Effect of Donor Cigarette Smoking in Kidney Transplantation: Re-Evaluation of Long-Term Outcomes.

Cigarette smoking is a common risk factor associated with negative long-term outcomes in kidney transplant recipients. However, whether donor smoking decreases graft longevity or negatively impacts recipient survival after kidney transplantation remains unknown. Therefore, this study aims to investigate the long-term outcome in patients who received a kidney graft from a deceased smoking or non-smoking donor. A total of 580 patients were divided into two groups: patients who received a graft from a smoking donor (n = 276) and those who received a graft from a non-smoking donor (n = 304). Analysis of demographic factors showed that the non-smoking cohort was older, had more extended criteria donors and longer warm ischemia times. The primary composite endpoint of patient and graft survival was better in the smoking donor cohort when analyzed using Kaplan-Meier method but not when controlled for covariates in multivariate analyses. These findings do not support a previously reported negative impact of deceased donor smoking on kidney transplant recipients. Thus, the underlying results should not be interpreted in favor of a positive donor smoking history, but rather remind the transplant community that donor smoking should not be considered as a deciding factor in refusing an otherwise acceptable kidney graft.

Viability assessment and transplantation of extended criteria donor liver grafts using normothermic machine perfusion.

BACKGROUND: The scarcity of available liver grafts necessitates the use of organs from extended criteria donors, a practice associated with an increased risk of graft failure. A notable percentage of deceased donor liver allografts are rejected due to subjective criteria. Normothermic machine perfusion holds promise for introducing objective parameters into this decision-making process. The aim of this study was to compare the outcomes of standard criteria and extended criteria donor allografts after liver transplantation, following viability assessment, using normothermic machine perfusion. METHODS: Liver allografts preserved by normothermic machine perfusion before liver transplantation at the University Hospital of Münster were retrospectively analyzed. Organs were stratified according to the Eurotransplant Donor Risk Index. In total, 101 liver grafts were included in this study and divided into 2 groups: (1) standard criteria donors with a Donor Risk Index <1.8 (DRI-low) and (2) extended criteria donors with a Donor Risk Index ≥1.8 (DRI-high). RESULTS: An increased risk profile of donor livers, as assessed by the Eurotransplant Donor Risk Index, did not correlate with patient or graft survival. High-risk liver grafts were effectively transplanted into recipients with different risk levels after viability assessment by normothermic machine perfusion. However, the recipients' model for end-stage liver disease scores showed a significant association with both overall patient and graft survival. CONCLUSION: The use of normothermic machine perfusion for viability assessment allows safe transplantation of high-risk donor livers and effectively addresses the disparity between donor liver availability and transplantation demand.

Radiomics-Based Prediction Model for Outcome of Radioembolization in Metastatic Colorectal Cancer.

PURPOSE: To evaluate the benefit of a contrast-enhanced computed tomography (CT) radiomics-based model for predicting response and survival in patients with colorectal liver metastases treated with transarterial Yttrium-90 radioembolization (TARE). MATERIALS AND METHODS: Fifty-one patients who underwent TARE were included in this single-center retrospective study. Response to treatment was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 3-month follow-up. Patients were stratified as responders (complete/partial response and stable disease, n = 24) or non-responders (progressive disease, n = 27). Radiomic features (RF) were extracted from pre-TARE CT after segmentation of the liver tumor volume. A model was built based on a radiomic signature consisting of reliable RFs that allowed classification of response using multivariate logistic regression. Patients were assigned to high- or low-risk groups for disease progression after TARE according to a cutoff defined in the model. Kaplan-Meier analysis was performed to analyze survival between high- and low-risk groups. RESULTS: Two independent RF [Energy, Maximal Correlation Coefficient (MCC)], reflecting tumor heterogeneity, discriminated well between responders and non-responders. In particular, patients with higher magnitude of voxel values in an image (Energy), and texture complexity (MCC), were more likely to fail TARE. For predicting treatment response, the area under the receiver operating characteristic curve of the radiomics-based model was 0.75 (95% CI 0.48-1). The high-risk group had a shorter overall survival than the low-risk group (3.4 vs. 6.4 months, p < 0.001). CONCLUSION: Our CT radiomics model may predict the response and survival outcome by quantifying tumor heterogeneity in patients treated with TARE for colorectal liver metastases.

