Management of asymptomatic, well-differentiated PNETs: results of the Delphi consensus process of the Americas Hepato-Pancreato-Biliary Association.

BACKGROUND: Variation in the management of PNETs exist due to the limited high-level evidence to guide clinical practice. The aim of this work is to generate consensus guidelines with a Delphi process for managing PNETs. METHODS: A panel of experts reviewed the surgical literature and scored a set of clinical case statements using a web-based survey to identify areas of agreement and disagreement. Results of the survey were discussed after each round of review. This cycle was repeated until no further likelihood of reaching consensus existed. RESULTS: Twenty-two case statements related to surgical indications, preoperative biopsy, extent of resection, type of surgery, and tumor location were scored. Using a pre-defined definition of consensus, the panel achieved consensus on the following: i) resection is not recommended forlesions; ii) resection is recommended for lesions greater than 2 cm; iii) lymph node dissection is recommended for radiographically-suspicious nodes with splenectomy for distal lesions; iv) tumor enucleation and central pancreatectomy are acceptable when technically feasible. No consensus was reached regarding issues of preoperative biopsy or 1-2 cm tumors. CONCLUSIONS: Using a structured, validated system for identifying consensus, an expert panel identified areas of agreement regarding critical management decisions for patients with PNET. Issues without consensus warrant additional clinical investigation

Surgery versus intra-arterial therapy for neuroendocrine liver metastasis: a multicenter international analysis

Management of patients with neuroendocrine liver metastasis (NELM) remains controversial. We sought to examine the relative efficacy of surgical management versus intra-arterial therapy (IAT) for NELM and determine factors predictive of survival

Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial.

IMPORTANCE: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood. OBJECTIVE: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment. INTERVENTION: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care). MAIN OUTCOMES AND MEASURES: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program. RESULTS: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P \u3c .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32). CONCLUSIONS AND RELEVANCE: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03269994

Assessment of functional capacity before major non-cardiac surgery: an international, prospective cohort study.

BACKGROUND: Functional capacity is an important component of risk assessment for major surgery. Doctors' clinical subjective assessment of patients' functional capacity has uncertain accuracy. We did a study to compare preoperative subjective assessment with alternative markers of fitness (cardiopulmonary exercise testing [CPET], scores on the Duke Activity Status Index [DASI] questionnaire, and serum N-terminal pro-B-type natriuretic peptide [NT pro-BNP] concentrations) for predicting death or complications after major elective non-cardiac surgery. METHODS: We did a multicentre, international, prospective cohort study at 25 hospitals: five in Canada, seven in the UK, ten in Australia, and three in New Zealand. We recruited adults aged at least 40 years who were scheduled for major non-cardiac surgery and deemed to have one or more risk factors for cardiac complications (eg, a history of heart failure, stroke, or diabetes) or coronary artery disease. Functional capacity was subjectively assessed in units of metabolic equivalents of tasks by the responsible anaesthesiologists in the preoperative assessment clinic, graded as poor (10). All participants also completed the DASI questionnaire, underwent CPET to measure peak oxygen consumption, and had blood tests for measurement of NT pro-BNP concentrations. After surgery, patients had daily electrocardiograms and blood tests to measure troponin and creatinine concentrations until the third postoperative day or hospital discharge. The primary outcome was death or myocardial infarction within 30 days after surgery, assessed in all participants who underwent both CPET and surgery. Prognostic accuracy was assessed using logistic regression, receiver-operating-characteristic curves, and net risk reclassification. FINDINGS: Between March 1, 2013, and March 25, 2016, we included 1401 patients in the study. 28 (2%) of 1401 patients died or had a myocardial infarction within 30 days of surgery. Subjective assessment had 19·2% sensitivity (95% CI 14·2-25) and 94·7% specificity (93·2-95·9) for identifying the inability to attain four metabolic equivalents during CPET. Only DASI scores were associated with predicting the primary outcome (adjusted odds ratio 0·96, 95% CI 0·83-0·99; p=0·03). INTERPRETATION: Subjectively assessed functional capacity should not be used for preoperative risk evaluation. Clinicians could instead consider a measure such as DASI for cardiac risk assessment. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.This study was supported by grants from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University (Melbourne, VIC, Australia). DNW is supported by a New Investigator Award from the Canadian Institutes of Health Research. DNW and BHC are partly supported by Merit Awards from the Department of Anesthesia at the University of Toronto. RMP is a Career Development Fellow for the British Journal of Anaesthesia and Royal College of Anaesthetists, and a professor for the UK National Institute for Health Research. TEFA is a clinical research training fellow for the UK Medical Research Council and British Journal of Anaesthesia. MPWG holds the British Oxygen Company Chair of Anaesthesia of the Royal College of Anaesthetists, which is awarded by the UK National Institute of Academic Anaesthesia. We thank the Li Ka Shing Knowledge Institute of St Michael's Hospital (Toronto, ON, Canada) for generously supporting the costs of international trial insurance for this study, and all the participating patients and staff across the 25 study sites