A Case of Metastatic Ampulla of Vater Carcinoma Masked Under Recurrent Acute Pancreatitis: A Diagnostic Challenge.

The ampulla of Vater is a small opening located at the point where bile and pancreatic ducts join and empty their secretions into the small intestine. Ampullary cancers are rare but aggressive malignancies that can present with symptoms similar to those of acute pancreatitis, including abdominal pain, nausea, vomiting, and obstructive jaundice. Clinicians must rely on a combination of blood tests, imaging, and biopsies to diagnose ampullary cancer, which may be a hidden cause of acute pancreatitis. In this report, we present the case of a 66-year-old female who presented to our hospital with recurrent admissions due to abdominal pain, nausea, and vomiting. The patient was found to have repeated episodes of acute pancreatitis and was later diagnosed with cancer of the ampulla of Vater. This case proved extremely complex and diagnostically challenging.

Clinicopathological Prognostic Factors and Chemotherapeutic Outcome for Two Histopathological Types of Ampulla of Vater Adenocarcinoma.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AAV) is standardly treated using a complex operation, a pancreatoduodenectomy (PD), to remove the tumor. However, dicision-making in AAV clinical treatment remains difficult due to the broad range of AAV types, outcomes, and responses to special chemotherapeutics. Thus, this study aimed to explore clinicopathological prognostic factors associated with overall survival, as well as post-chemotherapeutic effects related to curative resection of AAV. METHODS: We retrospectively reviewed data for clinicopathological outcome of 47 patients diagnosed with AAV that had underwent a PD. Overall survival probabilities were obtained using the Kaplan-Meier estimate method and a Cox proportional hazards model. RESULTS: Forty-five patients underwent LPD (laparoscopic pancreatoduodenectomy) and two patients underwent PD. The patient group was composed of 31 males (66%) and 16 females (34%) with a mean age of 65(34-91)years. We selected 45 patients for long-term survival analysis. One- and three-year overall survival rates after resection were 97.6% and 58.9% respectively. The median survival was 37.7 months for the intestinal-type and 26.9 months in pancreatobiliary-type ampullary tumors. Serum carbohydrate antigen (CA) 19-9 greater than 37 U/ml (HR 0.140, P = 0.007), perineural invasion (HR 0.141, P = 0.003), and classification as pancreatobiliary-type (HR 6.633, P = 0.006) were independently associated with poor survival. Serum carcinoembryonic antigen (CEA) greater than 5 µg/ml (P = 0.031), serum CA 19-9 greater than 37 U/ml (P = 0.002), tumor sizes greater than 2.5cm (P=0.002), and positive perineural invasion (P=0.003) were all associated with a poor prognosis in the histopathological subgroup. Serum CA 19-9 greater than 37 U/ml (P=0.002) and positive perineural invasion (P=0.001) were significantly associated with poor survival in of patients with intestinal-type ampullary tumors. Serum CEA greater than 5 µg/ml (P=0.013) and tumor sizes greater than 2.5cm (P=0.002) were significantly associated with poor survival in patients with pancreatobiliary-type ampullary tumors. CONCLUSIONS: Pancreatobiliary-type ampullary tumors were associated with poor survival. Serum CA 19-9 in the intestinal-type and CEA in the pancreatobiliary-type were significantly associated with poor survival. Ajuvant chemotherapy could not predict the survival of AAV patients.

High-Mobility Group Box 1 expression predicts survival of patients after resection of adenocarcinoma of the ampulla of Vater.

BACKGROUND: Expression of High-Mobility Group Box 1 (HMGB1), a multifunctional protein involved in DNA function as well as cell proliferation, inflammation, and the immune response, has been reported to be prognostic in several types of malignancies. However, the prognostic value of HMGB1 in ampullary cancer has not been studied. METHODS: Patients with adenocarcinoma of the ampulla of Vater who underwent R0 resection with pancreaticoduodenectomy between 2001 and 2011 were included in the present multi-institutional study. The degree of HMGB1 expression was examined in each resected specimen by immunohistochemical staining. RESULTS: A total of 101 patients were enrolled of which, 79 patients were eligible. High expression of HMGB1 was observed in 31 (39%) patients. Blood loss, transfusion, tumor stage, nodal status, and HMGB1 expression were identified as predictors with univariate analysis. Multivariate analysis showed that transfusion, lymph-node metastasis, and high HMGB1 expression were independent predictors of poor overall survival. Subgroup analysis showed that high HMGB1 expression was predictive, especially in patients who did not receive adjuvant chemotherapy. CONCLUSIONS: High HMGB1 expression is an independent predictor of poor prognosis in patients with adenocarcinoma of the ampulla of Vater not treated with adjuvant chemotherapy.

