Prolonged hypothermic machine perfusion enables daytime liver transplantation - an IDEAL stage 2 prospective clinical trial.

Background: Liver transplantation is traditionally performed around the clock to minimize organ ischemic time. However, the prospect of prolonging preservation times holds the potential to streamline logistics and transform liver transplantation into a semi-elective procedure, reducing the need for nighttime surgeries. Dual hypothermic oxygenated machine perfusion (DHOPE) of donor livers for 1-2 h mitigates ischemia-reperfusion injury and improves transplant outcomes. Preclinical studies have shown that DHOPE can safely extend the preservation of donor livers for up to 24 h. Methods: We conducted an IDEAL stage 2 prospective clinical trial comparing prolonged (≥4 h) DHOPE to conventional (1-2 h) DHOPE for brain-dead donor livers, enabling transplantation the following morning. Liver allocation to each group was based on donor hepatectomy end times. The primary safety endpoint was a composite of all serious adverse events (SAE) within 30 days after transplantation. The primary feasibility endpoint was defined as the number of patients assigned and successfully receiving a prolonged DHOPE-perfused liver graft. Trial registration at: WHO International Clinical Trial Registry Platform, number NL8740. Findings: Between November 1, 2020 and July 16, 2022, 24 patients were enrolled. The median preservation time was 14.5 h (interquartile range [IQR], 13.9-15.5) for the prolonged group (n = 12) and 7.9 h (IQR, 7.6-8.6) for the control group (n = 12; p = 0.01). In each group, three patients (25%; 95% CI 3.9-46%, p = 1) experienced a SAE. Markers of ischemia-reperfusion injury and oxidative stress in both perfusate and recipients were consistently low and showed no notable discrepancies between the two groups. All patients assigned to either the prolonged group or control group successfully received a liver graft perfused with either prolonged DHOPE or control DHOPE, respectively. Interpretation: This first-in-human clinical trial demonstrates the safety and feasibility of DHOPE in prolonging the preservation time of donor livers to enable daytime transplantation. The ability to extend the preservation window to up to 20 h using hypothermic oxygenated machine preservation at a 10 °C temperature has the potential to reshape the landscape of liver transplantation. Funding: University Medical Center Groningen, the Netherlands.

Nationwide Outcome after Pancreatoduodenectomy in Patients at very High Risk (ISGPS-D) for Postoperative Pancreatic Fistula.

OBJECTIVE: To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D. SUMMARY BACKGROUND DATA: Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking. METHODS: Nationwide retrospective analysis including consecutive patients undergoing ISGPS-D PD (i.e., soft texture and pancreatic duct ≤3 mm), using the mandatory Dutch Pancreatic Cancer Audit (2014-2021). Primary outcome was in-hospital mortality and secondary outcomes included major morbidity (i.e., Clavien-Dindo grade ≥IIIa) and POPF (ISGPS grade B/C). The use of prophylactic TP to avoid POPF during the study period was assessed. RESULTS: Overall, 1402 patients were included. In-hospital mortality was 4.1% (n=57), which decreased to 3.7% (n=20/536) in the last 2 years. Major morbidity occurred in 642 patients (45.9%) and POPF in 410 (30.0%), which corresponded with failure to rescue in 8.9% (n=57/642). Patients with POPF had increased rates of major morbidity (88.0% vs. 28.3%; P<0.001) and mortality (6.3% vs. 3.5%; P=0.016), compared to patients without POPF. Among 190 patients undergoing TP, prophylactic TP to prevent POPF was performed in 4 (2.1%). CONCLUSION: This nationwide series found a 4.1% in-hospital mortality after ISGPS-D PD with 45.9% major morbidity, leaving little room for improvement through prophylactic TP. Nevertheless, given the outcomes in 30% of patients who develop POPF, future randomized trials should aim to prevent and mitigate POPF in this high-risk category.

Is surgical subspecialization associated with hand grip strength and manual dexterity? A cross-sectional study.

BACKGROUND: The aim of this study was to compare hand grip strength (HGS) and manual dexterity of academic, subspecialized surgeons. METHODS: A single-center cross-sectional study was performed among 61 surgeons. HGS was analysed with a hand dynamometer and manual dexterity was extensively analysed with a Purdue Pegboard Test. Correlations between HGS and manual dexterity and specific characteristics of the surgeons were analysed using Pearson's correlation coefficient (r). RESULTS: HGS and manual dexterity were comparable between surgeons from different specialities. HGS was positively correlated with male gender (r = 0.59, p < 0.001) and hand glove size (r = 0.61, p < 0.001), whereas manual dexterity was negatively correlated with male gender (r = -0.35, p = 0.006), age (r = -0.39, = 0.002), and hand glove size (r = -0.46, p < 0.001). CONCLUSIONS: Surgical subspecialization was not correlated with HGS or manual dexterity. Male surgeons have greater HGS, whereas female surgeons have better manual dexterity. Manual dexterity is also correlated with age, showing better scores for younger surgeons.

