Objective To investigate the regulatory effect of somatostatin analogue (SMS201995,SMS) on proliferation and apoptosis in human cholangiocarcinoma cell line in vitro. MethodsProliferation curve, flow cytometry, agarose gel electrophoresis, Annexin VFITC and flow cytometric immunofluorescent technique were performed to identify the inhibitory effect on cell proliferation and the induction of apoptosis of human cholangiocarcinoma cells (SKChA1). ResultsSMS significantly reduced the SKChA1 cell growth by serum in long experiments and transiently accumulated it in G0/G1 phase. Dotplot analysis of cells duallabeled with Annexin VFITC and PI confirmed the induction of apoptosis by SMS in SKChA1 cells.AnnexinVFITC labeling was markedly enhanced following treatment with SMS for 24 h. DNA of treated SKChA1 cells appeared a ladder pattern characteristic of apoptosis. Besides, timedependent increase in bax and decrease in bcl2 occured during SMS treatment. Conclusion SMS could inhibit the proliferation activity and induce apoptosis of cholangiocarcinoma cell line SKChA1. The mechanisms of apoptosis might be correlated with the expression of apoptosisregulatory gene bax and bcl2.
ObjectiveTo investigate the expression of forkhead box A2 (FXOA2) in intrahepatic cholangiocarcinoma (ICC), and to analyze the relationship between expression of FOXA2 and patient's prognosis after liver resection. MethodsData of 85 patients with ICC who underwent liver resection between 2009 and 2013 in our hospital were collected retrospectively. The expression of FOXA2 was examined by immunohistochemical method, and then the relationship between expression of FOXA2 and patient's prognosis/clinical characteristics was expplored. ResultsAmong the 85 patients, low expression of FOXA2 was detected in 50 patients, whereas high expression was observed in 35 patients. More advanced tumor (Ⅲ+Ⅳ staging) was found in patients with low expression of FOXA2 than patients with high expression of FOXA2 (P < 0.050). The median follow-up time was 15-month (3-73 months). During the follow-up period, 65 patients suffered from recurrence, whereas 64 patients died. The multivariate analysis suggested that, postoperative recurrence was associated with low expression of FOXA2, evaluated preoperative CA19-9, and presence of satellite nodes (P < 0.050). Low expression of FOXA2, evaluated preoperative CA19-9, nerves invasion, and presence of satellite nodes were predictive factors for postoperative prognosis (P < 0.050). ConclusionLow expression of FOXA2 was associated with poor prognosis for patients with ICC after liver resection, and FOXA2 may be a prognostic factor for ICC.
ObjectiveTo investigate the value of diffusion weighted imaging (DWI) combined with three-dimensional volumetric interpolated breath-hold examination (3D-VIBE) in evaluating metastatic lymph nodes secondary to hilar cholangiocarcinoma. MethodsFrom July 2009 to March 2011, DWI examination was performed in 37 patients with hilar cholangiocarcinoma, which was compared with 3D-VIBE sequences. The morphological characteristics and distribution were analyzed for metastatic and nonmetastatic lymph nodes. Signal intensity (SI) was measured on DWI images and apparent diffusion coefficient (ADC) was calculated for each lymph node. The SI of lymph nodes (SILN） and liver (SIliver) were also measured and the ratio of SI was calculated. The ADC and the ratio of SI were compared between metastatic and nonmetastatic lymph nodes. ResultsThere were fifty-nine groups of lymph nodes in 37 patients with hilar cholangiocarcinoma, fifty-one groups were revealed in both DWI and 3D-VIBE sequences, and eight groups were only demonstrated in one sequence (P=0.070). The short diameters were (1.05±0.42) cm and (0.78±0.22) cm on 3D-VIBE images for metastatic and nonmetastatic lymph nodes, respectively (P=0.030). The ADC value in metastatic lymph nodes was (1.64±0.3)×10-3 mm2/s, which was significantly lower than that in nonmetastatic lymph nodes 〔(2.28±0.79)×10-3 mm2/s〕 on DWI images (P=0.033). There were no significant differences in SILN/SIliver between metastatic and nonmetastatic lymph nodes on images of portal venous phase and 3 min delayed contrast-enhanced phase. ConclusionsDifferences of ADC and short diameter can provide valuable information to differentiate metastatic lymph nodes with nonmetastatic lymph nodes. When combined with 3D-VIBE sequence, DWI is more effective in evaluating metastatic lymph nodes secondary to hilar cholangiocarcinoma.
