Background

This is a rare cancer that occurs at the junction of the pancreatic and biliary ducts. This usually forms a common opening into the small bowel. Due to its location, the most common presenting signs and symptoms are jaundice, occasionally associated with pain. The overall prognosis is poor although surgery may provide a good chance for survival if the tumor is found in an early stage.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
INCIDENCE/ PREVALENCE
Cancer of the ampulla of Vater: results of a 20-year population-based study. Benhamiche AM, Jouve JL, Manfredi S, Prost P, Isambert N, Faivre J. Registre Bourguignon des Cancers Digestifs (INSERM CRI 95 05), Faculte de Medecine, Dijon, France.	Eur J Gastroenterol Hepatol 2000 Jan;12(1):75-9 Abstract quote BACKGROUND: Relatively little attention has been given to the epidemiology and management of cancer of the ampulla of Vater. SETTING: A series of 111 patients with a cancer of the ampulla of Vater diagnosed over a 20-year period (1976-1995) in a well-defined French population was used to analyse its incidence, management and prognosis as well as to determine time trends. Prognosis was determined by using crude and relative survival rates. Factors predictive of survival were also identified using a relative survival model in a multivariate analysis. RESULTS: Age-standardized incidence rates were 3.8 per 1000000 inhabitants in men and 2.7 per 1000000 inhabitants in women. Incidence increased over time in men from 1.9 during the first period (1976-1980) to 5.9 during the last period (1991-1995). In women, incidence rates remained stable. A resection for cure was performed in 52 cases (48.1%). Overall, 9.9% of these cancers were classified TNM stage I and 54.1% stage IV. There was no significant variation in treatment modalities and in stage at diagnosis over the study period. The overall operative mortality rate was 7.5%. Relative survival rates were 58.9% at 1 year, 30.9% at 3 years and 20.9% at 5 years. Five-year relative survival rates varied from 72.8% in TNM stage I cancers to 6.6% in TNM stage IV cancers. Age, treatment procedure and stage at diagnosis significantly influenced the prognosis of cancer of the ampulla of Vater. In a multivariate analysis, stage at diagnosis remained the major prognostic factor (P<0.01). CONCLUSIONS: Although its incidence is increasing in men, cancer of the ampulla of Vater remains a rare tumour in both sexes. No improvements in the management and care of patients have been achieved. Further studies are needed to enhance the understanding of this cancer.

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
FAMILIAL ADENOMATOUS POLYPOSIS
Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: cumulative risks and APC gene mutations. Bjork J, Akerbrant H, Iselius L, Bergman A, Engwall Y, Wahlstrom J, Martinsson T, Nordling M, Hultcrantz R. Department of Gastroenterology and Hepatology, Karolinska Hospital, karolinska Institute, Stockholm, Sweden.	Gastroenterology 2001 Nov;121(5):1127-35 Abstract quote BACKGROUND & AIMS: Patients with familial adenomatous polyposis (FAP) have a high prevalence of duodenal adenomas, and the region of the ampulla of Vater is the predilection site for duodenal adenocarcinomas. This study assessed the risk of stage IV periampullary adenomas according to the Spigelman classification and periampullary adenocarcinomas in Swedish FAP patients screened by esophagogastroduodenoscopy (EGD). The genotype of patients with stage IV periampullary adenomas and periampullary adenocarcinomas was also investigated. METHODS: A retrospective study of 180 patients screened by EGD in 1982-1999 was undertaken. Kaplan-Meier analysis was performed to evaluate cumulative risk. Mutation analysis was carried out in patients with periampullary adenocarcinomas diagnosed outside the screening program, in addition to patients in the screening group with stage IV periampullary adenomas and adenocarcinomas. RESULTS: Periampullary adenoma stage IV was diagnosed in 14 patients (7.8%), with a cumulative risk of 20% at age 60 years. Periampullary adenocarcinoma was diagnosed in 5 patients (2.8%), with a cumulative risk of 10% at age 60. Three of the adenocarcinomas occurred in patients with stage IV periampullary adenomas compared with 2 in patients with less severe periampullary adenomatosis at screening (odds ratio, 31; 95% confidence interval, 4.6-215). Fifteen (88%) of the APC gene mutations were detected; 12 of these were located downstream from codon 1051 in exon 15. CONCLUSIONS: The life time risk of severe periampullary lesions in FAP patients is high, and an association between stage IV periampullary adenomas and a malignant course of the periampullary adenomatosis is strongly suggestive. Mutations downstream from codon 1051 seem to be associated with severe periampullary lesions.
LESER-TRELAT SIGN
The leser-trelat sign in association with carcinoma of the ampulla of Vater. Klimopoulos S, Kounoudes C, Pantelidaki C, Skrepetou K, Papoudos M, Katsoulis H. Second Surgical Department, Evangelismos Hospital, Athens, Greece.	Am J Gastroenterol 2001 May;96(5):1623-6 Abstract quote A 45-yr-old woman was admitted to our hospital for surgical treatment of obstructive jaundice. She was treated by a standard pancreatoduodenectomy (Whipple procedure). The biopsy of the specimen disclosed an adenocarcinoma of the ampulla of Vater. Six months before the appearance of the obstructive jaundice, she noted a sudden onset of many seborrheic keratoses on the upper part of her trunk and upper extremities. T his, to our knowledge, is the first case of Leser-Trelat sign associated with adenocarcinoma of the ampulla of Vater.
MALIGNANCIES
Carcinoma of the ampulla of Vater associated with other organ malignancies. Eriguchi N, Aoyagi S, Tamae T, Nishimura K, Hamada S, Kawabata M, Kodama T, Jimi A. Department of Surgery, Sasebo Kyosai Hospital, 10-17 Shimanji-cho, Sasebo 857-8575, Japan.	Kurume Med J 2001;48(4):255-9 Abstract quote Because of its location with respect to the biliary system, carcinoma of the ampulla of Vater is considered to manifest earlier in its course of development than carcinoma of the pancreas. The most common physical finding is jaundice, which occurs in 93-100% of cases. This retrospective study describes the results of the treatment and prognosis for double primary cancers in which cancer of the ampulla of Vater was associated with malignancies in other organs in 5 patients who were diagnosed and treated at Kurume University Hospital. The patients included 5 men with an average age of 72.8 years. There were 3 synchronous double and 2 metachronous double cancer patients. Regarding prognoses of these patients, 1 patient with associated lung cancer died because of postoperative complications after pneumonectomy, 1 patient died due to carcinomatosa peritonei developing from the ampulla Vater carcinoma, and 1 patient died because of metastatic liver tumors from the ampullary carcinoma. In multiple cancers including ampulla Vater carcinoma, gastrointestinal cancers such as gastric or colon cancer occur frequently. Therefore, a careful gastrointestinal examination should be done preoperatively. We report our experience with 5 cases of ampullary carcinoma associated with malignancies in other organs and review the literature.
MUIR-TORRE SYNDROME
Muir-Torre syndrome: a case for surveillance of the ampulla of Vater. Matthews JJ, Roberts R, O'Reilly DA, Schick S, Kingsnorth AN. Department of Surgery, Derriford Hospital, Plymouth, UK.	Dig Surg 2002;19(1):65-6 Abstract quote A 64-year-old man with Muir-Torre syndrome (MTS), a condition characterized by the association of multiple sebaceous tumours and kerato-acanthomas with internal malignancies, developed a carcinoma of the ampulla of Vater. This is the 2nd reported ampullary carcinoma in 205 reported cases of MTS, suggesting a higher prevalence in MTS patients than in the general population. As an ampullary carcinoma is potentially amenable to surgical resection, particularly when detected early, patients with MTS should undergo regular endoscopic surveillance of the ampulla of Vater.
NEUROFIBROMATOSIS
Ampullary adenocarcinoma in neurofibromatosis type 1. Case report and literature review. Costi R, Caruana P, Sarli L, Violi V, Roncoroni L, Bordi C. Department of Surgery, Institute of General Surgery, University of Parma School of Medicine, Via Gramsci 14, 43100 Parma, Italy.	Mod Pathol 2001 Nov;14(11):1169-74 Abstract quote Periampullary tumors in patients affected by Neurofibromatosis Type 1 (NF-1) are usually carcinoids or stromal tumors and, rarely, adenocarcinomas. We report a case of an adenocarcinoma of the ampulla of Vater in a 54-year-old woman with NF-1 admitted to the hospital with jaundice and undergoing pancreato-duodenectomy. Histologically, the resected specimen showed an adenocarcinoma of the ampulla as being a part of a complex atypical epithelial proliferation extended from the papilla to the mucosa of the duodenum and distal choledochus, islet-cell adenomatosis of the pancreas and multiple gastric, duodenal, jejunal stromal tumors. The ampullary and periampullary adenocarcinomas in NF-1 patients have peculiar features, suggesting a widespread predisposition to cancer development in periampullary tissues and requiring widely demolitive surgery. Moreover, they occur at a younger age than those occurring in non-NF-1 patients, may be associated with additional periampullary epithelial tumors, are often operable and may present long survival.
