The Predictive Value of Graft Viability and Bioenergetics Testing Towards the Outcome in Liver Transplantation.

Donor organ biomarkers with sufficient predictive value in liver transplantation (LT) are lacking. We herein evaluate liver viability and mitochondrial bioenergetics for their predictive capacity towards the outcome in LT. We enrolled 43 consecutive patients undergoing LT. Liver biopsy samples taken upon arrival after static cold storage were assessed by histology, real-time confocal imaging analysis (RTCA), and high-resolution respirometry (HRR) for mitochondrial respiration of tissue homogenates. Early allograft dysfunction (EAD) served as primary endpoint. HRR data were analysed with a focus on the efficacy of ATP production or P-L control efficiency, calculated as 1-L/P from the capacity of oxidative phosphorylation P and non-phosphorylating respiration L. Twenty-two recipients experienced EAD. Pre-transplant histology was not predictive of EAD. The mean RTCA score was significantly lower in the EAD cohort (-0.75 ± 2.27) compared to the IF cohort (0.70 ± 2.08; p = 0.01), indicating decreased cell viability. P-L control efficiency was predictive of EAD (0.76 ± 0.06 in IF vs. 0.70 ± 0.08 in EAD-livers; p = 0.02) and correlated with the RTCA score. Both RTCA and P-L control efficiency in biopsy samples taken during cold storage have predictive capacity towards the outcome in LT. Therefore, RTCA and HRR should be considered for risk stratification, viability assessment, and bioenergetic testing in liver transplantation.

Interleukin-6 Levels During Normothermic Machine Perfusion Impact Postreperfusion Hemodynamics of Liver Graft Recipients: A Prospective Single-center Observational Study.

BACKGROUND: Hemodynamic instability after liver graft reperfusion increases recipient morbidity after liver transplantation. The etiologies of hemodynamic disturbances appear to be multifactorial and are poorly understood. Normothermic machine perfusion (NMP) provides an opportunity to analyze graft quality prior to transplantation. In the present study, we aim to investigate the influence of interleukin-6 (IL-6) levels during NMP on postreperfusion hemodynamics of the recipient. METHODS: Consecutive NMP-liver transplants at a single-center were prospectively analyzed. Perfusate samples were collected at the beginning, after 6 h, and at the end of perfusion and analyzed for IL-6 levels. Mean arterial pressure (MAP) and catecholamine consumption during surgery were recorded. IL-6 levels at the end of NMP were correlated to donor and perfusion characteristics as well as changes in MAP and catecholamine requirements during the anhepatic and reperfusion phase. RESULTS: IL-6 perfusate measurements were assessed in 77 livers undergoing NMP and transplantation. Donor age, sex, cold ischemic time, and NMP time did not correlate with IL-6 levels. Perfusates of donation after circulatory death grafts showed higher IL-6 levels at the end of NMP than donation after brain death grafts. However, IL-6 levels at the end of NMP correlated with catecholamine requirements and MAP in the reperfusion phase. Per log10 increase in IL-6 levels, an increase of 42% points in administered catecholamine dose was observed, despite MAP being decreased by 3.6% points compared to baseline values. CONCLUSIONS: IL-6 levels may be a predictor for recipient hemodynamic instability during liver reperfusion. Larger studies are needed to confirm this finding.

48 h Normothermic Machine Perfusion With Urine Recirculation for Discarded Human Kidney Grafts.

Normothermic machine perfusion (NMP) has reshaped organ preservation in recent years. In this preclinical study, prolonged normothermic perfusions of discarded human kidney grafts were performed in order to investigate perfusion dynamics and identify potential quality and assessment indicators. Five human discarded kidney grafts were perfused normothermically (37°C) for 48 h using the Kidney Assist device with a red-blood-cell based perfusate with urine recirculation. Perfusion dynamics, perfusate and urine composition as well as injury markers were measured and analyzed. Donor age ranged from 41 to 68 years. All but one kidney were from brain dead donors. Perfusions were performed successfully for 48 h with all discarded kidneys. Median arterial flow ranged from 405 to 841 mL/min. All kidneys excreted urine until the end of perfusion (median 0.43 mL/min at the end of perfusion). While sodium levels were consistently lower in urine compared to perfusate samples, this was only seen for chloride and potassium in kidney KTX 2. Lactate, AST, LDH as well as pro-inflammatory cytokines increased over time, especially in kidneys KTX 3 and 4. Ex vivo normothermic perfusion is able to identify patterns of perfusion, biological function, and changes in inflammatory markers in heterogenous discarded kidney grafts.

Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcome.

BACKGROUND: Reliable biomarkers for organ quality assessment during normothermic machine perfusion (NMP) are desired. ATP (adenosine triphosphate) production by oxidative phosphorylation plays a crucial role in the bioenergetic homeostasis of the liver. Thus, detailed analysis of the aerobic mitochondrial performance may serve as predictive tool towards the outcome after liver transplantation. METHODS: In a prospective clinical trial, 50 livers were subjected to NMP (OrganOx Metra) for up to 24.ßh. Biopsy and perfusate samples were collected at the end of cold storage, at 1.ßh, 6.ßh, end of NMP, and 1.ßh after reperfusion. Mitochondrial function and integrity were characterized by high-resolution respirometry (HRR), AMP, ADP, ATP and glutamate dehydrogenase analysis and correlated with the clinical outcome (L-GrAFT score). Real-time confocal microscopy was performed to assess tissue viability. Structural damage was investigated by histology, immunohistochemistry and transmission electron microscopy. FINDINGS: A considerable variability in tissue viability and mitochondrial respiration between individual livers at the end of cold storage was observed. During NMP, mitochondrial respiration with succinate and tissue viability remained stable. In the multivariate analysis of the 35 transplanted livers (15 were discarded), area under the curve (AUC) of LEAK respiration, cytochrome c control efficiency (mitochondrial outer membrane damage), and efficacy of the mitochondrial ATP production during the first 6.ßh of NMP correlated with L-GrAFT. INTERPRETATIONS: Bioenergetic competence during NMP plays a pivotal role in addition to tissue injury markers. The AUC for markers of outer mitochondrial membrane damage, ATP synthesis efficiency and dissipative respiration (LEAK) predict the clinical outcome upon liver transplantation. FUNDING: This study was funded by a Grant from the In Memoriam Dr. Gabriel Salzner Stiftung awarded to SS and the Tiroler Wissenschaftsfond granted to TH.

Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality.

Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival. Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7. Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity. Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.

Post-Transplant Malignancies following Pancreas Transplantation: Incidence and Implications on Long-Term Outcome from a Single-Center Perspective.

Chronic immunosuppression is associated with an increased risk of malignancy. The main objective of this study is to evaluate the incidence and effect of post-transplant malignancies (PTMs) following pancreas transplantation. The 348 first pancreas transplants performed between 1985 and 2015 were retrospectively analyzed in this study. Incidences of PTMs, as well as patient and graft survival, were evaluated. Out of 348 patients, 71 (20.4%) developed a PTM. Median time to diagnosis was 130 months. Thirty-six patients (50.7%) developed skin cancers (four patients with melanoma, 32 with NMSCs). Solid organ malignancy occurred in 25 (35.2%), hematologic malignancy in ten patients (14.1%). Affected patients were transplanted earlier [2000 (IQR 1993-2004) vs. 2003 (IQR 1999-2008); p < 0.001]. No differences in induction therapy were seen, both groups demonstrated comparable patient and graft survival. Pancreas transplant recipients with solid organ and hematologic malignancies had a three- and six-fold increased hazard of death compared to those with skin cancers [aHR 3.04 (IQR 1.17-7.91); p = 0.023; aHR 6.07 (IQR 1.87-19.71); p = 0.003]. PTMs affect every fifth patient following pancreas transplantation. Skin cancers are the most common malignancies accounting for 50% of all PTMs. These results underscore the importance of close dermatologic follow-up.

Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs.

Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine perfusion (NMP) has the potential to extend the donor pool by facilitating the use of marginal quality organs such as those from donors after cardiac death (DCD) and extended criteria donors (ECD). NMP provides a platform for organ quality assessment but also offers the opportunity to treat and eventually regenerate organs during the perfusion process prior to transplantation. Due to their anti-inflammatory, immunomodulatory and regenerative capacity, mesenchymal stem cells (MSCs) are considered as an interesting tool in this model system. Only a limited number of studies have reported on the use of MSCs during ex situ machine perfusion so far with a focus on feasibility and safety aspects. At this point, no clinical benefits have been conclusively demonstrated, and studies with controlled transplantation set-ups are urgently warranted to elucidate favorable effects of MSCs in order to improve organs during ex situ machine perfusion.

Live Confocal Imaging as a Novel Tool to Assess Liver Quality: Insights From a Murine Model.

BACKGROUND: In an experimental murine liver clamping model, we aimed to investigate the efficacy of real-time confocal microscopy (RCM) in assessing viability of steatotic livers in comparison to standard assessment tools, including histopathological evaluation. METHODS: C57Bl/6 mice were subjected to a methionine-choline-deficient diet causing nonalcoholic fatty liver disease or to Lieber DeCarli diet causing ethanol-induced liver injury. Untreated animals served as controls. Liver biopsies were analyzed following challenge with 45 min of warm ischemia time and either 4 h of reperfusion or 24 h of cold storage. Organ quality assessment was performed at defined time points by RCM, histological staining, measurement of serum alanine aminotransferase activity, and expression analyses of proinflammatory cytokines. Additionally, survival analysis was performed. RESULTS: Cold as well as warm ischemia time resulted in a significant decrease in cell viability when compared with naive livers as well as nonischemic-challenged steatotic livers (P < 0.05) as assessed by RCM. Furthermore, RCM revealed the actual cellular damage at early time points, while established methods including H&E-staining and serum transaminase profile failed. CONCLUSIONS: In a translational attempt, we demonstrate that RCM is a suitable diagnostic tool to obtain information about functional damage of the liver apart from standard approaches.

Long-term outcome after hand and forearm transplantation - a retrospective study.

Between 2000 and 2014, five patients received bilateral hand (n = 3), bilateral forearm (n = 1), and unilateral hand (n = 1) transplants at the Innsbruck Medical University Hospital. We provide a comprehensive report of the long-term results at 20 years. During the 6-20 years follow-up, 43 rejection episodes were recorded in total. Of these, 27.9% were antibody-related with serum donor-specific alloantibodies (DSA) and skin-infiltrating B-cells. The cell phenotype in rejecting skin biopsies changed and C4d-staining increased with time post-transplantation. In the long-term, a change in hand appearance was observed. The functional outcome was highly depending on the level of amputation. The number and severity of rejections did not correlate with hand function, but negatively impacted on the patients´ well-being and quality of life. Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated at 7 years. The patient later died due to progressive gastric cancer. The other four patients are currently rejection-free with moderate levels of immunosuppression. Hand transplantation remains a therapeutic option for carefully selected patients. A stable immunologic situation with optimized and individually adopted immunosuppression favors good compliance and patient satisfaction and may prevent development of DSA.

Transplanting Marginal Organs in the Era of Modern Machine Perfusion and Advanced Organ Monitoring.

