The Impact of the COVID Pandemic on Adrenal Surgery at an Academic Endocrine Surgery Unit.

COVID-19 has severely affected the delivery of surgical care worldwide. The aim of the present study was to evaluate its impact on adrenal surgery at our academic endocrine center. All primary adrenal surgeries performed at the University Hospital of Cologne, Germany between 01.01.2019 and 31.07.2022 were included. This time frame was divided into pre-Covid (before 02/20), acute Covid (until 05/21), and post acute period (after 05/2021). Demographics, clinic-pathologic characteristics and treatment of these patients were analyzed. One hundred adrenalectomies were included: 22 before, 30 during, and 48 after the acute phase. The percentage of Conn adenomas and pheochromocytomas decreased during the acute phase (from 45.4 to 26.6% and from 18 to 10%, respectively) in favor of Cushing adenomas and suspicious tumors (from 4.5 to 20% and from 31.8 to 36.6%). About 90.9% of tumors resected for suspicion of malignancy were confirmed malignant by final histopathology, as opposed to 71.4% and 52.6% before and after the acute phase. The operative technique was similar during the three phases (63% retroperitoneoscopic, 34% laparoscopic and 2% open resections), with a significantly shorter operative time for retroperitoneoscopy (p=0.04). ICU monitoring demand increased during the acute phase (from 13.6% to 43.3%), according to the increase in Cushing adenomas and malignant tumors. During the acute phase of COVID-19 pandemic adrenal surgery for Cushing and malignant tumors increased, while a delay in pheochromocytoma surgery to the post acute phase was observed. The suspicion of malignancy formulated by the endocrine tumor board was accurate in 90.9% of cases.

Oligometastatic disease and visceral resections in advanced malignant melanoma: a propensity-matched analysis.

PURPOSE: Malignant melanoma is among the tumours with the highest increase in incidence of solid tumours in Germany. While most patients are diagnosed at an early stage and show a good prognosis, advanced stages of malignant melanoma are accompanied with a poor prognosis and limited treatment options. Comparable to other tumour entities, the resection of visceral metastases could lead to a better prognosis. Supplementary, the subgroup of oligometastatic patients might benefit from surgical therapy to a greater extent. METHODS: This retrospective study analysed 351 patients treated between 2006 and 2017 at the University Hospital of Cologne. A total of 121 patients showed visceral metastases, with which we compared patients with a diffuse tumour spread to patients in an oligometastatic state. Furthermore, we evaluated the effect of visceral resection of oligometastatic, malignant melanoma. RESULTS: Our analysis showed that patients with an oligometastatic malignant melanoma had a significantly better prognosis than patients with a diffuse pattern of metastases, if they showed visceral metastases. Furthermore, the resection of visceral metastases leads to a significant gain in median overall survival time (13.6 vs. 34.2 months) and in progression-free survival (9.6 vs. 3.8 months). CONCLUSION: The resection of visceral metastases is a rational treatment option in advanced malignant melanoma. Although our study is limited by a small cohort of patients (n = 18), we believe that the resection of visceral metastases will be fundamental in the treatment of malignant melanoma. In particular, patients in an oligometastatic stage could be an eligible group for surgical treatment.

Gender benefit in laparoscopic surgical performance using a 3D-display system: data from a randomized cross-over trial.

BACKGROUND: The use of 3D technique compared to high-resolution 2D-4K-display technique has been shown to optimize spatial orientation and surgical performance in laparoscopic surgery. Since women make up an increasing amount of medical students and surgeons, this study was designed to investigate whether one gender has a greater benefit from using a 3D compared to a 4K-display system. METHODS: In a randomized cross-over trial, the surgical performance of male and female medical students (MS), non-board certified surgeons (NBCS), and board certified surgeons (BCS) was compared using 3D- vs. 4K-display technique at a minimally invasive training parkour with multiple surgical tasks and repetitions. RESULTS: 128 participants (56 women, 72 men) were included. Overall parkour time in seconds was 3D vs. 4K for all women 770.7 ± 31.9 vs. 1068.1 ± 50.0 (p < 0.001) and all men 664.5 ± 19.9 vs. 889.7 ± 31.2 (p < 0.001). Regarding overall mistakes, participants tend to commit less mistakes while using the 3D-vision system, showing 10.2 ± 1.1 vs. 13.3 ± 1.3 (p = 0.005) for all women and 9.6 ± 0.7 vs. 12.2 ± 1.0 (p = 0.001) for all men. The benefit of using a 3D system, measured by the difference in seconds, was for women 297.3 ± 41.8 (27.84%) vs. 225.2 ± 23.3 (25.31%) for men (p = 0.005). This can be confirmed in the MS group with 327.6 ± 65.5 (35.82%) vs. 249.8 ± 33.7 (32.12%), p = 0.041 and in the NBCS group 359 ± 52.4 (28.25%) vs. 198.2 ± 54.2 (18.62%), p = 0.003. There was no significant difference in the BCS group. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 2D-4K technique for both women and men. The greatest 3D benefit was found for women with less surgical experience. As a possible result of surgical education, this gender specific difference disappears with higher grade of experience. Using a 3D-vision system could facilitate surgical apprenticeship, especially for women.

