09/22/2019] [Indexed: 11/24/2022]
Abstract
The classification of ampullary adenocarcinoma into intestinal and pancreatobiliary sub-types has been found to be important in predicting prognosis and determining therapeutic strategy. Due to considerable inter-observer variability in sub-typing based solely on morphology, higher frequency of poorly differentiated cancers and low incidence of the disease, the histomorphologic classification of ampullary adenocarcinoma remains one of the grey zones in surgical pathology. Pan-IN is a well recognized precursor to pancreatic adenocarcinoma. Three studies have shown concurrent Pan-IN in patients with ampullary carcinoma, but their association with the two sub-types has not yet been reported. Fourteen cases of surgical resection for ampullary adenocarcinoma were retrieved from the archives. The cases were classified into two groups based on the presence or absence of concomitant Pan-IN. All the cases were stained for CK7, CK 20, Villin and CDX 2 and were classified as intestinal or pancreatobiliary types based on the staining pattern. All the 10 cases with Pan-IN stained negative for CDX2 and were classified as pancreatobiliary type (p = 0.01). Of the cases without Pan-IN, 3 were classified as intestinal sub-type based on morphology and CDX2 positivity and 1 was classified as pancreatobiliary type. Concomitant Pan-IN was present in 91% of pancreatobiliary type of ampullary adenocarcinoma. The grade of Pan-IN did not influence the grade or stage of the adenocarcinoma (p > 0.05). The co-occurrence of Pan-IN in a high percentage of the pancreatobiliary sub-type and its complete absence in the intestinal sub-type may serve as a strong differentiator between the two sub-types.
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Affiliation(s)
- Kritika Krishnamurthy
- Arkadi M Rywlin Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, 4300 Alton road, Suite 2400, Miami Beach, FL, 33140, USA.
| | - Vathany Sriganeshan
- Arkadi M Rywlin Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, 4300 Alton road, Suite 2400, Miami Beach, FL, 33140, USA
- FIU Herbert Wertheim college of Medicine, Miami, FL, USA
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8
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Abstract
INTRODUCTION Endoscopic papillectomy (EP) has been established as a useful endoscopic therapy by the efforts of many pancreatobiliary endoscopists and is presently accepted as a reliable alternative therapy to surgery in patients with ampullary adenoma. Moreover, there have been numerous advancements in EP techniques in recent years. Various approaches and attempts toward expanding the indications of endoscopic resection have been reported. Furthermore, the management and prevention of adverse events (AEs) and endoscopic treatment for remnant or recurrent lesions have also been reported. In the present review, we focus on recent advancements in the EP technique, as well as speculate on the future issues of EP. AREA COVERED This review of EP encompasses the indications, preoperative assessments, endoscopic techniques, outcomes, and AEs of EP, post-EP surveillance techniques, and treatments for remnant or recurrence lesions. EXPERT OPINION The ultimate goal of EP is the complete resection of ampullary tumors, regardless of whether they are adenomatous or carcinomatous lesions, without causing any AEs. Therefore, the most important issue is preoperative evaluation, that is, the accurate diagnosis of lesions contraindicated for EP. In addition, further research on the prevention of AEs is also necessary towards establishing EP as a safe endoscopic procedure.
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Affiliation(s)
- Kenjiro Yamamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University , Tokyo, Japan
| | - Eisuke Iwasaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo, Japan
| | - Takao Itoi
- Department of Gastroenterology and Hepatology, Tokyo Medical University , Tokyo, Japan
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Ramai D, Ofosu A, Singh J, John F, Reddy M, Adler DG. Demographics, tumor characteristics, treatment, and clinical outcomes of patients with ampullary cancer: a Surveillance, Epidemiology, and End Results (SEER) cohort study. MINERVA GASTROENTERO 2018; 65:85-90. [PMID: 30488680 DOI: 10.23736/s1121-421x.18.02543-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Ampullary cancer accounts for only 0.2% of gastrointestinal cancers. The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with ampullary tumors. METHODS Data on ampullary cancer between 2004 and 2013 was extracted from the Surveillance, Epidemiology and End Results (SEER) Registry. The clinical epidemiology of these tumors was analyzed using SEER*Stat. RESULTS A total of 6803 patients with ampullary cancer were identified. Median age at diagnosis was 71±13 years. The overall age-adjusted incidence of ampullary cancer was 0.59 per 100,000 per year. A higher incidence of ampullary cancer was observed in males compared to females (0.74 vs. 0.48 per 100,000 per year). Most tumors were moderately differentiated (39.5%). The most common stage at presentation was Stage I (21%), followed by Stage II (20%). The majority (63%) of these tumors were surgically resected while 20% of patients received radiotherapy. One and 5-year cause-specific survival for ampullary cancer was 71.7% and 38.8% respectively, with a median survival of 31 months. On Cox regression analysis, black race, increasing cancer stage and grade, N1 stage, and non-surgical treatment were associated with poorer prognosis. Those who were not treated with surgical intervention were at 4.5 times increased risk for death (hazard ratio 4.5, 95% CI: 3.93-5.09, P=0.000). CONCLUSIONS The annual incidence of ampullary cancer has been fairly constant, though males are more likely to be affected. While its incidence increases with age, patients who are treated by surgical intervention have significantly better outcomes. Additionally, through the use of endoscopic techniques, ampullary cancer can be detected and treated much earlier.
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Affiliation(s)
- Daryl Ramai
- Department of Medicine, The Brooklyn Hospital Center, Brooklyn, NY, USA
| | - Andrew Ofosu
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Brooklyn, NY, USA
| | - Jameel Singh
- Department of Medicine, The Brooklyn Hospital Center, Brooklyn, NY, USA
| | - Febin John
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Brooklyn, NY, USA
| | - Madhavi Reddy
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Brooklyn, NY, USA
| | - Douglas G Adler
- Division of Gastroenterology and Hepatology, Huntsman Cancer Center, University of Utah School of Medicine, Salt Lake City, UT, USA -
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10
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Clinicopathological features related to survival in adenocarcinoma of the Vaterian system in a Mexican population. Hum Pathol 2018; 83:68-76. [PMID: 30179685 DOI: 10.1016/j.humpath.2018.08.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 08/17/2018] [Accepted: 08/23/2018] [Indexed: 11/23/2022]
Abstract
Adenocarcinomas of the ampulla of Vater account for 0.5% of malignant neoplasms of the gastrointestinal tract and 6% to 20% of malignant periampullary neoplasms, with most patients being candidates for elective surgery. Our objective was to evaluate the clinicopathological prognostic factors of ampullary adenocarcinomas after surgical resection in a Mexican population. From the records of the Department of Pathology at the Instituto Nacional de Cancerología, México, cases diagnosed as adenocarcinomas of the ampulla of Vater were selected over a period of 11 years, from January 2005 to September 2015. Cases with a pancreaticoduodenectomy report were included, and from each case, demographic and pathological data of the surgical specimen were obtained. Univariate and multivariate statistical analyses were performed using the log-rank test and Cox regression. Of 157 cases diagnosed as ampullary adenocarcinomas, 104 patients were excluded as not eligible for surgical treatment at the time of diagnosis. In the remaining 53 patients, a pancreaticoduodenectomy was performed. The mean age of the entire group was 55.4 years, and most were men. Intestinal-type adenocarcinomas were more frequent (77.4%) than pancreatobiliary-type (15.1%), with most being without perineural invasion, well to moderately differentiated, and less than 3 cm in size. Lymph node metastasis and age greater than 65 years had a negative impact on overall survival of the patients. The most convenient classification of malignant epithelial tumors of the Vaterian system is according to the histopathologic phenotype grouped into intestinal-, pancreatobiliary-, and mixed-type adenocarcinomas, as well as uncommon variants.