Organ transplantation is undergoing profound changes. Contraindications for donation have been revised in order to better meet the organ demand. The use of lower-quality organs and organs with greater preoperative damage, including those from donation after cardiac death (DCD), has become an established routine but increases the risk of graft malfunction. This risk is further aggravated by ischemia and reperfusion injury (IRI) in the process of transplantation. These circumstances demand a preservation technology that ameliorates IRI and allows for assessment of viability and function prior to transplantation. Oxygenated hypothermic and normothermic machine perfusion (MP) have emerged as valid novel modalities for advanced organ preservation and conditioning. Ex vivo prolonged lung preservation has resulted in successful transplantation of high-risk donor lungs. Normothermic MP of hearts and livers has displayed safe (heart) and superior (liver) preservation in randomized controlled trials (RCT). Normothermic kidney preservation for 24 h was recently established. Early clinical outcomes beyond the market entry trials indicate bioenergetics reconditioning, improved preservation of structures subject to IRI, and significant prolongation of the preservation time. The monitoring of perfusion parameters, the biochemical investigation of preservation fluids, and the assessment of tissue viability and bioenergetics function now offer a comprehensive assessment of organ quality and function ex situ. Gene and protein expression profiling, investigation of passenger leukocytes, and advanced imaging may further enhance the understanding of the condition of an organ during MP. In addition, MP offers a platform for organ reconditioning and regeneration and hence catalyzes the clinical realization of tissue engineering. Organ modification may include immunological modification and the generation of chimeric organs. While these ideas are not conceptually new, MP now offers a platform for clinical realization. Defatting of steatotic livers, modulation of inflammation during preservation in lungs, vasodilatation of livers, and hepatitis C elimination have been successfully demonstrated in experimental and clinical trials. Targeted treatment of lesions and surgical treatment or graft modification have been attempted. In this review, we address the current state of MP and advanced organ monitoring and speculate about logical future steps and how this evolution of a novel technology can result in a medial revolution.

Restoring Mitochondrial Function While Avoiding Redox Stress: The Key to Preventing Ischemia/Reperfusion Injury in Machine Perfused Liver Grafts?

Mitochondria sense changes resulting from the ischemia and subsequent reperfusion of an organ and mitochondrial reactive oxygen species (ROS) production initiates a series of events, which over time result in the development of full-fledged ischemia-reperfusion injury (IRI), severely affecting graft function and survival after transplantation. ROS activate the innate immune system, regulate cell death, impair mitochondrial and cellular performance and hence organ function. Arresting the development of IRI before the onset of ROS production is currently not feasible and clinicians are faced with limiting the consequences. Ex vivo machine perfusion has opened the possibility to ameliorate or antagonize the development of IRI and may be particularly beneficial for extended criteria donor organs. The molecular events occurring during machine perfusion remain incompletely understood. Accumulation of succinate and depletion of adenosine triphosphate (ATP) have been considered key mechanisms in the initiation; however, a plethora of molecular events contribute to the final tissue damage. Here we discuss how understanding mitochondrial dysfunction linked to IRI may help to develop novel strategies for the prevention of ROS-initiated damage in the evolving era of machine perfusion.

Live Confocal Tissue Assessment With SYTO16/PI and WGA Staining Visualizes Acute Organ Damage and Predicts Delayed Graft Function in Kidney Transplantation.

OBJECTIVE: The aim of our prospective clinical trial was to test a tissue staining technique (real-time confocal analysis [RTCA]) as a rapid assessment tool for donor kidney quality and function in human kidney transplantation. SUMMARY BACKGROUND DATA: Tools for objective graft tissue viability assessment before kidney transplantation are lacking. RTCA has recently been established and tested in a pilot study using rodent kidneys. METHODS: RTCA was performed in kidney biopsies stained with SYTO16/PI and WGA. A score between -3 (100% nonviable) and +3 (100% viable) describes the sum of viable cells divided by the number of nonviable cells per examined area (glomerulus, proximal, and distal tubules). The primary study endpoint was the delayed graft function (DGF). RESULTS: Seventy-one kidney transplant recipients were transplanted. The median recipient and donor age were 58.5 and 57 years, respectively. Cold ischemia time was 13.6 ±â€Š4.7 hours; anastomosis time was 30.8 ±â€Š8.7 minutes (mean ±â€ŠSD). Overall, 23 (33.8%) patients developed DGF. The RTCA score was significantly lower in kidneys developing DGF -0.43 ±â€Š1.78 versus no DGF 0.91 ±â€Š2.17, P = 0.01. The Remuzzi score did not differ between DGF and no DGF, P = 0.13. Remuzzi score and RTCA score correlate inversely significantly; P = 0.004. In the multivariate analysis, solely RTCA score was revealed as a significant independent factor predicting DGF; P = 0.015, Wald = 5.95, odds ratio = 0.72, 95% confidence interval = 0.55 to 0.94. CONCLUSIONS: Our data demonstrate that RTCA is feasible and clinically meaningful. The RTCA score predicts DGF and is a valid option to be applied in renal transplantation.

