Pre-Transplant Frequencies of FoxP3+CD25+ in CD3+CD8+ T Cells as Potential Predictors for CMV in CMV-Intermediate Risk Kidney Transplant Recipients.

Cytomegalovirus (CMV) infection detrimentally influences graft survival in kidney transplant recipients, with the risk primarily determined by recipient and donor serostatus. However, recipient CD8+ T cells play a crucial role in CMV control. The optimal preventive strategy (prophylaxis vs. pre-emptive treatment), particularly for seropositive (intermediate risk) recipients, remains uncertain. We investigated CD8+ T cell subpopulation dynamics and CMV occurrence (DNAemia ≥ 100 IU/mL) in 65 kidney transplant recipients, collecting peripheral blood mononuclear cells before (T1) and 1 year after transplantation (T2). Comparing the two timepoints, we found an increase in granulocyte, monocyte and CD3+CD8+ T cells numbers, while FoxP3+CD25+, LAG-3+ and PD-1+ frequencies were reduced at T2. CMV DNAemia occurred in 33 recipients (55.8%) during the first year. Intermediate risk patients were disproportionally affected by posttransplant CMV (N = 29/45, 64.4%). Intermediate risk recipients developing CMV after transplantation exhibited lower leukocyte, monocyte, and granulocyte counts and higher FoxP3+CD25+ frequencies in CD3+CD8+ T cells pre-transplantation compared to patients staying CMV negative. Pre-transplant FoxP3+CD25+ in CD3+CD8+ T cells had the best discriminatory potential for CMV infection prediction within the first year after transplantation (AUC: 0.746). The FoxP3+CD25+ CD3+CD8+ T cell subset may aid in selecting intermediate risk kidney transplant recipients for CMV prophylaxis.

Alternative intraoperative optical imaging modalities for fluorescence angiography in gastrointestinal surgery: spectral imaging and imaging photoplethysmography.

INTRODUCTION: Intraoperative near-infrared fluorescence angiography with indocyanine green (ICG-FA) is a well-established modality in gastrointestinal surgery. Its main drawback is the application of a fluorescent agent with possible side effects for patients. The goal of this review paper is the presentation of alternative, non-invasive optical imaging methods and their comparison with ICG-FA. MATERIAL AND METHODS: The principles of ICG-FA, spectral imaging, imaging photoplethysmography (iPPG), and their applications in gastrointestinal surgery are described based on selected published works. RESULTS: The main applications of the three modalities are the evaluation of tissue perfusion, the identification of risk structures, and tissue segmentation or classification. While the ICG-FA images are mainly evaluated visually, leading to subjective interpretations, quantitative physiological parameters and tissue segmentation are provided in spectral imaging and iPPG. The combination of ICG-FA and spectral imaging is a promising method. CONCLUSIONS: Non-invasive spectral imaging and iPPG have shown promising results in gastrointestinal surgery. They can overcome the main drawbacks of ICG-FA, i.e. the use of contrast agents, the lack of quantitative analysis, repeatability, and a difficult standardization of the acquisition. Further technical improvements and clinical evaluations are necessary to establish them in daily clinical routine.

Hyperspectral Imaging (HSI) of Human Kidney Allografts.

OBJECTIVE: Aim of our study was to test a noninvasive HSI technique as an intraoperative real time assessment tool for deceased donor kidney quality and function in human kidney allotransplantation. SUMMARY OF BACKGROUND DATA: HSI is capable to deliver quantitative diagnostic information about tissue pathology, morphology, and composition, based on the spectral characteristics of the investigated tissue. Because tools for objective intraoperative graft viability and performance assessment are lacking, we applied this novel technique to human kidney transplantation. METHODS: Hyperspectral images of distinct components of kidney allografts (parenchyma, ureter) were acquired 15 and 45 minutes after reperfusion and subsequently analyzed using specialized HSI acquisition software capable to compute oxygen saturation levels (StO2), near infrared perfusion indices (NIR), organ hemoglobin indices, and tissue water indices of explored tissues. RESULTS: Seventeen kidney transplants were analyzed. Median recipient and donor age were 55 years. Cold ischemia time was 10.8 ±â€Š4.1 hours and anastomosis time was 35 ±â€Š7 minutes (mean ±â€Šstandard deviation). Two patients (11.8%) developed delayed graft function (DGF). cold ischemia time was significantly longer (18.6 ±â€Š1.6) in patients with DGF (P < 0.01). Kidneys with DGF furthermore displayed significant lower StO2 (P = 0.02) and NIR perfusion indices, 15 minutes after reperfusion (P < 0.01). Transplant ureters displayed a significant decrease of NIR perfusion with increased distance to the renal pelvis, identifying well and poor perfused segments. CONCLUSION: Intraoperative HSI is feasible and meaningful to predict DGF in renal allografts. Furthermore, it can be utilized for image guided surgery, providing information about tissue oxygenation, perfusion, hemoglobin concentration, and water concentration, hence allowing intraoperative viability assessment of the kidney parenchyma and the ureter.

