Endoscopic management for congenital esophageal stenosis: A systematic review

Congenital esophageal stenosis(CES) is an extremely rare malformation, and standard treatment have not been completely established. By years of clinical research, evidence has been accumulated. We conducted systematic review to assess outcomes of the treatment for CES, especially the role of endoscopic modalities. A total of 144 literatures were screened and reviewed. CES was categorized in fibromuscularthickening, tracheobronchial remnants(TBR) and membranous web, and the frequency was 54%, 30% and 16%, respectively. Therapeutic option includes surgery and dilatation, and surgery tends to be reserved for ineffective dilatation. An essential point is that dilatation for TBR type of CES has low success rate and high rate of perforation. TBR can be distinguished by using endoscopic ultrasonography(EUS). Overall success rate of dilatation for CES with or without case selection by using EUS was 90% and 29%, respectively. Overall rate of perforation with or without case selection was 7% and 24%, respectively. By case selection using EUS, high success rate with low rate of perforation could be achieved. In conclusion, endoscopic dilatation has been established as a primary therapy for CES except TBR type. Repetitive dilatation with gradual step-up might be one of safe ways to minimize the risk of perforation.

Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma(HCC).METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers,including alpha fetoprotein(AFP) and proteins induced by vitamin K absence Ⅱ(PIVKA Ⅱ) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher's exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model.RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification,all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9,lung metastasis; 7,brain metastasis; 9,portal vein invasion;4,hepatic vein invasion; 4,bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%,respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP(HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA Ⅱ(HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo(95%CI: 5-15 mo). Terminal stage disease(HR = 9.809; 95%CI: 2.589-37.17,P < 0.001) and an AFP of more than 400 ng/m L(HR = 2.548; 95%CI: 1.070-6.068,P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy(HR = 0.274; 95%CI: 0.093-0.7541,P = 0.012) was associated with better survival. In the 52 cases of bone metastasis,36 patients(69%) achieved pain relief. One patient had cerebral bleeding and another patient had an esophageal ulcer after treatment.CONCLUSION: The Cyberknife can be safely administered to patients with advanced or terminal stage HCC. High AFP levels were associated with worse survival,but a higher radiation dose improved the survival.

Relationship between outcomes and relative dose intensity of lenvatinib treatment in patients with advanced hepatocellular carcinoma

Background and aims:Lenvatinib(LEN)is a newly developed tyrosine kinase inhibitor,and is approved as a first-line treatment for advanced hepatocellular carcinoma(HCC)in Japan.This retrospective multi-center study investigated the effect of the relative dose intensity(RDI)of LEN on response rate,progression-free survival(PFS),and overall survival(OS).Methods:This retrospective study enrolled 123 patients with advanced HCC who were treated with LEN at six hospitals in Japan between March 2018 and December 2019.These patients were divided into two groups:RDI≥70%(RDI 70 group,N=70)or RDI<70%(control group,N=53)in the first 30 days.The following data were compared between groups:patient backgrounds,adverse events,treatment out-comes,PFS,and OS.PFS and OS were analyzed using the Kaplan-Meier method,followed by the log-rank test.To identify significant factors that contributed to response,PFS,and OS,multivariate analysis was performed using factors for which P-values were<0.10 in univariate analysis.Results:The proportion of patients with Child-Pugh class 5A was significantly greater in the RDI 70 group than that in the control group(64.3%vs.28.3%,P<0.01).Dose interruption due to adverse events was significantly more common in the control group.The response rate was significantly higher in the RDI 70 group than that in the control group(35.7%vs.11.3%,P<0.01).Median PFS was significantly longer in the RDI 70 group(9.4 vs.4.7 months,P<0.01).Multivariate analysis showed that RDI≥70%(hazard ratio(HR)=0.55,P=0.025),hypertension grade≥2(HR=0.47,P=0.019),and response(HR=0.52,P=0.033)were independently associated with improved PFS.Median OS was also significantly longer in the RDI 70 group(20.0 vs.13.3 months,P=0.045).Multivariate analysis showed that female sex(HR=0.33,P=0.034)and disease control(HR=0.31,P<0.01)were independently associated with improved OS.RDI≥70%was not statistically significant in multivariate analysis.Conclusions:Our study revealed the importance of achieving RDI≥70%in the first 30 days of treatment to maximize the effects of LEN。