[Incidental Finding of Appendiceal Neuroendocrine Tumour]. / Zufallsbefund NEN Appendix.

With an incidence of 80%, neuroendocrine neoplasia (NEN) is the most common neoplasia of the appendix. In most cases, these tumours are diagnosed as an incidental finding after appendectomy with suspected appendicitis. They are usually highly differentiated neuroendocrine tumours. Due to their frequent location on the apex of the appendix, the NENs of the appendix are usually not the cause of the symptoms typical for appendicitis.Most patients (80-90%) receive adequate oncological treatment by laparoscopic or open appendectomy that has already been performed. However, if there are risk factors such as tumour size > 2 cm, location close to the base, angioinvasion, perforation or infiltration of neighbouring organs, proliferation index of > 2% or infiltration of the mesoappendix by more than 3 mm in the final histopathological finding, subsequent resection as an oncological right sided hemicolectomy is recommended .Due to their mostly early tumour stage at diagnosis without proven lymph node metastasis, patients with NEN of the appendix have an excellent 5-year survival rate of 70-85% across all tumour stages.

Learning curve of surgical novices using the single-port platform SymphonX: minimizing OR trauma to only one 15-mm incision.

BACKGROUND: Minimally invasive single-port surgery is always associated with large incisions up to 2-3 cm, complicated handling due to the lack of triangulation, and instrument crossing. The aim of this prospective study was to report how medical students without any laparoscopic experience perform several laparoscopic tasks (rope pass, paper cut, peg transfer, recapping, and needle threading) with the new SymphonX single-port platform and to examine the learning curves in comparison to the laparoscopic multi-port technique. METHODS: A set of 5 laparoscopic skill tests (Rope Pass, Paper cut, Peg Transfer, Recapping, Needle Thread) were performed with 3 repetitions. Medical students performed all tests with both standard laparoscopic instruments and the new platform. Time and errors were recorded. RESULTS: A total of 114 medical students (61 females) with a median age of 23 years completed the study. All subjects were able to perform the skill tests with both standard laparoscopic multi-port and the single-port laparoscopic system and were able to significantly improve their performance over the three trials for all five tasks-rope pass (p < 0.001), paper cut (p < 0.001), peg transfer (p < 0.001), needle threading (p < 0.001), and recapping (p < 0.001). In 3 out of 5 tasks, medical students performed the tasks faster using the standard multi-port system-rope pass (p < 0.001), paper cut (p < 0.001), and peg transfer (p < 0.001). In the task recapping, medical students performed the task faster using the new single-port system (p = 0.003). In the task needle threading, there was no significant difference between the standard multi-port system and the new single-port system (p > 0.05). CONCLUSION: This is the first study analyzing learning curves of the commercially available SymphonX platform for abdominal laparoscopic surgery when used by novices. The learning curve and the error rate are promising.

3D Versus 4K Display System - Influence of "State-of-the-art"-Display Technique on Surgical Performance (IDOSP-study) in Minimally Invasive Surgery: A Randomized Cross-over Trial.

