ObjectiveMorbidity and mortality involved in the resection of hilar cholangiocarcinoma were reviewed retrospectively. The clinicopathologic and laboratory parameters that might influence the patient's survival also were re-evaluated. Summary Background DataAlthough much progress has been made in the diagnosis and management of hilar cholangiocarcinoma, long-term outlook for most patients remains poor. Surgical resection is usually prohibited because of its local invasiveness, and most patients can only be managed by palliative drainage. Recently, many surgeons have adopted a more aggressive resection with varying degrees of success. Several prognostic factors in bile duct carcinoma have been proposed; however, no reports have specifically focused on resected hilar cholangiocarcinoma and its prognostic survival factors using multivariate analysis. MethodsThe clinical records and pathologic slides of 49 cases with resected hilar cholangiocarcinoma were reviewed retrospectively. Twenty clinical and laboratory parameters were evaluated for their correlation with postoperative morbidity and mortality, whereas 31 variables were evaluated for their significance with postoperative survival. Variables showing statistical significance in the first univariate analysis were included in the following multivariate analysis using stepwise logistic regression test for factors affecting morbidity and mortality and Cox stepwise proportional hazard model for factors influencing survival. ResultsThere were 5 in-hospital deaths, and the cumulative 5-year survival rate in 44 patients who survived was 14.9%, with a median survival of 14.0 months. Multivariate analysis disclosed that co-existent hepatolithiasis and lower serum asparate aminotransferase levels (<90 U/L) had a significant low incidence of postoperative morbidity, whereas a serum albumin of less than 3 g/dL was the only significant factor affecting mortality. Regarding survival, univariate analysis identified eight significant factors: 1) total bilirubin 210 mg/dL, 2) curative resection, 3) histologic type, 4) 384

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Large HCC had specific clinicopathological features. In selected patients, resection is safe and offers the chance of long-term disease-free survival.

Berberine is the major constituent of Coptis chinese and is commonly used in Chinese herbal medicine to treat patients with gastrointestinal disorders. In this study, using flow cytometry, we have found that a 24-h berberine treatment up-regulated the multidrug-resistant transporter (pgp-170) expression in two oral (KB, OC2), two gastric (SC-M1, NUGC-3) and two colon (COLO 205, CT 26) cancer cell lines. Decreased retention of rhodamine 123 was observed in berberine-treated cells as compared to vehicle control. To examine whether the berberine modulated pgp-170 expression in cancer cells is associated with changes in drug resistance, we determined the cytotoxicity, cell cycle progression and cell morphology of Paclitaxel-treated cells. Paclitaxel (1 n M –10 μ M ) treatment for 24 h induced cytotoxicity in OC2, SC-M1 and COLO 205 cells in a dose-dependent manner. Pretreatment of cells with 32 μ M berberine for 24 h prior to Paclitaxel treatment resulted in increased viability as compared to that of Paclitaxel-treated cells. In addition, Paclitaxel-induced apoptosis and/or G2/M arrest in these three cancer cell lines. Pretreatment of cells with berberine prior to Paclitaxel blocked the Paclitaxel-induced cell cycle responses and morphological changes. These results together suggest that berberine modulated the expression and function of pgp-170 that leads to reduced response to Paclitaxel in digestive track cancer cells. © 1999 Cancer Research Campaign

BackgroundImmune checkpoint inhibitors (ICIs) are promising agents for unresectable hepatocellular carcinoma (uHCC), but lack effective biomarker to predict outcomes. The gut microbiome can modulate tumor response to immunotherapy, but its effect on HCC remains unclear.MethodsFrom May 2018 to February 2020, patients receiving ICI treatment for uHCC were prospectively enrolled; their fecal samples were collected before treatment. The fecal microbiota and metabolites were analyzed from 20 patients with radiology-proven objective responses (OR) and 21 randomly selected patients with progressive disease (PD). After March 2020, 33 consecutive Child-Pugh-A patients were recruited as a validation cohort. Additionally, feces from 17 healthy volunteers were collected for comparison of background microbes.ResultsA significant dissimilarity was observed in fecal bacteria between patients with OR and patients with PD before immunotherapy. Prevotella 9 was enriched in patients with PD, whereas Lachnoclostridium, Lachnospiraceae, and Veillonella were predominant in patients with OR. Ursodeoxycholic acid and ursocholic acid were significantly enriched in the feces of patients with OR and strongly correlated with the abundance of Lachnoclostridium. The coexistence of Lachnoclostridium enrichment and Prevotella 9 depletion significantly predicted better overall survival (OS). In the validation cohort, better progression-free survival (PFS) and OS were noted in patients who had a preferable microbial signature in comparison with counter-group (PFS: 8.8 months vs 1.8 months; OS: not reached vs 6.5 months, both p<0.001).ConclusionsFecal microbiota and bile acids were associated with outcomes of immunotherapy for uHCC. These findings highlight the potential role of gut microbiota and metabolites as biomarkers to predict outcomes of ICI-treated HCC.