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11
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Jayaramayya K, Balachandar V, Santhy KS. Ampullary carcinoma-A genetic perspective. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2018; 776:10-22. [PMID: 29807574 DOI: 10.1016/j.mrrev.2018.03.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 03/14/2018] [Accepted: 03/14/2018] [Indexed: 12/19/2022]
Abstract
Ampulla of vater carcinoma (AVC) is a rare gastrointestinal tumour that is associated with a high mortality rate and it's often diagnosed at later stages due to lack of clinical symptoms. Early diagnosis of this condition is essential to effectively treat patients for better prognosis. A significant amount of advancement has been made in understanding the molecular nature of cancer in the past decade. A substantial number of mutations and alterations have been detected in various tumors. Despite the occurrence of AVC across the globe, the number of studies conducted on this tumor type remains low; this is largely due to its rare occurrence. Moreover, AVC tissues are complex and contain mutations in oncogenes, tumour suppressors, apoptotic proteins, cell proliferation proteins, cell signaling proteins, transcription factors, chromosomal abnormalities and cellular adhesion proteins. The frequently mutated genes included KRAS, TP53 and SMAD4 and are associated with prognosis. Several molecules of the PI3K, Wnt signaling, TGF-beta pathway and cell cycle have also been altered in AVCs. This review comprises of all the genetic mutations, associated pathways and related prognosis that are involved in AVCs from the year 1989 to 2017. This report can be used as a stepping-stone to establish biomarkers for early diagnosis of AVC and to discover molecular targets for drug therapy.
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Affiliation(s)
- Kaavya Jayaramayya
- Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women - Avinashilingam University for Women, Coimbatore 641 043, Tamil Nadu, India.
| | - Vellingiri Balachandar
- Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India
| | - Kumaran Sivanandan Santhy
- Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women - Avinashilingam University for Women, Coimbatore 641 043, Tamil Nadu, India
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12
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Tewari M, Swain JR, Dixit VK, Shukla HS. Molecular Aberrations in Periampullary Carcinoma. Indian J Surg Oncol 2017; 8:348-356. [DOI: 10.1007/s13193-017-0645-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Accepted: 03/15/2017] [Indexed: 11/29/2022] Open
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13
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Differentiation and prognostic markers in ampullary cancer: Role of p53, MDM2, CDX2, mucins and cytokeratins. Pathol Res Pract 2016; 212:1039-1047. [DOI: 10.1016/j.prp.2016.09.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2016] [Revised: 09/01/2016] [Accepted: 09/09/2016] [Indexed: 12/23/2022]
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14
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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
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Abstract
Ampullary cancers are rare, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. They arise from the ampullary complex, distal to the confluence of the common bile and pancreatic duct (Fig. 1). In contrast to other periampullary malignancies, true ampullary cancers present earlier in their disease course with symptoms that result from biliary obstruction. It is often difficult to distinguish primary ampullary cancers from other periampullary cancers preoperatively. In early stages, ampullary cancers are surgically treated, similar to pancreatic cancers, and typically with a pancreatico-duodenoectomy (or Whipple procedure). Because of their earlier presentation, resection rates for all patients are much higher than other periampullary carcinomas. Moreover, their prognosis tends to be better than those with other periampullary- and pancreatic-originating cancers. In patients with true ampullary cancer, there is very limited data to guide physicians on the choice of therapy, largely because of the rarity of the disease and the paucity of related research. Herein, we provide an overview of the biology, histology, current therapeutic strategies, and potential future therapies for carcinomas arising from the ampulla of Vater.
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Affiliation(s)
- Daniel H Ahn
- From the Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus OH
| | - Tanios Bekaii-Saab
- From the Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus OH
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16
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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.
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Affiliation(s)
- Keiichi Okano
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
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Perysinakis I, Margaris I, Kouraklis G. Ampullary cancer--a separate clinical entity? Histopathology 2014; 64:759-68. [PMID: 24456259 DOI: 10.1111/his.12324] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
AIMS Ampullary cancer is a relatively uncommon tumour, with a better prognosis than pancreatic cancer. The purpose of this study was to review the recent literature on ampullary adenocarcinoma, focusing on histological types and prognostic factors. METHODS AND RESULTS Using PubMed, we carried out a comprehensive search of the literature, which was extended to April 2013 to retrieve all additional publications. Ampullary cancer comprises two main histological subtypes, the pancreatobiliary type and the intestinal type. These subtypes have different pathogenetic and clinical characteristics. Clinical and histological parameters as well as immunohistochemical markers have been identified as significant prognostic factors in ampullary cancer. Moreover, several immunohistochemical markers have been studied, not only as prognostic factors but as a means of differentiating ampullary from other peri-ampullary tumours, and of identifying the exact histological subtype. CONCLUSIONS The considerable differences in the frequencies of the two subtypes of ampullary tumours reported in literature reinforce the necessity to define molecular markers to distinguish them. Until then, the significance of the histological subtype as a prognostic factor should be evaluated cautiously. Future research on the pathogenesis of ampullary cancer will possibly suggest that we should stop treating this type of cancer as a separate entity.
