ABCB4 gene mutation-associated liver cirrhosis with gallstones： A case report / 临床肝胆病杂志

The disease spectrum of ABCB4 gene mutation involves various diseases such as progressive familial intrahepatic cholestasis type 3 （PFIC3）， gallstone disease， intrahepatic cholestasis of pregnancy， portal hypertension， liver cirrhosis， and even primary hepatic and biliary malignancies. A young male patient was admitted to Department of Hepatobiliary Medicine， Eastern Hepatobiliary Surgery Hospital， and was initially diagnosed with liver cirrhosis and gallstones， and he was planned to receive laparoscopic cholecystectomy. Preoperative examination showed abnormal liver function， liver cirrhosis， splenomegaly， and mild esophageal varices， and next-generation sequencing was performed to make a confirmed diagnosis of ABCB4 gene mutation-associated liver cirrhosis with gallstones. The liver function of the patient gradually returned to normal after cholagogic treatment with ursodeoxycholic acid capsules.

Prognostic effects of type 2 diabetes mellitus on patients with different TNM stage of hepatocellular carcinoma after operation / 中华消化杂志

Objective:To investigate the effects of type 2 diabetes mellitus (T2DM) on the clinicopathological characteristics and prognosis of patients with hepatocellular carcinoma (HCC) after curative hepatectomy.Methods:From November 2009 to June 2011, the clinicopathological and survival data of HCC patients who underwent radical resection at Eastern Hepatobiliary Surgery Hospital of Naval Medical University were retrospectively analyzed. The patients were divided into T2DM group and non-T2DM group. Clinicopathological characteristics and prognosis of two groups were compared. Chi square test or Fisher exact test were used for statistical analysis. Kaplan-Meier test was used for univariate survival analysis, and Cox proportional hazard regression model was used for multivariate survival analysis.Results:A total of 1 691 patients with HCC were enrolled in this study. Among them, 142 patients (8.4%) were complicated with T2DM. The proportion of patients with onset age≥65 years old, the proportion of men, the proportion of patients with hypertension and γ-glutamyltranspeptidase >61 U/L in the T2DM group were higher than those in non-T2DM group (24.6%, 35/142 vs. 10.4%, 161/1 549; 92.3%, 131/142 vs. 85.7%, 1 327/1 549; 43.7%, 62/142 vs. 12.3%, 191/1 549; 58.5%, 83/142 vs. 49.4%, 765/1 549), while the proportion of patients with chronic hepatitis virus infection and α-fetoprotein >20 μg/L in the T2DM group were both lower than those in non-T2DM group (76.1%, 108/142 vs. 92.0%, 1 425/1 549; 47.2%, 67/142 vs. 59.9%, 928/1 549), and the differences were all statistically significant ( χ2=25.79, 4.75, 100.36, 4.28, 39.01 and 8.66, all P<0.05). The results of univariate survival analysis showed that there was no significant difference in the postoperative overall survival (OS) rate between T2DM group and non-T2DM group ( χ2=3.02, P=0.082). The results of further subgroup analysis showed that among HCC patients with TNM stage Ⅰ, there was statistically significant difference in the OS rate between T2DM group and non-T2DM group ( χ2=4.53, P=0.033). The OS rates at 1 year, 3 years and 5 years after curative resection of HCC patients in T2DM group were lower than those of patients in non-T2DM group (96.0%, 48/50 vs. 97.6%, 558/572; 78.0%, 39/50 vs. 88.6%, 507/572; 68.0%, 34/50 vs. 79.5%, 455/572). The results of multivariate Cox regression survival analysis demonstrated that T2DM was an independent risk factor for postoperative survival in patients with TNM stage Ⅰ HCC (odds ratio=1.663, 95% confidence interval 1.045 to 2.648, P=0.032). Conclusions:The effect of T2DM on prognosis of patients after radical resection of HCC is associated with TNM stage, and its effect may be limited on the early stage of HCC.

Adjuvant transcatheter arterial chemoembolization for curative hepatectomy of hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To explore the effect of transcatheter chemoembolization (TACE) on recurrence and survival time of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) following curative resection.Methods:Of 724 HBV-related HCC patients who underwent curative resection in the Third Affiliated Hospital of Naval Military Medical University from October 2009 to August 2010 were retrospectively analyzed. Patients who underwent resection only and no recurrence within 3 months after surgery were classified into control group, while those received adjuvant TACE were classified into intervention group. The patients were further divided into 4 sub-groups according to tumor size, tumor number and tumor thrombus which were defined as risk factors for recurrence. Tumor diameter ≤5 cm with low or high risk factors (tumor number ≥2 or presence tumor thrombus) were in group 1 and group 2 respectively, tumor diameter >5 cm with low or high risk factors for recurrence were in group 3 and group 4 respectively.Results:A total of 354 patients were classified in the control group and 370 patients were classified in the TACE group. Adjuvant TACE showed an overall survival benefit in patients with tumor diameter >5 cm and presenting high risk factors, the 1-, 3-, and 5-year cumulative survival rates were 90.1%, 67.6%, and 46.5%, respectively, for the lip-TACE group 83.3%, 52.4%, and 33.3%, respectively, for the control group ( P<0.05). Patients with the tumor diameter ≤5 cm, there was no significant difference in cumulative survival between the TACE group and the control group regardless of the risk level ( P>0.05). There was no significant difference in recurrence curve between TACE group and control group in each stratum. Conclusions:Adjuvant TACE had no preventive effect on recurrence, but TACE can prolong the survival time of HCC patients with high risk factors for recurrence.