Imaging-Derived Biomarkers Integrated with Clinical and Laboratory Values Predict Recurrence of Hepatocellular Carcinoma After Liver Transplantation.

Purpose: To investigate the prognostic value of computed tomography (CT) derived imaging biomarkers in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and develop a predictive nomogram model. Patients and Methods: This retrospective study included 178 patients with histopathologically confirmed HCC who underwent liver transplantation between 2007 and 2021 at the two academic liver centers. We evaluated dedicated imaging features from baseline multiphase contrast-enhanced CT supplemented by several clinical findings and laboratory parameters. Time-to-recurrence was estimated by Kaplan-Meier analysis. Univariable Cox proportional hazard regression and multivariable Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent prognostic factors for recurrence. A nomogram model was then built based on the independent factors selected through LASSO regression, to predict the probabilities of HCC recurrence at one, three, and five years. Results: The rate of HCC recurrence after LT was 17.4% (31 of 178). The LASSO analysis revealed six independent predictors associated with an elevated risk of tumor recurrence. These predictors included the presence of peritumoral enhancement, the presence of over three tumor lesions, the largest tumor diameter greater than 3 cm, serum alpha-fetoprotein (AFP) levels exceeding 400 ng/mL, and the presence of a tumor capsule. Conversely, a history of bridging therapies was found to be correlated with a reduced risk of HCC recurrence. In addition, Kaplan-Meier curves showed patients with irregular margin, satellite nodules, or small lesions displayed shorter time-to-recurrence. Our nomogram demonstrated good performance, yielding a C-index of 0.835 and AUC values of 0.86, 0.88, and 0.85 for the predictions of 1-year, 3-year, and 5-year TTR, respectively. Conclusion: Imaging parameters derived from baseline contrast-enhanced CT showing malignant behavior and aggressive growth patterns, along with serum AFP and history of bridging therapies, show potential as biomarkers for predicting HCC recurrence after transplantation.

Multi-organ Radiomics-Based Prediction of Future Remnant Liver Hypertrophy Following Portal Vein Embolization.

BACKGROUND: Portal vein embolization (PVE) is used to induce remnant liver hypertrophy prior to major hepatectomy. The purpose of this study was to evaluate the predictive value of baseline computed tomography (CT) data for future remnant liver (FRL) hypertrophy after PVE. METHODS: In this retrospective study, all consecutive patients undergoing right-sided PVE with or without hepatic vein embolization between 2018 and 2021 were included. CT volumetry was performed before and after PVE to assess standardized FRL volume (sFRLV). Radiomic features were extracted from baseline CT after segmenting liver (without tumor), spleen and bone marrow. For selecting features that allow classification of response (hypertrophy ≥ 1.33), a stepwise dimension reduction was performed. Logistic regression models were fitted and selected features were tested for their predictive value. Decision curve analysis was performed on the test dataset. RESULTS: A total of 53 patients with liver tumor were included in this study. sFRLV increased significantly after PVE, with a mean hypertrophy of FRL of 1.5 ± 0.3-fold. sFRLV hypertrophy ≥ 1.33 was reached in 35 (66%) patients. Three independent radiomic features, i.e. liver-, spleen- and bone marrow-associated, differentiated well between responders and non-responders. A logistic regression model revealed the highest accuracy (area under the curve 0.875) for the prediction of response, with sensitivity of 1.0 and specificity of 0.5. Decision curve analysis revealed a positive net benefit when applying the model. CONCLUSIONS: This proof-of-concept study provides first evidence of a potential predictive value of baseline multi-organ radiomics CT data for FRL hypertrophy after PVE.

Clinical impact of a celiac axis stenosis in patients undergoing hepatobiliary surgery.

