Neuroendocrine carcinoma of the ampulla of Vater:a clinicopathologic evaluation

BACKGROUND:Only 105 cases of neuroendocrine tumor(NET)of the ampulla of Vater have been described, mostly as single case reports.The incidence of NET is rising.The changes in incidence may result from changes in detection.This study was to determine the relative incidence and clinicopathological characteristics of high- grade neuroendocrine carcinoma(small cell carcinoma and large cell carcinoma)of the ampulla of Vater at a single institution. METHODS:Sections from paraffin blocks of tumors of the ampulla of Vater taken from 45 patients who underwent Whipple’s procedure and 6 patients who underwent palliative bypass between September 2003 and January 2007 were subjected to immunohistochemical analysis.The clinical and pathological data from 5 patients diagnosed with NET of the ampulla of Vater were analyzed. RESULTS:The patients were 3 men and 2 women,ranging in age from 39 to 47 years(mean 44 years).Operative procedures included Whipple’s procedure in 4 patients and palliative bypass in 1 patient.Histopathological examination revealed large-cell neuroendocrine carcinoma in 2 patients,small cell carcinoma in 2,and carcinoid in 1.Three patients with high-grade neuroendocrine carcinoma who had undergone Whipple’s procedure died at postoperatively 7,11,and 13 months.The patient who had undergone palliative triple bypass died 3 months after surgery.CONCLUSIONS:The relative incidence of high-grade neuroendocrine carcinomas of the ampulla of Vater is higher than that generally expected.The tumors behave aggressively and have a dismal prognosis despite aggressive treatment.

Mucins in neoplasms of pancreas,ampulla of Vater and biliary system

Tumors of the pancreas,the ampulla of Vater,and the extrahepatic and intrahepatic bile ducts have significant histological similarities due to the common embryonic origin of the pancreatobiliary system.This obviates the need for discovery of biomarkers with diagnostic and prognostic value for these tumors.Mucins,especially MUC-1,-2,-4 and-5AC,are important candidates for developing into such reliable biomarkers.Increased expression of MUC1 occurs in pancreatic ductal adenocarcinomas and is associated with increased degrees of dysplasia in pancreatic intraepithelial neoplasia(Pan IN).Positive expression of MUC2 in intraductal papillary mucinus neoplasms(IPMN) of the intestinal type indicates high potential progression to invasive carcinoma with de novo expression of MUC1,while absence of MUC2 expression in IPMNs of gastric type implies low potential to malignant evolution.De novo MUC4 expression correlates to the severity of dysplasia in Pan IN and is associated with a poor prognosis in patients with pancreatic ductal adenocarcinomas.In biliary intraepithelial neoplasia(Bil IN),increased expression of MUC1 is associated with higher degrees of dysplasia.Intrahepatic cholangiocarcinomas(ICC) are characterized by increased expression of all glycoforms of MUC1.Positive MUC2 expression in intraductal papillary neoplasm of the bile ducts(IPNB) of the intestinal type indicates high malignant potential with de novo expression of MUC1 in the invasive element.Absent MUC2 expression in any degree of Bil IN may prove useful in differentiating them from IPNB.De novo expression of MUC4 is associated with poor prognosis in patients with ICC or carcinoma of the extrahepatic bile ducts(EHBDC).High de novo expression of MUC5 AC is found in all degrees of Bil IN and all types of IPNB and ICC.The MUC5 AC is useful in the detection of neoplastic lesions of the bile duct at an early stage.Increased expression of mucin MUC1 in carcinoma of the ampulla of Vater associated with unfavorable behavior of the tumor,such as lymph node metastasis,infiltration of the pancreas and duodenum,advanced TNM classification and worse prognosis.Patients withintra-ampullary papillary-tubular neoplasm(IAPN) of the pancreatobiliary immunophenotype did not show MUC2,while those of the intestinal immunophenotype are MUC2 positive.The expression of MUC4 is associated with poor prognosis in patients with carcinoma of the ampulla of Vater favoring metastasis and making them resistant to apoptosis.Moreover,it appears that MUC4 positivity correlates with recurrence of the tumor.Expression of MUC5 AC is associated with the invasive potential of the tumor.

Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer

BACKGROUND Currently,there is no standard adjuvant therapy for patients with resected ampulla of Vater(AoV)cancer.AIM To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy(CCRT)in patients with advanced AoV cancer who underwent curative resection.METHODS This single-centered,retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and 2018.The impact of CCRT on advanced AoV cancer was analyzed.RESULTS The 1-,3-,and 5-yr recurrence-free survival(RFS)rates for patients with advanced AoV cancer were 82.8%,48.3%,and 40.8%,respectively,and the overall survival(OS)rates were 89.7%,62.1%,and 51.7%,respectively.Lymphovas-cular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis,whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate analysis.Compared to the patients who did not receive adjuvant CCRT,those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS,although they had a significantly lower average age and significantly higher platelet-to-lymphocyte ratio.CONCLUSION Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV cancer.These findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

Comparison of mismatch repair and immune checkpoint protein profile with histopathological parameters in pancreatic,periampullary/ampullary,and choledochal adenocarcinomas

BACKGROUND Pancreatic,periampullary/ampullary,and choledochal adenocarcinomas are aggressive malignancies with a poor prognosis.Immune checkpoint blockade is a promising treatment option for several tumor types.H long terminal repeatassociating 2(HHLA2),which is analogous to programmed death-ligand 1(PDL1),is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many malignancies.AIM To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to immunotherapy.METHODS Ninety-two adenocarcinoma cases located in the pancreas,ampulla,and distal common bile duct were identified.This study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and 2021.Immunohistochemistry was conducted to examine the expression of DNA mismatch repair(MMR),PD-L1,and HHLA2 proteins.RESULTS Patients with high HHLA2 expression had a higher mean age than those with low expression.Low HHLA2 expression was associated with high perineural invasion.HHLA2 expression was low in pathological stage T3(pT)3 cases and high in pathological stage T1,T2,and T4 cases.There was no correlation between HHLA2 expression and the expression of MMR proteins and PD-L1.CONCLUSION Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.

Rare histological subtype of invasive micropapillary carcinoma in the ampulla of Vater: A case report

BACKGROUND Carcinoma of the ampulla of Vater is an uncommon ampullo-pancreatobiliary neoplasm,and the most common histological type is adenocarcinoma with a tubular growth pattern.Invasive micropapillary carcinoma(IMPC)is an aggressive variant of adenocarcinoma in several organs that is associated with lymph node metastasis and poor prognosis.IMPC was first described as a histological subtype of breast cancer;however,IMPC of the ampulla of Vater is extremely rare,with only three articles reported in the English literature.CASE SUMMARY We have reported a case of IMPC of the ampulla of Vater in an 80-year-old man.Microscopically,the surface area of the carcinoma was composed of tubulopapillary structures mimicking intra-ampullary papillary-tubular neoplasm,and the deep invasive front area exhibited a pattern of IMPC.The carcinoma showed lymphatic invasion and extensive lymph node metastasis.The immunohistochemical study revealed mixed intestinal and gastric/pancreatobiliary phenotypes.CONCLUSION This rare subtype tumor in the ampulla of Vater showed a histologically mixed phenotype and exhibited aggressive behavior.

Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma

BACKGROUND Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater(AoV) carcinoma is limited.AIM To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival(DFS) rates than cases of observation following curative surgery.METHODS We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival(OS) in patients with stage IB-Ⅲ AoV carcinoma who underwent curative surgical resection. Fluorouracil-based adjuvant chemotherapy was administered after surgery at the discretion of the physician. Adjusted multivariate regression models were used to evaluate the association between adjuvant chemotherapy and survival outcomes.RESULTS Of the total 104 patients who underwent curative surgery, 52 received adjuvant chemotherapy. Multivariate analysis revealed that higher histologic grade [hazard ratio(HR) = 2.24, P = 0.046], advanced tumor stage(HR = 1.85, P = 0.030), and vascular invasion(HR = 2.14, P = 0.010) were associated with shorter DFS. Adjuvant chemotherapy improved DFS compared to the observation group(HR =0.50, P = 0.015) and tended to be associated with a longer OS, although the difference was not statistically significant(HR = 0.58, P = 0.098).CONCLUSION Among patients with resected AoV carcinoma, the adjuvant chemotherapy group was not associated with a significant survival benefit compared to the observation group. However, on multivariate analysis adjusting for prognostic factors, adjuvant chemotherapy following surgery was an independent prognostic factor for DFS in patients with resected AoV carcinoma. Further studies are needed to investigate the effectiveness of adjuvant chemotherapy according to histologic phenotype.

Ectopic pancreas at the ampulla of Vater diagnosed with endoscopic snare papillectomy: A case report and review of literature

BACKGROUND Ectopic pancreas is a rare developmental anomaly that results in a variety of clinical presentations.Patients with ectopic pancreas are mostly asymptomatic,and if symptomatic,symptoms are usually nonspecific and determined by the location of the lesion and the various complications arising from it.Ectopic pancreas at the ampulla of Vater(EPAV)is rare and typically diagnosed after highly morbid surgical procedures such as pancreaticoduodenectomy or ampullectomy.To our knowledge,we report the first case of confirmed EPAV with a minimally invasive intervention.CASE SUMMARY A 71-year-old male with coronary artery disease,presented to us with new-onset dyspepsia with imaging studies revealing a‘double duct sign’secondary to a small subepithelial ampullary lesion.His hematological and biochemical investigations were normal.His age,comorbidity,poor diagnostic accuracy of endoscopy,biopsies and imaging techniques for subepithelial ampullary lesions,and suspicion of malignancy made us acquire histological diagnosis before morbid surgical intervention.We performed balloon-catheter-assisted endoscopic snare papillectomy which aided us to achieve en bloc resection of the ampulla for histopathological diagnosis and staging.The patient’s post-procedure recovery was uneventful.The en bloc resected specimen revealed ectopic pancreatic tissue in the ampullary region.Thus,the benign histopathology avoided morbid surgical intervention in our patient.At 15 mo follow-up,the patient is asymptomatic.CONCLUSION EPAV is rare and remains challenging to diagnose.This rare entity should be included in the differential diagnosis of subepithelial ampullary lesions.Endoscopic en bloc resection of the papilla may play a vital role as a diagnostic and therapeutic option for preoperative histological diagnosis and staging to avoid morbid surgical procedures.

Trends in incidence and management of cancer of the ampulla of Vater

AIM: To provide trends in incidence, management and survival of cancer of the ampulla of Vater in a well-defined French population.

Ampullary neuroendocrine tumor diagnosed by endoscopic papillectomy in previously confirmed ampullary adenoma

Ampullary adenoma is a common indication for endoscopic papillectomy. Ampullary neuroendocrine tumor(NET) is a rare disease for which complete surgical resection is the treatment of choice. However, because of the morbidity and mortality associated with surgical resection, endoscopic papillectomy is increasingly used in selected cases of low grade, with no metastasis and no invasion of the pancreatic or bile duct. Also, confirmed and complete endoscopic resection of ampullary NET accompanied by adenoma has not been reported to date. We report herein a rare case of an ampullary NET accompanied with adenoma, which was successfully and completely resected via endoscopic papillectomy. Prior to papillectomy, this case was diagnosed as an ampullary adenoma.

