Prognostic Significance of Growth Pattern in Predicting Outcome of Opisthorchis viverrini-Associated Distal Cholangiocarcinoma in Thailand

Abstract

Distal cholangiocarcinoma (dCCA) is a rare type of CCA in Asia, even in Opisthorchis viverrini-prevalent Northeastern Thailand. The clinical ambiguity and imprecision of diagnosis surrounding this malignancy result in high mortality due often to advanced/metastatic disease on presentation. We aim to identify a prognostic factor that can improve the performance stratification and influence the outcome of dCCA patients after curative resection. A total of 79 patients who underwent curative-intended surgery for dCCA was enrolled. Possible risk factors for survival were analyzed with log-rank test, and independent factors with Cox regression model. dCCA patients were staged and classified according to the 8th edition the American Joint Committee on Cancer (AJCC) Staging Manual. Results were then compared with the revised classification employing the prognostic factor identified from multivariate analysis. Multivariate analysis revealed that growth pattern (p < 0.01) and distant metastasis (p = 0.012) were independent factors. Growth patterns comprise intraductal (ID), periductal infiltrating (PI), mass-forming (MF), and mixed types. When dCCA patients were grouped into those having good and poor outcomes (with and without ID components, respectively). The survival outcomes significantly differed among patients with and without ID components, which was better than with the 8th AJCC staging system in our cohort. Furthermore, Chi-square test showed that patterns without ID components (PI, MF, PI + MF) correlated with lymph node and distant metastasis. Therefore, classification of dCCA patients after curative-intended surgical resection based on growth pattern provides additional beneficial information for the prediction of survival in dCCA patients.

Prognostic significance of tumor-infiltrating lymphocytes in predicting outcome of distal cholangiocarcinoma in Thailand

“…Numerous reports have documented that dCCA appears more frequently in Western countries and North America, accounting for approximately 30% of all CCAs (8,9). In contrast, the incidence rate is low in Southeast Asia; however, about 10% of all CCAs occur in Thailand (6,7) with approximately 8% in our cohort (10). Most patients with dCCA have poor outcomes (latestage and short survival time) due to advanced disease at presentation with lymph node and distant metastasis (11).…”

“…In addition, some cohorts may have smaller number of patients leading to reduced stratification performance. Therefore, prognostic factors are proposed to replace or improve the eighth AJCC staging system (10,17,(34)(35)(36)(37)(38). Bolm et al investigated the correlation of cancer biomarkers, especially serum carbohydrate antigen 19-9 (CA19-9), with the survival of patients with dCCA.…”

“…The growth pattern estimation criteria were applied according to a previous report by Kunprom et al. ( 10 ). The resection specimens were trimmed and photographed with the tumor growth pattern/s recorded at the time of grossing, followed by subsequent histological confirmation.…”

“…Surgery is usually the first choice for palliative treatment, whereas chemotherapy and radiotherapy are the secondary options ( 12 ). The 5-year survival time and rate are approximately 17–20 months and 10%–25%, respectively ( 7 – 10 , 13 , 14 ). There is, therefore, an urgent need to improve the clustering of patients with dCCA for precise prognostication and management.…”

“…Some studies have demonstrated, particularly in dCCA, that the AJCC/UICC staging system is not satisfactory to classify patients, resulting in ambiguities in each staging. Hence, several prognostic factors, such as growth pattern ( 10 ), histological grade ( 15 , 16 ), and cancer markers ( 17 ), have been applied to predict the outcome of patients with CCA or improve the staging system for accurate classification.…”