Analysis of Volatile Anesthetic-Induced Organ Protection in Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia-reperfusion injury (IRI)-Remains a common cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients. METHODS: Medical data of 105 patients undergoing SPKT between 1998-2018 were retrospectively analyzed and stratified according to the used VAs. The primary study endpoint was the association and effect of VAs on pancreas allograft failure following SPKT; secondary endpoint analyses included "IRI- associated posttransplant clinical outcome" as well as long-term graft function and outcome. Additionally, peak serum levels of C-reactive protein (CRP) and lipase during the first 72 h after SPKT were determined and used as further markers for "pancreatic IRI" and graft injury. Typical clinicopathological characteristics and postoperative outcomes such as early graft outcome and long-term function were analyzed. RESULTS: Of the 105 included patients in this study three VAs were used: isoflurane (n = 58 patients; 55%), sevoflurane (n = 22 patients; 21%), and desflurane (n = 25 patients, 24%). Donor and recipient characteristics were comparable between both groups. Early graft loss within 3 months (24% versus 5% versus 8%, p = 0.04) as well as IRI-associated postoperative clinical complications (pancreatitis: 21% versus 5% versus 5%, p = 0.04; vascular thrombosis: 13% versus 0% versus 5%; p = 0.09) occurred more frequently in the Isoflurane group compared with the sevoflurane and desflurane groups. Anesthesia with sevoflurane resulted in the lowest serum peak levels of lipase and CRP during the first 3 days after transplantation, followed by desflurane and isoflurane (p = 0.039 and p = 0.001, respectively). There was no difference with regard to 10-year pancreas graft survival as well as endocrine/metabolic function among all three VA groups. Multivariate analysis revealed the choice of VAs as an independent prognostic factor for graft failure three months after SPKT (HR 0.38, 95%CI: 0.17-0.84; p = 0.029). CONCLUSIONS: In our study, sevoflurane and desflurane were associated with significantly increased early graft survival as well as decreased IRI-associated post-transplant clinical outcomes when compared with the isoflurane group and should be the focus of future clinical studies evaluating the positive effects of different VA agents in patients receiving SPKT.

The role of virtual reality simulation in surgical training in the light of COVID-19 pandemic: Visual spatial ability as a predictor for improved surgical performance: a randomized trial.

INTRODUCTION: Due to the current COVID-19 pandemic, surgical training has become increasingly challenging due to required social distancing. Therefore, the use of virtual reality (VR)-simulation could be a helpful tool for imparting surgical skills, especially in minimally invasive environments. Visual spatial ability (VSA) might influence the learning curve for laparoscopic surgical skills. However, little is known about the influence of VSA for surgical novices on VR-simulator training regarding the complexity of different tasks over a long-term training period. Our study evaluated prior VSA and VSA development in surgical trainees during VR-simulator training, and its influence on surgical performance in simulator training. METHODS: In our single-center prospective two-arm randomized trial, VSA was measured with a tube figure test before curriculum training. After 1:1 randomization, the training group (TG) participated in the entire curriculum training consisting of 48 different VR-simulator tasks with varying difficulty over a continuous nine-day training session. The control group (CG) performed two of these tasks on day 1 and 9. Correlation and regression analyses were used to assess the influence of VSA on VR-related surgical skills and to measure procedural abilities. RESULTS: Sixty students (33 women) were included. Significant improvements in the TG in surgical performance and faster completion times were observed from days 1 to 9 for the scope orientation 30° right-handed (SOR), and cholecystectomy dissection tasks after the structured 9-day training program. After training, the TG with pre-existing low VSA scores achieved performance levels similar to those with pre-existing high VSA scores for the two VR simulator tasks. Significant correlations between VSA and surgical performance on complex laparoscopic camera navigation SOR tasks were found before training. CONCLUSIONS: Our study revealed that that all trainees improved their surgical skills irrespective of previous VSA during structured VR simulator training. An increase in VSA resulted in improvements in surgical performance and training progress, which was more distinct in complex simulator tasks. Further, we demonstrated a positive relationship between VSA and surgical performance of the TG, especially at the beginning of training. Our results identified pre-existing levels of VSA as a predictor of surgical performance.

Impact of Body Mass Index on Tumor Recurrence in Patients Undergoing Liver Resection for Perihilar Cholangiocarcinoma (pCCA).