Impact of periampullary diverticula on the outcome and fluoroscopy time in endoscopic retrograde cholangiopancreatography

BACKGROUND: It is unclear whether the presence of periampullary diverticula (PAD) affects technical success and complication rates during endoscopic retrograde cholangio- pancreatography (ERCP). Moreover, the impact of PAD on fluoroscopy duration is still unknown. The present study aimed to investigate the success rate and difficulty of common bile duct (CBD) cannulation, post-procedure complications and fluoroscopy duration in patients with and without PAD. METHODS: Patients from January 2008 to December 2010 with PAD (group A) and without PAD (group B) and similar indications for therapeutic ERCP were prospectively compared. The comparison included patient characteristics, findings of ERCP, and details of procedure and fluoroscopy time. The influence of papilla’s location with respect to the diverticulum on procedure was also investigated. RESULTS: A total of 428 consecutive patients who had undergone therapeutic ERCP for similar indications were divided in two groups according to the presence (group A, 107 patients) or absence (group B, 321 patients) of PAD. The mean age and ASA score of the patients with PAD were significantly higher than those patients without PAD. The main indication was choledocholithiasis. Successful final CBD cannulation was achieved in 97.20% of the patients in group A vs 99.69% in group B (P=0.05). CBD diameter, number of stones and the largest stone size were significantly higher in group A thangroup B (P【0.001). Complete clearance of the CBD after the first attempt was achieved in 85.86% and 94.75% of the patients in groups A and B, respectively (P=0.03). In both groups, the time needed to complete the procedure and fluoroscopy time was significantly longer in patients with PAD (22.87 vs 18.99 minutes, P【0.001; 76.51 vs 47.42 seconds, P【0.001). There was no significant difference between the two groups in the complication rate. The type of papilla’s location with respect to the diverticulum did not influence the total cannulation rate and post-procedure complications. CONCLUSION: The presence of a PAD does not affect the success rate and complications of therapeutic ERCP in expert hands; however, the fluoroscopy time is significantly longer in patients with PAD.

KL-6 mucin expression in carcinoma of the ampulla of Vater: Association with cancer progression

AIM： To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater. METHODS： Ampullary carcinoma tissues were collected from 38 patients who underwent pancreatoduodenectomy or local resection. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS： Positive staining of ampullary carcinoma cells was observed in 26 （68.4%） cases. Staining was not found in the surrounding non-cancer regions of the ampullary tissues. Remarkable KL-6 expression was observed in invasive carcinoma cells in pancreatic and duodenal tissues and in metastatic carcinoma cells in lymph nodes. Positive KL-6 expression was related to lymph node metastasis （P = 0.020）, pancreatic invasion （P = 0.016）, duodenal invasion （P = 0.034）, and advanced stage of TNM clinical classification （P = 0.010）. Survival analysis showed that positive expression of KL-6 was related to a poorer prognosis （P = 0.029）. CONCLUSION： The aberrant expression of KL-6 mucin is significantly related to unfavorable behaviors of cardnoma of the ampulla of Vater.

Prognostic relevance of number and ratio of metastatic lymph nodes in resected carcinoma of the ampulla of Vater

Objectives： To explore the prognostic relevance of the number and ratio of metastatic lymph nodes in resected Carcinoma of the ampulla of Vater （CAV）. Methods： The clinical data of 155 patients who underwent pancreaticoduodenectomy （PD） for cancer of the ampulla of Vater between January 1990 and December 2010 were retrospectively analyzed. Kaplan- Meier method was used in survival analysis and Log rank method in comparison. Multivariate analysis was performed using Cox proportional hazards model. Results： Among these 155 patients, the in-hospital mortality rate was 4.5%, lymph node positive disease was 21.3%, and the 5-year survival rate was 51.6%. Patients with a lymph node ratio （LNR） 〉20% were more likely to have tumor differentiation, depth of duodenal involvement, depth of pancreatic invasion, T-stage and TNM-Stage. The number of the metastatic lymph nodes is important prognostic factors of the CAV. Univariate analysis showed that the factors associated with the prognosis included tumor size （P=0.036）, tumor differentiation （P=0.019）, LNR （P=0.032）, mtmber of metastatic lymph nodes （P=0.024）, lymph node metastasis （P=0.03）, depth of pancreatic invasion （P=0.001）, T-stage （P=0.002）, TNM stage （P=0.001）, elevated CA 19-9 （P=0.000）, and jaundice （P=0.021）. Multivariate analysis showed that the factors associated with the prognosis were the number of metastatic lymph nodes （P=0.032; RR： 1.283; 95% CI： 1.022-1.611）, tumor size （P=0.043; RR： 1.736; 95% CI： 1.017-2.963）, and elevated CA 19-9 （P=0.003; RR： 3.247; 95% CI： 1.504-7.010）. Conclusions： LNR is a useful factor for predicting the prognosis of the radical treatment for CAV,, whereas the number of metastatic lymph nodes is the most important factor. Further research on the locations, number, and LNR will be clinically meaningful to improve survival in patients with CAV.