PANCREATIC INTRADUCTAL NEOPLASIA
Neoplasms of the ampulla of vater with concurrent pancreatic intraductal neoplasia: a histological and molecular study. Agoff SN, Crispin DA, Bronner MP, Dail DH, Hawes SE, Haggitt RC. Department of Pathology, University of Washington Medical Center/Harborview Medical Center, Seattle, Washington 98104-2499, USA	Mod Pathol 2001 Mar;14(3):139-46 Abstract quote Adenoma and adenocarcinoma of the ampulla of Vater are uncommon neoplasms of the gastrointestinal tract. Only one report has analyzed the relationship between ampullary adenocarcinoma and pancreatic intraductal neoplasia (PanIN), the precursor lesion of pancreatic adenocarcinoma. An association between PanIN and ampullary adenoma has not been reported previously. Case reports have documented the progression of PanIN to invasive pancreatic adenocarcinoma. We reviewed five resected ampullary adenoma and 17 ampullary adenocarcinoma cases and evaluated the pancreas for PanIN. Pancreatic sections from 35 autopsies were reviewed as a control group. Immunohistochemistry for overexpression of p53 and COX-2 proteins was performed in selected cases, as was PCR analysis for K-ras mutations. Follow-up clinical data were obtained. All 22 ampullary neoplasms were associated with PanIN, which was high grade in two (40%) adenoma cases and seven (41%) adenocarcinoma cases. In 16 (73%) evaluable cases, PanIN extended to the pancreatic resection margin; two of which had high grade PanIN. Among the autopsy controls eight (23%) had low-grade PanIN. Seven of the 22 ampullary cases but none of the autopsy controls had coexistent pancreatitis. A smoking history was present in two of four autopsy cases in which this history was available. Overexpression of the p53 and COX-2 proteins was present in only one case of high-grade PanIN. K-ras mutations were present in four of four of the PanIN lesions evaluated, including one autopsy case. Clinical follow-up revealed no progression of PanIN to invasive carcinoma in the remnant pancreas, although the follow-up period was too short to adequately assess that risk (an average of 3.8 y for adenoma cases and 2.5 y for adenocarcinoma cases). We conclude that adenomas and carcinomas of the ampulla are associated with PanIN, and often high-grade PanIN. Although its malignant potential has not been fully established, PanIN is underreported and often unrecognized. PanIN may be analogous to colorectal adenoma in that both are prevalent in the older adult population, but few progress to carcinoma.

 

PATHOGENESIS	CHARACTERIZATION
GENERAL
The adenoma-carcinoma sequence applies to epithelial tumours of the papilla of Vater. Kaiser A, Jurowich C, Schonekas H, Gebhardt C, Wunsch PH. Institute of Pathology, Department of Abdonimal Surgery, Nurnberg, Germany.	Z Gastroenterol 2002 Nov;40(11):913-20 Abstract quote Adenomas of the papilla of Vater are relatively rare tumours. They are of particular interest, not only because of their particular topography, but also because the adenoma-carcinoma sequence - accepted in the colorectum - has also been postulated to apply to the papilla of Vater. In fact, ampullary adenoma is often considered to be a precancerous lesion. To investigate this hypothesis, we reviewed the surgical specimens obtained during Whipple's procedures carried out to treat histologically confirmed carcinoma of the ampulla. A total of 37 surgical specimens obtained since January 1991 were reexamined for the presence of coexisting adenomatous structures. Such adenomatous residues were confirmed in 24/37 (65 %) cases. In 13/37 (35 %) cases, no residual adenoma was found. A comparison of the two groups revealed that detection of coexisting adenomatous structures decreased with increasing tumour progression. In similar manner, this also applied to the degree of malignancy: with increasing grade of malignancy the rate of detectable adenomatous structures decreased significantly. It may be assumed that these observations are due to the 'overgrowth' of preexisting adenomas by carcinomatous tissue. Further evidence is provided by the histological observation of transitional stages from adenoma with mild, moderate and severe cellular atypia to invasive carcinoma. These findings support the hypothesis of an adenoma-carcinoma sequence.
Pancreatic tumours: molecular pathways implicated in ductal cancer are involved in ampullary but not in exocrine nonductal or endocrine tumorigenesis. Moore PS, Orlandini S, Zamboni G, Capelli P, Rigaud G, Falconi M, Bassi C, Lemoine NR, Scarpa A. Department of Pathology, Universita di Verona, Italy.	Br J Cancer 2001 Jan;84(2):253-62 Abstract quote Alterations of K- ras, p53, p16 and DPC4/Smad4 characterize pancreatic ductal cancer (PDC). Reports of inactivation of these latter two genes in pancreatic endocrine tumours (PET) suggest that common molecular pathways are involved in the tumorigenesis of pancreatic exocrine and endocrine epithelia. We characterized 112 primary pancreatic tumours for alterations in p16 and DPC4 and immunohistochemical expression of DPC4. The cases included 34 PDC, 10 intraductal papillary-mucinous tumours (IPMT), 6 acinar carcinomas (PAC), 5 solid-pseudopapillary tumours (SPT), 16 ampulla of Vater cancers (AVC) and 41 PET. All tumours were also presently or previously analysed for K- ras and p53 mutations and allelic loss at 9p, 17p and 18q. Alterations in K- ras, p53, p16 and DPC4 were found in 82%, 53%, 38% and 9% of PDC, respectively and in 47%, 60%, 25% and 6% of AVC. Alterations in these genes were virtually absent in PET, PAC or SPT, while in IPMT only K- ras mutations were present (30%). Positive immunostaining confirmed the absence of DPC4 alterations in all IPMT, SPT, PAC and PET, while 47% of PDC and 38% of AVC were immunonegative. These data suggest that pancreatic exocrine and endocrine tumourigenesis involves different genetic targets and that among exocrine pancreatic neoplasms, only ductal and ampullary cancers share common molecular events.
ONCOGENES
Role of the DPC4 Tumor Suppressor Gene in Adenocarcinoma of the Ampulla of Vater: Analysis of 140 Cases. McCarthy DM, Hruban RH, Argani P, Howe JR, Conlon KC, Brennan MF, Zahurak M, Wilentz RE, Cameron JL, Yeo CJ, Kern SE, Klimstra DS. Departments of Pathology (DMM, RHH, PA, REW, SEK), Oncology (RHH, CJY, SEK), Statistics (MZ), and Surgery (JLC, CJY), The Johns Hopkins Medical Institutions, Baltimore, Maryland.	Mod Pathol 2003 Mar;16(3):272-8 Abstract quote The K-ras oncogene is activated in approximately 90% of pancreatic adenocarcinomas, and the DPC4 (MADH4/SMAD4) tumor suppressor gene is inactivated in approximately 55% of pancreatic adenocarcinomas. The contributions of these genetic alterations to the development of adenocarcinoma of the ampulla of Vater have not been fully established. One hundred forty surgically resected ampullary adenocarcinomas (76 with associated adenomas with high-grade dysplasia) were immunohistochemically labeled for the DPC4 gene product, and in 85 cases the results were correlated with the status of the K-ras oncogene from previously reported data. The results were correlated with clinical outcome and with other pathologic predictors of prognosis. Complete loss of Dpc4 labeling was identified in 34% (95% confidence interval [CI]: 26%, 43%) of the invasive carcinomas and in none (upper 95% CI: 6%) of the associated adenomas. Focal loss of Dpc4 was seen in three (4%; 95% CI: 1%, 14%) of the areas of high-grade dysplasia. Complete loss of Dpc4 expression was seen in 28/77 intestinal-type tumors, in 17/46 pancreaticobiliary-type tumors, and in 0/10 colloid carcinomas. Activating point mutations in the K-ras gene were identified in 40% of the invasive cancers. There was no correlation between K-ras gene mutations and Dpc4 expression and no correlation between these variables and survival. The overall 5-year survival rate was 38%. Lymph node metastases were associated with shorter survival (P =.03). Loss of Dpc4 expression occurs in approximately one third of invasive ampullary cancers but is not seen in adenomas; thus, loss of Dpc4 expression occurs late in ampullary carcinogenesis. Although ampullary and pancreatic adenocarcinomas share histologic and molecular features, ampullary carcinomas are less likely to show loss of Dpc4 expression or K-ras gene mutations.
Analysis of K-ras gene mutations in rare pancreatic and ampullary tumours. Ebert MP, Hoffmann J, Schneider-Stock R, Kasper HU, Schulz HU, Lippert H, Roessner A, Malfertheiner P. Department of Gastroenterology, Otto-von-Guericke Universitat Magdeburg, Germany.	Eur J Gastroenterol Hepatol 1998 Dec;10(12):1025-9 Abstract quote OBJECTIVE: Mutation of the K-ras oncogene is a frequent event in pancreatic ductal carcinogenesis and it is believed to occur at an early stage in the development of pancreatic cancer. However, little is known of the role of K-ras mutations in rare pancreatic epithelial neoplasms, endocrine tumours or other non-epithelial tumours of the pancreas. Furthermore, limited data are available regarding the role of K-ras mutations in the pathogenesis of ampullary tumours. DESIGN AND METHODS: Using single-strand conformation polymorphism (SSCP) and direct sequencing of polymerase chain reaction (PCR)-amplified fragments, we analysed codons 12 and 13 for the presence of oncogenic mutations of the K-ras oncogene. Tissues were obtained from patients undergoing tumour resection for various rare pancreatic or ampullary neoplasms (number of cases in brackets): ampullary adenoma (1), neuro-endocrine tumour (3), malignant fibrous histiocytoma of the pancreas (1), pancreatic cystadenocarcinoma (1), serous cystadenoma (1), and primary and metastatic adenocarcinoma of the ampulla (5) and pancreas (3). RESULTS: K-ras gene mutations at codon 12 were detected in both pancreatic adenocarcinomas and in the metastatic lesion, whereas two ampullary cancers harboured a point mutation at codon 13: GGC-->GGG and GGC-->GGT. None of the other tumours exhibited a K-ras gene mutation at codons 12 or 13. CONCLUSION: Pancreatic tumours other than ductal adenocarcinoma of the pancreas do not harbour mutations of the K-ras oncogene. In addition, ampullary adenocarcinomas may present with codon 13 mutations; however, these mutations were not associated with amino acid substitution. Therefore, K-ras gene mutations seem to be a specific genetic alteration contributing to the pathogenesis of pancreatic ductal adenocarcinoma.