BACKGROUND: The association of body mass index (BMI) and long-term prognosis and outcome of patients with perihilar cholangiocarcinoma (pCCA) has not been well defined. The aim of this study was to evaluate clinicopathologic and oncologic outcomes with pCCA undergoing resection, according to their BMI. METHODS: Patients undergoing liver resection in curative intention for pCCA at a tertiary German hepatobiliary (HPB) center were identified from a prospective database. Patients were classified as normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (>30 kg/m2) according to their BMI. Impact of clinical and histo-pathological characteristics on recurrence-free survival (RFS) were assessed using Cox proportional hazard regression analysis among patients of all BMI groups. RESULTS: Among a total of 95 patients undergoing liver resection in curative intention for pCCA in the analytic cohort, 48 patients (50.5%) had normal weight, 33 (34.7%) were overweight and 14 patients (14.7%) were obese. After a median follow-up of 4.3 ± 2.9 years, recurrence was observed in totally 53 patients (56%). The cumulative recurrence probability was higher in obese and overweight patients than normal weight patients (5-year recurrence rate: obese: 82% versus overweight: 81% versus normal weight: 58% at 5 years; p = 0.02). Totally, 1-, 3-, 5- and 10-year recurrence-free survival rates were 68.5%, 44.6%, 28.9% and 13%, respectively. On multivariable analysis, increased BMI (HR 1.08, 95% CI: 1.01-1.16; p = 0.021), poor/moderate tumor differentiation (HR 2.49, 95% CI: 1.2-5.2; p = 0.014), positive lymph node status (HR 2.01, 95% CI: 1.11-3.65; p = 0.021), positive resection margins (HR 1.89, 95% CI:1.02-3.4; p = 0.019) and positive perineural invasion (HR 2.92, 95% CI: 1.02-8.3; p = 0.045) were independent prognostic risk factors for inferior RFS. CONCLUSION: Our study shows that a high BMI is significantly associated with an increased risk of recurrence after liver resection in curative intention for pCCA. This factor should be considered in future studies to better predict patient's individual prognosis and outcome based on their BMI.

Pre-operative ankle-brachial index for cardiovascular risk assessment in simultaneous pancreas-kidney transplant recipients: a simple and elegant strategy!

BACKGROUND: Patients with insulin-dependent diabetes mellitus type 1 (IDDM1) and end-stage kidney disease (ESKD) undergoing simultaneous pancreas kidney transplantation (SPKT) are a population with diffuse atherosclerosis and elevated risk of cardio- and cerebrovascular morbidity and mortality. We aimed to investigate the feasibility of preoperative screening for peripheral arterial disease (PAD), specifically ankle-brachial index (ABI) testing, to predict peri- and postoperative outcomes in SPKT recipients. METHODS: Medical data (2000-2016) from all patients with IDDM and ESKD undergoing SPKT at our transplant center were retrospectively analyzed. The correlation between PAD (defined by an abnormal ABI before SPKT and graft failure and mortality rates as primary end points, and the occurrence of acute myocardial infarction, cerebrovascular and peripheral vascular complications as secondary end points were investigated after adjustment for known cardiovascular risk factors. RESULTS: Among 101 SPKT recipients in our transplant population who underwent structured physiological arterial studies, 17 patients (17%) were diagnosed with PAD before transplantation. PAD, as defined by a low ABI index, was an independent and significant predictor of death (HR, 2.99 (95% CI 1.00-8.87), p = 0.049) and pancreas graft failure (HR, 4.3 (95% CI 1.24-14.91), p = 0.022). No significant differences were observed for kidney graft failure (HR 1.85 (95% CI 0.76-4.50), p = 0.178). In terms of the secondary outcomes, patients with PAD were more likely to have myocardial infarction, stroke, limb ischemia, gangrene or amputation (HR, 2.90 (95% CI 1.19-7.04), p = 0.019). CONCLUSIONS: Pre-transplant screening for PAD and cardiovascular risk factors with non-invasive ABI testing may help to reduce perioperative complications in high-risk patients. Future research on long-term outcomes might provide more in depth insights in optimal treatment strategies for PAD among SPKT recipients.

Prognostic Relevance of the Eighth Edition of TNM Classification for Resected Perihilar Cholangiocarcinoma.

OBJECTIVES: In our study, we evaluated and compared the prognostic value and performance of the 6th, 7th, and 8th editions of the American Joint Committee on Cancer (AJCC) staging system in patients undergoing surgery for perihilar cholangiocarcinoma (PHC). METHODS: Patients undergoing liver surgery with curative intention for PHC between 2002 and 2019 were identified from a prospective database. Histopathological parameters and stage of the PHC were assessed according to the 6th, 7th, and 8th editions of the tumor node metastasis (TNM) classification. The prognostic accuracy between staging systems was compared using the area under the receiver operating characteristic curve (AUC) model. RESULTS: Data for a total of 95 patients undergoing liver resection for PHC were analyzed. The median overall survival time was 21 months (95% CI 8.1-33.9), and the three- and five-year survival rates were 46.1% and 36.2%, respectively. Staging according to the 8th edition vs. the 7th edition resulted in the reclassification of 25 patients (26.3%). The log-rank p-values for the 7th and 8th editions were highly statistically significant (p ≤ 0.01) compared to the 6th edition (p = 0.035). The AJCC 8th edition staging system showed a trend to better discrimination, with an AUC of 0.69 (95% CI: 0.52-0.84) compared to 0.61 (95% CI: 0.51-0.73) for the 7th edition. Multivariate survival analysis revealed male gender, age >65 years, positive resection margins, presence of distant metastases, poorly tumor differentiation, and lymph node involvement, such as no caudate lobe resection, as independent predictors of poor survival (p < 0.05). CONCLUSIONS: In the current study, the newly released 8th edition of AJCC staging system showed no significant benefit compared to the previous 7th edition in predicting the prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma. Further research may help to improve the prognostic value of the AJCC staging system for PHC-for instance, by identifying new prognostic markers or staging criteria, which may improve that individual patient's outcome.

