Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Outcome of decompression using a transnasal ileus tube in malignant adhesive bowel obstruction: A retrospective study.

Malignant adhesive bowel obstruction caused by peritoneal carcinomatosis is a common complication of advanced abdominal malignancies, and surgical treatment provides little benefit. The present study was undertaken to evaluate the decompression efficacy of a transnasal ileus tube under X-ray guidance, with benign adhesive bowel obstruction patients serving as the control group. A total of 21 patients with malignant adhesive bowel obstruction and 60 patients with benign conditions were enrolled between February 2011 and March 2015. All the patients were treated with transnasal ileus intubation under X-ray guidance. A total of 9 of the 21 malignant cases and 44 of the 60 benign cases were successfully treated with transnasal ileus intubation (42.9 vs. 73.3%, respectively; P=0.01). Treatment in 8 malignant and 4 benign cases failed due to death, tube discharge, and/or therapy abandonment, all of which contributed to a significant difference between the two groups (38.1 vs. 6.7%, respectively; P=0.01). A total of 4 malignant cases and 12 benign adhesion cases received further surgical treatment, the success rate of which was 50 vs. 91.7%, respectively. The rate of successfully treated intubation cases in all resolution patients was similar between the two groups (81.8% in the malignant group and 80% in the benign group; P=0.89). In conclusion, ileus tube decompression in patients with malignant conditions was associated with a lower success rate and lower further surgical intervention success rate compared with that observed in patients with benign conditions. However, insertion of an ileus tube may successfully cure ~80% of all resolution patients in both groups; thus, it may be used as a feasible therapy in malignant adhesive bowel obstruction patients, similar to patients with benign obstruction.

Prognostic factors of spontaneously ruptured hepatocellular carcinoma.

AIM: To evaluate the prognostic factors in patients with spontaneously ruptured hepatocellular carcinoma (HCC). METHODS: Seventy-nine patients experiencing spontaneous rupture of HCC between April 2004 and August 2014 were enrolled in this study. The clinical features, treatment modalities and outcomes were reviewed. The statistical methods used in this work included univariate analysis, Kaplan-Meier survival analysis with log-rank tests, and multivariate analysis using a Cox regression hazard model. RESULTS: Of the 79 patients with HCC rupture, 17 (21.5%) underwent surgery, 32 (40.5%) underwent transarterial embolization (TAE), and 30 (38%) received conservative treatment. The median survival time was 125 d, and the mortality rate at 30 d was 27.8%. Multivariate analysis revealed that lesion length (HR = 1.46, P < 0.001), lesion number (HR = 1.37, P = 0.042), treatment before tumor rupture (HR = 4.36, P = 0.019), alanine transaminase levels (HR = 1.0, P = 0.011), bicarbonate levels (HR = 1.18, P < 0.001), age (HR = 0.96, P = 0.026), anti-tumor therapy during the follow-up period (HR = 0.21, P = 0.008), and albumin levels (HR = 0.89, P = 0.010) were independent prognostic factors of survival after HCC rupture. The Barcelona-Clinic Liver Cancer (BCLC) stage was also an important prognostic factor; the median survival times for BCLC stages A, B and C were 251, 175 and 40 d, respectively (P < 0.001). CONCLUSION: Anti-tumor therapy during the follow-up period, without a history of anti-tumor therapy prior to HCC rupture, small tumor length and number, and early BCLC stage are the most crucial predictors associated with satisfactory overall survival. Other factors play only a small role in overall survival.

Polymorphisms of TERT and CLPTM1L and the risk of hepatocellular carcinoma in Chinese males.

BACKGROUND: Telomerase reverse transcriptase (TERT) and cleft lip and palate trans-membrane 1 like (CLPTM1L) genes located on chromosome 5p15.33 are known to influence the susceptibility to various cancers. Here, we examined the association of TERT and CLPTM1L single nucleotide polymorphisms (SNPs) with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Genotyping of TERT SNP rs2736098 and CLPTM1L SNP rs401681 was performed using TaqMan allelic discrimination assays in a case-control study of 201 HCC cases and 210 controls in a Chinese male population. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analyses. RESULTS: Both the rs2736098 T allele of TERT and the rs401681 T allele of CLPTM1L were associated with a significantly increased risk of HCC (adjusted odds ratio [OR]=1.605, 95% confidence interval [CI]=1.164-2.213; adjusted OR=1.399, 95%CI=1.002-1.955, respectively). Individuals carrying both TERT and CLPTM1L risk genotypes had an even higher risk of HCC (adjusted OR=4.420, 95%CI= 2.319-8.425). The TERT rs2736098 T allele was also significantly associated with the level of the HCC clinical indicator alpha-fetoprotein (P=0.026). CONCLUSIONS: Our results show that genetic variants of TERT and CLPTM1L may contribute to HCC susceptibility in Chinese males.