Clinical significance of K-ras oncogene activation in ampullary neoplasms. Chung CH, Wilentz RE, Polak MM, Ramsoekh TB, Noorduyn LA, Gouma DJ, Huibregtse K, Offerhaus GJ, Slebos RJ. Department of Pathology, University of Amsterdam, Netherlands.	J Clin Pathol 1996 Jun;49(6):460-4 Abstract quote AIMS: To investigate the prevalence of K-ras codon 12 point mutations in ampullary neoplasms, to explore their clinical usefulness, and to test whether the detection of these mutations could be used to identify ampullary malignancies at an early stage. METHODS: Forty one tumour specimens from 28 patients with ampullary neoplasms were analysed for activating point mutations in K-ras codon 12 using a sensitive polymerase chain reaction (PCR) based assay. RESULTS: Eleven (39%) of the 28 primary tumours harboured point mutations in K-ras. Mutations were identified in seven (41%) of the 17 carcinomas and four (36%) of the 11 adenomas. Four of the possible six permutations in codon 12 were found in these 11 samples. This spectrum of mutations is different from pancreatic carcinoma but resembles that of colorectal neoplasms. Cytological brush specimens were available in 11 cases, and in all of these specimens, the K-ras status in the primary tumour and brush specimens was identical. CONCLUSIONS: K-ras codon 12 point mutations occur in about 40% of ampullary neoplasms at a relatively early stage in tumorigenesis. The pattern of mutations in these tumours resembles that of the adenoma-carcinoma sequence in the colorectum. These results indicate that ampullary neoplasms can be detected at an early stage by searching for genetic alterations in the K-ras oncogene in cytological brush specimens.
ras-family gene mutations in neoplasia of the ampulla of Vater. Scarpa A, Zamboni G, Achille A, Capelli P, Bogina G, Iacono C, Serio G, Accolla RS. Istituti di Anatomia Patologica, Universita di Verona, Italy.	Int J Cancer 1994 Oct 1;59(1):39-42 Abstract quote Mutations in the first and second exons of Ha-, Ki- and N-ras oncogenes were investigated in 17 epithelial tumors of the ampulla of Vater by single-strand conformation polymorphism analysis and direct sequencing of DNA fragments amplified by polymerase chain reaction. The panel included 12 intestinal-type adenocarcinomas, 3 villous adenomas, 1 papillary carcinoma and 1 neuroendocrine carcinoma. Six cases (35%) contained ras mutations, affecting codon 12 of Ki-ras in 2 adenomas and 3 carcinomas, and of N-ras in 1 adenoma. All mutations were found in adenomas and among cancers with adenomatous areas, whereas none of the cases lacking adenomatous areas contained mutations. This suggested that ampullary cancers represent heterogeneous diseases with respect to the presence or absence of adenomatous areas and, among those with adenomatous areas, with respect to the presence of activated ras genes. Ki-ras mutated cases included 3 of 4 tumors which mainly involved the intraduodenal bile duct, thus suggesting that a proportion of Ki-ras-mutated ampullary cancers might correspond to those originating from the epithelium of the bile duct component of the ampulla.
p53
Carcinoma of the ampulla of Vater associated with or without adenoma: a clinicopathologic analysis of 198 cases with reference to p53 and Ki-67 immunohistochemical expressions. Takashima M, Ueki T, Nagai E, Yao T, Yamaguchi K, Tanaka M, Tsuneyoshi M. Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.	Mod Pathol 2000 Dec;13(12):1300-7 Abstract quote Adenomatous areas are found frequently within or in the vicinity of carcinoma of the ampulla of Vater. This makes definite diagnosis difficult in the preoperative examination. The adenoma-carcinoma development hypothesis is generally accepted for colorectal tumors. Recently, a genetic alteration model during colorectal tumor development has attracted much attention, leading to various studies. We studied clinicopathologic features, prognostic factors, and the alteration of the p53 tumor suppressor gene using p53 immunohistochemical staining in pure adenomas, pure carcinomas, and carcinomas with adenomatous areas. A proliferative activity of the tumors using Ki-67 was also evaluated. Nine cases of pure adenoma and 198 cases of carcinoma of the ampulla of Vater were selected for this study. Among the 198 cases of thecarcinoma, 83 cases (42%) had adenomatous areas. Positivity of p53 immunohistochemical staining was 0% in pure adenomas, 36% in the adenomatous areas of carcinomas with adenomatous areas and 62% in the carcinomatous areas of carcinomas with adenomatous areas, and 56% in pure carcinoma. Accumulation of p53 protein and the Ki-67 labeling index revealed no significant difference in prognosis. The clinicopathological factors examined were as follows: degree of invasion of the surrounding tissue, such as duodenal wall; pancreatic parenchyma; the presence or absence of lymphatic permeation; venous invasion; perineural invasion; the presence of regional lymph node metastasis; and TNM stage. Each of the clinicopathological factors showed a significant difference. Multivariate analysis revealed strong predictors for a worse prognosis: presence of lymphatic permeation, invasion of the pancreas, and perineural invasion. In conclusion, our results are consistent with the adenoma--carcinoma development hypothesis. It would seem that the molecular events leading to p53 accumulation in neoplasms of the ampulla of Vater occur relatively late during the oncogenetic process. Moreover, we think it may be useful to refer to the p53 overexpression in the diagnosis of ampullary tumors.

 

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
MR imaging of ampullary carcinomas. Irie H, Honda H, Shinozaki K, Yoshimitsu K, Aibe H, Nishie A, Nakayama T, Masuda K. Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan	J Comput Assist Tomogr 2002 Sep-Oct;26(5):711-7 Abstract quote OBJECTIVE: The purpose of this study was to demonstrate the appearance of ampullary carcinomas on MR images. METHODS: Sixteen patients with ampullary carcinomas underwent MR imaging. Tumor detectability, signal intensity of the tumor, and enhancement pattern on dynamic study were analyzed. MR cholangiopancreatography (MRCP) findings were assessed and were compared with the endoscopic retrograde cholangiopancreatography (ERCP) findings. RESULTS: Signal intensities of the tumor on each image were various. Dynamic study detected all tumors except one, and all detected tumors showed delayed enhancement. MRCP delineated more than half of the tumors as a filling defect within the duodenal fluid and clearly demonstrated pancreaticobiliary ductal. CONCLUSIONS: Dynamic study is mandatory in diagnosing ampullary carcinoma, because it can depict most of the tumors, and delayed enhancement of such tumors is characteristic in case of ampullary carcinoma. MRCP can provide reliable information about pancreaticobiliary duct and it can replace diagnostic ERCP.
Differential diagnosis of periampullary carcinomas at MR imaging. Kim JH, Kim MJ, Chung JJ, Lee WJ, Yoo HS, Lee JT. Department of Diagnostic Radiology, Yonsei University College of Medicine, Seodaemun-ku, Shinchon-dong 134, Seoul 120-752, Korea.	Radiographics 2002 Nov-Dec;22(6):1335-52 Abstract quote Periampullary carcinomas arise within 2 cm of the major duodenal papilla and comprise carcinomas of the ampulla, distal common bile duct, pancreas, and duodenum. Their clinical features and anatomic locations are similar, as are the therapeutic approaches; however, their long-term outcomes vary. Magnetic resonance (MR) images of 89 pathologically proved periampullary carcinomas (29 ampullary carcinomas, 27 distal common bile duct carcinomas, 21 pancreatic carcinomas, six duodenal carcinomas, and six unclassified carcinomas) were reviewed. Ampullary carcinoma manifests as a small mass, periductal thickening, or bulging of the duodenal papilla. Pancreatic carcinoma is characterized by a discrete parenchymal mass, which enhances poorly on dynamic gadolinium-enhanced images. Sometimes, two proximal and two distal pancreatic and biliary ducts appear as four separate ducts (the four-segment sign). Dilatation of side branches of the pancreatic ducts is frequently seen in pancreatic carcinoma but not in other periampullary carcinomas. Distal bile duct carcinoma manifests as luminal obliteration and wall thickening or as an intraductal polypoid mass. A dilated proximal bile duct, a nondilated distal bile duct, and a dilated or nondilated pancreatic duct may form the three-segment sign. MR cholangiopancreatography and sectional MR imaging are useful in determining the origins of periampullary carcinomas.
