Neuroendocrine differentiation in extrahepatic bile duct carcinomas and its prognostic significance.

Neuroendocrine differentiation is known to be one of the prognostic factors in many carcinomas. However, the characteristics of neuroendocrine differentiation are not well elucidated in extrahepatic bile duct (EBD) carcinomas. One hundred ninety-four cases of EBD carcinomas were analyzed using immunohistochemistry with synaptophysin and chromogranin. The tumors were graded as degree 0, 1, and 2 when the positive tumor cells were 5% or less, 6% to 25%, and 26% or more, respectively. Immunohistochemical results were compared with clinicopathologic variables and survival rate. Synaptophysin and chromogranin were positive in 54 (27.8%) and 74 (38.1%) cases, respectively. Thirty-four cases (17.5%) were positive for both synaptophysin and chromogranin, 20 (10.3%) and 40 cases (20.6%) were positive only for synaptophysin and for chromogranin, respectively, and 100 cases (51.6%) were negative for both markers. There was a significant survival difference between overall synaptophysin-positive (median, 27 months) and synaptophysin-negative (38 months) groups (P < .05). However, there was no survival difference between chromogranin-positive and chromogranin-negative groups. There was a significant survival difference between the dual-positive expression to synaptophysin and chromogranin group (median, 21 months) and the dual-negative expression group (median, 35 months; P < .05). In summary, synaptophysin expression was an important prognostic factor because synaptophysin-positive cases showed a worse prognosis than synaptophysin-negative cases. The more tumor cells expressed chromogranin, the poorer the survival. Therefore, immunohistochemical studies for neuroendocrine differentiation may be helpful in routine pathological examinations for evaluating the survival and the prognosis of patients with EBD carcinomas.

Superficial vs deep pancreatic parenchymal invasion in the extrahepatic bile duct carcinomas: a significant prognostic factor.

Pancreatic invasion of the extrahepatic bile duct (EBD) carcinomas is known to have a poor outcome. We hypothesized that EBD carcinoma showing shallow invasion to the pancreas may have a better outcome than the usual deep pancreatic invasion. We divided 87 cases of the distal EBD carcinomas into superficial and deep pancreatic invasion groups according to degrees of the pancreatic invasion. The superficial pancreatic invasion group included cases with tumor abutting the pancreatic lobule or pancreatic parenchymal invasion equal to or less than 1 mm from the uppermost portion of the pancreatic lobule or tumors invading into the fibroadipose tissue between pancreatic lobules without parenchymal invasion. The deep invasion group consisted of tumors with more than 1 mm pancreatic parenchymal invasion. The cases with superficial pancreatic invasion showed significantly better survival rate than those with deep pancreatic invasion (P<0.001). Therefore, we recommend that a specific remark on the pathology report about the presence or absence of parenchymal invasion and the depth of invasion of the pancreas is required for managing patients and determining the prognosis. We also recommend that the current pT3 stage of distal EBD carcinomas be subdivided into superficial (pT3a) and deep pancreatic invasion (pT3b).

Analysis of extrahepatic bile duct carcinomas according to the New American Joint Committee on Cancer staging system focused on tumor classification problems in 222 patients.

BACKGROUND: Although the sixth edition of the American Joint Committee on Cancer (AJCC) staging system for extrahepatic bile duct carcinoma was updated, the system has a problem on T classification due to its ambiguous definition of T1 as "tumor confined to bile duct histologically" and T2 as "tumor invading beyond the bile duct." METHODS: The authors considered the outermost part of the muscle layer or fibrous tissue as within the extrahepatic bile duct and considered the area starting from large clusters of adipose tissue as beyond the extrahepatic bile duct. After designing a precise definition of the extrahepatic bile duct wall, they analyzed the new AJCC staging system in 222 patients with of extrahepatic bile duct carcinomas. Then, other clinicopathologic variables for prognosis were evaluated using univariate and multivariate analyses. RESULTS: The 5-year survival rates for patients with tumors that were classified as T1, T2, T3, and T4 were 53.1%, 29.7%, 24.9%, and 0%, respectively. There was a significant difference in survival between patients with T1 tumors and T2 tumors (P < 0.05), but not between patients with T2 tumors and T3 tumors. Significant prognostic factors included depth of invasion (P < 0.005), lymph node metastasis (P < 0.005), and patient age (P < 0.05). CONCLUSIONS: Based on a proposed histologic definition, depth of invasion was practical for evaluating the prognosis of patients with middle and upper extrahepatic bile duct carcinomas. Therefore, the authors recommended changing the current pT1 and pT2 classifications to more precise pathologic terminology.