Citations

Acute liver failure (ALF) is a catastrophic condition that can occur after major liver resection. The aim of this study was to determine the effects of the spheroid reservoir bio‐artificial liver (SRBAL) on survival, serum chemistry, and liver regeneration in posthepatectomy ALF pigs. Wild‐type large white swine (20 kg‐30 kg) underwent intracranial pressure (ICP) probe placement followed by 85% hepatectomy. Computed tomography (CT) volumetrics were performed to measure the extent of resection, and at 48 hours following hepatectomy to assess regeneration of the remnant liver. Animals were randomized into three groups based on treatment delivered 24‐48 hours after hepatectomy: Group1—standard medical therapy (SMT, n = 6); Group2—SMT plus bio‐artificial liver treatment using no hepatocytes (0 g, n = 6); and Group3—SMT plus SRBAL treatment using 200 g of primary porcine hepatocyte spheroids (200 g, n = 6). The primary endpoint was survival to 90 hours following hepatectomy. Death equivalent was defined as unresponsive grade 4 hepatic encephalopathy or ICP greater than 20 mmHg with clinical evidence of brain herniation. All animals in both (SMT and 0 g) control groups met the death equivalent before 51 hours following hepatectomy. Five of 6 animals in the 200‐g group survived to 90 hours ( P < 0.01). The mean ammonia, ICP, and international normalized ratio values were significantly lower in the 200‐g group. CT volumetrics demonstrated increased volume regeneration at 48 hours following hepatectomy in the 200‐g group compared with the SMT ( P < 0.01) and 0‐g (P < 0.01) groups. Ki‐67 staining showed increased positive staining at 48 hours following hepatectomy ( P < 0.01). Conclusion: The SRBAL improved survival, reduced ammonia, and accelerated liver regeneration in posthepatectomy ALF. Improved survival was associated with a neuroprotective benefit of SRBAL therapy. These favorable results warrant further clinical testing of the SRBAL.

Even after 2 decades of experience in laparoscopic hepatectomy, data on purely laparoscopic approach for donor hepatectomy in adult living donor liver transplantation (LDLT) are limited. We report our initial experience of a purely laparoscopic approach for donor hepatectomy for adult recipients to explore its potential application in the management of donors. We did a retrospective data analysis of 54 consecutive patients operated on between May 2013 and February 2015. There were 41 right, 10 extended right, and 3 left hepatectomies. The median operative time was 436 minutes (range 294‐684 minutes), and warm ischemia time was 6 minutes (2‐12 minutes). Estimated blood loss was 300 mL (10‐850 mL), and none of the patients required intraoperative transfusion. Four cases were converted to open laparotomy. The major complication rate was 16.7%, and biliary complication was the most frequent cause. Patients with normal anatomy had a major complication rate of 9.3% as compared with 45.5% in patients with anatomic variations. All patients recovered, and there was no mortality. In conclusion, a purely laparoscopic donor hepatectomy for adult LDLT recipients seems to be a feasible option; with careful patient selection and when performed by experienced surgeons, it may afford results comparable to the open method.

Expression of histone H3.3K27M mutant proteins in human diffuse intrinsic pontine glioma (DIPG) results in a global reduction of tri-methylation of H3K27 (H3K27me3), and paradoxically, H3K27me3 peaks remain at hundreds of genomic loci, a dichotomous change that lacks mechanistic insights. Here, we show that the PRC2 complex is sequestered at poised enhancers, but not at active promoters with high levels of H3.3K27M proteins, thereby contributing to the global reduction of H3K27me3. Moreover, the levels of H3.3K27M proteins are low at the retained H3K27me3 peaks and consequently having minimal effects on the PRC2 activity at these loci. H3K27me3-mediated silencing at specific tumor suppressor genes, including Wilms Tumor 1, promotes proliferation of DIPG cells. These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and contributes to tumorigenesis in part by locally enhancing H3K27me3, and hence silencing of tumor suppressor genes.

We report a case of a patient with severe postoperative bleeding complication, secondary to dietary and herbal supplements induced platelet dysfunction. This case demonstrates the importance of preoperative assessment which includes questioning the patient with regards to their dietary and herbal supplements and of stressing the importance of discontinuing them prior to surgery.

AbstractThe diagnosis of malignant biliary strictures remains problematic, especially in the perihilar region and in primary sclerosing cholangitis (PSC). Conventional cytology obtained during endoscopic retrograde cholangiography (ERC)-guided brushings of biliary strictures is suboptimal due to limited sensitivity, albeit it remains the gold standard with a high specificity. Emerging technologies are being developed and validated to address this pressing unmet patient need. Such technologies include enhanced visualization of the biliary tree by cholangioscopy, intraductal ultrasound, and confocal laser endomicroscopy. Conventional cytology can be aided by employing complementary and advanced cytologic techniques such as fluorescent in situ hybridization (FISH), and this technique should be widely adapted. Interrogation of bile and serum by examining extracellular vesicle number and cargo, and exploiting next-generation sequencing and proteomic technologies, is also being explored. Examination of circulating cell-free deoxyribonucleic acid (cfDNA) for differentially methylated regions is a promising test which is being rigorously validated. The special expertise required for these analyses has to date hampered their validation and adaptation. Herein, we will review these emerging technologies to inform the reader of the progress made and encourage further studies, as well as adaptation of validated approaches.