Is endosonography an effective method for detection and local staging of the ampullary carcinoma? A prospective study. Skordilis P, Mouzas IA, Dimoulios PD, Alexandrakis G, Moschandrea J, Kouroumalis E. University Hospital of Crete, Gastroenterology Department.	MC Surg 2002 Mar 25;2(1):1 Abstract quote BACKGROUND: The relatively rare carcinoma of the ampulla of Vater is a neoplasia with a good prognosis compared to pancreatic cancer. Preoperative staging is important in planning the most suitable surgical intervention. AIM: To prospectively evaluate the diagnostic accuracy of Endoscopic Ultrasonography (EUS) in comparison with conventional US and CT scan, in staging of patients with ampullary carcinoma. PATIENTS AND METHODS: 20 patients (7 women and 13 men) with histologically proven carcinoma of the ampulla of Vater were assessed by EUS, CT scan and US. Results were compared to surgical findings. RESULTS: Endoscopic biopsies were diagnostic in 76% of the patients. Detection of ampullary cancer with US and CT scan was 15% and 20% respectively. Only indirect signs of the disease were identified in the majority of cases using these methods. Overall accuracy of EUS in detection of ampullary tumours was 100%. The EUS was significantly (p < 0.001) superior than US and CT scan in ampullary carcinoma detection. Tumour size, tumour extension and the existence of metastatic lymph nodes were also identified and EUS proved to be very useful for the preoperative classification both for the T and the N components of the TNM staging of this neoplasia. The diagnostic accuracy for tumour extension (T) was 82% and for detection of metastatic lymph nodes (N) was 71%. CONCLUSION: EUS is more accurate in detecting ampullary cancer than US and CT scan. Tumor extension and locally metastatic lymph nodes are more accurately assessed by means of EUS than with other imaging methods.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GASTROINTESTINAL HEMORRHAGE
Unusual manifestation of an ampullary tumor presenting with severe upper gastrointestinal bleeding. Ashkar K, Deeb LS, Bikhazi K, Arnaout MS. Department of Family Medicine, American University of Beirut Medical Center, Beirut, Lebanon	Digestion 1999 Nov-Dec;60(6):583-6 Abstract quote Ampullary tumors can occasionally ulcerate and present as frank gastrointestinal bleeding. The most common clinical presentation is jaundice like in other tumors of the biliary tree. We report on a 68-year-old man who presented with severe upper gastrointestinal hemorrhage secondary to an asymptomatic mass of the ampulla of Vater. An endoscopic biopsy specimen revealed a villous adenoma with moderate dysplasia. A curative resection was performed, and pathological work-up revealed the presence of an infiltrating, moderately differentiated ampullary adenocarcinoma.
PANCREATITIS
Carcinoma of Papilla Vateri presenting as recurrent acute pancreatitis. Tanasijtchouk T, Vaisbein E, Lachter J, Nassar F. Department of Internal Medicine H, Western Galilee Hospital, Nahariya, Israel.	Acta Gastroenterol Belg. 2004 Jul-Sep;67(3):309-10. Abstract quote   Tumors of the Papilla of Vater can cause several clinical symptoms, the most prominent being jaundice, weight loss, anorexia, fever, abdominal pain and itching (1). Acute pancreatitis as a presenting symptom of ampullary carcinoma is rare. Few previous cases have been described in the literature (2,3). The prognosis of patients with jaundice is unfavorable in comparison with non icteric patients at the time of diagnosis (4) due to different staging, hence more complications, but not due to different histology. We report here a case of recurrent pancreatitis that was the only presentation of Vater ampullary carcinoma diagnosed by endoscopic ultrasound followed by duodenoscopy with guided biopsy. Recurrent pancreatitis without identifiable cause, particularly in elderly patients, could suggest tumor of the head of pancreas or the periampullary region among other causes such as intraductal papillary mucinous tumor, microlithiasis etc. An endoscopic ultrasound can allow earlier diagnosis and mandates biopsy in these cases.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
Carcinoma of the Ampulla of Vater: Comparative Histologic/ Immunohistochemical Classification and Follow-up. Zhou H, Schaefer N, Wolff M, Fischer HP. Departments of *Pathology and daggerSurgery, University of Bonn, Bonn, Germany.	Am J Surg Pathol. 2004 Jul;28(7):875-882. Abstract quote A broad histomorphologic spectrum of ampullary carcinomas of Vater make a reproducible histologic classification difficult. Using cytokeratin immunohistochemistry, we present a new classification of ampullary carcinomas and analyze their clinical significance. Fifty-five invasive carcinomas of Vater's ampulla were histologically classified into pancreaticobiliary, intestinal, and other types. Serial sections of all carcinoma specimens were additionally stained with antibodies to cytokeratins (CK7, CK20), apomucins (MUC1, MUC2, MUC5AC), CEA, CA19-9, Ki67, and p53. Follow-up of patients from 4 months to 22 years after surgery (mean interval, 51.6 months) was evaluated. Most carcinomas of the ampulla of Vater were of immunohistochemically pancreaticobiliary type (iPT, CK7+, CK20-; 54.5%) or intestinal type (immunohistochemically intestinal type [iIT], CK7-, CK20+; 23.6%). Some carcinomas of immunohistochemically "other" type (iOT both CK7+ and CK20+ or CK7- and CK20-; 21.8%) had precursor lesions of iIT or iPT. Carcinomas positive for MUC2 or CEA were associated with iIT (MUC2, P < 0.001; CEA, P = 0.003), whereas MUC5AC-positive carcinomas were related to iPT (P = 0.005). Our classification based on cytokeratin-immunohistochemistry correlated well with the histologic classification according to published criteria (kappa-coefficient = 0.398; P < 0.001). Furthermore, histologically unusual types could be histogenetically related to pancreaticobiliary duct mucosa or intestinal mucosa. Therefore, all 4 signet-ring cell carcinomas were iIT carcinomas. Thus, cytokeratin immunohistochemistry allows a reproducible, histogenetically based categorization of ampullary carcinomas. However, neither histopathologic nor immunohistochemical subgroups significantly correlated with clinical outcome in our German collective. The overall survival was significantly shorter in males (P = 0.032) and patients with positive nodal stage (N1 < N0; P = 0.0025).
VARIANTS
ADENOSQUAMOUS CARCINOMA
Adenosquamous cell carcinoma arising from the papilla major. Ueno N, Sano T, Kanamaru T, Tanaka K, Nishihara T, Idei Y, Yamamoto M, Okuno T, Kawaguchi K. Department of Surgery, Kita-Osaka Hospital, Yodogawa-ku, 532-0004 Osaka, Japan.	Oncol Rep 2002 Mar-Apr;9(2):317-20 Abstract quote A 47-year-old man was admitted to hospital with complaint of general fatigue. Shortly before the admission a suspected obstructive jaundice was diagnosed at a local hospital. On admission, the physical examination was significant for jaundice; total bilirubin was 6.43 mg/dl. The tumor marker CA19-9 was 2056 U/ml. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and showed dilatation of common bile duct and main pancreatic duct, accompanied with an endoscopic naso-biliary drainage (ENBD) in order to reduce the jaundice. The duodenoscopy showed enlarged and deformed papilla. Hypotonic duodenography showed a filling defect at the medial side of the second portion of the duodenum. Ultrasonography (US) showed a hyperechoic lesion, sized 15 mm in diameter, at the pancreas head with dilatation of biliary tract and main pancreatic duct. An abdominal enhanced CT scan showed a mass sized 15 mm at the lower edge of the common bile duct. A selective hepatic arteriography showed no special finding. We performed a pancreatoduodenectomy with dissection of the lymph nodes. The tumor, sized 22x15x20 mm, was white colored and solid on the papilla. Histopathological inspection of the specimen showed an adenosquamous cell carcinoma of the bile duct in the papilla. The tumor was found to infiltrate the neighboring pancreas and to contain metastasis in lymph nodes in the hepatoduodenal ligament, post pancreaticoduodenal and para-aortic lymph nodes. This is the first report on a case of adenosquamous carcinoma of the papilla major.
NEUROENDOCRINE CARCINOMA
High-grade neuroendocrine carcinoma of the ampulla of vater: a clinicopathologic and immunohistochemical analysis of 14 cases. Nassar H, Albores-Saavedra J, Klimstra DS. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.	Am J Surg Pathol. 2005 May;29(5):588-94. Abstract quote   We describe the clinical and pathologic features of 14 cases of high-grade neuroendocrine carcinoma (HGNEC) of the ampulla of Vater classified according to WHO classification of lung tumors into small cell carcinoma (SCC, 6 cases) and large cell neuroendocrine carcinoma (LCNEC, 8 cases) types. The immunohistochemical findings were compared with those of 13 cases of primary poorly differentiated ampullary adenocarcinomas (PDACA) lacking neuroendocrine morphology. The mean age of 10 males and 4 females was 70 years. The mean tumor size was 2.5 cm. Ten of 13 patients had lymph node metastases (mean, 2.3 nodes involved). Documented sites of distant metastases included brain and liver. Overall, 64% of patients with ampullary HGNEC died of disease (mean follow-up, 14.5 months). Four patients had no evidence of disease after resection (mean, 20 months). Half of the tumors were associated with adenomas of the adjacent mucosa, 2 with high-grade dysplasia. Two HGNECs were combined with a conventional adenocarcinoma and another with a squamous cell carcinoma component. By immunohistochemistry, the HGNECs were positive for cytokeratins (AE1/AE3, 100%; Cam5.2, 67%; CK7, 87%; CK20, 38%), similar to the pattern found in PDACAs. p27 expression was lost in 1 case of HGNEC and in all PDACAs. Retinoblastoma (Rb) protein expression was lost in 60% of HGNECs and in none of the PDACA cases. In conclusion, HGNECs of the ampulla are rare (2%-3% of ampullary tumors in our material). The clinical course parallels that of their pulmonary counterparts and appears to be worse than that of locally advanced ampullary adenocarcinomas. The association with adenoma and or conventional adenocarcinoma components may suggest a common pathway in the initial carcinogenesis of these two types of tumors. Loss of Rb expression, a characteristic finding in pulmonary SCCs, is present in almost half of ampullary HGNECs. In contrast, p27 expression is lost in PDACAs and retained in most HGNECs. Thus, there are differences in the molecular phenotypes of these two types of ampullary carcinoma, supporting the distinction of poorly differentiated carcinomas with a neuroendocrine phenotype from those without.