Impact of Complications After Pancreatoduodenectomy on Mortality, Organ Failure, Hospital Stay, and Readmission: Analysis of a Nationwide Audit.

OBJECTIVE: To quantify the impact of individual complications on mortality, organ failure, hospital stay, and readmission after pancreatoduodenectomy. SUMMARY OF BACKGROUND DATA: An initial complication may provoke a sequence of adverse events potentially leading to mortality after pancreatoduodenectomy. This study was conducted to aid prioritization of quality improvement initiatives. METHODS: Data from consecutive patients undergoing pancreatoduodenectomy (2014-2017) were extracted from the Dutch Pancreatic Cancer Audit. Population attributable fractions (PAF) were calculated for the association of each complication (ie, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, wound infection, and pneumonia) with each unfavorable outcome [ie, in-hospital mortality, organ failure, prolonged hospital stay (>75th percentile), and unplanned readmission), whereas adjusting for confounders and other complications. The PAF represents the proportion of an outcome that could be prevented if a complication would be eliminated completely. RESULTS: Overall, 2620 patients were analyzed. In-hospital mortality occurred in 95 patients (3.6%), organ failure in 198 patients (7.6%), and readmission in 427 patients (16.2%). Postoperative pancreatic fistula and postpancreatectomy hemorrhage had the greatest independent impact on mortality [PAF 25.7% (95% CI 13.4-37.9) and 32.8% (21.9-43.8), respectively] and organ failure [PAF 21.8% (95% CI 12.9-30.6) and 22.1% (15.0-29.1), respectively]. Delayed gastric emptying had the greatest independent impact on prolonged hospital stay [PAF 27.6% (95% CI 23.5-31.8)]. The impact of individual complications on unplanned readmission was smaller than 11%. CONCLUSION: Interventions focusing on postoperative pancreatic fistula and postpancreatectomy hemorrhage may have the greatest impact on in-hospital mortality and organ failure. To prevent prolonged hospital stay, initiatives should in addition focus on delayed gastric emptying.

Outcome after cholecystectomy in the elderly.

BACKGROUND: Cholecystectomy is considered the standard treatment for acute cholecystitis and symptomatic gallstones. An increasing number of frail elderly patients are being referred for this surgical treatment. A better understanding of surgical outcome in the elderly is needed to improve quality of care. METHODS: A retrospective analysis of 565 patients who underwent cholecystectomy was performed. Focus of the analyses was on postoperative complications and its predictors. RESULTS: The study population was divided in two cohorts; aged <70. More complications were found in patients aged ≥70 years. More elderly patients were admitted to the intensive care, respectively 4.0% and 14.1% (P = 0.045). Hospital mortality was 6% in patients aged ≥70 years vs 0.6% in patients <70. CONCLUSION: In elderly patients, the complication and mortality rate following cholecystectomy is higher than previously reported. For high-risk patients aged ≥70 with cholecystitis, alternative therapies should be considered as a bridge to surgery or definite treatment.

Risk factors for postoperative delirium after colorectal operation.

BACKGROUND: A clear understanding of risk factors for postoperative delirium helps in the selection of individuals who might benefit from targeted perioperative intervention. The aim of this study was to identify risk factors for postoperative delirium after colorectal operation for malignancy. METHODS: All consecutive patients who underwent elective or emergency operation because of malignancy of the colon, sigmoid, or rectum between 2009 and 2012 were included in this study. Potential risk factors for postoperative delirium were selected based on previous studies. These candidate factors were analyzed using univariate and multivariate logistic regression analysis. Based on this analysis, odds ratios and 95% confidence intervals were estimated. RESULTS: A total of 436 patients underwent an oncologic resection of the colon, sigmoid, or rectum. Postoperative delirium was observed in 45 (10.3%) patients. Patients with a delirium had a greater in-hospital mortality rate (8.9% vs 3.6%, P = .09), spent more days in the intensive care unit, and had a longer total hospital stay. Variables associated with postoperative delirium in univariate analyses were age, American Society of Anesthesiologists classification, blood transfusion, history of psychiatric disease, history of cerebrovascular disease, postoperative pain management, postoperative renal impairment, C-reactive protein levels, leukocyte blood count, and postoperative complications. Independent risk factors were history of psychiatric disease (odds ratio 8.38, 95% confidence interval: 1.50-46.82), age (odds ratio 4.01, 95% confidence interval; 1.55-10.37), and perioperative blood transfusion (odds ratio 2.37, 95% confidence interval; 1.11-5.06). CONCLUSION: This study shows that postoperative delirium is a frequently encountered complication after colorectal operation. Three independent risk factors for postoperative delirium were identified (history of psychiatric disease, age, and perioperative transfusion) that may contribute to risk estimation in this patient population.