Objective To investigate the roles of NF-κB and EGFR in hepatolithiasis associated with intrahepatic cholangiocarcinoma. Methods Ninety cases of liver tissue specimens from hepatectomies performed in the 2nd Affiliated Hospital of Sun Yat-sen University between August 1989 and June 2009 were enrolled in the study. Among them, 33 cases of hepatolithiasis associated with intrahepatic cholangiocarcinoma were considered as observing group, 32 cases of hepatolithiasis as control group, and 25 cases of normal bile duct tissues as normal control group. The SP method of immunohistochemical staining was applied to detect the expressions of NF-κB and EGFR in intrahepatic biliary ducts epithelial cells, and their relations with clinicopathologic factors and the accumulated survival rate of hepatolithiasis associated with intrahepatic cholangiocarcinoma were analyzed. Results Expression rates of NF-κB and EGFR were gradually raised from normal control group, control group to observing group (Plt;0.01). Expression of EGFR in tumor patients was related to histopathologic differentiation grading and the depth of tumor invasion (Plt;0.05), but not to gender, age, or lymph node metastasis (Pgt;0.05)； there were no significant relationships between the expression of NF-κB and factors described above (Pgt;0.05). The survival rate of patients with tumor expressed EGFR was significantly lower than that of patients with tumor non-expressed EGFR (Plt;0.01). Conclusions NF-κB expression is in the early stage during intrahepatic cholangiocarcinoma genesis. NF-κB and EGFR play cooperating roles during hepatolithiasis carcinogenesis process. Over expression of EGFR is related with poor differentiation and prognosis of tumor.
Objective To obtain the full-length gene and functional domains of FXYD6 gene which is a cholangiocarcinoma related gene. Methods A new strategy with the integration of bioinformatics and molecular biology was used. Bioinformatical methods were used to analyze the full-length sequence, and to predict the functional domains of its protein. And the full-length sequence of FXYD6 was isolated by polymerase chain reaction from fetal hepatic, brain and spleen cDNA libraries, and then cloned in pGEM-T vector for sequence analyzing. Goldkey Sequence Analyzing Software was used to analyze the sequence of candidate domain without signal peptide.Results The full-length sequence of FXYD6 was isolated by Touch-down PCR from fetal hepatic and brain cDNA library, but was not from spleen cDNA library. The open reading frame Finder software was used in the National Center for Biotechnology Information website to find the most probable encoding regions of FXYD6 gene. And the +1 phase was selected as the template sequence, from 67 bp to 354 bp, to predict the functional domains by Goldkey Sequence Analyzing Software. The signal peptide was located from 1 amino acid (aa) to 17 aa， and the main domain was composed from 18 aa to 34 aa. The region between 35 aa and 57 aa was the transmembrane region. The FHYD peptide chain was highly conserved amino acids. Conclusion The study of full-length cDNA cloning of FXYD6 gene and its functional domains provides the basis for understanding the relationship between the structure and function of FXYD6. More work shall be performed on FXYD6 protein and its influence on the mechanism of cholangiocarcinoma.
ObjectiveRecent advancements in the researches on cholangiocarcinoma (CC) related genes methylation in CC were reviewed and the clinical significances of aberrant DNA methylation for the diagnosis and treatment of CC were discussed. MethodsRelevant literatures about the relation between CC-related genes methylation and CC published recently were collected and reviewed. ResultsThe genesis of CC resulted from abnormal expressions of many genes. Many researches had shown that the abnormal methylation of CC-related genes had a close relation with CC. Epigenetic alteration had been acknowledged as an important mechanism contributing to early CC carcinogenesis. ConclusionsAbnormal methylation of CC-related genes is related with CC. The detection of CC-related genes methylation might provide new specific biomarkers for early noninvasive diagnosis of this disease. Using epigenetic agents such as azacytidine to modulate the activities of DNA methyltransferase and reverse the methylation status of CC-related gene might be an attractive strategy for future treatment of CC, which could be combined with conventional therapies.
ObjectiveTo investigate the expressions of Patched-1 (Ptch1) and glioma-associated oncogene homologl (Gli1) protein of sonic hedgehog signaling pathway in cholangiocarcinoma tissues, and explore their correlations to the occurrence and development of cholangiocarcinoma. MethodsThe expressions of Ptch1 and Gli1 protein in 62 specimens of cholangiocarcinoma and its bile duct tissues adjacent to cancer were detected by immunohistochemistry, and their positive rate correlated with patients, age, tumor size, differentiation grade, tumor location, lymph node metastasis, TNM stage, operation mode, and postoperative survival time were investigated by statistical analysis. ResultsThe positive rates of Ptch1 and Gli1 protein were significantly higher in cholangiocarcinoma than in tissues adjacent to cancer (74.2% vs. 14.5%, 88.7% vs. 9.7%, P < 0.05). The expressions of Ptch1 and Gli1 protein in cholangiocarcinoma had no correlation to patients age, tumor size, and tumor location (P > 0.05), but were correlated to the operation mode, differentiation grade, lymph node metastasis, TNM stage, and postoperative survival time of patients (P < 0.05). ConclusionsThe elevated expressions of Ptch1 and Gli1 protein of Hh signaling pathway participated in the occurrence and development of cholangiocarcinoma. They may be ideal targets for therapy against cholangiocarcinoma.
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.
Objective To summarize the research status and prospect of immunotherapy for biliary tract cancer (BTC). Method The literatures about immunotherapy of BTC at home and abroad in recent years were reviewed. Results Surgical resection was still the first choice and only radical treatment for BTC. However, the recurrence rate of BTC was high, and most of the patients were in the middle and late stage with metastasis and lose the opportunity of operation. Patients with local progression, metastasis or recurrence could only receive chemotherapy and other comprehensive treatment, but they could not get satisfactory results. The continuous update of targeted drugs brings new hope for drug therapy of BTC, and immunotherapy had become a new treatment of tumor targeted therapy following radiotherapy and chemotherapy. ConclusionImmunotherapy can be used as an option for the treatment of advanced BTC and its postoperative recurrence and metastasis, and has attracted more and more attention.
Objective To explore favorable factors of reducing incidence of postoperative liver failure after radical resection of Bismuth-Corlette type Ⅳ hilar cholangiocarcinoma in condition of hyperbilirubinemia. Methods All the clinical data of one patient with Bismuth-Corlette type Ⅳ hilar cholangiocarcinoma underwent radical resection in June 2017 in the West China Hospital of Sichuan University were collected. The preoperative total bilirubin level of this patient was 470.3 μmol/L, the patient didn’t receive preoperative biliary drainage. The preoperative jaundice time and cholangitis were calculated accurately. A 3D imaging system for quantitative evaluation of the liver was used to reconstruct the images with contrast-enhanced CT images of this patient. And the total liver volume and the future liver remnant volume (FLRV) were calculated. Finally, 6 months of follow-up were conducted after surgery. Results The exact jaundice time was 20 d and there was no preoperative cholangitis. The postoperative FLRV accounted for about 70%. No postoperative liver failure occurred. No recurrence of tumor and death of patient occurred after 6 months of follow-up. Conclusions Radical resection of hilar cholangiocarcinoma in condition of hyperbilirubinemia is not an absolute contraindication for surgery, but indications should be strictly controlled. For special patient whose jaundice with short duration, no preoperative cholangitis and a high FLRV may be treated with directly radical surgery to prevent for losting the best time of surgery.