Large cell neuroendocrine carcinoma of the ampulla of vater. Cavazza A, Gallo M, Valcavi R, De Marco L, Gardini G. Department of Pathology, S. Maria Nuova Hospital, Reggio Emilia, Italy	Arch Pathol Lab Med 2003 Feb;127(2):221-3 Abstract quote We report a large cell neuroendocrine carcinoma arising in the ampulla of Vater. The patient, a 74-year-old woman, presented with a 3-cm ulcerated mass located in the ampullary region. She died of disease 8 months after surgery. Microscopically, the tumor was extensively necrotic. It was composed of islands and trabeculae irregularly infiltrating the muscular wall of the duodenum. Neoplastic cells were large and had a high mitotic index. Immunohistochemically, they expressed cytokeratin, chromogranin, synaptophysin, and neuron-specific enolase. Large cell neuroendocrine carcinoma is very rare in the ampulla of Vater, and it shares with its more common pulmonary counterpart the same morphology and probably the same poor prognosis.
Mixed acinar-endocrine carcinoma arising in the ampulla of Vater. Moncur JT, Lacy BE, Longnecker DS. Department of Pathology, Walter Reed Army Medical Center, Washington, DC 20307, USA.	Hum Pathol 2002 Apr;33(4):449-51 Abstract quote We present a case of mixed acinar-endocrine carcinoma arising in the periampullary region of the duodenum. The patient was a 78-year-old male with a periampullary mass diagnosed during upper endoscopy. On gross dissection, the mass was 2.3 cm in diameter, noncystic, and confined to the duodenal submucosa. Microscopically, the tumor formed nests that were positive for amylase, trypsin (weakly), and synaptophysin (diffusely). Ultrastructurally, the tumor had 2 populations of granules with mean diameters of 175 nm and 540 nm, consistent with endocrine and zymogen granules, respectively. These studies were consistent with a mixed acinar-endocrine carcinoma that arose in the duodenum. A review of the literature revealed 1 report of an acinar cell carcinoma arising in jejunal pancreatic heterotopia. The present article is the first reported case of an acinar cell carcinoma arising in the periampullary region of the duodenum, possibly in a focus of pancreatic heterotopia.
SIGNET RING CELL ADENOCARCINOMA
Signet-ring cell carcinoma of the ampulla of Vater. Li L, Chen QH, Sullivan JD, Breuer FU. Department of Pathology, North Shore University Hospital, Manhasset, New York 11030, USA.	Ann Clin Lab Sci. 2004 Autumn;34(4):471-5. Abstract quote   Signet-ring cell carcinoma (SRCC) of the alimentary canal is a variant of adenocarcinoma that has a poor clinical prognosis. SRCC of the ampulla of Vater is extremely uncommon with < 12 cases reported in the literature. SRCC of the ampulla of Vater occurs in an older age group (mean age 60 yr) when compared to SRCC of the stomach (under 45 yr), but is similar to SRCC of the large intestine. We report a case of SRCC of the ampulla of Vater with unusual histopathologic features in a 56-yr-old woman who presented with a small tumor at the orifice of the ampulla, associated with extensive lymphovascular invasion and multiple regional lymph node involvement.

 

SPECIAL STAINS/ IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE
Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Chu PG, Schwarz RE, Lau SK, Yen Y, Weiss LM. Division of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA.	Am J Surg Pathol. 2005 Mar;29(3):359-67. Abstract quote Pancreatobiliary and ampulla of Vater adenocarcinomas frequently metastasize to regional lymph nodes, liver, or lung and are difficult to diagnose because they lack specific immunohistochemical markers. We studied the expression of cytokeratin 7 (CK7), cytokeratin 17 (CK17), cytokeratin 20 (CK20), CDX2, mucin 1 (MUC1), mucin 2 (MUC2), and mucin 5AC (MUC5AC) in 46 cases of pancreatic ductal carcinoma, 18 ampulla of Vater adenocarcinomas, and 24 intrahepatic cholangiocarcinomas. The expression of MUC1 and CK17 was restricted to pancreatic ductal carcinoma (41 of 46, 89%; 38 of 46, 83%, respectively), the ampullary carcinoma of pancreatobiliary origin (6 of 6, 100%; 5 of 6, 83%, respectively), and intrahepatic cholangiocarcinoma (20 of 24, 83%; 17 of 24, 71%, respectively). More than 50% of cases of pancreatobiliary adenocarcinomas showed diffuse cytoplasmic CK17 positivity. In contrast, less than 5% cases (8 of 184) of extra-pancreatobiliary nonmucinous adenocarcinomas expressed CK17, and only 3 of them showed diffuse CK17 positivity. The expression of MUC2 and CDX2 was restricted to the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin (9 of 11, 82%; 11 of 11, 100%, respectively). MUC2 was rarely expressed in pancreatic ductal carcinoma (1 of 46, 2%) and was negative in the ampullary carcinoma of pancreatobiliary origin and in intrahepatic cholangiocarcinoma. A heterogeneous CDX2 staining pattern was seen in 1 of 6 cases of the ampullary carcinoma of pancreatobiliary origin (17%), 5 of 24 intrahepatic cholangiocarcinomas (21%), and 10 of 46 (22%) pancreatic ductal carcinomas. In contrast, all 11 cases of the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin showed homogeneous CDX2 nuclear positivity. We concluded that CK17 is a useful marker in separating pancreatobiliary adenocarcinomas from extra-pancreatobiliary nonmucinous adenocarcinomas, including adenocarcinomas from the colon, breast, gynecologic organs, stomach, lung, prostate, thyroid, kidney, and adrenal gland, and malignant mesothelioma. MUC1+/CK17+ can be used as positive markers for pancreatic ductal carcinomas, the ampullary carcinoma of pancreatobiliary origin, and cholangiocarcinomas with positive predictive values of 76%, 83%, and 58%, respectively. MUC2+/CDX2+ can be used as positive markers for the intestinal-type adenocarcinoma of duodenal papillary origin with a positive predictive value of 82%.
CYTOKERATINS
Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold. Goldstein NS, Bassi D. Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, MI, USA.	Am J Clin Pathol 2001 May;115(5):695-702 Abstract quote We studied reactivity of cytokeratins (CK) 7, 17, and 20 in 64 pancreaticobiliary adenocarcinomas to examine the effect of different cut-point thresholds on "positive" results, compare ampulla of Vater and pancreas adenocarcinomas, and provide additional experience with CK17 reactivity. Almost all neoplasms had extensive CK7 reactivity. The number of CK20-positive cases decreased from 29 (45%; any stained cells) to 19 (30%; > 25% staining) to 14 (22%; > 50% staining) with an increasing threshold of reactive cells. Similar shifts in the distribution of CK7 and CK20 reactivity occurred when different thresholds of reactivity were used for a positive result. There were no differences in CK7 or CK20 reactivity in pancreas only, ampulla only, and neoplasms involving both sites. Of 64 adenocarcinomas, 29 (45%) had no or single-cell CK17 reactivity, and 19 (30%) had reactivity in more than 50% of neoplastic cells. Ampulla of Vater and pancreas adenocarcinomas have similar CK immunophenotypes that cannot assist in distinguishing ampullary from pancreatic neoplasms on endoscopically procured tissue. CK17 staining occurs in approximately 50% of pancreaticobiliary adenocarcinomas and is usually patchy. Single antibody staining results, especially CK7 and CK20 coordinate reactivity, are influenced by the reactivity threshold used.
Expression of cytokeratins 7 and 20 in carcinomas of the extrahepatic biliary tract, pancreas, and gallbladder. Duval JV, Savas L, Banner BF. Department of Pathology, UMass Memorial Health Care, Worcester, MA 01655, USA.	Arch Pathol Lab Med 2000 Aug;124(8):1196-200 Abstract quote BACKGROUND: Expression of cytokeratins 7 (CK7) and 20 (CK20) may help distinguish the site of origin for metastatic carcinomas. Little is known regarding their expression in biliary tract and pancreatic carcinomas. Our aim was to study the expression of CK7 and CK20 in these tumors. DESIGN: Fifty-three carcinomas of the extrahepatic bile ducts (n = 8), ampulla of Vater (n = 7), gallbladder (n = 11), and pancreas (n = 27), were retrieved from the surgical pathology files of the University of Massachusetts Medical Center. Formalin-fixed, paraffin-embedded sections were immunostained with mouse monoclonal antibodies to CK7 and CK20 using an avidin-biotin immunoperoxidase technique with microwave antigen retrieval. The percentage of cells positive for each antibody was assessed on a scale of 0 to 3 (0, <10%; 1+, 10% to 50%; 2+, 51% to 90%; 3+, >90%). RESULTS: The majority of carcinomas in all groups were positive for CK7 (CK7+) and negative for CK20 (CK20-). Of the CK7+ tumors, the majority of tumors in each group were 3+ positive. CONCLUSIONS: (1) Carcinomas of the extrahepatic biliary tract and pancreas are strongly positive for CK7 and negative for CK20 and can be included in the differential diagnosis of other carcinomas with this profile in metastatic sites. (2) The CK7/CK20 immunostaining profile will not identify the site of origin for tumors with extensive growth in the porta hepatis region.