ObjectiveTo explore the clinicopathological characteristics of combined hepatocellular and cholangiocarcinoma (cHCC-CC), and the prognostic factors associated with survival. MethodesThe clinical features of 31 patients with cHCC-CC from 1995 to 2010 in West China Hospital of Sichuan University underwent liver resection were analyzed retrospectively. The prognostic factors were analyzed by using univariate and multivariate analysis. ResultsOf these 31 patients, 25 men and 6 women, with a median age of 58 years, underwent liver resection for cHCC-CC. Twentythree cases (74.2%) showed positive of hepatitis B surface antigen (HBsAg), 13 cases (41.9%) had elevated AFP≥20μg/L, 18 cases (58.1%) with liver cirrhosis, 8 cases (25.8%) showed presence of lymph node metastases. The 1-, 3-, and 5-year overall survival rates of these patients were 61.3%, 32.3%, and 12.9%, respectively. Univariate analysis showed that invasion of portal vein, microscopic tumor thrombi, positive resection margins, and lymph node involvement were significant prognostic factors. Multiple analysis revealed the positive resection margins and lymph node involvement were independent prognostic factors for overall survival. ConclusionsThe prognosis of patients with cHCC-CC is poor. R0 resection is the only available treatment in curing these patients.
ObjectiveTo explore the feasibility and safety of modified semi-ex vivo small intestinal autotransplantation (IAT) in patients with distal cholangiocarcinoma (CC) involving mesenteric root. MethodThe clinicopathologic data of the patient with relapse after CC surgery admitted to Sichuan Provincial People’s Hospital on October 2022 were retrospectively analyzed. ResultsThe patient was a 40 years old male. The preoperative imaging showed that the superior mesenteric artery (SMA) and jejunal artery was surrounded by the tumor. The preoperative condition was good and the heart, lung, liver, and kidney functions were normal. The patient could tolerate surgery, then the modified semi-ex vivo IAT was performed. The patient recovered well after surgery and discharged on the 14th postoperative day. The postoperative pathological diagnosis result showed that it was CC. The patient was well and without recurrence or metastasis during following-up in the outpatient service for 5 months until April 2023. ConclusionsFrom the retrospective analysis of this case, it can be realized that the modified semi-ex vivo IAT for patients with tumor involving themesenteric root, it is safe and feasible. A treatment option can be provided for such patient.
Objective To summarize the multi disciplinary team (MDT) discussion in the treatment of intrahepatic cholangiocarcinoma (ICC) involving inferior vena cava (IVC). Method The clinical data of a difficult ICC patient diagnosed and treated in Gansu Provincial Hospital in September 2020 were analyzed retrospectively, and the clinical features, diagnosis, treatment decision and prognosis of ICC were summarized. Results The patient was initially diagnosed as liver malignant tumor, which invaded the right adrenal gland and inferior vena cava. After MDT discussion, the patient decided to undergo surgical treatment, and successfully underwent radical resection of liver tumor combined with right adrenal gland and partial inferior vena cava and vascular reconstruction. The operation lasted 300 minutes, and the intraoperative bleeding was about 600 mL. The results of postoperative pathological examination indicated that it conformed to ICC, and carcinomatous tissues involvement could be seen in inferior vena cava and adrenal gland. The patient had no complication after operation and was discharged from hospital at 2 weeks after operation. The patient had been followed up for half a year and had been regularly treated with gemcitabine combined with platinum for 6 phases. No tumor recurrence or metastasis had been found. Conclusions The onset of ICC is concealed and its invasiveness is strong. The preliminary diagnosis can be determined by imaging examination combined with detection of tumor markers. Radical surgery is the main treatment. After MDT discussion, the formulation of a comprehensive treatment plan, including surgical strategy, local treatment and systemic treatment, can improve the prognosis and prolong the survival time of patients.
ObjectiveTo detect the expressions of takeda G protein-coupled receptor 5 (TGR5) and mortalin protein 75 in the tissues of patients with intrahepatic cholangiocarcinoma (ICC), and to explore their relationship with prognosis.MethodsA total of 94 ICC patients who were admitted to Anyang District Hospital and received surgical treatment from March 2015 to March 2018 were selected as the research objects. The expressions of TGR5 and mortalin protein 75 in ICC cancer tissues and adjacent tissues were detected by immunohistochemistry and Western blot (WB). The relationship between the expressions of TGR5 and mortalin protein 75 in ICC cancer tissues and clinicopathological parameters and prognosis was analyzed. Multivariate Cox proportional hazards regression was used to analyze the risk factors of poor prognosis in patients with ICC. ROC curve was used to analyze the diagnostic value of TGR5 and mortalin protein 75 for poor prognosis in patients with ICC.ResultsImmunohistochemical results showed that the positive expression rates of TGR5 and mortalin protein 75 in cancer tissues were significantly higher than those in adjacenttissues (P<0.05). WB results showed that the protein expression levels of TGR5 and mortalin protein 75 in cancer tissues were significantly higher than those in adjacent tissues (P<0.05). The expression of TGR5 protein in cancer tissues of ICC patients was correlated with gender, tumor diameter, degree of differentiation, TNM staging, satellite focus, and liver cirrhosis (P<0.05). The expression of mortalin protein 75 was correlated