Coexistence of small cell neuroendocrine carcinoma and villous adenoma in the ampulla of Vater

Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an adenocarcinoma. Their coexistence has been rarely reported in the literature. We herein describe an unusual case of a small cell neuroendocrine carcinoma associated with a villous adenoma in the ampulla of Vater with emphasis on computed tomography (CT) and histopathological findings. We also discuss their clinical, histopathological and radiological features as well as possible histogenesis.

Melanoma in the ampulla of Vater

BACKGROUND:The most common tumors in the ampulla of Vater are adenocarcinomas.Although malignant melanoma usually occurs on the skin,it can also arise in the gastrointestinal and biliary tract.METHOD:We present a case of a 52-year-old,previously healthy man who presented with painless jaundice.RESULTS:Clinical examination revealed dilated intrahepatic and extrahepatic bile ducts and pancreatic duct due to the obstructive mass in the ampulla of Vater.The patient underwent pancreaticoduodenectomy and histopathological diagnosis of the resected tumor mass was malignant melanoma.Thorough clinical examination was preformed,but no other primary or metastatic site of melanoma could be found.In the next few months,the patient developed multiple liver metastases and died.CONCLUSION:An isolated amelanotic lesion in the ampulla of Vater can be a potential diagnostic pitfall,especially in patients who have had melanoma.

Gastrointestinal stromal tumor of the ampulla of Vater:A case report

Gastrointestinal stromal tumors (GISTs) usually develop in the stomach and small intestine and only rarely occur at the ampulla of Vater, with only 11 cases reported in the literature. We report a case of a GIST of the ampulla of Vater. A 36-year-old, previously healthy man presented with a loss of consciousness lasting a few minutes. A gastroduodenal endoscopy revealed a submucosal tumor with central ulceration at the ampulla of Vater. The enhanced computed tomography scan revealed a smooth-outlined hypervascular solid mass (24 mm × 30 mm) in the second part of the duodenum. Neither lymphadenopathy nor metastasis was observed. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed normal bile and pancreatic ducts. Biopsies were collected from the ulcerative lesion, and the tumor was diagnosed as a GIST. A submucosal tumor with central ulceration may be a characteristic form of GISTs of the ampulla of Vater, and biopsy studies are useful for the diagnosing such tumors. The patient underwent pancreatoduodenectomy, and the operative specimen revealed a 2.2-cm GIST with 1 mitosis per 50 high-power fields. The gold standard for treatment of GISTs is surgical resection without rupture of a capsule. If technically possible, local resection may be considered. However, when the location of the lesion presents challenges, a pancreatoduodenectomy should be performed for GIST of the ampulla of Vater.