OBJECTIVE: To evaluate if "state-of-the-art" 3D- versus 4K-display techniques could influence surgical performance. BACKGROUND: High quality minimally invasive surgery is challenging. Therefore excellent vision is crucial. 3D display technique (3D) and 2D-4K technique (4K) are designed to facilitate surgical performance, either due to spatial resolution (3D) or due to very high resolution (4K). METHODS: In randomized cross-over trial the surgical performance of medical students (MS), non-board certified surgeons (NBC), and board certified surgeons (BC) was compared using 3D versus 4K display technique at a minimally invasive training Parkour. RESULTS: One hundred twenty-eight participants were included (February 2018 through October 2019, 49 MS, 39 NBC, 40 BC). The overall Parkour time (s) 3D versus 4K was 712.5 s ± 17.5 s versus 999.5 s ±â€Š25.1 s (P < 0.001) for all levels of experience. It was (3D vs 4K) for MS (30 tasks) 555.4 s ±â€Š28.9 s versus 858.7 s ±â€Š41.6 s, (P < 0.0001), for NBC (42 tasks) 935.9 s ±â€Š31.5 s versus 1274.1 s ±â€Š45.1 s (P =< 0.001) and for BC (42 task) 646.3 s ±â€Š30.9 s versus 865.7 s ±â€Š43.7 s (P < 0.001). The overall number of mistakes was (3D vs 4K) 10.0 ±â€Š0.5 versus 13.3 ±â€Š0.7 (P < 0.001), for MS 8.9 ±â€Š0.9 versus 13.1 ±â€Š1.1 (P < 0.001), for NBC 12.45 ±â€Š1.0 versus 16.7 ±â€Š1.2 (P < 0.001) and for BC 8.8 ±â€Š1.0 versus 10.0 ±â€Š1.2 (P = 0.18). MS, BC, and NBC showed shorter performance time in 100% of the task with 3D (significantly in 6/7 tasks). For number of mistakes the effect was less pronounced for more experienced surgeons. The National Aeronautics and Space Administration-task load index was lower with 3D. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 4K technique. Surgeons benefit from the improved visualization regardless of their individual surgical expertise.

True single-port cholecystectomy with ICG cholangiography through a single 15-mm trocar using the new surgical platform "symphonX": first human case study with a commercially available device.

BACKGROUND: Minimally invasive single-port surgery is often associated with large incisions up to 2-3 cm, complicated handling due to the lack of triangulation, and instrument crossing. Aim of this prospective study was to perform true single-port surgery (cholecystectomy) without the use of assisting trocars using a new surgical platform that allows for triangulation incorporating robotic features, and to measure the perioperative outcome and cosmetic results. METHODS: As the first European site after FDA and CE-mark approval, the new device has been introduced to our academic center. In patients with cholecystitis and cholecystolithiasis, the operation was performed through only one 15-mm trocar. For patients safety, intraoperative cholangiography using intravenous ICG and a standard Stryker 1588 system was routinely performed. RESULTS: Symphonx was used in n = 12 patients for abdominal surgery (6 females, mean age 42.5 [30-77], mean BMI 26.2 [19.3-38.9]. A total of 8 patients underwent surgery using no additional ports besides the 15-mm trocar; in the remaining patients, one assisting instrument (3-5 mm) was used. Mean OR time was 107 [72-221] minutes. The postoperative course was uneventful in 11 patients; in one patient, a seroma at the surgical site required interventional drainage 1 month postoperatively. No intraoperative complications occurred. CONCLUSION: This is the first human case series using the commercially available symphonX platform for abdominal laparoscopic surgery and the first series using the system without assisting instruments. Laparoscopic cholecystectomy in patients with cholecystitis and cholecystolithiasis using the symphonX platform through only one 15-mm trocar is feasible, safe, and more cost-efficient compared to robotic platforms.

Rescue allocation and recipient oriented extended allocation in kidney transplantation-influence of the EUROTRANSPLANT allocation system on recipient selection and graft survival for initially nonaccepted organs.

Nonaccepted kidneys grafts enter the rescue allocation (RA) process to avoid discards. In December 2013, recipient oriented extended allocation (REAL) was introduced to improve transparency. The aim of this study was to evaluate the influence of REAL on recipients' selection and graft function compared to the formerly existing RA as well as to identify factors that influence graft outcome. Therefore, a multicenter study of 10 transplant centers in the same region in Germany was performed. All transplantations after RA or REAL from December 1, 2012, until December 31, 2014, with a follow-up time until December 31, 2015 were analyzed. 113 of 941 kidney transplantations were performed after RA or REAL (12%). With REAL, the number of refusals before transplantation had increased (12 ± 7.1 vs. 8.6 ± 8.6, P = 0.036), and cold ischemia time has decreased (13.6 ± 3.6 vs. 17.2 ± 4.8 h, P = 0.019). Recipients after REAL needed significantly more allocation points compared to RA to receive a kidney. One-year graft survival was comparable. If kidneys from the same donor were transplanted to two recipients at one center, the greater the difference in recipient age, the greater the difference in serum creatinine after 12 months (-0.019 mg/dl per year, P = 0.011) was, that is older recipients showed lower creatinine. REAL influences selection of the recipients compared to the former RA era for successful organ receipt. Graft function is comparable and seems to be influenced by recipient age.

