Endoplasmic reticulum stress triggers delanzomib-induced apoptosis in HCC cells through the PERK/eIF2α/ATF4/CHOP pathway.

For limited clinical benefits and acquired resistance by sorafenib, new therapeutic strategies and molecular targets for the treatment of advanced hepatocellular carcinoma (HCC) are urgently needed. This study aimed to evaluate the potential antitumor effects of the second-generation proteasome inhibitor delanzomib on HCC. The results demonstrated that delanzomib displayed excellent antitumor activity on HCC cells with sensitivity or resistance to sorafenib in a time- and dose-response manner, by inducing G2/M cell cycle arrest and apoptosis in vitro. Cell cycle arrest was associated with the activation of p21/Cdc2/cyclin B1 pathway, and cell apoptosis was confirmed by PARP and caspase-3 cleavage. In addition, delanzomib induced endoplasmic reticulum stress (ERS) in HCC cells by activating the PERK and ERS-associated proteins including p-eIF2α, ATF4 and CHOP. Selective inhibition of eIF2α dephosphorylation by salubrinal could significantly reduce delanzomib-induced apoptosis in HCC cells. In vivo, delanzomib could also exhibit effective antitumor properties on patient-derived xenograft mouse model of HCC with relative low drug-associated cytotoxicity. Compared to control group, 3 and 10 mg/kg of delanzomib significantly reduced the tumor volume by 33.1% and 87.2% respectively after 3 weeks treatment, with no significant change on the body weight and the level of serum biochemical indexes including ALT, AST and BUN. In conclusion, delanzomib could exhibit good pre-clinical antitumor effects against HCC cells by inducing ERS and activating the PERK/eIF2α/ATF4/CHOP pathway, as potential drug candidate on treatment of advanced HCC patients.

Risk factors for postoperative pancreatic fistula after laparoscopic distal pancreatectomy using stapler closure technique from one single surgeon.

Laparoscopic distal pancreatectomy (LDP) is a safe and reliable treatment for tumors in the body and tail of the pancreas. Postoperative pancreatic fistula (POPF) is a common complication of pancreatic surgery. Despite improvement in mortality, the rate of POPF still remains high and unsolved. To identify risk factors for POPF after laparoscopic distal pancreatectomy, clinicopathological variables on 120 patients who underwent LDP with stapler closure were retrospectively analyzed. Univariate and multivariate analyses were performed to identify risk factors for POPF. The rate of overall and clinically significant POPF was 30.8% and13.3%, respectively. Higher BMI (≥25kg/m2) (p-value = 0.025) and longer operative time (p-value = 0.021) were associated with overall POPF but not clinically significant POPF. Soft parenchymal texture was significantly associated with both overall (p-value = 0.012) and clinically significant POPF (p-value = 0.000). In multivariable analyses, parenchymal texture (OR, 2.933, P-value = 0.011) and operative time (OR, 1.008, P-value = 0.022) were risk factors for overall POPF. Parenchymal texture was an independent predictive factor for clinically significant POPF (OR, 7.400, P-value = 0.001).

Laparoscopic ligation of celiac trunk and splenic artery aneurysms with function preservation.

Celiac trunk aneurysms (CTAs) are rare and usually asymptomatic. Although most of these aneurysms can be treated with percutaneous embolization, some uncommon locations of the aneurysm may make this approach impossible. We report a patient with a celiac trunk aneurysm (CTA) and a proximal splenic artery aneurysm (SAA). Due to the size and location of these two aneurysms, after multidisciplinary discussion, endovascular management was considered inappropriate and they were treated by laparoscopic ligation of the two aneurysms and revascularization. This procedure offers good postoperative recovery with good preservation of the visceral function. Some collateral vessels in the viscera were obvious on postoperative day 7.

Intracorporeal esophagojejunostomy after totally laparoscopic total gastrectomy: A single-center 7-year experience.

AIM: To assess the efficacy and safety of intracorporeal esophagojejunostomy in patients undergoing laparoscopic total gastrectomy (LTG) for gastric cancer. METHODS: A retrospective review of 81 consecutive patients who underwent LTG with the same surgical team between November 2007 and July 2014 was performed. Four types of intracorporeal esophagojejunostomy using staplers or hand-sewn suturing were performed after LTG. Data on clinicopatholgoical characteristics, occurrence of complications, postoperative recovery, anastomotic time, and operation time among the surgical groups were obtained through medical records. RESULTS: The average operation time was 288.7 min, the average anastomotic time was 54.3 min, and the average estimated blood loss was 82.7 mL. There were no cases of conversion to open surgery. The first flatus was observed around 3.7 d, while the liquid diet was started, on average, from 4.9 d. The average postoperative hospital stay was 10.1 d. Postoperative complications occurred in 14 patients, nearly 17.3%. However, there were no cases of postoperative death. CONCLUSION: LTG performed with intracorporeal esophagojejunostomy using laparoscopic staplers or hand-sewn suturing is feasible and safe. The surgical results were acceptable from the perspective of minimal invasiveness.

Robotic versus Laparoscopic Distal Pancreatectomy: A Meta-Analysis of Short-Term Outcomes.

AIM: To compare the safety and efficacy of robotic-assisted distal pancreatectomy (RADP) and laparoscopic distal pancreatectomy (LDP). METHODS: A literature search of PubMed, EMBASE, and the Cochrane Library database up to June 30, 2015 was performed. The following key words were used: pancreas, distal pancreatectomy, pancreatic, laparoscopic, laparoscopy, robotic, and robotic-assisted. Fixed and random effects models were applied. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Seven non-randomized controlled trials involving 568 patients met the inclusion criteria. Compared with LDP, RADP was associated with longer operating time, lower estimated blood loss, a higher spleen-preservation rate, and shorter hospital stay. There was no significant difference in transfusion, conversion to open surgery, R0 resection rate, lymph nodes harvested, overall complications, severe complications, pancreatic fistula, severe pancreatic fistula, ICU stay, total cost, and 30-day mortality between the two groups. CONCLUSION: RADP is a safe and feasible alternative to LDP with regard to short-term outcomes. Further studies on the long-term outcomes of these surgical techniques are required. CORE TIP: To date, there is no consensus on whether laparoscopic or robotic-assisted distal pancreatectomy is more beneficial to the patient. This is the first meta-analysis to compare laparoscopic and robotic-assisted distal pancreatectomy. We found that robotic-assisted distal pancreatectomy was associated with longer operating time, lower estimated blood loss, a higher spleen-preservation rate, and shorter hospital stay. There was no significant difference in transfusion, conversion to open surgery, overall complications, severe complications, pancreatic fistula, severe pancreatic fistula, ICU stay, total cost, and 30-day mortality between the two groups.