The future of organ perfusion and re-conditioning.

Organ preservation and re-conditioning using machine perfusion technologies continue to generate promising results in terms of viability assessment, organ utilization and improved initial graft function. Here, we summarize the latest findings and study the results of ex-vivo/ex-situ hypothermic (HMP) and normothermic machine perfusion (NMP) in the area of abdominal organ transplantation (kidney, liver, pancreas and intestine). We also consider the potential role of normothermic regional perfusion (NRP) to re-condition donors after circulatory death organs before retrieval. The findings from clinical studies reported to date suggest that machine perfusion will offer real benefits when compared with conventional cold preservation. Several randomized trials are expected to report their findings within the next 2 years which may shed light on the relative merits of different perfusion methods and could indicate which perfusion parameters may be most useful to predict organ quality and viability. Further work is needed to identify composite endpoints that are relevant for transplanted organs that have undergone machine preservation. Multi-centre trials to compare and analyse the combinations of NRP followed by HMP and/or NMP, either directly after organ retrieval using transportable devices or when back-to-base, are needed. The potential applications of machine preservation technology beyond the field of solid organ transplantation are also considered.

Twenty-four-hour normothermic perfusion of discarded human kidneys with urine recirculation.

Transportable normothermic kidney perfusion for 24 hours or longer could enable viability assessment of marginal grafts, increased organ use, and improved transplant logistics. Eleven clinically declined kidneys were perfused normothermically, with 6 being from donors after brain death (median cold ischemia time 33 ± 36.9 hours) and 5 being from donors after circulatory death (36.2 ± 38.3 hours). Three kidneys were perfused using Ringer's lactate to replace excreted urine volume, and 8 kidneys were perfused using urine recirculation to maintain perfusate volume without fluid replenishment. In all cases, normothermic perfusion either maintained or slightly improved the histopathologically assessed tubular condition, and there was effective urine production in kidneys from both donors after brain death and donors after circulatory death (2367 ± 1798 mL vs 744.4 ± 198.4 mL, respectively; P = .44). Biomarkers, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were successfully detected and quantified in the perfusate. All kidneys with urine recirculation were readily perfused for 24 hours (n = 8) and exhibited physiological perfusate sodium levels (140.7 ± 1.2 mmol/L), while kidneys without urine recirculation (n = 3) achieved a reduced normothermic perfusion time of 7.7 ± 1.5 hours and significantly higher perfusate sodium levels (159.6 ± 4.63 mmol/:, P < .01). Normothermic machine perfusion of human kidneys for 24 hours appears to be feasible, and urine recirculation was found to facilitate the maintenance of perfusate volume and homeostasis.

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period-a Prospective, Randomized Placebo-Controlled Trial.

Introduction: Although prone to a higher degree of ischemia reperfusion injury (IRI), the use of extended criteria donor (ECD) organs has become reality in transplantation. We therefore postulated that peri-operative perfusion of renal transplants with anti-human T-lymphocyte globulin (ATLG) ameliorates IRI and results in improved graft function. Methods: We performed a randomized, single-blinded, placebo-controlled trial involving 50 kidneys (KTx). Prior to implantation organs were perfused and incubated with ATLG (AP) (n = 24 kidney). Control organs (CP) were perfused with saline only (n = 26 kidney). Primary endpoint was defined as graft function reflected by serum creatinine at day 7 post transplantation (post-tx). Results: AP-KTx recipients illustrated significantly better graft function at day 7 post-tx as reflected by lower creatinine levels, whereas no treatment effect was observed after 12 months surveillance. During the early hospitalization phase, 16 of the 26 CP-KTx patients required dialysis during the first 7 days post-tx, whereas only 10 of the 24 AP-KTx patients underwent dialysis. No treatment-specific differences were detected for various lymphocytes subsets in the peripheral blood of patients. Additionally, mRNA analysis of 0-h biopsies post incubation with ATLG revealed no changes of intragraft inflammatory expression patterns between AP and CP organs. Conclusion: We here present the first clinical study on peri-operative organ perfusion with ATLG illustrating improved graft function in the early period post kidney transplantation. Clinical Trial Registration: www.ClinicalTrials.gov, NCT03377283.