MUCINS
Prognostic value of mucins in the classification of ampullary carcinomas. Paulsen FP, Varoga D, Paulsen AR, Corfield A, Tsokos M. Department of Anatomy and Cell Biology, Martin-Luther-University of Halle-Wittenberg, D-06097 Halle (Saale), Germany.	Hum Pathol. 2006 Feb;37(2):160-7. Abstract quote   The ampulla of Vater is of high clinical relevance with regard to influx of chyme, ascending inflammation, intubation during diagnostic and therapeutic endoscopic investigation, therapeutic papillotomy, and especially to malignant transformation. Little is known about the distribution of mucins in the ampulla. In this study, we have investigated the mucin distribution in the normal ampulla of Vater and compared it to duodenal mucosa and Brunner glands. Expression of mucins in the ampulla of Vater and duodenum was monitored by reverse transcription-polymerase chain reaction and localization of the products by immunohistochemistry. The samples investigated originated from 30 autopsy cases. Mucins MUC1, MUC3, MUC4, MUC5AC, MUC5B, MUC6, MUC7, and MUC8 were expressed in the ampulla of Vater. Immunohistochemistry revealed production of MUC4, MUC5AC, MUC5B, and MUC6. The mucin composition varied in comparison with the duodenum referring to MUC2, MUC7, and MUC8. Detected mucins contribute to innate immunity, epithelial restitution, and protection against the aggressive secretions of the liver, gall bladder, and pancreas. By cross-linking, they influence the rheological properties of the secretions in the ampulla and facilitate unidirectional flow into the duodenum. Knowledge of their pattern of expression has prognostic value with regard to the detection of malignancy. The observed differences in the mucin distribution between the duodenum and the ampulla of Vater support the use of MUC2, MUC7, and MUC8 as useful tool in the classification of ampullary carcinomas.

 

PROGNOSIS	CHARACTERIZATION
GENERAL
Ampulla of vater cancers: T-stage and histological subtype but not Dpc4 expression predict prognosis. Beghelli S, Orlandini S, Moore PS, Talamini G, Capelli P, Zamboni G, Falconi M, Scarpa A. Department of Pathology, University of Verona, Strada Le Grazie, 37134 Verona, Italy.	Virchows Arch 2002 Jul;441(1):19-24 Abstract quote Loss of immunohistochemical expression of Dpc4 occurs in about 50% of pancreatic ductal cancers and its loss correlates with DPC4/Smad4 gene inactivation. Dpc4 expression was also lost in 6 of 16 (37%) ampulla of Vater cancers (AVCs) previously analyzed. Furthermore, chromosomal losses involving 18q, where DPC4 is located, have been observed in 34% of AVCs and are associated with decreased survival. To evaluate the possibility that expression of Dpc4 may be correlated with survival, we analyzed 89 AVCs for inactivation of DPC4 by immunohistochemical staining. Thirty-seven cases showed no expression of Dpc4 (41%). Multivariate survival analysis was performed including age, sex, tumor size, histological subtype (intestinal or pancreatobiliary), grade of differentiation, T-stage, lymph-node metastases and Dpc4 status. T-stage and histological subtype were selected as independent prognostic factors, while Dpc4 immunostaining was not significantly associated with any clinicopathological variable, including histological subtype. Although Dpc4 expression is of no clinical relevance, its involvement in AVC gives additional weight to the hypothesis that, among all pancreatic exocrine and endocrine tumors, only AVC and common ductal adenocarcinomas have similar molecular fingerprints. Moreover, comparison of the frequencies of allelic loss on chromosomal arm 18q and the loss of Dpc4 expression (34% and 41%, respectively) is highly suggestive that DPC4 is the major target of these losses.
Factors influencing survival after resection for periampullary neoplasms. Bouvet M, Gamagami RA, Gilpin EA, Romeo O, Sasson A, Easter DW, Moossa AR. Department of Surgery and UCSD Cancer Center, University of California San Diego, San Diego, California, USA.	Am J Surg 2000 Jul;180(1):13-7 Abstract quote BACKGROUND: The purpose of this study was to determine predictors of survival after resection for periampullary neoplasms. METHODS: Over a 15-year period, 208 patients underwent laparotomy for periampullary neoplasms. Data were analyzed to assess predictors of survival. RESULTS: Pathologic examination showed pancreatic cancer (n = 136; 65%), ampullary cancer (n = 28; 13%), distal common bile duct cancer (n = 10; 5%), duodenal cancer (n = 4; 2%), neuroendocrine tumor (n = 11; 5%), cystadenocarcinoma (n = 4; 2%), cystadenoma (n = 5; 2%), and other (n = 10; 5%). A total of 129 patients underwent pancreatic resection (71 Whipples, 35 total pancreatectomies, 21 distal pancreatectomies, and 2 partial pancreatectomies) whereas 79 patients were found to be unresectable and underwent palliative bypass and/or biopsy. Median survival was 20.4 months for resectable patients versus 4.5 months for unresectable patients (P<0.001). Of the 129 resected patients, factors significantly (P<0.05) favoring long-term survival on univariate analysis included well-differentiated histology, common bile duct or ampullary adenocarcinoma, early stage, tumor diameter <2 cm, negative margins, and absence of lymph node metastases, perineural, or vascular invasion. Age, sex, race, and type of procedure had no influence on survival. On multivariate analysis, only tumor differentiation appeared independently related to survival. Using Kendall's tau analysis, tumor type and grade correlated significantly with all other predictors. CONCLUSIONS: Of all variables studied, tumor type and poor tumor differentiation in periampullary neoplasms appear to be markers that predict a constellation of other adverse findings.
Carcinoma of the ampulla of vater: determinants of long-term survival in 94 resected patients. Klempnauer J, Ridder GJ, Maschek H, Pichlmayr R. Clinic of Abdominal and Transplantation Surgery, Hannover Medical School, Germany.	HPB Surg 1998;11(1):1-11 Abstract quote This retrospective study details 94 patients after surgical resection of carcinoma of the ampulla of Vater to determine prognostic factors. The tumour was limited to the ampulla of Vater in 32%, invaded the duodenal wall in 34%, infiltrated 2 cm or less into the pancreas in 22%, and invaded more than 2 cm into the pancreas and/or other adjacent structures in 11%. Curative resection was accomplished in 97% of cases. After exclusion of perioperative deaths the 1-, 5- and 10-year survival rates were 79.6%, 38.2%, and 31.6%, respectively with a median survival of 3.68 years. 26 patients survived more than five and 15 patients more than ten years. In an univariate analysis advanced tumour size, poor tumour grading, lymph node metastases and advanced UICC stage significantly decreased survival. Comparison of short and long survivors confirmed tumour size, lymph node status and UICC stage as significant prognostic factors. In a multivariate analysis (Cox model), only tumour size was a statistically independent predictor of prognosis. The survival probability increased with each year a patient survived after resection. When a patient had already survived five years after resection, the probability to survive another five years was 83%. Careful clinicopathologic staging is important for the prognosis after resection.
BAX
Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma. Santini D, Tonini G, Vecchio FM, Borzomati D, Vincenzi B, Valeri S, Antinori A, Castri F, Coppola R, Magistrelli P, Nuzzo G, Picciocchi A. University Campus Bio-Medico University, Via Emilio Longoni, 83, 00155 Rome, Italy.	J Clin Pathol. 2005 Feb;58(2):159-65. Abstract quote   BACKGROUND: There is a lack of data in the literature concerning the identification of potential prognostic factors in ampullary adenocarcinoma. AIMS: To examine the prognostic significance of Bax, Bcl-2, and p53 protein expression and the apoptotic index in a large cohort of uniformly treated patients with radically resected ampullary cancer. METHODS: All patients with a pathological diagnosis of ampullary cancer and radical resection were evaluated. Expression analysis for p53, Bax, and Bcl-2 was performed by immunohistochemistry. Apoptotic cells were identified by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Thirty nine tumour specimens from patients with radically resected ampullary adenocarcinoma were studied. A positive significant correlation between Bax and p53 expression was found by rank correlation matrix (p < 0.001). A trend towards a positive correlation was found between the apoptotic index and p53 expression (p = 0.059). By univariate analysis, overall survival was influenced by Bax expression, p53 expression, and TUNEL staining (p = 0.001, p = 0.01, and p = 0.03, respectively). Bcl-2 expression did not influence overall survival in these patients (p = 0.55). By multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was Bax expression (p = 0.020). CONCLUSIONS: These results provide evidence that apoptosis may be an important prognostic factor in patients with radically resected ampullary cancer. This study is the first to assess the clinical usefulness of Bax expression in radically resected ampullary cancer.