Distinct immunological properties of the two histological subtypes of adenocarcinoma of the ampulla of Vater.

Adenocarcinoma of the ampulla of Vater (AOV) is classified into intestinal type (IT) and pancreatobiliary type (PB); however, the immunological properties of these subtypes remain to be characterized. Here, we evaluated the clinical implications of PD-L1 expression and CD8+ T lymphocyte density in adenocarcinomas of the AOV and their potential association with Yes-associated protein (YAP). We analyzed 123 adenocarcinoma-of-the-AOV patients who underwent surgical resection, and tumors were classified into IT or PB type. Tumor or inflammatory cell PD-L1 expression, CD8+ T lymphocyte density in the cancer cell nest (intratumoral) or in the adjacent stroma, and YAP localization and intensity were analyzed using immunohistochemical staining. PB-type tumors showed higher tumoral PD-L1 expression than IT-type tumors, and tumoral PD-L1 expression was associated with a shorter disease-free survival (DFS) [hazard ratio (HR), 1.77; p = 0.045] and overall survival (OS) (HR 1.99; p = 0.030). Intratumoral CD8+ T lymphocyte density was higher in IT type than in PB type and was associated with a favorable DFS (HR 0.47; p = 0.022). The nuclear staining pattern of YAP in tumor cells, compared to non-nuclear staining patterns, was more frequently associated with PB type and increased tumoral PD-L1 expression. Nuclear YAP staining was a significant prognostic factor for OS (HR 2.21; p = 0.022). These results show that the two subtypes of adenocarcinoma of the AOV exhibit significant differences in tumoral PD-L1 expression and intratumoral CD8+ T lymphocyte density, which might contribute to their distinct clinical features.

Exceptional Response to Nanoparticle Albumin-Bound Paclitaxel and Gemcitabine in a Patient with a Refractory Adenocarcinoma of the Ampulla of Vater.

Ampullary carcinoma is a rare tumor and evidence on the treatment of recurrent metastatic disease is scarce. We report the case of a 60-year-old patient with an R0-resected node-positive adenocarcinoma of the papilla of Vater of an initially diagnosed intestinal subtype who developed pulmonary metastases 2 months after adjuvant gemcitabine chemotherapy and, subsequently, liver metastases. Palliative combination chemotherapy with standard regimens for intestinal-type adenocarcinoma (FOLFOX and FOLFIRI) failed. However, subsequent combination chemotherapy with nanoparticle albumin-bound paclitaxel and gemcitabine, a regimen with proven efficacy in metastatic adenocarcinoma of the pancreas, resulted in a durable, very good partial remission. Treatment was manageable and well tolerated. Primary tumor and metastatic tissue were reassessed by immunohistochemistry and had to be reclassified to a mixed phenotype containing predominant elements of the pancreatobiliary subtype. Our case suggests that combination chemotherapy with nanoparticle albumin-bound paclitaxel and gemcitabine could represent a promising option for the treatment of this rare disease and warrants further investigation within controlled clinical trials. Moreover, thorough characterization of ampullary carcinomas by histomorphology and additional immunohistochemistry should become mandatory in order to start a chemotherapeutic regimen tailored for the definitive subtype.

Sensibilidad y especificidad del CA 19-9 para el diagnóstico de neoplasias pancreatobiliares en pacientes con ictericia de origen obstructivo / Sensitivity and specificity of CA-19-9 for the diagnosis of pancreatobiliary neoplasms in patients with obstructive-origin jaundice