Meeting Report of the 13th Congress of the International Society of Vascularized Composite Allotransplantation.

The International Society of Vascularized Composite Allotransplantation held its 13th congress "Defining Success" in October 2017 in Salzburg, Austria. A total of 122 delegates from 22 countries representing 5 continents attended the conference. The theme strived to provide pathways to accomplish best possible outcomes in this unique and multifaceted field of transplantation. "Ignite talks," a new feature introduced for the first time at the Salzburg meeting served as key elements for productive discussions on both congress days. The "ignitors" had been selected as experts from Europe, the Americas and Asia in vascularized composite allotransplantation and neighboring disciplines and provided a global perspective of their topic. Posttransplant treatment regimens, including the most burdensome side effects of immunosuppressants in addition to novel and future therapeutic options were discussed in depth. An additional ethics symposium summarized and advanced topics that had been discussed during the first international workshop on bioethical challenges in reconstructive transplantation held earlier in 2017.

Laparoscopic sleeve gastrectomy: gateway to kidney transplantation.

BACKGROUND: The prevalence of obesity and obesity-related morbidity in end-stage renal disease patients is rising. Although it is established that obesity does not abrogate the transplant benefit with respect to lower long-term mortality and cardiovascular risk, it is associated with increased graft failure, delayed graft function, surgical complications, prolonged hospital stay, and costs. OBJECTIVES: To examine the safety and efficacy of LSG (laparoscopic sleeve gastrectomy) in renal transplant candidates and evaluate transplant outcomes. SETTING: Single-center prospective nonrandomized trial METHODS: We here report on a prospective single-center trial establishing a 2-step approach for obese renal transplant candidates. Patients with end-stage renal disease and a BMI (body mass index) of 35 kg/m2 or higher underwent laparoscopic sleeve gastrectomy. After reaching a BMI of<35 kg/m2, patients were waitlisted for kidney transplantation. Age, gender, body mass index (BMI), associated co-morbidities, cause of end-stage renal disease, surgical complications, and outcome after kidney transplantation (graft survival, incidence of delayed graft function, incidence of rejection, serum creatinine) were collected. RESULTS: LSG was performed in 8 renal transplant candidates with a mean BMI of 38.8 kg/m2 each. BMI dropped to below 35 kg/m2 within a median of 3 months. Percent excess body mass index loss (%EBMIL) was 62.7% at 1 year after LSG. Within 17 months (mean) after metabolic surgery, 7 patients underwent kidney transplantation. All transplants were successful with a serum creatinine of 1.9±.8 mg/dL at discharge and stable allograft function thereafter. Mean follow-up was 3.2±1.4 years; no patient was lost to follow-up. CONCLUSION: LSG is safe and efficacious for treatment of obesity in renal transplant candidates. Rapid and sustained weight loss and subsequent waitlisting for kidney transplantation may reduce overall and in particular posttransplant patient morbidity.

Causes, predictors and consequences of conversion from VATS to open lung lobectomy.