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Affiliation(s)
- Iraklis Perysinakis
- Third Department of Surgery, 'George Gennimatas' General Hospital, Athens, Greece
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18
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Konstantinidis IT, Vinuela EF, Tang LH, Klimstra DS, D'Angelica MI, Dematteo RP, Kingham TP, Fong Y, Jarnagin WR, Allen PJ. Incidentally discovered pancreatic intraepithelial neoplasia: what is its clinical significance? Ann Surg Oncol 2013; 20:3643-7. [PMID: 23748606 DOI: 10.1245/s10434-013-3042-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2013] [Indexed: 01/30/2023]
Abstract
PURPOSE Pancreatic intraepithelial neoplasia (PanIN) is a presumed precursor of pancreatic ductal adenocarcinoma (PDAC). We assessed the relationship between incidental PanIN after resection of non-adenocarcinoma lesions and the development of metachronous PDAC in the remnant. METHODS We retrospectively reviewed the clinicopathologic data of patients who underwent pancreatectomy for non-PDAC from January 2000 to January 2010. Intraductal papillary mucinous lesions were excluded. All available postoperative imaging and clinical follow-up data were reviewed; the risk of developing PDAC was assessed in patients with a minimum follow-up time of 6 months and with imaging studies available for review. RESULTS A total of 584 patients were analyzed. Median age was 59 years (range 10-85 years), and 338 (58 %) were female. The most common lesions for which resection was performed were serous cystic neoplasms (17 %), pancreatic neuroendocrine tumors (38 %), metastatic tumors (9 %), and mucinous cystic neoplasms (7 %). PanIN was identified in 153 (26 %) patients. The majority of these patients had PanIN-1 or -2 (50 and 41 %, respectively), whereas 13 (8 %) had PanIN-3. Of the 506 (87 %) patients with adequate follow-up (median 3.7 years, range 0.5-12.6 years), 1 patient (0.2 %) with PanIN identified at the time of initial resection developed cancer in the remnant. This occurred 4.4 years after a distal pancreatectomy in the setting of PanIN-1B. No patient with PanIN-3 developed cancer during follow-up. CONCLUSIONS PanIN was identified in 26 % of patients who underwent resection for histopathology other than PDAC. The presence of PanIN of any grade did not result in an appreciable cancer risk in the pancreatic remnant after short-term follow-up.
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Frequencies and prognostic role of KRAS and BRAF mutations in patients with localized pancreatic and ampullary adenocarcinomas. Pancreas 2012; 41:759-66. [PMID: 22699145 DOI: 10.1097/mpa.0b013e31823cd9df] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The frequencies and prognostic role of KRAS and BRAF mutations in patients operated on for pancreatic ductal adenocarcinomas (PDACs) and ampullary adenocarcinomas (A-ACs) are scantily studied. METHODS KRAS and BRAF mutations were analyzed in formalin-fixed, paraffin-embedded tumor samples from primarily chemotherapy-naive patients operated on with radical intentions for PDAC (n = 170) and A-AC (n = 107). RESULTS Eighty percent of PDAC patients had KRAS mutations (codon 12 mutations: 74%) and 67% with A-AC (codon 12 mutations: 54%). BRAF mutations were less common, 16% in PDAC and 12% in A-AC, and no V600E mutations were found. Fourteen percent with PDAC and 7% with A-AC had mutations in both KRAS and BRAF. Multivariate analysis, including KRAS status, stage, and American Society of Anesthesiologists physical status classification system score, demonstrated that KRAS mutations in patients with A-AC were associated with short recurrence-free survival (RFS) (hazard ratio, 2.45; 95% confidence interval, 1.19-5.06; P = 0.015) and overall survival (OS) (1.93, 95% 1.12-3.31; P = 0.018). KRAS mutations in patients with PDAC were not associated with RFS and OS. BRAF mutations were not associated with RFS and OS. CONCLUSIONS KRAS mutations frequencies were high in PDAC and A-AC. KRAS mutations were associated with poor prognosis in patients with A-AC, but not in patients with PDAC.
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20
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Verbeke CS, Gladhaug IP. Resection margin involvement and tumour origin in pancreatic head cancer. Br J Surg 2012; 99:1036-49. [PMID: 22517199 DOI: 10.1002/bjs.8734] [Citation(s) in RCA: 112] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/16/2012] [Indexed: 12/26/2022]
Abstract
BACKGROUND Assessment of the origin of adenocarcinoma in pancreatoduodenectomy specimens (pancreatic, ampullary or biliary) and resection margin status is not performed in a consistent manner in different centres. The aim of this review was to identify the impact of such variations on patient outcome. METHODS A systematic literature search for articles on pancreatic, ampullary, distal bile duct and periampullary cancer was performed, with special attention to data on resection margin status, pathological examination and outcome. RESULTS The frequent reclassification of tumour origin following slide review, and the wide variation in published incidence of pancreatic (33-89 per cent), ampullary (5-42 per cent) and distal bile duct (5-38 per cent) cancers indicate that the histopathological distinction between the three cancer groups is less accurate than generally believed. Recent studies have shown that the wide range of rates of microscopic margin involvement (R1) in pancreatoduodenectomy specimens (18-85, 0-27 and 0-72 per cent respectively for pancreatic, ampullary and distal bile duct cancers) is mainly caused by differences in pathological assessment rather than surgical practice and patient selection. As a consequence of the existing inconsistency in reporting of these data items, the clinical significance of microscopic margin involvement in each of the three cancer groups remains unclear. CONCLUSION Inaccurate and inconsistent distinction between pancreatic, ampullary and distal bile duct cancer, combined with inaccuracies in resection margin assessment, results in obfuscation of key clinicopathological data. Specimen dissection technique plays a key role in the quality of the assessment of both tumour origin and margin status. Unless the pathological examination is meticulous and standardized, comparison of results between centres and observations in multicentre trials will remain of limited value.
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Affiliation(s)
- C S Verbeke
- Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
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21
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Romiti A, Barucca V, Zullo A, Sarcina I, Di Rocco R, D'Antonio C, Latorre M, Marchetti P. Tumors of ampulla of Vater: A case series and review of chemotherapy options. World J Gastrointest Oncol 2012; 4:60-7. [PMID: 22468185 PMCID: PMC3312930 DOI: 10.4251/wjgo.v4.i3.60] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2011] [Revised: 03/03/2012] [Accepted: 03/10/2012] [Indexed: 02/05/2023] Open
Abstract
Carcinomas of the Ampulla of Vater are rare tumors, accounting for 0.2% of gastrointestinal cancers. Compared with other biliary tract neoplasms, these tumors have a relatively favorable prognosis after surgical resection. Based on their epithelium of origin, two subtypes of ampullary carcinoma have been recently distinguished: intestinal and pancreatobiliary. This study evaluates histopathological features and outcomes of ampullary carcinoma and to compares the survival of these tumors to that of other biliary tract tumors. The chemotherapic options available for ampullary cancer are also reviewed. We analyzed data from 20 consecutive patients with ampullary carcinomas and 26 patients with other biliary tract carcinomas, observed in our Institution. Statistical analysis was performed by using either Fisher’s exact test or χ2 test for categorical variables. Median time of survival was calculated and compared using the Log-Rank test. Similar distribution of demographic characteristics and stage between ampullary and other biliary tract cancers was observed. Patients with ampullary cancer underwent surgery more frequently than other biliary cancers while chemotherapy and radiotherapy were used equally. In accordance with the literature, a longer median survival was observed in the group of ampullary carcinomas.
