Practice variation in anastomotic leak after esophagectomy: Unravelling differences in failure to rescue.

INTRODUCTION: Failure to rescue (FTR) is an important outcome measure after esophagectomy and reflects mortality after postoperative complications. Differences in FTR have been associated with hospital resection volume. However, insight into how centers manage complications and achieve their outcomes is lacking. Anastomotic leak (AL) is a main contributor to FTR. This study aimed to assess differences in FTR after AL between centers, and to identify factors that explain these differences. METHODS: TENTACLE - Esophagus is a multicenter, retrospective cohort study, which included 1509 patients with AL after esophagectomy. Differences in FTR were assessed between low-volume (<20 resections), middle-volume (20-60 resections) and high-volume centers (≥60 resections). Mediation analysis was performed using logistic regression, including possible mediators for FTR: case-mix, hospital resources, leak severity and treatment. RESULTS: FTR after AL was 11.7%. After adjustment for confounders, FTR was lower in high-volume vs. low-volume (OR 0.44, 95%CI 0.2-0.8), but not versus middle-volume centers (OR 0.67, 95%CI 0.5-1.0). After mediation analysis, differences in FTR were found to be explained by lower leak severity, lower secondary ICU readmission rate and higher availability of therapeutic modalities in high-volume centers. No statistically significant direct effect of hospital volume was found: high-volume vs. low-volume 0.86 (95%CI 0.4-1.7), high-volume vs. middle-volume OR 0.86 (95%CI 0.5-1.4). CONCLUSION: Lower FTR in high-volume compared with low-volume centers was explained by lower leak severity, less secondary ICU readmissions and higher availability of therapeutic modalities. To reduce FTR after AL, future studies should investigate effective strategies to reduce leak severity and prevent secondary ICU readmission.

[Gallbladder torsion]. / Torsie van de galblaas.

BACKGROUND: Gallbladder torsion or gallbladder volvulus is a rare condition of the hepatobiliary system, defined as a rotation of the gallbladder along its long axis causing an interruption of the vascular and biliary flow. It clinically mimics acute cholecystitis which makes accurate preoperative diagnosis challenging. CASE DESCRIPTION: We present the case of an 81-year-old woman with a three day history of upper-right quadrant pain, nausea, vomiting and no evidence of cholelithiasis on imaging. Emergency cholecystectomy was performed, intraoperative findings included a necrotic gallbladder with complete torsion. After the secondary diagnosis of gallbladder torsion, the clinical and radiologic findings were reviewed retrospectively. CONCLUSION: The acute onset of abdominal pain without clear progression over time should initially be the trigger for differential diagnostic consideration of gallbladder torsion. This combined with the previously described risk factors and radiological characteristics could result in successful pre-operative diagnosis of gallbladder torsion.

Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma.

Patients with gastric and esophageal (GE) adenocarcinoma tumors in which the oncogene ERBB2 has been amplified are routinely treated with a combination of cytotoxic chemotherapy and the ERBB2-directed antibody trastuzumab; however, the addition of trastuzumab, even when tested in a selected biomarker-positive patient population, provides only modest survival gains. To investigate the potential reasons for the modest impact of ERBB2-directed therapies, we explored the hypothesis that secondary molecular features of ERBB2-amplified GE adenocarcinomas attenuate the impact of ERBB2 blockade. We analyzed genomic profiles of ERBB2-amplified GE adenocarcinomas and determined that the majority of ERBB2-amplified tumors harbor secondary oncogenic alterations that have the potential to be therapeutically targeted. These secondary events spanned genes involved in cell-cycle regulation as well as phosphatidylinositol-3 kinase and receptor tyrosine kinase signaling. Using ERBB2-amplified cell lines, we demonstrated that secondary oncogenic events could confer resistance to ERBB2-directed therapies. Moreover, this resistance could be overcome by targeting the secondary oncogene in conjunction with ERBB2-directed therapy. EGFR is commonly coamplified with ERBB2, and in the setting of ERBB2 amplification, higher EGFR expression appears to mark tumors with greater sensitivity to dual EGFR/ERBB2 kinase inhibitors. These data suggest that combination inhibitor strategies, guided by secondary events in ERBB2-amplified GE adenocarcinomas, should be evaluated in clinical trials.