Objetivo: Describir el comportamiento biológico del CA 19-9 en colestasis para determinar su utilidad para el diagnóstico de cáncer pancreatobiliar en pacientes con ictericia de origen obstructivo. Sede: Hospital General de México, O.D. Diseño: Prospectivo, longitudinal y comparativo. Análisis estadístico: prueba t y Kolmogorov-Smirnov para muestras independientes; prueba de valor diagnóstico (sensibilidad, especificidad y valor global). Se realizó análisis con curvas ROC para identificar sensibilidad y especificidad con los diferentes puntos de corte. Pacientes y métodos: Se incluyeron 54 pacientes con diagnóstico de ictericia de origen obstructivo. Se dividieron en dos grupos de acuerdo al diagnóstico final, enfermedad maligna vs enfermedad benigna. Se realizó determinación sérica de CA 19-9 al ingreso y al resolver la colestasis y se correlacionaron los niveles con el diagnóstico final. Resultados: En pacientes ictéricos, con un punto de corte de 60 U/mL para distinguir entre enfermedad maligna y benigna, el CA 19-9 tiene una sensibilidad de 80% y una especificidad de 90%. Una vez resuelta la colestasis con punto de corte de 39 U/mL se obtiene una sensibilidad de 71% con una especificidad de 96%. La normalización del marcador después del drenaje biliar es altamente sugerente de patología benigna. La persistencia de niveles elevados (mayores de 60 U/mL) es altamente sugerente de malignidad con una sensibilidad de 58% y especificidad de 100%. Conclusiones: La colestasis sí modifica la sensibilidad y especificidad del CA 19-9 para el diagnóstico de neoplasias malignas pancreatobiliares, por lo que en presencia de ictericia de origen obstructivo el punto de corte de 60 U/mL ofrece una sensibilidad de 80% con una especificidad de 90% para distinguir entre enfermedad benigna y maligna. Una vez resuelta la colestasis, la persistencia de niveles elevados es altamente sugerente de malignidad.

Objective: To describe the biological behavior of the tumor marker CA 19-9 in cholestasis to determine its usefulness for the diagnosis of pancreatobiliary cancer in patients with obstructive-origin jaundice. Sede: General Hospital of Mexico, third level health care center. Mexico City. Design: Prospective, longitudinal, and comparative study. Statistical analysis: T and Kolmogorov Smirnov tests for independent samples; diagnostic value test (sensitivity, specificity, and global value). Analysis with ROC curves was performed to identify sensitivity and specificity at the different cutting points. Patients and methods: We included 54 patients with a diagnosis of obstructive-origin jaundice. They were divided in two groups according to the final diagnosis, malignant disease vs. benign disease. Serum CA 19-9 was determined at admittance and once cholestasis had been resolved, and the levels were correlated with the final diagnosis. Results: In jaundice patients, with a cut point of 60 U/mL to distinguish between malignant and benign disease, the CA 19-9 marker has a sensitivity of 80% and a specificity of 90%. Once cholestasis had been resolved with a cut point of 39 U/mL, sensitivity was of 71% with a 96% specificity. Normalization of the marker after bile drainage is highly suggestive of benign pathology. The persistence of high levels (higher than 60 U/mL) is highly suggestive of malignancy with a sensitivity of 58% and specificity of 100%. Conclusions: Cholestasis does modify the sensitivity and specificity of the CA 19-9 marker for the diagnosis of pancreatobiliary malignant neoplasms; therefore, in the presence of obstructive-origin jaundice, the 60 U/mL cut point offers a sensitivity of 80% with a specificity of 90% to be able to distinguish between malignant and benign disease. Once cholestasis has been resolved, persistence of high levels is highly suggestive of malignancy.

A Case of Synchronous Double Cancer: Klatskin's Tumor and Ampullary Adenocarcinoma / 대한소화기내시경학회지

Multiple cancers in the extrahepatic biliary tree are relatively rare. Many such cases are a double cancer of the common bile duct and the gallbladder. We report a case of a double primary cancer that occurred synchronously at the hilum of the extrahepatic duct and the ampulla of Vater with a review of the relevant literature. A 57-year-old man was admitted to our institution after a 15 day of painless jaundice and a urine color change. Ultrasonography showed a dilation of both intrahepatic ducts. Upper endoscopy revealed a protruding ulcerative mass at the ampulla of Vater and endoscopic retrograde cholangiography showed a dilated common bile duct and a mildly dilatated pancreatic duct, but both intrahepatic bile ducts were not visualized. An upper abdominal CT scan showed a dilation of both intrahepatic bile ducts and an infiltrating mass at the bifurcation area. Magnetic resonance cholangiopanreatography showed narrowing bile duct lumen that was obstructed by the tumor at the hepatic duct bifurcation, which dilated both intrahepatic ducts. A histological examination of the ampulla of Vater revealed a well differentiated adenocarcinoma of the ampulla of Vater. The final diagnosis was a synchronous double cancer of Klatskin's tumor and an adenocarcinoma of the ampulla of Vater.