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Affiliation(s)
- Adriana Romiti
- Adriana Romiti, Viola Barucca, Ida Sarcina, Roberta Di Rocco, Chiara D'Antonio, Paolo Marchetti, Oncology Unit, University "La Sapienza", Sant'Andrea Hospital, via di Grottarossa 1035, 00189 Rome, Italy
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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.
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Affiliation(s)
- Woo Seok Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Albores-Saavedra J, Chable-Montero F, Angeles-Albores D, Schwartz A, Klimstra DS, Henson DE. Early gallbladder carcinoma: a clinicopathologic study of 13 cases of intramucosal carcinoma. Am J Clin Pathol 2011; 135:637-42. [PMID: 21411787 DOI: 10.1309/ajcpfrkcfedlv03y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
We report the clinicopathologic features of 13 cases of intramucosal carcinoma (IMC) of the gallbladder. All IMCs were incidental findings in cholecystectomy specimens for cholelithiasis. However, one of the patients had a carcinoma of the pancreas, and the gallbladder incidentally removed during the Whipple procedure showed an IMC. Another patient had a small cell carcinoma of the gallbladder, and one of the sections showed an IMC. Of the IMCs, 10 were well-differentiated adenocarcinomas, 1 was a moderately differentiated adenocarcinoma, 1 was an undifferentiated carcinoma, and 1 was a squamous cell carcinoma. Of the patients, 8 were disease-free from 3 to 11 years, and 2 patients died, one as a result of the pancreatic ductal carcinoma and the other with disseminated metastases of the small cell carcinoma. The follow-up of another patient was too short to be significant. Two patients were lost to follow-up. Our findings suggest that a simple cholecystectomy is a curative procedure for IMCs of the gallbladder.
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Haugk B. Pancreatic intraepithelial neoplasia-can we detect early pancreatic cancer? Histopathology 2010; 57:503-14. [PMID: 20875068 DOI: 10.1111/j.1365-2559.2010.03610.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Haugk B
(2010) Histopathology 57, 503-514
Pancreatic intraepithelial neoplasia - can we detect early pancreatic cancer? Pancreatic cancer is one of the most lethal cancers, with an incidence equalling mortality. Pancreatic cancer is a heterogeneous group in which pancreatic ductal adenocarcinoma (PDAC) is the most common. It is now established that PDAC develops through stepwise progression from precursor lesions. Detection and treatment of these precursor lesions would allow curative treatment. Three precursor lesions for PDAC have been identified. Two of these - mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) - are rare, radiologically detectable, cystic precursor lesions which can be cured if treated at the preinvasive stage. The third and most common precursor lesion has recently been defined as pancreatic intraepithelial neoplasia (PanIN). PanINs are microscopic lesions with no clinical correlate. They display a spectrum of cyto-architectural changes (PanIN-1, PanIN-2 and PanIN-3) mirrored in an increasing accumulation of molecular genetic changes, with PanIN-3 sharing many of the alterations with PDAC. Great advances in the understanding of pancreatic carcinogenesis have opened avenues for diagnosis and chemoprevention. However, access to the pancreas is limited, molecular tests are at the early stages and too little is known about the natural history of early PanINs to justify resection. Currently, screening focuses upon high-risk individuals only.
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Affiliation(s)
- Beate Haugk
- Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
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Abstract
PURPOSE OF REVIEW This manuscript reviews the recent literature on ampullary cancer, including new staging definitions, histological characteristics and treatment options. RECENT FINDINGS Recent publications emphasize the importance of the histological differentiation (intestinal vs. pancreatobiliary), which is one of the most important prognostic factors for ampullary cancer. These histological subtypes can be differentiated by immunohistochemistry: while positivity for mucin-2 (MUC2) and caudal homeobox gene transcription factor-2 (CDX2) excludes the pancreatobiliary subtype, positivity for MUC1 and cytokeratin-17 (CK17) excludes the intestinal subtype. Also, different mechanisms of cancer development have been described, which might be related to the type of differentiation. Due to the very low risk of lymphatic spread, local resections appear sufficient for well differentiated T1 cancer smaller than 1 cm, whereas larger, less differentiated or more invasive cancer requires a radical resection. As cancer with intestinal differentiation shares a similar biology with colon cancer, and the pancreatobiliary differentiation is close to ductal adenocarcinoma of the pancreas, adjuvant chemotherapy should probably be given according to colon cancer (intestinal) and pancreatic cancer (pancreatobiliary), respectively. However, randomized trials are lacking. SUMMARY The recent research suggests that the histological differentiation of periampullary cancer is more important than the anatomical location (ampulla). Future studies are required to take this emerging issue into account.
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de Paiva Haddad LB, Patzina RA, Penteado S, Montagnini AL, da Cunha JEM, Machado MCC, Jukemura J. Lymph node involvement and not the histophatologic subtype is correlated with outcome after resection of adenocarcinoma of the ampulla of vater. J Gastrointest Surg 2010; 14:719-28. [PMID: 20107918 DOI: 10.1007/s11605-010-1156-4] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2009] [Accepted: 01/04/2010] [Indexed: 01/31/2023]
Abstract
BACKGROUND Intestinal and pancreaticobiliary types of Vater's ampulla adenocarcinoma have been considered as having different biologic behavior and prognosis. The aim of the present study was to determine the best immunohistochemical panel for tumor classification and to analyze the survival of patients having these histological types of adenocarcinoma. METHOD Ninety-seven resected ampullary adenocarcinomas were histologically classified, and the prognosis factors were analyzed. The expression of MUC1, MUC2, MUC5AC, MUC6, CK7, CK17, CK20, CD10, and CDX2 was evaluated by using immunohistochemistry. RESULTS Forty-three Vater's ampulla carcinomas were histologically classified as intestinal type, 47 as pancreaticobiliary, and seven as other types. The intestinal type had a significantly higher expression of MUC2 (74.4% vs. 23.4%), CK20 (76.7% vs. 29.8%), CDX2 (86% vs. 21.3%), and CD10 (81.4% vs. 51.1%), while MUC1 (53.5% vs. 82.9%) and CK7 (79.1% vs. 95.7%) were higher in pancreatobiliary adenocarcinomas. The most accurate markers for immunohistochemical classification were CDX2, MUC1, and MUC2. Survival was significantly affected by pancreaticobiliary type (p = 0.021), but only lymph node metastasis, lymphatic invasion, and stage were independent risk factors for survival in a multivariate analysis. CONCLUSION The immunohistochemical expression of CDX2, MUC1, and MUC2 allows a reproducible classification of ampullary carcinomas. Although carcinomas of the intestinal type showed better survival in the univariate analysis, neither histological classification nor immunohistochemistry were independent predictors of poor prognosis.