Effects of simultaneous pancreas-kidney transplantation and kidney transplantation alone on the outcome of peripheral vascular diseases.

BACKGROUND: The effects of Simultaneous Pancreas Kidney Transplantation (SPKT) on Peripheral Vascular Disease (PVD) warrants additional study and more target focus, since little is known about the mid- and long-term effects on the progression of PVD after transplantation. METHODS: 101 SPKT and 26 Kidney Transplantation Alone (KTA) recipients with insulin-dependent diabetes mellitus (IDDM) were retrospectively evaluated with regard to graft and metabolic outcome. Special subgroup analysis was directed towards the development and progression of peripheral vascular complications (PVC) (amputation, ischemic ulceration, lower extremity angioplasty/ bypass surgery) after transplantation. RESULTS: The 10-year patient survival was significantly higher in the SPKT group (SPKT: 82% versus KTA 40%; P < 0.001). KTA recipients had a higher prevalence of atherosclerotic risk factors, including coronary artery disease (P < 0.001), higher serum triglyceride levels (P = 0.049), higher systolic (P = 0.03) and diastolic (P = 0.02) blood pressure levels. The incidence of PVD before transplantation was comparable between both groups (P = 0.114). Risk factor adjusted multivariate analysis revealed that patients with SPKT had a significant lower amount (32%) of PVCs (32 PVCs in 21 out of 101 SPKT; P < 0.001) when compared to the KTA patients who developed a significant increase in PVCs to 69% of cases (18 PVCs in 11 out of 26 KTA; P < 0.001). In line mean values of HbA1c (P < 0.01) and serum triglycerides (P < 0.01) were significantly lower in patients with SPKT > 8 years after transplantation. CONCLUSION: SPKT favorably slows down development and progression of PVD by maintaining a superior metabolic vascular risk profile in patients with IDDM1.

The challenge of liver resection in benign solid liver tumors in modern times - in which cases should surgery be done?

Background Due to improved diagnostical and therapeutical approaches, benign liver tumors represent a challenge in clinical management. We here report our experience with patients undergoing liver resection for benign liver tumors. Methods 188 One hundred eighty-eight consecutive patients, who underwent surgery for solid benign liver tumors from 1992 - 2014, were analyzed retrospectively. The focus was on diagnostic pathways, indications for surgery, and perioperative and postoperative quality of life (QoL). Results Of 188 patients, 100 had focal nodular hyperplasia (FNH) (53.2 %), 33 had hepatocellular adenoma (17.5 %), and 55 had hemangioma (29.3 %). In most patients, there was more than one 1 indication for liver resection, including tumor-associated symptoms (n = 82, 43.6 %), suspicion of malignancy (n = 104, 55.3 %), tumor disease in the medical history (n = 48, 25.5 %), or tumor enlargement (n = 27, 14.4 %). Serious complications (>grade III;, Clavien-Dindo) occurred in 9.5 % of patients. Perioperative mortality was 0.5 %. Patient pain scores decreased over time (p < 0.001). QoL after liver resection significantly improved (p = 0.007). Conclusion Uncertainty of the tumor entity remains an issue in preoperative diagnostics. If indicated, liver resection for benign liver tumors represents a safe approach and leads to significant improvements of QoL.

Inhaled carbon monoxide protects time-dependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice.

BACKGROUND: Inhaled carbon monoxide (CO) appears to have beneficial effects on endotoxemia-induced impairment of hypoxic pulmonary vasoconstriction (HPV). This study aims to specify correct timing of CO application, it's biochemical mechanisms and effects on inflammatory reactions. METHODS: Mice (C57BL/6; n = 86) received lipopolysaccharide (LPS, 30 mg/kg) intraperitoneally and subsequently breathed 50 ppm CO continuously during defined intervals of 3, 6, 12 or 18 h. Two control groups received saline intraperitoneally and additionally either air or CO, and one control group received LPS but breathed air only. In an isolated lung perfusion model vasoconstrictor response to hypoxia (FiO2 = 0.01) was quantified by measurements of pulmonary artery pressure. Pulmonary capillary pressure was estimated by double occlusion technique. Further, inflammatory plasma cytokines and lung tissue mRNA of nitric-oxide-synthase-2 (NOS-2) and heme oxygenase-1 (HO-1) were measured. RESULTS: HPV was impaired after LPS-challenge (p < 0.01). CO exposure restored HPV-responsiveness if administered continuously for full 18 h, for the first 6 h and if given in the interval between the 3(rd) and 6(th) hour after LPS-challenge (p < 0.05). Preserved HPV was attributable to recovered arterial resistance and associated with significant reduction in NOS-2 mRNA when compared to controls (p < 0.05). We found no effects on inflammatory plasma cytokines. CONCLUSION: Low-dose CO prevented LPS-induced impairment of HPV in a time-dependent manner, associated with a decreased NOS-2 expression.