Optimizing a living kidney donation program: transition to hand-assisted retroperitoneoscopic living donor nephrectomy and introduction of a passive polarizing three-dimensional display system.

BACKGROUND: Optimizing a living kidney donation program is important to guarantee a high grade of acceptance among potential donors. Hand-assisted retroperitoneoscopic donor nephrectomy (HARP) is an alternative to the open anterior approach (AA) technique. Problems associated to the learning curve could hinder a transition. 3D display technique seems to ease minimally invasive surgery. Aim of this study was to evaluate the learning curve during the transition from AA to HARP and the influence of the 3D display system on the established technique. METHODS: Observational study (n = 207) during transition to HARP and introduction of 3D display technique. RESULTS: Operation time (OT), warm ischemia time (WIT) and blood loss (BL) of HARP decreased during transition. Pairwise group comparison for OT showed a significant learning effect for the first 30 out of 50 HARPs without influence on graft function. Between AA and HARP no significant difference in OT (133 ± 24 vs. 127 ± 19 min, p = 0.25) but for WIT (23 ± 28 vs. 126 ± 40 s, p < 0.005) and BL (328 ± 207 vs. 54 ± 35 ml, p < 0.005) was seen. There was neither a significant difference in donors' nor recipients' eGFR. OT (98 ± 16 vs. 106 ± 19 min, p = 0.036) and WIT (97 ± 37 vs. 120 ± 57 s, p = 0.023) were significantly shorter for the 3D technique compared to 2D. CONCLUSION: A transition to HARP is possible without additional risk for the donor or loss of quality for the recipient. The learning curve for HARP is steep and short. The introduction of 3D display technique after transition facilitates the surgical preparation and could further help to optimize HARP.

Graft rinse prior to reperfusion in liver transplantation: literature review and online survey within the Eurotransplant community.

Graft rinse prior reperfusion in liver transplantation (LT) is believed to reduce the incidence of postreperfusion syndrome and improve clinical outcome. A MEDLINE search was performed to obtain a comprehensive review of the published literature dealing with graft rinse in LT. Moreover, all thirty-four LT centers in the Eurotransplant (ET) region were invited to participate in an online survey to whether or not graft rinse is performed and whether further research in the field is needed. Seventeen reports have been found to investigate graft rinse protocols in 1894 LT recipients. Eighteen of the thirty centers that participated in the online survey performed graft rinse prior reperfusion in LT. The most commonly used rinse solution was albumin. Nineteen centers stated interest in participating in a multicenter RCT in the field. The published literature does not provide concluding appraisal of the benefit of graft rinse in LT. Graft rinse protocols are not standardized and are based on personal experience. Appropriately designed clinical trials addressing the topic are demanded. The online survey appears to be a helpful tool for the evaluation of clinical practice and future research topics in the transplant community.

3D immersive patient simulators and their impact on learning success: a thematic review.

BACKGROUND: Immersive patient simulators (IPSs) combine the simulation of virtual patients with a three-dimensional (3D) environment and, thus, allow an illusionary immersion into a synthetic world, similar to computer games. Playful learning in a 3D environment is motivating and allows repetitive training and internalization of medical workflows (ie, procedural knowledge) without compromising real patients. The impact of this innovative educational concept on learning success requires review of feasibility and validity. OBJECTIVE: It was the aim of this paper to conduct a survey of all immersive patient simulators currently available. In addition, we address the question of whether the use of these simulators has an impact on knowledge gain by summarizing the existing validation studies. METHODS: A systematic literature search via PubMed was performed using predefined inclusion criteria (ie, virtual worlds, focus on education of medical students, validation testing) to identify all available simulators. Validation testing was defined as the primary end point. RESULTS: There are currently 13 immersive patient simulators available. Of these, 9 are Web-based simulators and represent feasibility studies. None of these simulators are used routinely for student education. The workstation-based simulators are commercially driven and show a higher quality in terms of graphical quality and/or data content. Out of the studies, 1 showed a positive correlation between simulated content and real content (ie, content validity). There was a positive correlation between the outcome of simulator training and alternative training methods (ie, concordance validity), and a positive coherence between measured outcome and future professional attitude and performance (ie, predictive validity). CONCLUSIONS: IPSs can promote learning and consolidation of procedural knowledge. The use of immersive patient simulators is still marginal, and technical and educational approaches are heterogeneous. Academic-driven IPSs could possibly enhance the content quality, improve the validity level, and make this educational concept accessible to all medical students.