BACKGROUND: Celiac axis stenosis (CAS) often is an incidental finding in terms of diagnostic for hepatobiliary surgery since most cases remain asymptomatic. It remains unclear whether CAS is a risk factor for postoperative complications after hepatobiliary surgery. Therefore, the aim of this study was to evaluate the impact of an asymptomatic CAS on the postoperative morbidity and survival of patients undergoing hepatobiliary surgery. METHODS: We retrospectively analyzed CT scans and clinicopathological data of 250 consecutive patients undergoing hepatobiliary surgery between 2011 and 2018 in our tertiary center. We compared the postoperative course between patients with and without an incidental CAS as well as their overall survival. RESULTS: CAS was caused by atherosclerotic stenosis in 16 (64%) patients, by ligamentous stenosis in 4 (16%) and by combined conditions in 5 cases (20%). Mean age of patients in the CAS group was significantly higher in comparison to patients of the non-CAS group (71.0 vs. 59.1 years, p < 0.001). Major hepatectomy was conducted in 40% of the CAS patients and 19.6% of non-CAS patients, respectively (p = 0.036). Interestingly, no statistically significant differences in postoperative morbidity (40 vs. 46.2%, p = 0.673) or in overall survival between the groups (41.3 vs. 51.9 months, p = 0.611) were observed. CONCLUSION: Our analysis found no correlation between an asymptomatic celiac axis stenosis and postoperative complications or overall survival after hepatobiliary surgery. Which impact the incidental CAS may have in highly complex cases remains unclear. Further studies are needed to identify patients who benefit from CAS treatment before hepatobiliary surgery.

Resection margin status at the portomesenteric axis may not determine oncologic outcome after pancreaticoduodenectomy for lymph node-positive pancreatic ductal adenocarcinoma.

BACKGROUND: Lymph node and resection margin status are associated with oncologic outcomes after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. However, surgical radicality at the portomesenteric axis in case of suspected infiltration remains controversial. METHODS: Clinicopathological data of patients who underwent a partial or total pancreaticoduodenectomy for PDAC between 2012 to 2019 in 2 major hepato-pancreato-biliary centers in Germany and Switzerland were assessed. We evaluated the impact of positive resection margins at the vascular, parenchymal, and retropancreatic surfaces on overall survival in patients with and without lymph node involvement. Margin-positive vascular resection included both patients with positive margins at the vascular groove and the resected venous wall. RESULTS: During the study period, 217 patients underwent partial/total pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. After excluding 7 patients suffering postoperative complications resulting in mortality within 90 days after surgery (3%), 169 patients had lymph node involvement (80%). In the entire study cohort, margin-positive resection (33%) was significantly associated with worse overall survival (3-year overall survival: margin-positive resection: 27% vs margin-negative resection: 43%, P = .014). Among patients with positive lymph nodes, margin-positive vascular resection (n = 48, 28%) was not significantly associated with impaired overall survival (3-year overall survival: margin-positive vascular resection: 28% vs margin-negative vascular resection: 36%, P = .065). On the contrary, margin-positive parenchymal resection (n = 7, 4%) (3-year overall survival: margin-positive parenchymal resection: 0% vs margin-negative parenchymal resection: 35%, P < .0001) and margin-positive retropancreatic resection (n = 21, 12%) (3-year overall survival: margin-positive retropancreatic resection: 6% vs margin-negative retropancreatic resection: 39%, P < .0001) significantly diminished overall survival in univariate and multivariate analysis in all patients. Among patients without lymph node involvement (n = 41, 20%), there were no margin-positive parenchymal or margin-positive retropancreatic resections. In contrast, only 5 patients had margin-positive vascular resection (12%), with overall survival compared to those with margin-negative vascular resection. CONCLUSIONS: In patients with pancreatic ductal adenocarcinoma and lymph nodal positivity, resection status at the parenchymal and retropancreatic surface but probably not at the portal and/or superior mesenteric vein is a determinant of survival. Therefore, margin-negative resection should be pursued during pancreaticoduodenectomy. However, radical venous resection and/or reconstruction for suspected tumor infiltration may not be necessary for patients with intraoperatively detected lymph node metastases.

Struggle in the bubble - a prospective study on the effect of remote learning and distance education on confidence in practical surgical skills acquired during COVID-19.