Advances in the study of programmed cell death protein 1 and its ligand inhibitors in the treatment of late stage HCC / 中华肝脏病杂志

The treatment of late stage hepatocellular carcinoma (HCC) presently remains a great challenge. A very few drugs have been recently approved for clinical use except sorafenib and lenvatinib. After decades of failure and experience with molecular targeted and immunosuppressive therapy, immune checkpoint inhibitors are becoming one of the potentially effective therapies for patients with HCC, whose tumor is in the middle and late stages. Moreover, immune checkpoint is one of the main mechanisms of tumor immune evasion; of which programmed cell death protein 1 and its ligand (PD1/PD-L1) are important immune checkpoint targets, and its related pathway has shown to have an antitumor effect in a variety of solid or hematologic tumors and its inhibitors can effectively exert antitumor immunosuppressive effects. This review summarizes the current role of PD1/PD-L1 inhibitors in the treatment of late stage HCC, and explores the forecasting value of combined therapy strategy for HCC.

A comparative study of intrahepatic cholangiocarcinoma and hepatocellular carcinoma with reference to clinical features and prognosis / 中华肝脏病杂志

Objective@#To comparatively study intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) with reference to clinical features and prognosis in Chinese Han population.@*Methods@#699 cases of HCC and 170 cases of ICC confirmed by surgical pathological files from 2009 to 2010 were included and followed-up. The differences in demographic characteristics, hepatitis B virus infection, clinical characteristics, biochemical indexes, tumor markers and prognosis of HCC and ICC were analyzed retrospectively by means of paired t-test, analysis of variance, chi-square test and Pearson’s correlation coefficient.@*Results@#Among 869 cases of primary liver cancer, HCC and ICC accounted for 80.43% and 19.57%. The old aged (P < 0.001) male incidence of HCC was higher than that of ICC (P < 0.001). The infection rates of hepatitis B virus were 89.84% and 35.88% in HCC and ICC, respectively, and the infection rates of hepatitis B, serum HBsAg postive rate and DNA account in HCC were higher than ICC (P < 0.001). The incidence of liver cirrhosis and hepatic schistosomiasis in HCC was also significantly different from that in ICC (both P < 0.01). Pearson’s correlation analysis showed that there was a significant negative correlation between HCC or ICC tumor type and hepatic schistosomiasis (r = -0.018, P < 0.001), and there was a significant positive correlation between HCC and hepatic cirrhosis (r = 0.179, P < 0.001, and r = 0.528, P < 0.001, respectively). However, the proportion of cirrhosis and schistosomiasis in hepatitis B positive ICC cases was not significantly different from that in HCC cases (P > 0.05). Among the biochemical indicators, there were significant differences between HCC and ICC in the abnormal rate of ALT(P < 0.01), AST(P < 0.05), ALP (P < 0.01), GGT (P < 0.01) and TBIL (P < 0.01) while there was no significant difference between ALB and pre-ALB (P > 0.05) in HCC and ICC groups. The content and abnormal rate of alpha-fetoprotein were higher in HCC (P < 0.01), while the content and abnormal rate of carcinoembryonic antigen and carbohydrate antigen 19-9 were higher in ICC (P < 0.01). The 10-year survival rate and median survival time (46.92% and 80.3 months) of HCC were higher than those of ICC (12.57% and 12.4 months) (P < 0.01).@*Conclusion@#In the study population, compared with ICC cases, the old aged male HCC cases are more common and has higher infection rate of hepatitis B virus and cirrhosis, but liver schistosomiasis is less common. The inflammatory damage, secretion and metabolic function of HCC were different from that of ICC cases, while the synthetic reserve function was similar to that of ICC and the prognosis of HCC cases was significantly better. The incidence of cirrhosis and schistosomiasis in ICC cases with positive hepatitis B virus infection was not significantly different from that of HCC cases.