Impact of de novo donor-specific HLA antibodies detected by Luminex solid-phase assay after transplantation in a group of 88 consecutive living-donor renal transplantations.

De novo donor-specific HLA antibodies (DSA) after renal transplantation are known to be correlated with poor graft outcome and the development of acute and chronic rejection. Currently, data for the influence of de novo DSA in patient cohorts including only living-donor renal transplantations (LDRT) are limited. A consecutive cohort of 88 LDRT was tested for the occurrence of de novo DSA by utilizing the highly sensitive Luminex solid-phase assay for antibody detection. Data were analyzed for risk factors for de novo DSA development and correlated with acute rejection (AR) and graft function. Patients with de novo DSA [31 (35%)] showed a trend for inferior graft function [mean creatinine change (mg/dL/year) after the first year: 0.15 DSA (+) vs. 0.02 DSA (-) (P = 0.10)] and a higher rate of AR episodes, especially in case of de novo DSA of both class I and II [6 (55%), (P = 0.05)]. Antibody-mediated rejection (AMR) appeared in five patients and was significantly correlated with de novo DSA (P = 0.05). Monitoring for de novo DSA after LDRT may help to identify patients at risk of declining renal function. Especially patients with simultaneous presence of de novo DSA class I and class II are at a high risk to suffer AR episodes.

Reperfusion of liver graft during transplantation: techniques used in transplant centres within Eurotransplant and meta-analysis of the literature.

It remains unclear which liver graft reperfusion technique leads to the best outcome following transplantation. An online survey was sent to all transplant centres (n = 37) within Eurotransplant (ET) to collect information on their technique used for reperfusion of liver grafts. Furthermore, a systematic review of all literature was performed and a meta-analysis was conducted based on patients' mortality, number of retransplantations and incidence of biliary complications, depending on the technique used. Of the 28 evaluated centres, 11 (39%) reported performing simultaneous reperfusion (SIMR), 13 (46%) perform initial portal vein reperfusion (IPR), 1 (4%) performs an initial hepatic artery reperfusion (IAR) and 3 (11%) perform retrograde reperfusion (RETR). In 21 centres (75%), one reperfusion technique is used as a standard, but in only one centre is this decision based on available literature. Twenty centres (71%) said they would agree to participate in randomized controlled trials (RCT) if required. For meta-analysis, IAR vs. IPR, SIMR vs. IPR and RETR vs. IPR were compared. There was no difference between any of the techniques compared. There is no consensus on a preferable reperfusion technique. Available evidence does not help in the decision-making process. There is thus an urgent need for multicentric RCTs.

The laparoscopic approach for radiofrequency ablation of hepatocellular carcinoma--indication, technique and results.

BACKGROUND: The therapeutic regimen for patients suffering of HCC in liver cirrhosis must pay attention to the underlying liver disease. Surgical resection is often limited by liver function and transplantation, as an optimal therapy for many early diagnosed HCC, by the availability of organs. Due to three prospective, randomized trials radiofrequency ablation (RFA) is the standard method of local ablation. RFA compared with resection for HCC in liver cirrhosis yields similar results concerning overall survival but a lower rate of complications. The laparoscopic approach may be advantageous concerning the major drawback of RFA which is still the rate of local failure as shown by a meta-analysis of local recurrences. METHOD: Indication for RFA was HCC in liver cirrhosis either as a definite therapy or as a bridging procedure for transplantation if the expected waiting time exceeded 6 months. Laparoscopic ultrasound, standardized algorithm of laparoscopic RFA procedure, track ablation and a Trucut biopsy were performed. The postoperative follow-up was done according to institutional standards. Patient data and parameters of laparoscopic RFA were prospectively documented, analyzed and compared with the results of previously published series found in a Medline search. RESULTS: 34 patients were treated by laparoscopic RFA. The average time of follow-up was 36.9 ± 28.3 months. There was no procedure-related mortality or surgical complications. An upstaging of the tumor stage by laparoscopic ultrasound was achieved in 32 % of the patients. The overall survival of these patients was 44.7 ± 6.9 months. The intrahepatic recurrence rate was 61.8 % based on the number of patients treated. The results have been analyzed and compared with six independent papers identified in a Medline search that report on the treatment of patients with HCC in a liver cirrhosis by laparoscopic RFA with a mean follow-up of 12 or more months. CONCLUSIONS: Laparoscopic RFA is a feasible and reliable therapy for unresectable HCCs in patients with cirrhosis. The laparoscopic RFA combines the advantage of a minimally invasive procedure concerning liver dysfunction with the ability of an accurate intraoperative staging by laparoscopic ultrasound.