BACKGROUND: The coronavirus disease (COVID-19) has significantly changed healthcare systems and medical education. Universities were required to develop innovative curricula based on remote and distance education to continue medical education. This prospective questionnaire-based study aimed to investigate the impact of COVID-19-associated remote learning on the surgical training of medical students. METHODS: A 16-item questionnaire-based survey was distributed to medical students at the University Hospital of Münster before and after a surgical skills laboratory (SSL). Two cohorts were included: summer semester 2021 (COV-19), with rigorous social-distancing restrictions requiered SSL to be remotely, and winter semester 2021 (postCOV-19), in which the SSL was provided as a face-to-face, hands-on course. RESULTS: Both, cohorts showed a significant improvement in self-assessment of pre- and post-course confidence. While no significant difference in the average gain in self-confidence for sterile working was observed between the two cohorts, improvement in self-confidence was significantly higher in the COV-19 cohort regarding skin suturing and knot tying (p < 0.0001). However the average improvement regarding history and physical was significantly higher in the postCOV-19 cohort (p < 0.0001). In subgroup analysis, gender-associated differences varied in the two cohorts and were not related to specific subtasks, while age-stratified analysis revealed superior results for younger students. CONCLUSION: The results of our study underline the usability, feasibility, and adequacy of remote learning for the surgical training of medical students. The on-site distance education version, presented in the study, allows the continuing of hands-on experience in a safe environment in compliance with governmental social-distancing restrictions.

Ex situ arterial reconstruction prior normothermic machine perfusion of liver grafts.

PURPOSE: Atypical variants of the hepatic artery are common and pose a technical challenge for normothermic machine perfusion (NMP). The transplant surgeon has three options when confronted with hepatic arterial variation in a liver graft to be subjected to NMP: to perform arterial reconstruction (i) prior, (ii) during, or (iii) following NMP. METHODS: Herein, we report our experience and technical considerations with pre-NMP reconstruction. Out of 52 livers, 9 had an atypical hepatic artery (HA): 3 replaced right HA, 3 replaced left HA, 1 accessory left HA, 1 accessory left and right HA, and 1 replaced left and right HA. RESULTS: Reconstruction was conducted during back-table preparation. A single vascular conduit was created in all grafts to allow single arterial cannulation for NMP, necessitating only one arterial anastomosis within the recipient. All grafts were subjected to NMP and subsequently successfully transplanted. CONCLUSION: Our approach is being advocated for as it preserves the ability to alter the reconstruction in case of problems resulting from the reconstruction itself, thereby allowing functional evaluation of the reconstruction prior transplantation, permitting simultaneous reperfusion in the recipient, and providing the shortest possible duration for vascular reconstruction once the graft is rewarming non-perfused within the recipient. In addition, in light of the frequency of technically demanding reconstructions with very small vessels, we consider our technique beneficial as the procedure can be performed under ideal conditions at the back-table.

Liver Resection for Primary Hepatic Angiosarcoma: Bicentric Analysis of a Challenging Entity.

Primary hepatic angiosarcoma (PHA) is a rare malignant tumor of the liver, and data on patient outcome after surgical treatment are scarce. The aim of this study was to evaluate postoperative morbidity and overall survival (OS) of patients who underwent hepatectomy for PHA. This is a bicentric retrospective analysis of all consecutive patients who underwent liver resection in curative intent for PHA between 2012 and 2019 at the University Hospital of Muenster and the University Hospital of Bern. Nine patients (five female, four male) were included from both centers. Median age was 72 years (44-82). Most lesions (77.8%) were larger than 5 cm, and mean size of the biggest lesion was 9.4 ± 4.5 cm. Major hepatectomy was performed in four (44.4%), and radical resection (R0) was achieved in six (66.7%) patients. Postoperative complication rate was 88.8%, including 44.4% higher than 3a in the Clavien-Dindo classification. OS survival rates at 1, 2, and 3 years were 44.4%, 22.2%, and 12.5%, respectively, and median OS was 5 months. OS was significantly better after radical resection (R0: 15 months vs. R1: 0 months, p = 0.04), whereas presentation with tumor rupture at diagnosis was associated with the worst OS (0 months vs. 15 months, p = 0.005). Disease recurrence occurred in three patients (33.3%) between three and seven months after surgery. Radical resection remains the only potentially curative treatment option for PHA. However, postoperative morbidity is high, and the overall prognosis remains poor. Multimodal therapy options and management strategies are urgently needed and could improve the prognosis of patients suffering from PHA in the future.

Hyperspectral imaging for quantitative assessment of hepatic steatosis in human liver allografts.