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Affiliation(s)
- Luciana Bertocco de Paiva Haddad
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo School of Medicine, R Aracaju 42, ap 41, Higienopolis, São Paulo 0501240030, Brazil.
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Slim K, Blay JY, Brouquet A, Chatelain D, Comy M, Delpero JR, Denet C, Elias D, Fléjou JF, Fourquier P, Fuks D, Glehen O, Karoui M, Kohneh-Shahri N, Lesurtel M, Mariette C, Mauvais F, Nicolet J, Perniceni T, Piessen G, Regimbeau JM, Rouanet P, sauvanet A, Schmitt G, Vons C, Lasser P, Belghiti J, Berdah S, Champault G, Chiche L, Chipponi J, Chollet P, De Baère T, Déchelotte P, Garcier JM, Gayet B, Gouillat C, Kianmanesh R, Laurent C, Meyer C, Millat B, Msika S, Nordlinger B, Paraf F, Partensky C, Peschaud F, Pocard M, Sastre B, Scoazec JY, Scotté M, Triboulet JP, Trillaud H, Valleur P. [Digestive oncology: surgical practices]. ACTA ACUST UNITED AC 2009; 146 Suppl 2:S11-80. [PMID: 19435621 DOI: 10.1016/s0021-7697(09)72398-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- K Slim
- Chirurgien Clermont-Ferrand.
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Henson DE, Schwartz AM, Nsouli H, Albores-Saavedra J. Carcinomas of the pancreas, gallbladder, extrahepatic bile ducts, and ampulla of vater share a field for carcinogenesis: a population-based study. Arch Pathol Lab Med 2009; 133:67-71. [PMID: 19123739 DOI: 10.5858/133.1.67] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2008] [Indexed: 11/06/2022]
Abstract
CONTEXT Carcinomas co-occur in the pancreas, extrahepatic bile ducts, and ampulla of Vater. We investigated whether cancers originating in these sites represent a field effect similar to that observed in the lung and upper aerodigestive tract. OBJECTIVE To determine whether a field effect for carcinogenesis exists in the ampulla of Vater, extrahepatic bile ducts, gallbladder, and pancreas. DESIGN Data were obtained from National Cancer Institute's Surveillance Epidemiology and End Results Program from 1973 through 2005. Cases were compared by age frequency density plots, age-specific incidence rates, and logarithmic plots of the age-specific incidence rates and age of diagnosis. RESULTS Incidence rates were 11.71, 1.43, 0.88, and 0.49 per 100,000 persons at risk for pancreatic, gallbladder, extrahepatic bile ducts, and ampullary carcinomas, respectively. Age frequency density plots were congruent for cancers originating in all 4 sites. Logarithmic plots of the age-specific incidence rates with age of diagnosis produced parallel linear rate patterns for the 4 sites indicative of similar populations for tumor development. However, density and logarithmic plots of pancreatic endocrine carcinomas, a tumor of different cellular differentiation and carcinogenic pathway, served as a comparison. The endocrine carcinomas showed a different age distribution and nonparallel rate patterns with ductal carcinomas. CONCLUSIONS Carcinomas of the pancreas, gallbladder, extrahepatic bile ducts, and ampulla have a common embryonic cellular ancestry, differentiation pathways, mucosal histologic patterns, and population-related tumor development indicating a field effect in carcinogenesis. Parallel linear rate patterns indicate (1) the rate of cancer development is similar in all 4 sites even though the absolute incidence rates vary and (2) regardless of location, the ductal epithelium is equally susceptible to malignant transformation. If carcinogenic pathways to cancer are similar, then the different incidence rates seen clinically may depend on the relative surface area of the ductal system in these sites. Pancreatic cancers are most common because the surface area of the pancreas' ductal system is greater than that of the gallbladder, extrahepatic bile ducts, and ampulla.
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Affiliation(s)
- Donald Earl Henson
- George Washington University Cancer Institute, Washington, DC 20037, USA.
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Abstract
PURPOSE OF REVIEW Although few controlled trials exist in the field, endoscopic papillectomy has evolved over the recent years with new data on preoperative staging and improved methods for its safe and successful completion. In 2006, a consensus guideline was published by the American Society of Gastrointestinal Endoscopy evaluating the role of endoscopy in managing ampullary adenomas. RECENT FINDINGS The recent literature of endoscopic papillectomy has focused on the preoperative management of ampullary tumors, with a paper evaluating the role of endoscopic ultrasound. Also, a randomized controlled trial has shown that the use of pancreatic duct stents is associated with less incidence of postendoscopic papillectomy pancreatitis, although the study was probably underpowered. Several methods can be used to help locate the pancreatic duct postendoscopic papillectomy (endoscopic ultrasound-guided rendezvous and methylene blue injection). The recurrence and complication rate in more recent papers continue to be acceptable, at about 30 and 20%, respectively. SUMMARY Endoscopic papillectomy is a reasonable alternative to transduodenal surgical excision, but more controlled studies with long-term data are needed to evaluate preoperative staging accuracy and recurrence rates.
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Carter JT, Grenert JP, Rubenstein L, Stewart L, Way LW. Tumors of the ampulla of vater: histopathologic classification and predictors of survival. J Am Coll Surg 2008; 207:210-8. [PMID: 18656049 DOI: 10.1016/j.jamcollsurg.2008.01.028] [Citation(s) in RCA: 116] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2007] [Revised: 01/23/2008] [Accepted: 01/23/2008] [Indexed: 12/21/2022]
Abstract
BACKGROUND The histology and clinical behavior of ampullary tumors vary substantially. We speculated that this might reflect the presence of two kinds of ampullary adenocarcinoma: pancreaticobiliary and intestinal. STUDY DESIGN We analyzed patient demographics, presentation, survival (mean followup 44 months), and tumor histology for 157 consecutive ampullary tumors resected from 1989 to 2006. Histologic features were reviewed by a pathologist blinded to clinical outcomes. Survival was compared using Kaplan-Meier/Cox proportional hazards analysis. RESULTS There were 33 benign (32 adenomas and 1 paraganglioma) and 124 malignant (118 adenocarcinomas and 6 neuroendocrine) tumors. One hundred fifteen (73%) patients underwent a Whipple procedure, 32 (20%) a local resection, and 10 (7%) a palliative operation. For adenocarcinomas, survival in univariate models was affected by jaundice, histologic grade, lymphovascular, or perineural invasion, T stage, nodal metastasis, and pancreaticobiliary subtype (p < 0.05). Size of tumor did not predict survival, nor did cribriform/papillary features, dirty necrosis, apical mucin, or nuclear atypia. In multivariate models, lymphovascular invasion, perineural invasion, stage, and pancreaticobiliary subtype predicted survival (p < 0.05). Patients with pancreaticobiliary ampullary adenocarcinomas presented with jaundice more often than those with the intestinal kind (p = 0.01) and had worse survival. CONCLUSIONS In addition to other factors, tumor type (intestinal versus pancreaticobiliary) had a major effect on survival in patients with ampullary adenocarcinoma. The current concept of ampullary adenocarcinoma as a unique entity, distinct from duodenal and pancreatic adenocarcinoma, might be wrong. Intestinal ampullary adenocarcinomas behaved like their duodenal counterparts, but pancreaticobiliary ones were more aggressive and behaved like pancreatic adenocarcinomas.
