Feasibility of personalized treatment concepts in gastrointestinal malignancies： Sub-group results of prospective clinical phase Ⅱ trial EXACT

Objective： Advances in high-throughput genomic profiling and the development of new targeted therapies improve patient＇s survival. In gastrointestinal （GI） malignancies, the concept of personalized medicine （PM） was not investigated so far. The aim of this prospective study was to evaluate the efficacy of a personalized treatment in GI patients who failed standard treatment. Methods： Out of the original prospective clinical phase II EXACT trial, 21 （38%） GI cancer patients who had no further treatment options were identified. A molecular profile （MP） via a 50 gene next generation sequencing （NGS） panel in combination with immunohistochemistry （IHC） was conducted using real-time biopsy tumor material. Results were discussed by a multidisciplinary team （MDT） to translate the individual MP in an experimental treatment. Results： Of the 55 patients originally included in the EXACT trial, 21 （38%） suffered from GI malignancies. The final analysis showed that 15 （71%） patients had experienced a longer progression-free survival （PFS） upon experimental targeted treatment （124 d, quartiles 70/193 d）, when compared with the PFS achieved by the previous conventional therapy （62 d, quartiles 55/83 d） （P=0.014）. Thirteen （62%） patients receiving targeted treatment experienced a disease control according to Response Evaluation Criteria in Solid Tumors （RECIST）. Median overall survival （OS） from the start of experimental therapy to time of censoring or death was 193 d （quartiles 115/374 d）. Conclusions： PM was not investigated in GI malignancies so far in a prospective trial. This study shows that treatment based on real-time molecular tumor profiling led to a superior clinical benefit, and survival as well as response was significantly improved when compared with previous standard medications.

Irreversible electroporation versus radiofrequency ablation for malignant hepatic tumor:A prospective single-center double-arm trial

Objective:Irreversible electroporation(IRE)is a nonthermal ablation technique for the treatment of malignant liver tumors.IRE has demonstrated efficacy and safety in the treatment of malignant liver tumors and its unique advantages in the treatment of nearby vascular lesions.This study aimed to compare the efficacy,safety,and intermediate-term outcomes of IRE and radiofrequency(RF)therapy in malignant liver tumors.Methods:Twenty-four patients with primary or secondary liver malignancies were included in this prospective,double-arm clinical trial.Patients were randomly divided into the IRE and RF groups.The primary outcome was the efficacy(local ablation control evaluation at 90 days).The secondary outcomes were safety(procedure-related complications at≤90 days)and intermediate-term survival(at 24 months).Results:The ablation assessment at 90 days after surgery with m RECIST for IRE versus RF were 70%,20%,0%,and 10%versus 92.9%,7.1%,0%,and 0%(CR,PR,SD,and PD,respectively).The complication rates of IRE versus RF with Clavien-Dindo classification were 16.7%,25%,0%,8.3%,and 8.3%versus 8.3%,50%,0%,0%,and 0%(Grade I,II,Ⅲ,IV,and V,respectively).The average overall survival(OS)was 17.55 months in the IRE group(95%CI 15.13-22.37)and 18.75 months in the RF group(95%CI 12.48-22.61).There was no statistical difference between the IRE and RF groups in terms of efficacy(p=0.48),safety(p=0.887),or 24-month OS(p=0.959).Conclusions:IRE ablation revealed similar efficacy and safety in a short-term follow-up,and similar OS in midterm survival as RF ablation in treating malignant hepatic tumors.

Activating Blood Circulation to Remove Stasis Treatment of Hypertensive Intracerebral Hemorrhage:A Multi-Center Prospective Randomized Open-Label Blinded-Endpoint Trial

Objective： To investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation （TRABC） in treatment of hypertensive intracerebral hemorrhage （HICH）. Methods： This was a multi-center prospective randomized open-label blinded-endpoint （PROBE） trial with HICH admitted to 12 hospitals. Totally 240 participants were randomized to the treatment group treated with TRABC in addition to conventional Western treatment or the control group with conventional Western treatment equally for 3 months. Primary outcome was degree of disability as measured by modified Rankin Scale （mRS）. Secondary outcomes were the absorption of hematoma and edema, National Institutes of Health Stroke Scale （NIHSS） scores and patient-reported outcome measures for stroke and Barthel activities of daily living index. Adverse events and mortality were also recorded. Results： After 3 months of treatment, the rate of mRS 0-1 and mRS 0-2 in the treatment group was 72.5% and 80.4%, respectively, and in the control group 48.1% and 63.9%, respectively, with a significant difference between groups （P〈0.01）. Hematoma volume decreased significantly at day 7 of treatment in the treatment group than the control group （P=0.038）. Average Barthel scores in the treatment group after treatment was 89.11 ＋ 19.93, and in the control group 82.18 ＋ 24.02 （P=0.003）. NIHSS scores of the two groups after treatment decreased significantly compared with before treatment （P=0.001）. Patient-reported outcomes in the treatment group were lower than the control group at day 21 and 3 months of treatment （P〈0.05）. There were 4 deaths, 2 in each group, and 11 adverse events, 6 in the treatment group and 5 in the control group. Conclusion： The integrative therapy combined TRABC with conventional Western treatment for HICH could promote hematoma absorption thus minimize neurologic impairment, without increasing intracerebral hematoma expansion and re-bleeding.

Meta-analysis of pancreaticoduodenectomy prospective controlled trials： pancreaticogastrostomy versus pancreaticojejunostomy reconstruction

Background Pancreaticogastrostomy （PG） has been proposed as an alternative to pancreaticojejunostomy （PJ）, assuming that postoperative complications are less frequent. The aim of this research was to compare the safety of PG with PJ reconstruction after pancreaticoduodenectomy.

Modified Helicobacter test using a new test meal and a 13C-urea breath test in Helicobacter pylori positive and negative dyspepsia patients on proton pump inhibitors

AIM To determine the sensitivity and specificity of the ^(13)C-urea breath test(UBT) in patients taking proton pump inhibitors(PPIs), using a new test meal Refex. METHODS One hundred and fourteen consecutive patients with dyspepsia, 53 Helicobacter pylori(H. pylori) positive, 49 H. pylori negative, were included in the study. The patients were then given esomeprazole 40 mg for 29 consecutive days, and the ^(13)C-UBT with the new test meal was performed the next morning. RESULTS The sensitivity of the ^(13)C-UBT with a cut off 2.5‰ was92.45%(95%CI: 81.79%-97.91%) by per-protocol(PP) analysis and 78.13 %(95%CI: 66.03%-87.49%) by intention-to-treat(ITT) analysis. The specificity of the ^(13)C-UBT test was 96.00 % in the ITT population(95%CI: 86.29%-99.51%) and 97.96% in the PP population(95%CI: 89.15%-99.95%).CONCLUSION The new test meal based ^(13)C-UBT is highly accurate in patients on PPIs and can be used in those unable to stop their PPI treatment.