Mucinous cystic neoplasm or non-parasitic liver cyst? - A challenging diagnosis.

BACKGROUND/AIMS: Mucinous cystic neoplasms (MCN) are rare liver lesions. Radiological features include internal septa or septal thickening. Imaging often fails in the differential diagnosis to non-parasitic liver cysts (NPLC), resulting in inadequate surgery. The aim of the study was to evaluate if both lesions could be differentiated pre-operatively. METHODOLOGY: Retrospective study with literature review. RESULTS: Twenty-six patients (22 female, 68±12 years) underwent laparoscopic deroofing for NPLC. Histo-pathological specimens showed 2 MCN (both female) with recurrence rates of 4% (NPLC) and 100% (MCN), and a time-to-recurrence of 3 months. In both cases no radiological features of MCN were seen pre-operatively. Follow-up time was 7 and 12 years with emergence of radiological features of MCN in one case. PubMed search showed 137 hits for "MCN" and 540 hits for "mucinous cystadenoma" and "liver"; 207 studies were reviewed: one prospective, 13 non-systematic reviews, 57 retrospective, 120 case reports and 16 expert opinions. The largest MCN-series included 44 subjects. CONCLUSIONS: If MCN shows no characteristic radiological features, thus mimicking NPLC, pre-operative radiological differentiation is impossible. During long time course characteristic radiological morphology of MCN could appear. Early recurrence of a supposed NPLC is suspicious for MCN. Due to the literature review pre-operative imaging is inaccurate for the differential diagnosis and complete surgical excision of MCN is crucial.

Imaged guided surgery during arteriovenous malformation of gastrointestinal stromal tumor using hyperspectral and indocyanine green visualization techniques: A case report.

BACKGROUND: This case report demonstrates the simultaneous development of a gastrointestinal stromal tumour (GIST) with arteriovenous malformations (AVMs) within the jejunal mesentery. A 74-year-old male presented to the department of surgery at our institution with a one-month history of abdominal pain. Contrast-enhanced computed tomography revealed an AVM. During exploratory laparotomy, hyperspectral imaging (HSI) and indocyanine green (ICG) fluorescence were used to evaluate the extent of the tumour and determine the resection margins. Intraoperative imaging confirmed AVM, while histopathological evaluation showed an epithelioid, partially spindle cell GIST. CASE SUMMARY: This is the first case reporting the use of HSI and ICG to image GIST intermingled with an AVM. The resection margins were planned using intraoperative analysis of additional optical data. Image-guided surgery enhances the clinician's knowledge of tissue composition and facilitates tissue differentiation. CONCLUSION: Since image-guided surgery is safe, this procedure should increase in popularity among the next generation of surgeons as it is associated with better postoperative outcomes.

High RIPK3 expression is associated with a higher risk of early kidney transplant failure.

Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.

Post-transplant Malignancies Show Reduced T-cell Abundance and Tertiary Lymphoid Structures as Correlates of Impaired Cancer Immunosurveillance.