with tumor diameter, TNM staging, nerve involvement, satellite focus, and liver cirrhosis (P<0.05). There were significant differences in gender, tumor diameter, TNM staging, microvascular invasion, satellite focus, liver cirrhosis, and the expressions of TGR5 and mortalin protein 75 between the poor prognosis group and the good prognosis group (P<0.05). The cumulative 3-year overall survival rate of TGR5 positive patients (32.00%) was significantly lower than that of TGR5 negative patients (63.16%), χ2=6.228, P=0.013; the cumulative 3-year overall survival rate of mortalin protein 75 positive patients (32.91%) was significantly lower than that of mortalin protein 75 negative patients (66.67%), χ2=6.079, P=0.014. Multivariate Cox proportional hazards regression analysis showed that the positive expression of TGR5 and mortalin protein 75, TNM Ⅲ+Ⅳphase, satellite focus, and cirrhosis were risk factors for poor prognosis in ICC patients (P<0.05). ROC results showed that when the expression level of TGR5 was 0.932 as the cut-off value, its AUC in the diagnosis of poor prognosis of ICC patients was 0.783, the sensitivity was 72.4%, the specificity was 72.2%; when the expression level of mortalin protein 75 was 0.756 as the cut-off value, its AUC in the diagnosis of poor prognosis of ICC patients was 0.805, the sensitivity was 84.4%, the specificity was 63.9%; the AUC of combined diagnosis of TGR5 and mortalin protein 75 was 0.884, the sensitivity was 79.3%, the specificity was 83.3%.ConclusionsThe high expressions of TGR5 and mortalin protein 75 in cancer tissues of ICC patients are associated with poor prognosis, and they are risk factors for poor prognosis. The combined detection of TGR5 and mortalin protein 75 has a certain value in predicting poor prognosis, and can be used as potential biological indicators.
At present, the application of extended radical surgery in hilar cholangiocarcinoma (hCCA) remained controversial. The author reviewed the relevant literatures published in recent years and combined with his own experience, preliminarily discussed the application value of extended radical surgery in hCCA, and believed that: for some strictly selected cases of hCCA, under the premise of ensuring patient safety, extended radical surgery was an important treatment method for hCCA patients to obtain R0 removal, and the survival status of patients was better than that of palliative surgery, but the indications need to be strictly mastered. For patients with hCCA, whether to adopt extended radical surgery and the specific scope of surgical resection should be based on the scope of lesions and the involved organs, tissues and blood vessels to implement an individualized surgical program on the premise of comprehensive evaluation and full preparation before surgery. Do not blindly carry out extended radical surgery.
ObjectiveTo summarize the incidence, patterns and laws of perineural invasion, and explore the path and the influencing factors of perineural invasion in hilar cholangiocarcinoma. MethodsA clinicopathologic study was conducted on sections from 52 patients with hilar cholangiocarcinoma to summarize the incidence and patterns of perineural invasion. The relationship of perineural invasion to lymph node metastasis, serum CA19-9, CEA, total bilirubin (TBIL) level, Bismuth-Corllet classification, or tumor penetration depth of bile duct walls was analyzed by association analysis. ResultsThe overall incidence of perineural invasion was 90.38% (47/52). However, the incidences of perineural invasion had no significant differences among various differentiated adenocarcinoma groups (P > 0.05). The incidences of perineural invasion were not correlated with the lymph node metastasis, serum CA19-9, CEA, TBIL level, and Bismuth-Corlette classification (P > 0.05), which was correlated with the tumor penetration depth of bile duct walls (P < 0.01). There were four patterns of perineural invasion, sequenced them according their incidences from high to low as follows: typeⅡ> typeⅢ> typeⅣ> typeⅠ. The pattern of perineural invasion was correlated with the degree of tumor differentiation (χ2=31.04, P < 0.01). ConclusionsThe incidence of perineural invasion is very high in hilar cholangiocarcinoma. The patterns of perineural invasion are similar in the same patient, and a variety of invasion patterns might coexist. While the pattern of perineural invasion is correlated with the degree of tumor differentiation. The incidence of perineural invasion is correlated with the tumor penetration depth of bile duct walls.
ObjectiveTo develop and validate a nomogram for predicting the cancer-specific survival in patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy. MethodsSuitable patient cases were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms were established based on the independent prognostic factors identified by COX and Lasso regression models. The performance of the nomograms was validated internally and externally by using the concordance index (c-index), calibration plot, and decision curve analysis. ResultsThe multi factor COX regression results showed that: age, gender, T stage, tumor grade, tumour diameter and number of positive lymph nodes were independent prognostic predictors for cancer-specific survival (CSS) in ICC patients. Nomogram predicting CSS had a c-index of 0.66 (95%CI 0.64 to 0.69) in the training cohort and 0.67 (95%CI 0.63 to 0.72) in the internal validation cohort. The 1-, 3- and 5-year areas under the curve (AUC) of nomogram were 0.68, 0.74 and 0.75 in the training cohort respectively. In the validation cohort, the 1-, 3- and 5-year AUC of nomogram were 0.69, 0.68 and 0.71, respectively. ConclusionThe prediction model constructed based on six factors, including age, gender, pathological stage, T-stage, tumour diameter and number of positive lymph nodes, shows good prediction accuracy.