BACKGROUND: To analyze causes, predictors and consequences of conversions from intended VATS lobectomy to open surgery. METHODS: This is a retrospective analysis of a prospectively maintained database. RESULTS: From 2009 until December 2012, 232 patients were scheduled for anatomical VATS resection. Conversion to open surgery was necessary in 15 (6.5 %) patients. Reasons for conversion were bleeding in six, oncologic in five and technical in four patients (adhesions after pleuritis or radiotherapy for other tumors: 3; limited space: 1). In a univariable exact logistic regression analysis, conversion rate was significantly higher in patients after induction therapy (p = 0.019). There was also a statistical trend to a higher conversion rate in patients with larger tumor size (<3 vs. ≥3 cm, p = 0.117) and during the first half of our series (p = 0.107). Conversion rate was not influenced by patient age, nodal stage (pN0 vs. pN+), body mass index, the presence of chronic obstructive pulmonary disease, lung function (FEV1) or benign disease. In a multivariable exact logistic regression, induction treatment (p = 0.013) and tumor size (p = 0.04) were independent significant risk factors for conversion. Conversion did not translate into higher overall postoperative complication rate (33.3 vs. 29.5 %), longer chest drain duration (median, 5 vs. 5 days) or in-hospital mortality (0 vs. 1 %). However, length of hospital stay was significantly longer in the conversion group (median 11 vs. 9 days, p = 0.028). CONCLUSIONS: Induction therapy was an independent risk factor for conversion to thoracotomy in this VATS lobectomy series. Following induction therapy, patients should be carefully selected for a VATS approach. Conversion to thoracotomy did not increase the postoperative rate of complications or mortality, but significantly increased length of hospital stay.

Impact of abdominal drainage systems on postoperative complication rates following liver transplantation.

BACKGROUND: Depending on the extent of surgery, coagulation status and the number of anastomoses, drains are routinely used during liver transplantation. The aim of this study was to compare different drain types with regard to abdominal complication rates. METHODS: All consecutive full-size orthotopic liver transplantations (LTX) performed over a 7-year period were included in this retrospective analysis. Abdominal drain groups were divided into open-circuit drains and closed-circuit drains. Data are reported as total number (%) or median (range); for all comparisons a p value <0.05 was considered statistically significant. RESULTS: A total of 256 LTX [age 56.89 (0.30-75.21) years; MELD 14.5 (7-40)] was included; 56 (21.8 %) patients received an open-circuit Easy Flow Drain (Group 1) and 200 (78.2 %) a closed-circuit Robinson Drainage System (Group 2). For Groups 1 and 2, overall infection rates were 78.6 and 56 % (p = 0.001), abdominal infection rates 50.82 and 21.92 % (p = 0.001), yeast infection rates 37 and 23 % (p = 0.02), abdominal bleeding rates 26.78 and 17 % (p = 0.07), biliary complication rates 14.28 and 13.5 % (p = 0.51), respectively. CONCLUSIONS: In this retrospective series, open-circuit drains were associated with more abdominal complications, mainly due to intraabdominal infections, than were closed-circuit drains.

Outcome analysis of laparoscopic incisional hernia repair and risk factors for hernia recurrence in liver transplant patients.

INTRODUCTION: Incisional hernia is a common complication after liver transplantation (LT). Immunosuppression, obesity, and use of steroids are known risk factors. The purpose of the retrospective study was to summarize and evaluate experiences and results of laparoscopic intraperitoneal onlay mesh (IPOM) hernia repair. METHODS: We reviewed our liver transplant patients over a seven-yr period with laparoscopic incisional hernia repair (LIHR) to direct our attention on risk factors for hernia recurrence after hernia repair. RESULTS: Fifty-four patients after LT with incisional hernia were treated with laparoscopic repair, 42 male and 12 female patients of overall mean age of 58 ± 9 yr and body mass index (BMI) of 25 ± 4 kg/m(2) . A total of 755 LTs were performed at our institution in this time period, resulting in 7.15% of patients undergoing laparoscopic hernia repair. The mean postoperative hospital stay after was nine d. During the follow-up, nine recurrent hernias were noted (17%). BMI (p = 0.001) and sirolimus as immunosuppressive therapy were significantly associated with hernia recurrence (p = 0.014). CONCLUSION: LIHR is a safe and feasible method to treat hernias after LT. BMI and sirolimus as immunosuppressive therapy are risk factors for recurrence of hernia after laparoscopic hernia repair.