METALLOPROTEINASES
Predictive value of lymph node and tumor matrix metalloproteinase expression in the analysis of metastatic periampullary tumors. McKenna GJ, Meneghetti A, Chen YL, Mui AL, Ong C, Scudamore CH, McMaster WR, Owen DA, Chung SW. Department of Surgery, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, British Columbia, Canada.	J Surg Oncol. 2005 Jun 15;90(4):239-46. Abstract quote   BACKGROUND AND OBJECTIVES: Matrix metalloproteinases (MMP) are endogenous peptidases capable of degrading various components of the basement membrane. The ability of malignant epithelial cells to degrade extracellular matrix and basement membrane is an important step in the process of metastatic invasion. In this study, we prospectively compared the outcome of patients undergoing laparotomy for resection of periampullary malignancies with lymph node and tumor MMP expression to determine if there was a correlation between metalloproteinase expression and patient outcome. METHODS: Sixteen patients undergoing operation were followed prospectively. Expression of MMP-2 and -9 and their inhibitors TIMP (tissue inhibitor of matrix metalloproteinase) -1 and -2 were measured in lymph node and tumor samples by semiquantitative PCR analysis. RESULTS: All patients who died from their disease process had significantly greater MMP-2 expression in their lymph nodes relative to TIMP-2 expression. In contrast, patients with prolonged disease-free survival had decreased nodal MMP-2/TIMP-2 expression (P = 0.001). Patients with relatively higher MMP-2/TIMP-2 expression in their tumors also had a worse prognosis (P = 0.06). CONCLUSION: The data demonstrate that the mRNA expression of MMPs and TIMPs in the draining lymph node of patients with periampullary adenocarcinomas may hold prognostic significance for patient survival. This prognostic information may be of use in patients when planning future adjuvant therapies.
METASTASIS
Patterns of lymph node metastasis in carcinoma of the ampulla of Vater. Yoshida T, Matsumoto T, Shibata K, Yokoyama H, Morii Y, Sasaki A, Kitano S. Department of Surgery I, Oita Medical University, Japan.	Hepatogastroenterology 2000 May-Jun;47(33):880-3 Abstract quote BACKGROUND/AIMS: Identification of lymph node metastasis may guide surgical therapy. The aim of this study was to clarify the lymphatic spread in ampullary carcinoma in relation to local tumor extent (pT category in the pTNM classification). METHODOLOGY: The distribution and number of lymph node metastases were histologically examined in 35 patients with ampullary carcinoma. RESULTS: Lymph node metastases were present in 10 of 15 patients (67%) with pT2 tumor and in 10 of 11 (91%) with pT3 tumor. Nodal involvement was not identified in 9 patients with pT1 tumor. The incidence of node-positive patients was higher in pT2 and pT3 tumors than in pT1 tumors (P < 0.01). The total number of positive nodes per node-positive patient was greater in pT3 tumors than in pT2 tumors (mean 3.50 vs. 1.30, P < 0.001). All node-positive patients had metastasis to the posterior pancreaticoduodenal node. The number of positive nodes per node-positive patient in both the posterior pancreaticoduodenal and the superior mesenteric region was greater in pT3 tumors than in pT2 tumors (P < 0.01 and P < 0.05). CONCLUSIONS: With increasing pT category in ampullary carcinoma, lymphatic spread extended from the posterior pancreaticoduodenal region to the superior mesenteric nodes.
PLOIDY
Ampullary carcinoma: prognostic significance of ploidy, cell-cycle analysis and proliferating cell nuclear antigen (PCNA). Crucitti A, Masetti R, Breccia C, Coppola R, Magistrelli P, Nuzzo G, Maggiano N, Picciocchi A. Department of General Surgery, Catholic University of the Sacred Heart, Rome, Italy.	Hepatogastroenterology 1999 Mar-Apr;46(26):1187-91 Abstract quote BACKGROUND/AIMS: The aim of the present study is to assess the nuclear DNA ploidy patterns, the fraction of cells in the various phases of the cell cycle as determined by flow cytometry and to evaluate Proliferative cell-nuclear antigen (PCNA) expression in order to examine the relationships between phase-two molecular factors, clinicopathological aspects and outcome of patients with cancers of the ampulla of Vater. METHODOLOGY: Paraffin-embedded specimens from 18 cases of cancers of ampulla of Vater radically resected between 1985 and 1995 were analyzed by flow-cytometry and immunohistochemical staining with monoclonal antibody to the PCNA. The relationships between cell-proliferation kinetics, PCNA-positive cancer cells, clinicopathological findings and the clinical course were evaluated. RESULTS: Pathologist reports documented 17 papillary adenocarcinomas and one case of mucinous carcinoma. According to the TNM classification, 4 patients were in stage I, 7 in stage II and 7 in stage III. Locally advanced ampullary tumors (T3-T4) had a significantly worse prognosis (p = 0.01); survival at 3 and 5 years for stage I-II patients (11 cases) was 90% and 79% as compared to 42% and 42% for patients with stage III (8 cases), respectively (p = n.s.). Thirteen cancers (72%) were diploid and 5 (28%) aneuploid. Patients with aneuploid tumors were younger (mean age: 59 years) than patients with diploid tumors (mean age: 66 years; p = 0.04). No significant correlation was found between size of the tumor (T), lymphnodal status (N), grading (G) or aneuploidy. Difference in terms of survival between aneuploid and diploid patients was relevant (16 vs. 121 months) but, due to the small number of cases, was not statistically significant (p = n.s). The mean value of S-phase fraction (SPF) was 14.8%. PCNA positive rate significantly correlates with size of the tumor (T1-T2 vs. T3-T4; p = 0.03). Actuarial overall survival resulted in 70%, 63% and 31% at 1, 5 and 10 years, respectively. The high rate of diploidy (72%) supports the relative benign behavior of ampullary cancers. CONCLUSIONS: PCNA positive rate significantly correlates with size of the disease. Aneuploidy, although without significant prognostic value, correlates well with survival. Because of the wide range of all variables, more data are needed to establish the relationships between pathological factors, DNA ploidy and PCNA rate and their significance as molecular predictors of prognosis in ampulla of Vater cancers.
REPLICATION ERROR PHENOTYPE
Cancers of the papilla of vater: mutator phenotype is associated with good prognosis. Achille A, Biasi MO, Zamboni G, Bogina G, Iacono C, Talamini G, Capella G, Scarpa A. Istituto di Anatomia Patologica, Universita di Verona, I-37134 Verona, Italy.	Clin Cancer Res 1997 Oct;3(10):1841-7 Abstract quote Cancer of the papilla (ampulla) of Vater is an uncommon disease that kills 60% of affected patients. There is general agreement that local spread of the tumor (T stage) is the only significant and independent prognostic factor for this cancer, whereas the predictive value of tumor grade and lymph node metastases is controversial. The genetic anomalies involved in this process have the potential to serve as additional prognostic markers. We explored 25 ampullary cancers for the occurrence of instability at simple repeat DNA sequences (microsatellites) of the type seen in replication error phenotype (RER-positive) cancers. Ten microsatellites from five different chromosomes were amplified by PCR from both normal and cancer tissue DNA of the same patients. A tumor was defined as RER-positive when microsatellite instability was found in the majority (>/=6) of the loci analyzed. Five cancers (20%) showed a RER phenotype and were associated with long survival of patients (32-96 months), whereas RER-negative cancers had a significantly poorer prognosis (Mantel-Cox test; P = 0.0084), with a median actuarial survival of 17 months. We also report that three (12%) patients belonged to cancer-prone families and four (16%) were cancer-prone individuals.

 

TREATMENT	CHARACTERIZATION
GENERAL	Surgical, dependent upon stage
Prognostic factors in patients with carcinoma of the papilla of Vater. Tanaka S, Hirohashi K, Tanaka H, Yamamoto T, Kubo S, Shuto T, Takemura S, Kinoshita H. Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.	Hepatogastroenterology 2002 Jul-Aug;49(46):1116-9 Abstract quote BACKGROUND/AIMS: The prognosis after curative resection for patients with carcinoma of the papilla of Vater is relatively better than that for other peripancreatic cancer. However, prognostic factors after resection of the carcinoma have not been identified. METHODOLOGY: From 1983 to 1999, 16 patients with carcinoma of the papilla of Vater underwent standard pancreatoduodenectomy and dissection of regional lymph nodes. We followed the patients for 63 days to 17 years (median, 27 months) and analyzed clinicopathologic variables in relation to prognosis. RESULTS: The survival rate at 5 years was 50.5%. The morphologic factors predicting poor outcome were macroscopic ulcer formation and microscopic pancreatic, venous, or perineural invasion. Tumors with ulcer formation tended to infiltrate into the duodenum and pancreas, but not into veins or the perineural space. Eight of 16 patients died due to recurrence of the cancer; liver metastasis (n = 6) or peritoneal dissemination (n = 2). CONCLUSIONS: Patients with carcinoma of the papilla of Vater demonstrating ulcer formation or invasion into the pancreas, vein, or perineural space may benefit from adjuvant therapy to reduce the risk of liver metastasis. Careful observation is essential for liver metastasis or peritoneal dissemination after surgery; especially in patients with ulcer formation or venous invasion.