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Affiliation(s)
- Jonathan T Carter
- Department of Surgery, University of California, San Francisco, CA 94143-0475, USA
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Hruban RH, Maitra A, Kern SE, Goggins M. Precursors to pancreatic cancer. Gastroenterol Clin North Am 2007; 36:831-49, vi. [PMID: 17996793 PMCID: PMC2194627 DOI: 10.1016/j.gtc.2007.08.012] [Citation(s) in RCA: 150] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Infiltrating ductal adenocarcinoma of the pancreas is believed to arise from morphologically distinct noninvasive precursor lesions. These precursors include the intraductal papillary mucinous neoplasm, the mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia. Intraductal papillary mucinous neoplasms are grossly visible mucin-producing epithelial neoplasms that arise in the main pancreatic duct or one of its branches. The cysts of mucinous cystic neoplasms do not communicate with the major pancreatic ducts, and these neoplasms are characterized by a distinct ovarian-type stroma. Pancreatic intraepithelial neoplasia is a microscopic lesion. This article focuses on the clinical significance of these three important precursor lesions, with emphasis on their clinical manifestations, detection, and treatment.
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Affiliation(s)
- Ralph H. Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD,Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Anirban Maitra
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD,Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD,Institute for Genetic Medicine, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Scott E. Kern
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD,Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Michael Goggins
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD,Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD,Department of Gastroenterology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD
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Perrone G, Santini D, Zagami M, Vincenzi B, Verzì A, Morini S, Borzomati D, Coppola R, Antinori A, Magistrelli P, Tonini G, Rabitti C. COX-2 expression of ampullary carcinoma: correlation with different histotypes and clinicopathological parameters. Virchows Arch 2006; 449:334-40. [PMID: 16906389 DOI: 10.1007/s00428-006-0255-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2006] [Accepted: 06/16/2006] [Indexed: 10/24/2022]
Abstract
Epidemiological studies suggest that regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced incidence of gastrointestinal cancer. Several lines of evidence indicate that the antineoplastic effect of NSAIDs is attributable to COX-2 inhibition. The aim of our study was to assess COX-2 expression in a series of primary untreated ampullary carcinomas and its possible correlation with clinicopathological parameters. In the present study, 45 surgical specimens of invasive ampullary carcinomas were histologically classified into pancreaticobiliary, intestinal, and unusual types. COX-2 expression by immunohistochemical method was analyzed. High COX-2 expression was detected in 35 (77.8%) ampullary carcinomas. Among these, 20/21 (95.2%) were classified as intestinal, 9/18 (50%) pancreaticobiliary, and 6/6 (100%) unusual type. A significant statistical difference in terms of COX-2 expression was found between pancreaticobiliary vs intestinal type (P=0.002). Furthermore, a negative significant statistical correlation was found between T factor and COX-2 expression (P=0.047). The different COX-2 expression among histopathological types supports the concept of histogenetical difference of ampullary carcinomas. Furthermore, the high rate of COX-2 expression in the intestinal subtype of ampullary carcinoma may represent the rational for a histotype-tailored therapy targeting COX-2.
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Affiliation(s)
- Giuseppe Perrone
- Surgical Pathology, Campus Bio-Medico University, Via Emilio Longoni, Rome, 83 00155, Italy.
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Crowell PL, Schmidt CM, Yip-Schneider MT, Savage JJ, Hertzler DA, Cummings WO. Cyclooxygenase-2 expression in hamster and human pancreatic neoplasia. Neoplasia 2006; 8:437-445. [PMID: 16820089 PMCID: PMC1601471 DOI: 10.1593/neo.04700] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2004] [Revised: 04/27/2006] [Accepted: 05/01/2006] [Indexed: 12/21/2022]
Abstract
Cyclooxygenase-2 (COX-2) has been implicated in the development of gastrointestinal malignancies. The aim of the present study was to determine COX-2 expression/activity throughout stages of experimental and human pancreatic neoplasia. COX-2 immunohistochemistry was performed in pancreata of hamsters subjected to the carcinogen N-nitrosobis-(2-oxopropyl)amine (BOP) and in human pancreatic tumors. COX-2 activity was determined by prostaglandin E2 assay in tumor versus matched normal pancreatic tissues. The activity of the COX inhibitor sulindac was tested in the PC-1 hamster pancreatic cancer model. COX-2 expression was elevated in all pancreatic intraepithelial neoplasias (PanINs) and adenocarcinomas. In BOP-treated hamsters, there were significant progressive elevations in COX-2 expression throughout pancreatic tumorigenesis. In human samples, peak COX-2 expression occurred in PanIN2 lesions and remained moderately elevated in PanIN3 and adenocarcinoma tissues. COX-2 activity was significantly elevated in hamster and human pancreatic cancers compared to pair-matched normal pancreas. Furthermore, hamster pancreatic tumor engraftment/formation in the PC-1 hamster pancreatic cancer model was reduced 4.9-fold by oral administration of sulindac. Increased COX-2 expression is an early event in pancreatic carcinogeneses. The BOP-induced hamster carcinogenesis model is a representative model used to study the role of COX-2 in well-differentiated pancreatic tumorigenesis. COX inhibitors may have a role in preventing tumor engraftment/formation.