PURPOSE: An increased risk to develop cancer is one of the most challenging negative side effects of long-term immunosuppression in organ transplant recipients and impaired cancer immunosurveillance is assumed as underlying mechanism. This study aims to elucidate transplant-related changes in the tumor immune microenvironment (TME) of cancer. EXPERIMENTAL DESIGN: Data from 123 organ transplant recipients (kidney, heart, lung, and liver) were compared with historic data from non-immunosuppressed patients. Digital image analysis of whole-section slides was used to assess abundance and spatial distribution of T cells and tertiary lymphoid structures (TLS) in the TME of 117 tumor samples. Expression of programmed cell death 1 ligand 1 (PD-L1) and human-leucocyte-antigen class I (HLA-I) was assessed on tissue microarrays. RESULTS: We found a remarkably reduced immune infiltrate in the center tumor (CT) regions as well as the invasive margins (IM) of post-transplant cancers. These differences were more pronounced in the IM than in the CT and larger for CD8+ T cells than for CD3+ T cells. The Immune-score integrating results from CT and IM was also lower in transplant recipients. Density of TLS was lower in cancer samples of transplant recipients. The fraction of samples with PD-L1 expression was higher in controls whereas decreased expression of HLA-I was more common in transplant recipients. CONCLUSIONS: Our study demonstrates the impact of immunosuppression on the TME and supports impaired cancer immunosurveillance as important cause of post-transplant cancer. Modern immunosuppressive protocols and cancer therapies should consider the distinct immune microenvironment of post-transplant malignancies.

Impact of duct-to-mucosa pancreaticojejunostomy with external drainage of the pancreatic duct after pancreaticoduodenectomy.

BACKGROUND: A variety of different techniques are established for the management of the pancreatic remnant after partial pancreaticoduodenectomy. Although pancreaticojejunostomy is one of the most favored methods, technical details are still under discussion. We report about a series of duct-to-mucosa pancreaticojejunostomies with total external drainage of the pancreatic duct. PATIENTS AND METHODS: Between 1998 and 2007 257 patients underwent surgical therapy for malignant disease of the pancreas and the periampullary region and for chronic pancreatitis. Of these, 153 partial pancreaticoduodenectomies (85 pylorus preserving resections and 68 Whipple's procedures) were performed. In all of these cases, the pancreatic remnant was drained by a duct-to-mucosa pancreaticojejunostomy with external drainage of the pancreatic duct. Presence of postoperative pancreatic fistula (PPF) was defined according to the International Study Group on Pancreatic Fistula (ISGPF). RESULTS: Postoperative mortality was 1.9%. The incidence of postoperative pancreatic fistula (PPF) was 19.6% according to the ISGPF criteria. Only one patient required re-laparotomy for complications caused by PPF. Patients with PPF had a significantly longer operation time (7.3 h versus 6.6 h; P=0.041). Incidence of PPF was not influenced by histology. In all cases the fistulas resolved under conservative treatment. CONCLUSION: Duct-to-mucosa PJ with external drainage is a safe procedure to enteralize the pancreatic stump after partial pancreaticoduodenectomy.

Hand-Assisted Retroperitoneoscopic Donor Nephrectomy Compared to Anterior Approach Open Donor Nephrectomy: Improved Long-Term Physical Component Score in Health-Related Quality of Life in Living Kidney Donors.

BACKGROUND: Health-related quality of life (HRQL), fatigue, anxiety, and depression are crucial for the living kidney donor (LKD). Follow-up data for HRQL of LKDs comparing surgical techniques, especially regarding hand-assisted retroperitoneoscopic donor nephrectomy (HARP), are sparse. The aim of this study was to evaluate the influence of abdominal wall trauma minimized by HARP in comparison to open anterior approach donor nephrectomy (AA) on HRQL and additional psychosocial aspects of LKDs during the long-term follow-up. MATERIAL AND METHODS: This is a cross-sectional study comparing psychosocial aspects of LKD between HARP and AA. RESULTS: This study included 100 LKDs (68 HARP, 28 AA, and 4 were excluded secondary to incomplete data). The time to follow-up was 22.6 ± 11.7 (HARP) vs 58.7 ± 13.9 (AA) months (P < .005). Complications ≥3a° due to Clavien-Dindo classification was 0% in both groups. There were higher scores in all physical aspects for HARP donors vs AA donors at that time (physical function: 89.8 ± 14.6 vs 80.0 ± 19.9, P = .008, and the physical component score: 53.9 ± 7.6 vs 48.6 ± 8.5, P = .006). One year later (follow-up time + 12 months), HRQL for HARP donors was still higher. Mental items showed no significant differences. HARP donors showed better physical scores compared to the age-matched nondonor population (AA donors had lower scores). Neither the Multidimensional Fatigue Inventory-20 (MFI-20) or the Hospital Anxiety and Depression Scale (HADS) showed any differences between the 2 groups. Fatigue scores were higher for HARP and for AA compared to the age-matched population. CONCLUSIONS: LKDs undergoing HARP showed better physical performance as part of HRQL in the long-term follow-up.