Comparison between transpapillary versus transmural endoscopic ultrasound-guided decompression for biliary obstruction: a meta-analysis.

BACKGROUND: Recent advances have led to the development of transmural endoscopic ultrasound guided biliary drainage (EUS-BD) for cases where the duodenal papilla cannot be accessed. OBJECTIVES: We performed a meta-analysis comparing efficacy and complications of both approaches for biliary drainage. REVIEW METHODS: English articles were searched in PubMed. Primary outcomes included technical success and complications. Secondary outcomes were clinical success and subsequent stent malfunction. Patient demographics and etiology of obstruction were collected and relative risk ratios and 95% CIs were calculated. P-value <0.05 was considered as statistically significant. RESULTS: Initial database search yielded 245 studies from which 7 were chosen based upon inclusion criteria for final analysis. There was no statistically different relative risk for technical success when comparing primary EUS-BD to endoscopic retrograde cholangiopancreatography (ERCP) (RR: 1.04) or overall procedural complication rate (RR 1.39). EUS-BD did have increased specific risk of cholangitis (RR: 3.01). Likewise, primary EUS-BD and ERCP had similar RR for clinical success (RR: 1.02) and overall stent malfunction (RR: 1.55), but stent migration was higher in the primary EUS-BD group (RR: 5.06). CONCLUSIONS: Primary EUS-BD may be considered when the ampulla cannot be accessed, when there is gastric outlet obstruction, or presence of a duodenal stent.

Drosophila histone H2A variant (H2Av) controls poly(ADP-ribose) polymerase 1 (PARP1) activation in chromatin.

According to the histone code hypothesis, histone variants and modified histones provide binding sites for proteins that change the chromatin state to either active or repressed. Here, we identify histone variants that regulate the targeting and enzymatic activity of poly(ADP-ribose) polymerase 1 (PARP1), a chromatin regulator in higher eukaryotes. We demonstrate that PARP1 is targeted to chromatin by association with the histone H2A variant (H2Av)--the Drosophila homolog of the mammalian histone H2A variants H2Az/H2Ax--and that subsequent phosphorylation of H2Av leads to PARP1 activation. This two-step mechanism of PARP1 activation controls transcription at specific loci in a signal-dependent manner. Our study establishes the mechanism through which histone variants and changes in the histone modification code control chromatin-directed PARP1 activity and the transcriptional activation of target genes.

Perforated Sigmoid Diverticulitis Within a Strangulated Inguinal Hernia.

We present a rare case of perforated diverticulitis within an inguinal hernia sac adjacent to a synthetic mesh from a prior incisional hernia. An 80-year-old-female presented to the ED with abdominal pain. Cross-sectional imaging was significant for a small bowel obstruction with a transition point in the right lower quadrant (RLQ). On physical exam, the patient had palpable bilateral inguinal hernias that were reducible; however, after 48 hours of nonoperative management she failed to progress. Repeat imaging was concerning for incarcerated bowel within the inguinal hernia sac. She was taken to the operating room for exploratory laparotomy where the right inguinal hernia sac was found to contain sigmoid colon with diverticular perforation. A small bowel resection, right hemicolectomy and Hartmann's procedure were performed. The previously placed synthetic mesh was not contaminated during this operation and was not removed. Her hospital course was otherwise unremarkable but prolonged by the patient's deconditioned state.

T-tube Duodenostomy for the Difficult Duodenum.

Tube duodenostomy has been described as a useful technique in the management of difficult duodenum arising from a variety of pathologies. In addition, the use of a t-tube for the duodenostomy presents a resourceful option in the event of Malecot or other such catheter unavailability. The aim of our study is to describe the technique and outcomes associated with this approach. During a six-month period in 2020, t-tube duodenostomies were performed in three patients for duodenal stump perforation: the first case involved a patient with Roux-en-Y esophagojejunostomy anatomy; the second involved duodenal stump closure security following Billroth II gastrectomy for peptic ulcer disease; and the third involved decompression following primary closure of duodenal perforation. All duodenostomies were performed with a t-tube that was trimmed with the back wall divided and then secured via the Witzel approach. The t-tube duodenostomies were performed during the index operations of all patients. No patient required additional operations. There was no mortality. All patients were closely monitored postoperatively with duodenostomies kept in place for six weeks. One patient developed a small leak after a trial of tube clamping, which was managed with continued tube drainage and antibiotics prior to definitive removal. The mean length of stay was 20.3 days with two patients being discharged to rehab. T-tube duodenostomy is a simple technique that helps avoid the blowout of the vulnerable duodenal stump in situations of biliopancreatic limb pathology, ulcerative disease, or injury.

Characterization of a carcinogenesis rat model of ovarian preneoplasia and neoplasia.

Animal models of ovarian cancer are crucial for understanding the pathogenesis of the disease and for testing new treatment strategies. A model of ovarian carcinogenesis in the rat was modified and improved to yield ovarian preneoplastic and neoplastic lesions that pathogenetically resemble human ovarian cancer. A significantly lower dose (2 to 5 mug per ovary) of 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the one ovary to maximally preserve its structural integrity. DMBA-induced mutagenesis was additionally combined with repetitive gonadotropin hormone stimulation to induce multiple cycles of active proliferation of the ovarian surface epithelium. Animals were treated in three arms of different doses of DMBA alone or followed by hormone administration. Comparison of the DMBA-treated ovaries with the contralateral control organs revealed the presence of epithelial cell origin lesions at morphologically distinct stages of preneoplasia and neoplasia. Their histopathology and path of dissemination to other organs are very similar to human ovarian cancer. Hormone cotreatment led to an increased lesion severity, indicating that gonadotropins may promote ovarian cancer progression. Point mutations in the Tp53 and Ki-Ras genes were detected that are also characteristic of human ovarian carcinomas. Additionally, an overexpression of estrogen and progesterone receptors was observed in preneoplastic and early neoplastic lesions, suggesting a role of these receptors in ovarian cancer development. These data indicate that this DMBA animal model gives rise to ovarian lesions that closely resemble human ovarian cancer and it is adequate for additional studies on the mechanisms of the disease and its clinical management.

Small-molecule collection and high-throughput colorimetric assay to identify PARP1 inhibitors.

During the last few years, poly(ADP-ribose)polymerase (PARP) proteins became a very popular target for anticancer treatment. Many PARP inhibitors have been generated and tested by pharmacological industry. However, most of them were designed to disrupt the DNA-dependent PARP1 protein activation pathway and were based on a competition with NAD for a binding site on PARP molecule and, therefore, on disruption of PARP-mediated enzymatic reaction. This limitation resulted in a discovery of mainly nucleotide-like PARP1 inhibitors which may target not only PARP, but also other pathways involving NAD and other nucleotides. Here, we describe a strategy for the identification of PARP inhibitors that target a different pathway, the histone H4-dependent PARP1 activation. Besides the identification of NAD competitors in a small-molecule collection, this approach allows finding novel classes of PARP inhibitors that specifically disrupt H4-based PARP activation.