Hyperspectral Imaging as a Tool for Viability Assessment During Normothermic Machine Perfusion of Human Livers: A Proof of Concept Pilot Study.

Normothermic machine perfusion (NMP) allows for ex vivo viability and functional assessment prior to liver transplantation (LT). Hyperspectral imaging represents a suitable, non-invasive method to evaluate tissue morphology and organ perfusion during NMP. Liver allografts were subjected to NMP prior to LT. Serial image acquisition of oxygen saturation levels (StO2), organ hemoglobin (THI), near-infrared perfusion (NIR) and tissue water indices (TWI) through hyperspectral imaging was performed during static cold storage, at 1h, 6h, 12h and at the end of NMP. The readouts were correlated with perfusate parameters at equivalent time points. Twenty-one deceased donor livers were included in the study. Seven (33.0%) were discarded due to poor organ function during NMP. StO2 (p < 0.001), THI (p < 0.001) and NIR (p = 0.002) significantly augmented, from static cold storage (pre-NMP) to NMP end, while TWI dropped (p = 0.005) during the observational period. At 12-24h, a significantly higher hemoglobin concentration (THI) in the superficial tissue layers was seen in discarded, compared to transplanted livers (p = 0.036). Lactate values at 12h NMP correlated negatively with NIR perfusion index between 12 and 24h NMP and with the delta NIR perfusion index between 1 and 24h (rs = -0.883, p = 0.008 for both). Furthermore, NIR and TWI correlated with lactate clearance and pH. This study provides first evidence of feasibility of hyperspectral imaging as a potentially helpful contact-free organ viability assessment tool during liver NMP.

Recipient obesity as a risk factor in kidney transplantation.

BACKGROUND: The aim of the study was to investigate the effect of recipient obesity on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). PATIENTS AND METHODS: A total of 578 patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into normal weight (BMI 18.5-24.9 kg/m2; N = 304), overweight (BMI 25-29.9 kg/m2; N = 205) and obese (BMI ≥ 30 kg/m2; N = 69) groups. Their clinicopathological characteristics, outcomes, and survival rates were analyzed retrospectively. RESULTS: Obesity was associated with an increased rate of surgical complications such as wound infection (P < 0.001), fascial dehiscence (P = 0.023), and lymphoceles (P = 0.010). Furthermore, the hospital stay duration was significantly longer in the groups with obese patients compared to normal weight and overweight patients (normal weight: 22 days, overweight: 25 days, and obese: 33 days, respectively; P < 0.001). Multivariate analysis showed that recipient obesity (BMI ≥ 30) was an independent prognostic factor for delayed graft function (DGF) (OR 2.400; 95% CI, 1.365-4.219; P = 0.002) and postoperative surgical complications (OR 2.514; 95% CI, 1.230-5.136; P = 0.011). The mean death-censored graft survival was significantly lower in obese patients (normal weight: 16.3 ± 0.6 years, overweight: 16.3 ± 0.8 years, obese 10.8 ± 1.5 years, respectively; P = 0.001). However, when using the Cox proportional hazards model, the association between recipient obesity and death-censored renal graft failure disappeared, after adjustment for important covariates, whereas the principal independent predictors of graft loss were recipient diabetes mellitus and hypertension and kidneys from donors with expanded donor criteria. CONCLUSION: In conclusion, obesity increases the risk of DGF and post-operative surgical complications after primary KT. Appropriate risk-adapted information concerning this must be provided to such patients before KT. Furthermore, obesity-typical concomitant diseases seem to negatively influence graft survival and need to be considered after the transplantation of obese patients.

[Resection and transplantation for hepatocellular carcinoma and intrahepatic cholangiocarcinoma]. / Resektion und Transplantation bei hepatozellulärem Karzinom und intrahepatischem Cholangiokarzinom.