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Affiliation(s)
- Pamela L Crowell
- Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA
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Goldstein NS, Bosler DS. Immunohistochemistry of the Gastrointestinal Tract, Pancreas, Bile Ducts, Gallbladder and Liver. DIAGNOSTIC IMMUNOHISTOCHEMISTRY 2006:442-508. [DOI: 10.1016/b978-0-443-06652-8.50019-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Albazaz R, Verbeke CS, Rahman SH, McMahon MJ. Cyclooxygenase-2 expression associated with severity of PanIN lesions: a possible link between chronic pancreatitis and pancreatic cancer. Pancreatology 2005; 5:361-9. [PMID: 15980665 DOI: 10.1159/000086536] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2004] [Accepted: 03/10/2005] [Indexed: 12/11/2022]
Abstract
BACKGROUND Cyclooxygenase-2 (COX-2) is a key modulatory molecule in inflammation and neoplasia. Increasing evidence suggests a role for COX-2 in pancreatic cancer (PAC). However, expression of COX-2 in pancreatic intraepithelial neoplasia (PanIN), the precursor lesion of PAC which is often present in chronic pancreatitis (CP), has received little attention. METHOD COX-2 immunostaining was performed on sections of PAC (n = 26), CP (n = 34), PanIN (n = 68) and normal pancreas (n = 11). Sections were also stained for macrophages (CD68), activated pancreatic stellate cells (alphaSMA), and collagen (Sirius Red) as markers of fibrosis. Semiquantitative scoring was based on the extent and intensity of immunostaining. RESULTS COX-2 expression was increased in PAC compared to normal (p = 0.02) with 89% of cases exceeding COX-2 immunostaining in normal ducts. In PanIN lesions, COX-2 expression increased with escalating severity of the PanIN change (p < or = 0.01). COX-2 expression was increased in PanIN-2/3 compared to normal pancreas and CP (p < or = 0.001). In ducts of CP, COX-2 expression did not differ from that in normal tissue. There was no association between COX-2 expression and clinicopathological variables. CONCLUSION The high level of COX-2 expression in PanIN lesions suggests that this enzyme could be a therapeutic target at a non-invasive stage of pancreatic carcinogenesis and feasible for chemoprevention in CP.
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Affiliation(s)
- R Albazaz
- Academic Unit of Surgery, The General Infirmary at Leeds, St James's University Hospital, Leeds, UK
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Löhr M, Klöppel G, Maisonneuve P, Lowenfels AB, Lüttges J. Frequency of K-ras mutations in pancreatic intraductal neoplasias associated with pancreatic ductal adenocarcinoma and chronic pancreatitis: a meta-analysis. Neoplasia 2005; 7:17-23. [PMID: 15720814 PMCID: PMC1490318 DOI: 10.1593/neo.04445] [Citation(s) in RCA: 238] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Molecular analyses have demonstrated mutations in the K-ras gene at codon 12 in the majority of pancreatic ductal adenocarcinomas (PDACs). In order to determine whether the K-ras mutation rate increases parallel to the grade of dysplasia in duct lesions, we performed a meta-analysis of the studies published between 1988 and 2003 that provide information on K-ras mutations in hyperplastic and dysplastic duct lesions in the pancreas. The described duct lesions were reclassified according to the nomenclature for pancreatic intraepithelial neoplasia (PanIN), and the molecular methods for detecting K-ras were reviewed. In PanIN lesions from pancreata of patients with PDAC, there was a stepwise increase in K-ras mutations that correlated with the grade of dysplasia of the PanIN lesion. K-ras mutations were found in 36%, 44%, and 87% of PanIN-1a, 1b, and 2-3 lesions, respectively (trend statistic P <.001). Mutation-enriched polymerase chain reaction (PCR) resulted in higher rates of K-ras mutations in PanIN than plain PCR did. The incidence of K-ras mutations in PanIN lesions associated with chronic pancreatitis (CP) or normal pancreas was low (around 10%). In CP, K-ras mutations were only found after a disease duration of 3 years. The correlation of the incidence of K-ras mutations with the grade of dysplasia in PanIN and the occurrence of these mutations in CP with a duration of more than 3 years underlines the importance of this genetic change for the development of PDAC.
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Affiliation(s)
- Matthias Löhr
- Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
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Albores-Saavedra J, Wu J, Crook T, Amirkhan RH, Jones L, Hruban RH. Intestinal and oncocytic variants of pancreatic intraepithelial neoplasia. A morphological and immunohistochemical study. Ann Diagn Pathol 2005; 9:69-76. [PMID: 15806512 DOI: 10.1016/j.anndiagpath.2004.12.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
We report 2 previously undescribed morphological variants of pancreatic intraepithelial neoplasia (PanIN). The first variant with an intestinal phenotype was associated with mucinous carcinomas that occurred in the tail of the pancreas of 2 men (60 and 65 years old). The carcinomas lacked the characteristic ovarian-like stroma of mucinous cystic neoplasms observed in female patients and did not show a papillary architecture. Whether they represent mucinous cystadenocarcinomas or mucinous carcinomas that arose from the flat variant of intraductal papillary mucinous neoplasms could not be determined with certainty. Microscopically, the intestinal type of PanIN was composed of pseudostratified columnar cells similar to those of colonic adenomas and showing variable degrees of dysplasia. A significant increase in the MIB-1 labeling index correlated with the severity of dysplasia. In contrast to conventional PanIN, the intestinal variant expressed MUC-2 and was MUC-1 negative. The second type of PanIN had an oncocytic phenotype, coexpressed MUC-2 and MUC-1 mucins, and was associated with intraductal oncocytic papillary carcinomas that showed a similar immunohistochemical mucin profile. Both intestinal and oncocytic types of PanIN expressed DPC4 and lacked p53 reactivity. The anatomical separation of the PanINs from the carcinomas and the gradual progression of cytological and architectural abnormalities in both variants of PanIN argue against ductal spread (cancerization of the ducts). The intestinal and oncocytic variants of PanIN broaden the morphological spectrum of this intraductal lesion. Although their significance is unknown, the possibility that these PanIN variants represent cancer precursors should be considered.
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Affiliation(s)
- Jorge Albores-Saavedra
- Department of Pathology, Louisiana State University Health Sciences Center School of Medicine, Shreveport, LA 71130, USA
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Hruban RH, Takaori K, Klimstra DS, Adsay NV, Albores-Saavedra J, Biankin AV, Biankin SA, Compton C, Fukushima N, Furukawa T, Goggins M, Kato Y, Klöppel G, Longnecker DS, Lüttges J, Maitra A, Offerhaus GJA, Shimizu M, Yonezawa S. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol 2004; 28:977-87. [PMID: 15252303 DOI: 10.1097/01.pas.0000126675.59108.80] [Citation(s) in RCA: 720] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including a distinct ovarian-type stroma, and a consistent nomenclature are well established for mucinous cystic neoplasms. By contrast, consistent nomenclatures and diagnostic criteria have been more difficult to establish for PanINs and IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic proliferations of columnar, mucin-containing cells with a variable degree of papilla formation, the distinction between these two classes of precursor lesions remains problematic. Thus, considerable ambiguities still exist in the classification of noninvasive neoplasms in the pancreatic ducts. A meeting of international experts on precursor lesions of pancreatic cancer was held at The Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms. We present a consensus classification of the precursor lesions in the pancreatic ducts, PanINs and IPMNs.