A rare case of periampullary carcinoma with ectopic ending of Vater's ampulla

A 71-year-old woman was referred to our department complaining of painless progressive jaundice for the last 3 too. Magnetic resonance imaging and magnetic resonance cholangiopancreatography （MRCP） showed the ectopic hepatopancreatic ampulla draining into the fourth part of the duodenum adjacent to the duodenojejunal flexure; the irregular morphology of the duodenojejunal flexure likely due to a soft tissue mass. Laparotomy confirmed the presence of the abnormal ampulla of Vater located at the fourth part of the duodenum and a soft tissue tumor about 6 cm × 5 cm×5 cm with a peduncle adjoining the ampulla. Resection of the tumor, including some peripheral tissue, and a Roux-Y loop anastomosis choledochojejunostomy were performed. Pathological examination indicated an intestinal villous adenoma accompanied by severe dysplasia and focal canceration. Periampullary carcinoma with ectopic ending of the Vater＇s ampulla into the fourth part of the duodenum is rather rare. The embryonic genetic background of this anomaly has not yet been fully explained. It is worth mentioning that MRCP is useful for demonstrating anomalies and anatomic variants of the biliary tract system and pancreatic duct.

Endoscopic ultrasound in the papilla and the periampullary region

Endoscopic ultrasound (EUS) provides relevant information when an ampullary or periampullary tumor is suspected.Early detection, T and N staging and Fine Needle Aspiration plus cithologic confirmation, are some of the expected benefits. Exclusion of benign findings like choledocholithiasis or chronic pancreatitis is also important. A correct understanding of the complex ampullary and periampullary anatomy is needed. Knowledge of the individual clinical history and other previous diagnostic images all contribute to a successful EUS examination. Radial and lineal EUS images are uniquely detailed and, at the moment, it seems to be the best way to exclude or confirm malignant or benign findings. We propose a procedural algorithm, including EUS,for suspected ampullary or periampullary tumors. This review summarizes the vast amount of information to be found spread in the literature, and recognizes this small anatomic area as the origin for a clinical entity with proper clinical presentation, proper imaging and proper therapeutic resolutions. The benefits of performing EUS for its study are highlighted.

Amiodarone hepatotoxicity complicating obstructive jaundice due to ampullary cancer

BACKGROUND:The presence of dual pathology can cause diagnostic dilemmas. We present a case of adenocarcinoma of the ampulla of Vater with concurrent amiodarone hepatotoxicity. METHODS:Painless jaundice associated with a palpable gallbladder was investigated clinically,radiologically endoscopically and via liver biopsy. RESULTS:Liver biopsy showed amiodarone hepatotoxicity Endoscopic biopsy identified an ampullary adenoma However,the endoscopic ultrasound and intra-operative findings suggested a malignancy,which was confirmed postoperatively. CONCLUSIONS:While the classic findings of Courvoisier’s Law are borne out in this case,the etiology of jaundice is twofold. Although dual pathology is uncommon it should always be considered.

Signet-ring cell carcinoma of ampulla of Vater:Contrast-enhanced ultrasound findings

Signet-ring cell carcinoma(SRCC) of ampulla of Vater is extremely uncommon,and less than 15 cases have been reported so far in literature.It mainly occurs in elderly people(median age 57 years).We report a rare case of SRCC of the ampulla of Vater in a 38-year-old woman who presented with a small tumor at the Vater,discovered by the contrast-enhanced ultrasound(CEUS).Histopathological examination showed prominent signet-ring features.We also describe the imaging features of SRCC of ampulla of Vater in CEUS.

miR-215 overexpression distinguishes ampullary carcinomas from pancreatic carcinomas

Distinguishing ampullary carcinoma from pancreatic carcinoma is important because of their different prognoses. microRNAs are differentially expressed according to the tissue of origin. However, there is rare research on the differential diagnosis between the two types of cancers by microRNA in periampullary cancers. The present study was undertaken to compare microRNA profiles between ampullary and pan- creatic carcinomas using microarrays, miR-215 was most significantly overexpressed in ampullary carcinomas; whereas the expressions of miR-134 and miR-214 were significantly lower in ampuUary carcinomas than in pancreatic carcino- mas. When these discriminatory microRNAs were applied to liver metastases, they were correctly predicted for the tissue of origin. Although this study is limited by small sample size, striking difference in microRNA expression and concordant expression of discriminating microRNAs in primary tumors and metastases suggest that these novel discriminatory mi- croRNAs warrant future validation.