Prognostic implications of immune classification using IDO1 expression in extrahepatic bile duct carcinoma.

Indoleamine 2, 3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme that catalyzes the degradation of tryptophan to kynurenine and induces immune tolerance in tumor cells. The effects of IDO1 on extrahepatic bile duct carcinoma (EHBDC) are poorly understood. Therefore, the present study aimed to investigate the expression and prognostic significance of IDO1 in EHBDC. An immunohistochemical microarray analysis of IDO1 expression was performed for 76 surgically resected cases of EHBDC. CD8+ tumor infiltrating lymphocytes (TILs) were also investigated through a combination analysis with IDO1 expression. IDO1 was highly expressed in 25 of 76 (32.9%) cases. High expression of IDO1 was associated with decreased numbers of CD8+ TILs (P=0.008), a higher pN category (P=0.007), an advanced overall stage (P=0.001) and frequent recurrence (P=0.018). When IDO1 expression was further stratified with CD8+ TIL state, the IDO1high/CD8low subgroup was decreased in terms of overall survival (P=0.025) and disease-free survival (P=0.015) compared with IDO1high/CD8high, IDO1low/CD8high and IDO1low/CD8low subgroups. High IDO1 expression was associated with a decreased number of CD8+ TILs and associated with a poor prognosis. As IDO1 may be a new target of immunotherapy applications, IDO1/CD8+ TIL subgrouping can be a useful prognostic and predictive tool in patients with EHBDC.

Novel Biomarker Panels Discriminating between Pancreatic Ductal Adenocarcinoma and Extrahepatic Bile Duct Carcinoma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic bile duct carcinoma (EBDC) are distinct entities with different clinicopathological implications. Therefore, research to differentiate between the two diseases is compulsory. In this study, four biomarkers were selected (Hippocalcin-like 1 (HPCAL1); annexin A10 (ANXA10); MUC5AC; sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)) and focus was placed on clarifying the diagnostic performance of each biomarker and pioneering novel-combined biomarker panels to discriminate between PDAC and EBDC. PROCEDURES: An immunohistochemical microarray analysis of HPCAL1, ANXA10, MUC5AC, and ATP1B1 was conducted for surgically resected 55 PDACs and 77 EBDCs. The diagnostic performance discriminating between PDAC and EBDC was evaluated using four biomarkers and the combined biomarker panels. RESULTS: PDACs exhibited more positive expressions for HPCAL1, ANXA10, and MUC5AC, whereas EBDCs exhibited more ATP1B1-positive expressions. The PDAC panel with the best diagnostic performance was the profile of (+ in ≥ 2 among HPCAL1, ANXA10, MUC5AC)/ATP1B1-. The immunophenotype pattern of (- in ≥ 1 among HPCAL1, ANXA10, MUC5AC)/ATP1B1+ is the EBDC panel with the most excellent discriminating power. CONCLUSION: The suggested combined biomarker panels demonstrate the distinguishing diagnostic ability between PDAC and EBDC is better than previous studies. Therefore, for differentiation between PDAC and EBDC, these panels are expected to help unravel the clinicopathological enigma as promising biomarker panels in the future.

Castleman disease of the abdomen--single-center experience of 13 surgically treated patients over 11 years.

BACKGROUND/AIMS: Castleman disease (CD) is a lymphocytic hyperplastic disease, also known as angiofollicular lymphoid hyperplasia and giant lymph node hyperplasia, which rarely occurs in the abdomen. We analyzed the clinical manifestations in 13 patients treated surgically at our center for abdominal CD lesions. METHODOLOGY: We retrospectively reviewed the medical records of 13 patients with abdominal CD who underwent surgery at our institution in the 11-year period from January 1998 to May 2009. RESULTS: Of the 13 patients, 8 were women; their mean +/- SD age was 47.1 +/- 12.0 years. CD was incidentally found in seven patients with no symptoms. Only 3 patients were preoperatively suspected of CD, with 10 suspected of other diseases. Twelve of the 13 patients (92.3%) underwent excisional surgery, with 11, 1 and 1 undergoing R0, R1, and R2 resections, respectively. Eleven tumors were hyaline vascular type and two were plasma cell type. After a mean follow-up of 63.3 months, only one patient showed recurrence, but this patient remains progression-free 7 years after repeat resection. CONCLUSIONS: Abdominal CD is a rare disease that is often misdiagnosed due to the absence of specific clinical manifestations. Definitive diagnosis requires histologic examination of the surgical specimen. Excisional surgery is the method of choice for unicentric abdominal CD, and is associated with a low incidence of recurrence.