Advances in the application of artificial intelligence in cancer diagnosis and treatment / 中华肝脏病杂志

The application of artificial intelligence is developing rapidly in various fields with the improvement of computing power, big data processing, and diversity of algorithms. It has a great potential value in the field of medical and healthcare, especially in the field of cancer diagnosis and treatment. In addition, it can analyze a large amount of data, information, and knowledge instantaneously. Therefore, it serves as a powerful tool for doctors to make the best treatment decisions. Notably, the development of science and technology truly transform into the actual interests of patients. This paper introduces advances in the application of artificial intelligence in diagnosis and treatment of cancer through digital pathology, medical imaging, and genomic medicine.

Modern knowledge and development trend of intrahepatic cholangiocellular carcinoma / 中华肝脏病杂志

Although intrahepatic cholangiocellular carcinoma (ICC) has a relatively low incidence rate, it ranks the second in the most common primary malignant liver tumors, with hepatocellular carcinoma ranking the first. Meanwhile, its incidence and mortality rates tend to increase significantly in the past decades. On the one hand, due to a lack of characteristic clinical symptoms, specific tumor markers, and imaging findings, early diagnosis of ICC is extremely difficult; on the other hand, ICC has highly malignant biological behaviors and early extrahepatic metastasis, so patients often experience early recurrence even if surgical resection is performed, which leads to the poor prognosis of such patients. Unfortunately, since ICC has a low incidence rate and relatively few patients, it is not taken seriously in clinical practice. Since there is a lack of clinical data, specimens, and in-depth studies on ICC, its pathogenesis remains unclear. This article discusses recent advances in ICC, including risk factors, molecular mechanism, new diagnostic markers, and therapies (including molecular targeted drugs).

Challenges in precise treatment for primary liver cancer based on gene mutation / 临床肝胆病杂志

Gene mutation is the molecular basis of the pathogenesis of primary liver cancer, and precise treatment based on gene mutation is an important direction for the treatment of liver cancer in future.This article introduces the current status, complexity, and prospects and future directions of precise treatment for liver cancer from the aspects of complex gene mutations in liver cancer, level of mutation detection, and limitations of clinical trials.It is pointed out that there are many challenges in precise treatment for liver cancer, but precise treatment still has a promising future.

Efficacy and safety of the duette multiband mucosectomy for esophageal submucosal tumors / 中华消化内镜杂志

Objective To investigate clinical efficacy and safety of endoscopic multiband mucosec-tomy(EMBM)for esophageal submucosal tumors(SMTs).Methods Data of 51 patients with SMTs diag-nosed between Jan 2012 and Aug 2014 were retrospectively studied.Of the 51 patients,33 patients(34 le-sions)received EMBMand 18 patients received endoscopic submucosal resection(ESMR).The operation success rates,complete resection rates,procedure time,complications and the follow-up of group EMBMand group ESMR were compared.Results All of 51 cases had successful endoscopic treatment with no perfora-tion,infection or obvious bleeding.Follow-up showed no recurrence after operation.Compared with group ESMR,group EMBM had higher complete resection rate [97.1% (33 /34)VS 61.1% (11 /18 ),P =0.010],shorter operation time[(6.3 ±1.8)min VS (21.4 ±3.8)min,P =0.001]and lower complication rate[6.1%(2 /33)VS 27.8%(5 /18),P =0.024].Conclusion EMBM is simple,safe and effective for treating SMTs originating from muscularis mucosa or submucosa which are less than 2.0 cm in diameter.

Clinical and pathological features of seventeen cases of hepatic epithelioiad hemangioendothelioma / 中华消化杂志

Objective To investigate the clinical and pathological features of primary hepaticepithelioid hemangio endothelioma (EHE) and try to improve the understanding and diagnosis of this disease.Methods From January 2007 to January 2013,the data of 17 patients with hepatic EHE were retrospectively analyzed,which included clinical,pathological and radiological characteristics,treatment and survival condition of these patients.Results Among 17 cases of hepatic EHE,there were 11 female and six male with the mean age of 46.2 years.Seven patients had right upper quadrant pain of dull pain in liver and the left 10 cases were without any symptoms.The liver function of most patients (15 cases) was normal.The admission diagnosis was mostly misdiagnosed as hepatocellular carcinoma (metastatic liver carcinoma six cases,primary liver carcinoma four cases).Extrahepatic metastasis was found in three patients before operation.The major lesion of the tumor was multiple nodules (10 cases) and most of which were under liver capsule.Retraction of the liver capsule was found in the imaging examination.The features of pathology were intracellular lumen and vacuoles formed in small cells,in which single or couple red blood cells could be found.Nuclear deviation was found in single tumor cell which looked like signet ring cells.The results of immunohistochemistry indicated the positive rate of factor vimentin (4/5) antigen and CD34 (15/17) was high.Surgical resection (14 cases) was the main treatment of hepatic EHE.Fourteen patients were still alive followed up for two to 72 months after operation.Conclusions The incidence of hepatic EHE is low,and it was susceptible to middle aged women and without obvious symptom.No obvious abnormality is found in laboratory examination.Surgical resection is the main treatment which enabled a good prognosis.