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Affiliation(s)
- Ralph H Hruban
- Department of Pathology, The Johns Hopkins Medical Institutions, 401 N. Broadway, Weinberg 2242, Baltimore, MD 21231-2410, USA.
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Komenaka IK, Mir R, de Graft-Johnson JB, Wise L. Severe high-grade dysplasia and in-situ carcinoma of the common bile duct and pancreatic duct. Lancet Oncol 2003; 4:373-5. [PMID: 12788411 DOI: 10.1016/s1470-2045(03)01096-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Ian K Komenaka
- Department of Surgery, New York Methodist Hospital, Brooklyn, NY 11215, USA.
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40
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Fischer HP, Zhou H. [Pathogenesis and histomorphology of ampullary carcinomas and their precursor lesions. Review and individual findings]. DER PATHOLOGE 2003; 24:196-203. [PMID: 12739053 DOI: 10.1007/s00292-003-0617-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Most adenomas and carcinomas of small intestine and extrahepatic bile ducts arise in the region of Vater's papilla. In FAP it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis in an early tumor stage. In about 80% curative intended resection is possible. Operability is the most relevant prognostic factor. Inflammatory changes, fibrosis, regeneratory changes after endoscopic manipulation, hyperplasia, preneoplastic lesions close to carcinoma, deeply sited carcinomas under protruded, non-neoplastic duodenal mucosa make the diagnosis difficult on biopsy material. Histologically, intestinal type adenocarcinoma, pancreatobiliary type adenocarcinoma, undifferentiated carcinomas and unusual types can be differentiated. In our own series comprising 45 resected ampullary carcinomas 6 from 10 intestinal type adenocarcinomas, and 4 carcinomas of unusual types expressed the immunohistochemical marker profile of intestinal mucosa (keratin 7-, keratin 20+, MUC2+). 17 from 21 pancreatobiliary type adenocarcinomas, 4 undifferentiated carcinomas, as well as 3 papillary carcinomas showed the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20-, MUC2-). 3 invasive carcinomas which were negative for these markers, showed one of these characteristic marker-combinations in non-invasive adenomatous parts. These findings support the concept of histogenetically different ampullary carcinomas which are developing from the intestinal or from the pancreaticobiliary type mucosa of Vater's papilla. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear in different frequencies. In future studies molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. The histologic classification should reflect consequently the histogenesis of ampullary tumors from the two different types of papillary mucosa.
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Maitra A, Ashfaq R, Gunn CR, Rahman A, Yeo CJ, Sohn TA, Cameron JL, Hruban RH, Wilentz RE. Cyclooxygenase 2 expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia: an immunohistochemical analysis with automated cellular imaging. Am J Clin Pathol 2002; 118:194-201. [PMID: 12162677 DOI: 10.1309/tpg4-ck1c-9v8v-8awc] [Citation(s) in RCA: 135] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
We immunohistochemically examined material from 36 pancreata (adenocarcinomas, 30 lesions; pancreatic intraepithelial neoplasia [PanIN], 65; normal pancreatic ducts, 30) for cyclooxygenase 2 (COX-2) with an automated platform. We analyzed 7 to 10 discrete foci and generated an average percentage of positive cells and average staining intensity for each lesion. These 2 values were then multiplied to create an overall "HistoScore" for each lesion. COX-2 demonstrated considerable heterogeneity of expression between and within cases. The overall average percentage of positive cells in adenocarcinomas was 47.3%; in PanINs, 36.3%; and in normal ducts, 19.2%. COX-2 was expressed in more than 20% of cells in 23 adenocarcinomas (77%), 42 PanINs (65%), and 12 normal ducts (40%). The overall average HistoScore for adenocarcinomas was 6.1; for PanINs, 5.4; and for normal ducts, 3.5. Significant differences in COX-2 expression were demonstrable in adenocarcinomas vs normal ducts, PanINs vs normal ducts, and PanIN 2/3 vs PanIN 1a/1b. In general, the pattern of COX-2 expression increased from normal to PanIN to adenocarcinoma. The up-regulation of COX-2 in a subset of noninvasive precursor lesions makes it a potential target for chemoprevention with selective COX-2 inhibitors.
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Affiliation(s)
- Anirban Maitra
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA
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Pirog EC, Baergen RN, Soslow RA, Tam D, DeMattia AE, Chen YT, Isacson C. Diagnostic Accuracy of Cervical Low-Grade Squamous Intraepithelial Lesions Is Improved With MIB-1 Immunostaining. Am J Surg Pathol 2002; 26:70-5. [PMID: 11756771 DOI: 10.1097/00000478-200201000-00008] [Citation(s) in RCA: 65] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
There is considerable interobserver variation in the diagnosis of low-grade squamous intraepithelial lesion that involves mature squamous epithelium. Our aim was to evaluate the utility of MIB-1 immunostaining as an adjunct test to increase diagnostic accuracy. Consecutive cervical biopsies originally diagnosed as normal (n = 26) or low-grade squamous intraepithelial lesion (n = 23) were reviewed by three pathologists to obtain a consensus diagnosis. MIB-1 immunostaining was performed, and positive staining was defined as a cluster of at least two stained nuclei in the upper two thirds of the epithelial thickness. Human papillomavirus (HPV) DNA detection was performed using a polymerase chain reaction assay. All cases were subsequently reclassified as low-grade squamous intraepithelial lesion (LSIL) or normal (NL) when two or three of three gold standard criteria were satisfied (LSIL gold standard criteria = consensus diagnosis of LSIL, HPV+, MIB-1+; NL gold standard criteria = consensus diagnosis of NL, HPV-, MIB-1-). Using the gold standard diagnoses, we have identified that 14 normal cases (36%) were originally overdiagnosed as LSIL, and one LSIL case (10%) was originally underdiagnosed as normal. All MIB-1-positive cases were HPV+ and identified as LSIL in the consensus review. All MIB-1-negative cases were NL by gold standard criteria. The sensitivity (1.0) and the specificity (1.0) of MIB-1 staining for identifying LSIL were superior to the sensitivity (0.9) and the specificity (0.8) of HPV testing. In conclusion, MIB-1 is a highly sensitive and specific marker for identifying low-grade squamous intraepithelial lesion and is helpful in verifying the diagnosis of equivocal cases.
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Affiliation(s)
- Edyta C Pirog
- Department of Pathology, Weill Medical College of Cornell University, New York, NY 10021, USA.
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