CLINICAL ISSUE: Treatment of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) has markedly improved in recent years. STANDARD TREATMENT: Liver resection and, for HCC, liver transplantation are essential components of curative treatment in the nonmetastatic stage. TREATMENT INNOVATIONS: In the current S3 guideline, the role of the interdisciplinary tumor board is strengthened for the individual therapy decision. Overall, liver transplantation offers the best long-term results in terms of survival and relapse rate for selected patients. For liver resection, the use of minimally invasive resection techniques can significantly reduce perioperative morbidity and mortality compared to open liver surgery, so that it can be used both as a curative therapeutic approach and as part of bridging strategies for liver transplantation. PERFORMANCE: The 5­year survival rate after liver transplantation in selected, nonresectable patients who fulfil and also those who do not fulfil the Milan criteria is above 70%, compared with about 30% without liver transplantation under locoregional therapy. ACHIEVEMENTS: The following article reports the status of evidence-based surgical therapy for HCC and iCCA based on the recommendations of the current German S3 guideline. PRACTICAL RECOMMENDATIONS: The differentiated local therapy of HCC in cirrhosis is based on many patient- and tumor-specific factors. In addition to surgical resection, liver transplantation plays an important role as a curative therapy for patients with irresectable HCCs regardless of whether they meet the Milan criteria. For resectable iCCA or HCC without cirrhosis in the nonmetastatic stage, surgical resection represents the treatment of choice.

Total Laparoscopic Resection of Hilar Cholangiocarcinoma Type 3b: Applying a Parachute Technique for Hepaticojejunostomy.

BACKGROUND: Laparoscopic liver resection for perihilar cholangiocarcinoma (pCCA) is still in its infancy. The biliary-enteric reconstruction represents one of the most delicate parts of this minimally invasive procedure. METHODS: In this study, a 78-year old woman with perihilar cholangiocarcinoma (pCCA) type 3b underwent a hepaticojejunostomy performed by a parachute technique. RESULTS: The operation, performed totally by minimally invasive resections, was completed in 386 min, with a blood loss of less than 400 ml and no transfusion requirements. Two intraluminal stents were placed during the hepaticojenunostomy for splinting of the biliary-enteric anastomosis. The patient required prolonged antibiotic treatment for postoperative cholangitis and finally was discharged on postoperative day 15. The histopathologic grading displayed a G 2-3 adenocarcinoma, pT3 pN0, M0, L1, V1, pN1, UICC IIIc R0, and the patient was referred to adjuvant chemotherapy. CONCLUSION: Resections of pCCAs, performed totally by minimally invasive techniques, may be feasible and safe for a selected group of patients. With this approach, a running-suture hepaticojejunostomy using the parachute technique represents a worthwhile strategy for biliary-enteric reconstruction.

Comparison of hyperspectral imaging and fluorescence angiography for the determination of the transection margin in colorectal resections-a comparative study.

PURPOSE: One relevant aspect for anastomotic leakage in colorectal surgery is blood perfusion of both ends of the anastomosis. The clinical evaluation of this issue is limited, but new methods like fluorescence angiography with indocyanine green or non-invasive and contactless hyperspectral imaging have evolved as objective parameters for perfusion evaluation. METHODS: In this prospective, non-randomized, open-label and two-arm study, fluorescence angiography and hyperspectral imaging were compared in 32 consecutive patients with each other and with the clinical assessment by the surgeon. After preparation of the bowel and determination of the surgical resection line, the tissue was evaluated with hyperspectral imaging for 5 min before and after cutting the marginal artery and assessed by 6 hyperspectral pictures followed by fluorescence angiography with indocyanine green. RESULTS: In 30 of 32 patients, the image data could be evaluated and compared. Both methods provided a comparable borderline between well-perfused and poorly perfused tissue (p = 0.704). In 15 cases, the surgical resection line was shifted to the central position due to the imaging. The border zone was sharper in fluorescence angiography and best assessed 31 s after injection. With hyperspectral imaging, the border zone was visualized wider and with more differences between proximal and distal border. CONCLUSION: Hyperspectral imaging and fluorescence angiography provide similar results in determining the perfusion border. Both methods allow a good and safe visualization of the blood perfusion at the central resection margin to create a well-perfused anastomosis. TRIAL REGISTRATION: This study was registered at Clinicaltrials.gov ( NCT04226781 ) on January 13, 2020.

[New intraoperative fluorescence-based and spectroscopic imaging techniques in visceral medicine - precision surgery in the "high tech"-operating room]. / Neue intraoperative fluoreszenzbasierte und spektroskopische Bildgebungsverfahren in der Viszeralmedizin ­ Präzisionschirurgie im "Hightech"-OP.

