OBJECTIVE To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD). BACKGROUND Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative. METHODS This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class 3) and a cohort treated by minimally invasive approaches. RESULTS Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA 3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases. CONCLUSION The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.

Steatosis is the most common consequence of acute alcohol abuse and may predispose to more severe hepatic disease. Increased lipogenesis driven by the sterol response element binding protein (SREBP) transcription factors is essential for steatosis associated with chronic alcohol ingestion, but the mechanisms underlying steatosis following acute alcohol exposure are unknown. Zebrafish larvae represent an attractive vertebrate model for studying alcoholic liver disease (ALD), because they possess the pathways to metabolize alcohol, the liver is mature by 4 days post-fertilization (dpf), and alcohol can be simply added to their water. Exposing 4 dpf zebrafish larvae to 2% ethanol (EtOH) for 32 hours achieves ϳ80 mM intracellular EtOH and upregulation of hepatic cyp2e1, sod, and bip, indicating that EtOH is metabolized and provokes oxidant stress. EtOH-treated larvae develop hepatomegaly and steatosis accompanied by changes in the expression of genes required for hepatic lipid metabolism. Based on the importance of SREBPs in chronic ALD, we explored the role of Srebps in this model of acute ALD. Srebp activation was prevented in gonzo larvae, which harbor a mutation in the membrane-bound transcription factor protease 1 (mbtps1) gene, and in embryos injected with a morpholino to knock down Srebp cleavage activating protein (scap). Both gonzo mutants and scap morphants were resistant to steatosis in response to 2% EtOH, and the expression of many Srebp target genes are down-regulated in gonzo mutant livers. Conclusion: Zebrafish larvae develop signs of acute ALD, including steatosis. Srebp activation is required for steatosis in this model. The tractability of zebrafish genetics provides a valuable tool for dissecting the molecular pathogenesis of acute ALD. (HEPATOLOGY 2009;49:443-452.)

Objective To prospectively assess the construct and criterion validity of ClassIntra version 1.0, a newly developed classification for assessing intraoperative adverse events. Design International, multicentre cohort study. Setting 18 secondary and tertiary centres from 12 countries in Europe, Oceania, and North America. Participants The cohort study included a representative sample of 2520 patients in hospital having any type of surgery, followed up until discharge. A follow-up to assess mortality at 30 days was performed in 2372 patients (94%). A survey was sent to a representative sample of 163 surgeons and anaesthetists from participating centres. Main outcome measures Intraoperative complications were assessed according to ClassIntra. Postoperative complications were assessed daily until discharge from hospital with the Clavien-Dindo classification. The primary endpoint was construct validity by investigating the risk adjusted association between the most severe intraoperative and postoperative complications, measured in a multivariable hierarchical proportional odds model. For criterion validity, inter-rater reliability was evaluated in a survey of 10 fictitious case scenarios describing intraoperative complications. Results Of 2520 patients enrolled, 610 (24%) experienced at least one intraoperative adverse event and 838 (33%) at least one postoperative complication. Multivariable analysis showed a gradual increase in risk for a more severe postoperative complication with increasing grade of ClassIntra: ClassIntra grade I versus grade 0, odds ratio 0.99 (95% confidence interval 0.69 to 1.42); grade II versus grade 0, 1.39 (0.97 to 2.00); grade III versus grade 0, 2.62 (1.31 to 5.26); and grade IV versus grade 0, 3.81 (1.19 to 12.2). ClassIntra showed high criterion validity with an intraclass correlation coefficient of 0.76 (95% confidence interval 0.59 to 0.91) in the survey (response rate 83%). Conclusions ClassIntra is the first prospectively validated classification for assessing intraoperative adverse events in a standardised way, linking them to postoperative complications with the well established Clavien-Dindo classification. ClassIntra can be incorporated into routine practice in perioperative surgical safety checklists, or used as a monitoring and outcome reporting tool for different surgical disciplines. Future studies should investigate whether the tool is useful to stratify patients to the appropriate postoperative care, to enhance the quality of surgical interventions, and to improve long term outcomes of surgical patients. Trial registration ClinicalTrials.gov NCT03009929 .

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