CHEMOTHERAPY
Adjuvant chemoradiotherapy for "unfavorable" carcinoma of the ampulla of Vater: preliminary report. Mehta VK, Fisher GA, Ford JM, Poen JC, Vierra MA, Oberhelman HA, Bastidas AJ. Department of Radiation Oncology, Stanford University Medical Center, 300 Pasteur Dr, Stanford, CA 94305, USA.	Arch Surg 2001 Jan;136(1):65-9 Abstract quote HYPOTHESES: Adjuvant chemoradiotherapy decreases the risk of local recurrence in patients with adenocarcinoma of the ampulla of Vater and high-risk features. Adjuvant chemoradiotherapy for this population can be administered safely and without much morbidity. DESIGN: Controlled, prospective, single-arm study. SETTING: Tertiary care referral hospital. PATIENTS: From June 1995 to March 1999, 12 patients (7 men and 5 women; median age, 66 years; age range, 38-78 years) with "unfavorable" ampullary carcinoma were treated with adjuvant chemoradiotherapy. All patients underwent pancreaticoduodenectomy, and all pathologic findings were confirmed at Stanford University Medical Center, Stanford, Calif. Unfavorable features were defined as involved lymph nodes (n = 10), involved surgical margins (n = 1), poorly differentiated histological features (n = 3), tumor size greater than 2 cm (n = 6), or the presence of neurovascular invasion (n = 4). INTERVENTIONS: Four to 6 weeks after undergoing pylorus-preserving pancreaticoduodenectomy with regional lymphadenectomy, patients began adjuvant chemoradiotherapy consisting of concurrent radiotherapy (45 Gy) and fluorouracil by protracted venous infusion (225-250 mg/m(2) per day, 7 days per week) for 5 weeks. MAIN OUTCOME MEASURES: Local recurrence, distant recurrence, overall survival rate, and treatment-related toxic effects. RESULTS: All patients completed the prescribed treatment course. Toxic effects were assessed twice a week during treatment and graded according to the National Cancer Institute Common Toxicity Criteria Scale. One patient required a treatment interruption of 1 week for grade III nausea/vomiting. No grade IV or V toxic effects were observed. At median follow-up of 24 months (range, 13-50 months), 8 of 12 patients were alive and disease free. One patient was alive but had disease recurrence. Three patients died of this disease (liver metastases). Actuarial overall survival at 2 years was 89%, and median survival was 34 months. One surviving patient developed a local recurrence and a lung lesion. Actuarial overall survival and median survival were better than in a parallel cohort with resected high-risk pancreatic cancer (n = 26) treated with the same adjuvant chemoradiotherapy regimen (median survival, 34 vs 14 months; P<.004). CONCLUSIONS: Adjuvant chemoradiotherapy for carcinoma of the ampulla of Vater is well tolerated and might improve control of this disease in patients with unfavorable features.
DYSPLASIA IN ADENOMA
Impact of grade of dysplasia in villous adenomas of Vater's papilla. Heidecke CD, Rosenberg R, Bauer M, Werner M, Weigert N, Ulm K, Roder JD, Siewert JR. Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universitat Munchen, Ismaningerstrasse 22, 81675 Munich, Germany.	World J Surg 2002 Jun;26(6):709-14 Abstract quote Therapeutic strategies for villous adenoma of the papilla of Vater remain controversial. This study evaluates the accuracy of preoperative histopathologic diagnosis and the impact of the grade of dysplasia on recurrence as well as on potential alteration of the surgical approach. A series of 32 patients with an adenoma of Vater's papilla who underwent local resection or pylorus-preserving pancreaticoduodenectomy between January 1990 and August 2000 were reviewed retrospectively. Multiple endoscopic biopsies had been performed preoperatively. The histopathology of the preoperatively obtained biopsy specimens and subsequent surgical specimens were evaluated for grade of dysplasia by two pathologists and correlated with the clinical course after operative treatment. Altogether, 3 of 11 patients (27%) with a low-grade (LG) dysplasia adenoma and 6 of 21 patients (29%) with a high-grade (HG) dysplasia adenoma in the initial endoscopic biopsy specimens exhibited invasive carcinoma at the postoperative histologic examination (NS). Recurrence was not observed in the 6 patients from the LG dysplasia adenoma group following local resection and benign postoperative histology. In contrast, recurrence of villous adenoma was discovered in 2 of 12 patients (17%) and development of invasive carcinoma in 5 of 12 patients (42%) from the preoperative HG dysplasia group (p <0.05). The overall risk of carcinoma after primary diagnosis of an HG dysplasia adenoma was 44% (14/32). Adenoma of the papilla of Vater including HG dysplasia appears to be associated with a high risk of exhibiting invasive carcinoma postoperatively and a high rate of recurrence. Therefore pylorus-preserving pancreaticoduodenectomy should be offered to patients with an HG dysplasia adenoma.
SURGERY
Transduodenal ampullectomy in the treatment of villous adenomas and adenocarcinomas of the Vater's ampulla. [Article in English, Spanish] Fraguela Marina JA. General Surgery Department A, Complejo Hospitalario Universitario Juan Canalejo, A Coruna, Spain.	Rev Esp Enferm Dig. 2004 Dec;96(12):829-34. Abstract quote   INTRODUCTION: Adenomas are the most frequent tumors of the Vater s ampulla. Their capacity for malignant transformation following the adenoma-carcinoma sequence is well known. It is because of this that resection after diagnosis is required. The identification of the appropriate technique according to tumor features would require that patients not be undertreated or overtreated, which would give rise to serious consequences derived from their location. PATIENTS AND METHODS: Villous adenomas and adenocarcinomas of the Vater s ampulla candidates for local resection were revised from January 1st, 1998 through June 30th, 2003. We describe the methods of diagnosis and ampulectomy techniques we performed. RESULTS: We performed an ampulectomy by first intention in all 8 patients included in this study. However, pancreatoduodenectomy was necessary in two patients because of the closeness of resection margins. We had no mortality in this series, and morbidity was limited to two episodes of digestive bleeding that were controlled by electrocoagulation and embolization. The mean follow-up was 28.5 months (range, 6-72 months). CONCLUSIONS: The difficulty of precise preoperatory diagnosis in adenomas of the Vater s ampulla demands resection after identification. Ampulectomy is the treatment of choice for villous adenomas and T1 adenocarcinomas, with 1 cm of resection margin to avoid local recurrence.
Surgical management of neoplasms of the ampulla of Vater: local resection or pancreatoduodenectomy and prognostic factors for survival. de Castro SM, van Heek NT, Kuhlmann KF, Busch OR, Offerhaus GJ, van Gulik TM, Obertop H, Gouma DJ. Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.	Surgery. 2004 Nov;136(5):994-1002. Abstract quote   BACKGROUND: Neoplasms of the ampulla of Vater have a better 5-year survival than pancreatic and bile duct neoplasms after resection. This study was performed to analyze the outcome after local resection and pancreatoduodenectomy (PD) and to identify predictive factors for survival. METHODS: We used a prospective database to evaluate 145 patients (1992-2002) with a neoplasm of the ampulla of Vater. RESULTS: The median age of the entire cohort was 66 years. Agreement between preoperative biopsies and definite resection specimen was 58% for invasive adenocarcinoma. Local resection was performed in 25 patients, but the operation was adequate therapy in only 16 patients (64%). Subsequent PD (n=9) was performed in the remaining patients because of an R1 resection. Other patients (n=120) underwent an elective PD. Hospital mortality was 4.0% (1/25) after local resection and 5.0% (6/120) after PD. Multivariate analysis revealed that advanced invasion and nodal status were independent predictive factors for survival. The overall 5-year actuarial survival of patients with adenocarcinoma after PD was 37%. CONCLUSIONS: Preoperative biopsies have a poor diagnostic accuracy. Local resection is an adequate surgical treatment for adenomas. In experienced hands, PD is the preferred treatment for patients with adenocarcinoma.
New reconstructive surgery of remnant pancreas in cases of cancer of Vater's papilla. Arkossy P, Toth P, Kovacs I, Sapy P. 2nd Department of Surgery, University Medical School of Debrecen, Moricz Zs. Krt. 22, 4004 Debrecen, Hungary.	Hepatogastroenterology 2002 Jan-Feb;49(43):255-7 Abstract quote BACKGROUND/AIMS: The radical surgical procedure for treatment of the carcinoma of papilla of Vater is the pancreatoduodenectomy. The mortality rate of the surgery highly decreased in the last decade, nevertheless there are complications related to the complication of anastomosis of the remnant pancreas. METHODOLOGY: The authors introduce a new reconstructional procedure to decrease the complications. After the removal of the pancreatic head and body an end-to-side anastomosis was performed between the pancreatic duct and a Roux-en jejunal loop. The second anastomosis of the procedure was an end-to-side choledochojejunostomy, the third was an end-to-side duodenojejunostomy. The duodenojejunostomy is about 40 cm from the pancreatic anastomosis, keeping food far from the pancreas with the help of peristaltic waves. This method was applied in 6 patients. RESULTS: It was found that the new reconstructional procedure had generally favorable results without complication. CONCLUSIONS: This method of reconstruction allows for spontaneous closure and safe drainage of potential insufficient pancreaticojejunostomy. The recovered patients support future favorable usage of this new reconstructional surgical procedure.
Ampullectomy of carcinoma of the papilla of vater in an elderly patient without jaundice. Hamazaki K, Sakai H, Amano T, Ichiki K, Hamada H, Yamauchi T. Department of Surgery, Kurashiki Medical Center, Japan.	Hiroshima J Med Sci 2000 Sep;49(3):139-44 Abstract quote A 79 year-old woman was admitted to Aioi City Hospital for a closer examination of hepatic dysfunction. A filling defect was observed at the distal end of the intrapancreatic common bile duct by computed tomography combined with drip infusion cholangiography. The diagnosis of adenoma with dysplasia at the papilla of Vater was obtained by a biopsy performed during duodenoscopy. As a result, we performed an ampullectomy. Histologic examination revealed a papillary adenocarcinoma which partly extended just beyond the muscle of Oddi. The patient made an uneventful recovery and was discharged on the 35th postoperative day. Here, based upon our experience, we discuss such problems as the accuracy of preoperative diagnosis and the indications for ampullectomy.

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