INTRODUCTION: Fluorescence angiography (FA) with indocyanine green (ICG) and hyperspectral imaging (HSI) are novel intraoperative visualization techniques in abdominal, vascular and transplant surgery. With the purpose of precision surgery, and in order to increase patient's safety, these new tools aim at reducing postoperative morbidity and mortality. This review discusses and highlights recent developments and the future potential of real-time imaging modalities. METHODS: The underlying mechanisms of the novel imaging methods and their clinical impact are displayed in the context of avoiding anastomotic leaks, the most momentous complications in gastrointestinal surgery after oncologic resections. RESULTS: While FA is associated with the admission of a fluorescence agent, HSI is contact-free and non-invasive. Both methods are able to record physiological tissue properties in real-time. Additionally, FA also measures dynamic phenomena. The techniques take a few seconds only and do not hamper the operative workflow considerably. With regard to a potential change of the surgical strategy, FA and HSI have an equal significance. Our own advancements reflect, in particular, the topics of data visualization and automated data analyses together with the implementation of artificial intelligence (AI) and minimalization of the current devices to install them into endoscopes, minimal-invasive and robot-guided surgery. CONCLUSION: There are a limited number of studies in the field of intraoperative imaging techniques. Whether precision surgery in the "high-tech" OR together with FA, HSI and robotics will result in more secure operative procedures to minimize the postoperative morbidity and mortality will have to be evaluated in future multicenter trials.

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

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

Current State and Future Possibilities in Liver Transplantation.

Due to medical and surgical progress, liver transplantation (LT) is is nowadays a routine treatment for terminal liver failure and hepatic malignancies. However, in recent years there has been a change in the indications for LT. Especially in western industrialized countries, the use of LT for chronic hepatis B and hepatitis C cirrhosis is continuously decreasing since the introduction of effective antiviral drugs. Liver cirrhosis due to non-alcoholic steatohepatitis (NASH), alcoholic liver disease and hepatocellular carcinoma (HCC) in cirrhosis are now among the leading indications for LT. Due to tremendous progress in oncology, immunology, and technical aspects, multidisciplinary cancer treatment increasingly includes LT for non-HCC hepatobiliary malignancies. Excellent 5-year survival rates of 75 to 80% can now be achieved after LT. However, in patients with liver cirrhosis, the implementation of a 'sickest first' principle for liver allocation has led to an increasing number of critically ill patients undergoing liver transplantation. This results in an increased morbidity and mortality after liver transplantation. Moreover, donor characteristics have markedly shifted to less ideal grafts due to an increasing shortage of donor organs in many countries. In this context, normothermic machine perfusion with oxygenated blood components using pulsatile flow has been shown to reduce liver damage despite a prolonged preservation time and might be able to provide viability testing for otherwise discarded organs. With favorable donor and recipient conditions, excellent long-term results can be obtained with a 10-year survival rate of close to 70%. However, in patients with a high MELD score (>30), survival rates markedly decrease by 12-18%. Future research should focus on optimization of organ allocation, optimization of immunosuppression including tolerance induction, and on increasing the donor organ pool to further improve and the numbers of successful LT.

Impact of pre-transplant dialysis modality on the outcome and health-related quality of life of patients after simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) profoundly improves the health-related quality of life (HRQoL) of recipients. However, the influence of the pre-transplant dialysis modality on the success of the SPKT and post-transplant HRQoL remains unknown. METHODS: We analyzed the surgical outcome, long-term survival, as well as HRQoL of 83 SPKTs that were performed in our hospital between 2000 and 2016. Prior to transplant, 64 patients received hemodialysis (HD) and nineteen patients received peritoneal dialysis (PD). Physical and mental quality of life results from eight basic scales and the physical and mental component summaries (PCS and MCS) were measured using the Short Form 36 (SF-36) survey. RESULTS: Peri- and postoperative complications, as well as patient and graft survival were similar between the two groups. Both groups showed an improvement of HRQoL in all SF-36 domains after transplantation. Compared with patients who received HD before transplantation, PD patients showed significantly better results in four of the eight SF-36 domains: physical functioning (mean difference HD - PD: - 12.4 ± 4.9, P = < 0.01), bodily pain (- 14.2 ± 6.3, P < 0.01), general health (- 6.3 ± 2.8, P = 0.04), vitality (- 6.8 ± 2.6, P = 0.04), and PCS (- 5.2 ± 1.5, P < 0.01) after SPKT. In the overall study population, graft loss was associated with significant worsening of the HRQoL in all physical components (each P < 0.01). CONCLUSIONS: The results of this analysis show that pre-transplant dialysis modality has no influence on the outcome and survival rate after SPKT. Regarding HRQoL, patients receiving PD prior to SPKT seem to have a slight advantage compared with patients with HD before transplantation.