[Efficacy and safety of combination of sorafenib and transarterial chemoembolization in treating primary hepatocellular carcinoma].

OBJECTIVE: To evaluate the efficacy and safety of the combination of sorafenib and transarterial chemoembolization (TACE)in the treatment of primary hepatocellular carcinoma (HCC). METHODS: The clinical data of 10 patients with unresectable HCC treated by sorafenib combined with TACE in the Department of Radiology, the First Hospital of China Medical University were retrospectively analyzed. The efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors assessment. Survival was analyzed by Kaplan-Meier method. Safety was evaluated according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0. RESULTS: Among the 10 patients, 2 achieved complete response, 3 achieved partial response, 3 achieved stable disease, and 2 experienced progressive disease. The median overall survival of the cohort was 29.5 months. Different degree of adverse drug reactions (ADRs) occurred in 9 patients but all were at grade 3 or lower. The most common ADRs were hand-foot skin reaction (7/10) and diarrhea (6/10). CONCLUSION: The combination of sorafenib and TACE is an effective and safe treatment for HCC.

[Analysis of severe complications after transcatheter arterial chemoembolization for primary hepatocellular carcinoma].

OBJECTIVE: To investigate the cause and treatment as well as prevention measures of rarely occurring severe complications after transcatheter arterial chemoembolization (TACE) for primary hepatic carcinoma. METHODS: 573 consecutive patients with primary hepatic carcinoma underwent a total of 1252 TACE procedures from January 2005 to July 2007. All the patients who developed complications after TACE received imaging and biochemical examinations. The cause, treatment and preventive measures of the complications in the 573 cases were analyzed. RESULTS: There were upper gastrointestinal hemorrhage in 3 cases, hepatic failure in 4, pulmonary embolism in 1, cholecystitis in 4, hepatic encephalopathy in 2, gastric perforation in 1, and intrahepatic biloma in 2 cases. Two patients died of the complications: 1 of hepatic failure and 1 of gastric perforation. CONCLUSION: The rarely occurring severe complications after transcatheter arterial chemoembolization for primary hepatic carcinoma is correlated with poor hepatic function and portal hypertension before therapy, overdose and reflux of chemotherapeutic agents or allotopic chemoembolism, etc. It can be reduced or prevented through careful selection of proper cases before the treatment, close observation, and protection of hepatic function and gastric mucosa after treatment.

[Pharmacodynamics of China-made rapamycin-polylactide-co-glycolide peripheral arterial eluting stent membrane: in vitro experiment].

OBJECTIVE: To evaluate the property and drug releasing pattern of the China-made rapamycin-polylactide-co-glycolide (PLGA) peripheral arterial eluting stent membrane. METHODS: Rapamycin was put into PLGA so as to made rapamycin-PLGA complex. Twelve nickel-titanium self-expanding stents were dipped into the complex to make drug-eluting stents. Somatotype microscope was used to observe the macro-form of the surface of the eluting membrane, and atom force microscope was used to analyzing the three-dimensional appearance and surface roughness of the membrane. The stents were put into fluid with platelets to observe the form of platelets blood compatibility by scanning electron microscopy. The extra degradation of the coating layer, by putting the stents into a simulation system of internal environment. High efficacy liquid chromatography was used to study the pharmacokinetics of the stents. Standard curve and stimulative curve, and drug release curve of multiple stents were drawn and analyzed. RESULTS: The membranes of all 12 stents had smooth surfaces and regular thickness and no membrane falling-off was observed. The platelets on the surfaces of the stents were inactivated and the number of the platelets adhering to the surfaces of the stents were reduced obviously in comparison with the blank control. PLGA degraded by 20% within 2 weeks and then the degradation speed accelerated until complete degradation occurred within 6 weeks, and the drug releasing lasted more than 50 days. The percentage of accumulative drug release was 11.02% in 24 hours, 41.23% in 9 days, and 79.44% in 30 days. CONCLUSION: Smooth and even, and capable of controlling the drug release, rapamycin-PLGA peripheral arterial eluting stent membrane coating has the potential clinical value in preventing in-stent stenosis.