INTRODUCTION: In liver transplantation (LT), steatosis is commonly judged to be a risk factor for graft dysfunction, and quantitative assessment of hepatic steatosis remains crucial. Liver biopsy as the gold standard for evaluation of hepatic steatosis has certain drawbacks, that is, invasiveness, and intra- and inter-observer variability. A non-invasive, quantitative modality could replace liver biopsy and eliminate these disadvantages, but has not yet been evaluated in human LT. METHODS: We performed a pilot study to evaluate the feasibility and accuracy of hyperspectral imaging (HSI) in the assessment of hepatic steatosis of human liver allografts for transplantation. Thirteen deceased donor liver allografts were included in the study. The degree of steatosis was assessed by means of conventional liver biopsy as well as HSI, performed at the end of back-table preparation, during normothermic machine perfusion (NMP), and after reperfusion in the recipient. RESULTS: Organ donors were 51 [30-83] years old, and 61.5% were male. Donor body mass index was 24.2 [16.5-38.0] kg/m2 . The tissue lipid index (TLI) generated by HSI at the end of back-table preparation correlated significantly with the histopathologically assessed degree of overall hepatic steatosis (R2 = .9085, P < .0001); this was based on a correlation of TLI and microvesicular steatosis (R2 = .8120; P < .0001). There is also a linear relationship between the histopathologically assessed degree of overall steatosis and TLI during NMP (R2 = .5646; P = .0031) as well as TLI after reperfusion (R2 = .6562; P = .0008). CONCLUSION: HSI may safely be applied for accurate assessment of hepatic steatosis in human liver grafts. Certainly, TLI needs further assessment and validation in larger sample sizes.

Portal and hepatic vein embolization prior to major hepatectomy.

PURPOSE: To analyze safety and effectiveness of simultaneous portal and hepatic vein embolization (PHVE) or sequential hepatic vein embolization (HVE) compared to portal vein embolization (PVE) for future remnant liver (FRL) hypertrophy prior to major hepatic surgery. METHODS: Patients undergoing PVE, PHVE or HVE at our tertiary care center between 2018 and 2020 were retrospectively included. FRLV, standardized FRLV (sFRLV) and sFRLV growth rate per day were assessed via volumetry, as well as laboratory parameters. RESULTS: 36 patients (f = 15, m = 21; median 64.5 y) were included, 16 patients received PHVE and 20 patients PVE, of which 4 received sequential HVE. Significant increase of FRLV was achieved with both PVE and PHVE compared to baseline (p < 0.0001). sFRLV growth rate did not significantly differ following PHVE (2.2 ±â€Š1.2 %/d) or PVE (2.2 ±â€Š1.7 %/d, p = 0.94). Left portal vein thrombosis (LPVT) was observed after PHVE in 6 patients and in 1 patient after PVE. Sequential HVE showed a considerably high growth rate of 1.42 ±â€Š0.45 %/d after PVE. CONCLUSION: PHVE effectively induces FRL hypertrophy but yields comparable sFRLV to PVE. Sequential HVE further induces hypertrophy after insufficient growth due to PVE. Considering a potentially higher rate of LPVT after PHVE, PVE might be preferred in patients with moderate baseline sFRLV, with optional sequential HVE in non-sufficient responders.

Robotic Liver Surgery - Current Standards and Future Perspectives.

BACKGROUND: Robotic liver surgery is emerging as the future of minimal invasive surgery. The robotic surgical system offers a stable camera platform, elimination of physiologic tremor, augmented surgical dexterity as well as improved ergonomics because of a seated operating position. Due to the theoretical advantages of the robotic assisted system, complex liver surgery might be an especially interesting indication for a robotic approach since it demands delicate tissue dissection, precise intracorporeal suturing as well as difficult parenchymal transection with subsequent need for meticulous hemostasis and biliostasis. MATERIAL AND METHODS: An analysis of English and German literature on open, laparoscopic and robotic liver surgery was performed and this review provides a general overview of the existing literature along with current standards and aims to specifically point out future directions of robotic liver surgery. RESULTS: Robotic liver surgery is safe and feasible compared to open and laparoscopic surgery, with improved short-term postoperative outcomes and at least non-inferior oncological outcomes. CONCLUSION: In complex cases including major hepatectomies, extended hepatectomies with biliary reconstruction and difficult segmentectomies of the posterior-superior segments, robotic surgery appears to emerge as a reasonable alternative to open surgery rather than being an alternative to laparoscopic procedures.