Short and long-term metabolic outcomes in patients with type 1 and type 2 diabetes receiving a simultaneous pancreas kidney allograft.

BACKGROUND: In contrast to insulin-dependent type 1 diabetes mellitus (T1DM), the indication for Simultaneous pancreas-kidney transplantation (SPK) in patients with type 2 diabetes mellitus (T2DM) is still ambiguous and wisely Eurotransplant (ET) only granted transplant-permission in a selected group of patients. However, with regard to improvement of metabolic conditions SPK might still be a considerable treatment option for lean insulin dependent type 2 diabetics suffering from renal disease. METHODS: Medical data (2001-2013) from all consecutive T1DM and T2DM patients who received a SPK or kidney transplant alone (KTA) at the University Hospital of Leipzig were analyzed. Donor, recipients and long-term endocrine, metabolic and graft outcomes were investigated for T1DM and T2DM-SPK recipients (transplanted upon a special request allocation by ET) and T2DM patients who received a KTA during the same period. RESULTS: Eighty nine T1DM and 12 T2DM patients received a SPK and 26 T2DM patients received a KTA. Patient survival at 1 and 5 years was 89.9 and 88.8% for the T1DM group, 91.7 and 83.3% for the T2DM group, and 92.3 and 69.2% for the T2DM KTA group, respectively (p < 0.01). Actuarial pancreas graft survival for SPK recipients at 1 and 5 years was 83.1 and 78.7% for the T1DM group and 91.7 and 83.3% for the T2DM group, respectively (p = 0.71). Kidney allograft survival at 5 years was 79.8% for T1DM, 83.3% for T2DM, and 65.4% for T2DM KTA (p < 0.01). Delayed graft function (DGF) rate was significantly higher in type 2 diabetics received a KTA. Surgical, immunological and infectious complications showed similar results for T1DM and T2DM recipients after SPK transplant and KTA, respectively. With regard to the lipid profile, the mean high-density lipoprotein (HDL)- cholesterol levels were significantly higher in T1DM recipients compared to T2DM patients before transplantation (p = 0.02) and remained significantly during follow up period. CONCLUSION: Our data demonstrate that with regard to metabolic function a selected group of patients with T2DM benefit from SPK transplantation. Consensus guidelines and further studies for SPK transplant indications in T2DM patients are still warranted.

[Laparoscopic Left Hemihepatectoy Applying Intraoperative Indocyanine Green Fluorescence Detection Counter Perfusion Method for Visualization]. / Laparoskopische Hemihepatektomie links mit intraoperativer Indocyaningrün-Perfusionsbildgebung.

Intraoperative indocyanine green (ICG) fluorescence detection by the "counter perfusion method" is a useful tool to identify hepatic segments and intersegmental planes during anatomic liver resection. We report of a 54-year old patient with recurrent cholangitis due to Caroli disease, who underwent a laparoscopic hemihepatectomy. To determine the resection line and resection plane, we injected ICG intravenously after clamping/ligating the left hepatic artery and left portal vein. Before and during resection the liver was observed under visible light and under near-infrared (NIR) light. This method allowed for precise anatomical resection of non-perfused liver segments 2, 3 and 4.

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

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

Donor Dopamine Does Not Affect Liver Graft Survival: Evidence of Safety From a Randomized Controlled Trial.

Treatment of donation after brain death (DBD) donors with low-dose dopamine improves the outcomes after kidney and heart transplantation. This study investigates the course of liver allografts from multiorgan donors enrolled in the randomized dopamine trial between 2004 and 2007 (clinicaltrials.gov identifier: NCT00115115). There were 264 hemodynamically stable DBDs who were randomly assigned to receive low-dose dopamine. Dopamine was infused at 4 µg/kg/minute for a median duration of 6.0 hours (interquartile range, 4.4-7.5 hours). We assessed the outcomes of 212 liver transplantations (LTs) performed at 32 European centers. Donors and recipients of both groups were very similar in baseline characteristics. Pretransplant laboratory Model for End-Stage Liver Disease score was not different in recipients of a dopamine-treated versus untreated graft (18 ± 8 versus 20 ± 8; P = 0.12). Mean cold ischemia time was 10.6 ± 2.9 versus 10.1 ± 2.8 hours (P = 0.24). No differences occurred in biopsy-proven rejection episodes (14.4% versus 15.7%; P = 0.85), requirement of hemofiltration (27.9% versus 31.5%; P = 0.65), the need for early retransplantation (5.8% versus 6.5%; P > 0.99), the incidence of primary nonfunction (7.7% versus 8.3%; P > 0.99), and in-hospital mortality (15.4% versus 14.8%; P > 0.99). Graft survival was 71.2% versus 73.2% and 59.6% versus 62.0% at 2 and 3 years (log-rank P = 0.71). Patient survival was 76.0% versus 78.7% and 65.4% versus 69.4% at 1 and 3 years (log-rank P = 0.50). In conclusion, donor pretreatment with dopamine has no short-term or longterm effects on outcome after LT. Therefore, low-dose dopamine pretreatment can safely be implemented as the standard of care in hemodynamically stable DBDs.

Evolution of laparoscopic liver surgery as standard procedure for HCC in cirrhosis?

Patients with hepatocellular carcinoma (HCC) in cirrhosis have an increased risk for postoperative complications including liver failure. However, there is some evidence that the use of laparoscopy markedly decreases this risk. Patients Between 2010 - 2015, a total of 21 laparoscopic liver resections were performed for HCC in Child-A cirrhosis at our center. Mean MELD score was 9 (6 - 12), and the mean LiMAx was 261 µg/h/kg (101 - 489). All resections were performed by conventional laparoscopy using 4 - 6 trocars. Liver parenchyma was transected using ultrasonic shears. Hilar occlusion was used on demand. In the earlier years, laparoscopic resections were performed occasionally and mainly if tumors were easily accessible. With increasing experience, currently most HCC in cirrhosis are resected laparoscopically. Likewise, 12 out of the 21 resections were performed within the last 12 months, including 2 anatomic left hemihepatectomies. Results Conversion rate, postoperative mortality, and operative revision rate were all 0 %. Four patients (19 %) developed mild complications Clavien-Dindo grade 1 or 2 (ascites, transfusion, pneumonia, renal impairment). One patient (4.8 %) developed a grade 3 event (bile leak, percutaneous drainage). All but 1 early patient underwent R0 resection (95 %). The mean duration of hospital stay was 10.5 days (5 - 21), and the mean duration of ICU stay was 1.8 days (1 - 7). No case of decompensation of liver cirrhosis was observed. In 1 case, a prolonged production of ascites evolved. Conclusion Even in patients with severely impaired liver function, no severe complications and especially no decompensation of cirrhosis was observed. Therefore, in accordance with other single center experiences, liver resection for HCC in cirrhosis should be performed preferentially by laparoscopy.

Predictive factors for extrahepatic recurrence of hepatocellular carcinoma following liver transplantation.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) in patients treated with liver transplantation (LT) is associated with diminished survival. Particularly, extrahepatic localization of HCC recurrence contributes to poor prognosis. PATIENTS AND METHODS: Clinicopathological data of patients who underwent LT for HCC between 1989 and 2010 in a high-volume transplant center were retrospectively evaluated, and predictors of extrahepatic recurrence were identified. RESULTS: Three hundred and sixty-four patients underwent LT for HCC. After a median follow-up time of 78 months, 93 patients (25%) were diagnosed with a recurrence. Median time to recurrence was 19 months. Recurrence was located exclusively in the liver in 19 cases (20%), and 74 patients (80%) had extrahepatic recurrence. Factors associated with extrahepatic recurrence in multivariate analysis included HCC beyond the Milan criteria (p < 0.0001) and the presence of macrovascular tumor invasion (p = 0.035). In patients with HCC beyond the Milan criteria who developed a recurrence (N = 73), macrovascular invasion was the only positive predictor of extrahepatic recurrence in multivariate analysis (p < 0.0001). In patients with HCC within the Milan criteria who recurred after LT (N = 20), DNA-index >1.5 (p = 0.013) was the only predictive factor for extrahepatic recurrence in multivariate analysis. CONCLUSIONS: Advanced HCC beyond the Milan criteria and the presence of macrovascular invasion are associated with an increased risk for extrahepatic recurrence and are currently considered as relative contraindications to LT. In patients with HCC within the Milan criteria, the DNA-index represents a valuable prognostic marker for the development of extrahepatic recurrence and may support the selection of patients for intensified postoperative tumor surveillance.