The GALAD score and the BALAD-2 score correlate with transarterial and systemic treatment response and survival in patients with hepatocellular carcinoma.

PURPOSE: The GALAD score and the BALAD-2 score are biomarker-based scoring systems used to detect hepatocellular carcinoma (HCC). Both incorporate levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Our objective was to examine the relationship between the GALAD score as well as the BALAD-2 score and treatment response to transarterial or systemic treatments in patients with HCC. METHODS: A total of 220 patients with HCC treated with either transarterial (n = 121) or systemic treatments (n = 99; mainly Sorafenib) were retrospectively analyzed. The GALAD score and the BALAD-2 score were calculated based on AFP-L3, AFP, and DCP levels measured in serum samples collected before treatment. The results were correlated with 3-month treatment efficacy based on radiologic mRECIST criteria. RESULTS: The GALAD score showed a strong correlation with BCLC stage (p < 0.001) and total tumor diameter before treatment (p < 0.001).The GALAD score at baseline was significantly lower in patients with a 3-month response to transarterial (p > 0.001) than in refractory patients. Among patients receiving systemic treatment, the median BALAD-2 score at baseline showed a strong association with response at month 3 (p < 0.001). In the transarterial treatment group, the GALAD score (AUC = 0.715; p < 0.001) as well as the BALAD score (AUC = 0.696; p < 0.001) were associated with overall survival, hereby outperforming AFP, AFP-L3 and DCP. CONCLUSION: The GALAD score as well as the BALAD-2 score hold significant promise as a prognostic tool for patients with early or intermediate-stage HCC who are undergoing transarterial or systemic treatments.

Rescue Allocation Modes in Eurotransplant Kidney Transplantation: Recipient Oriented Extended Allocation Versus Competitive Rescue Allocation-A Retrospective Multicenter Outcome Analysis.

BACKGROUND: Whenever the kidney standard allocation (SA) algorithms according to the Eurotransplant (ET) Kidney Allocation System or the Eurotransplant Senior Program fail, rescue allocation (RA) is initiated. There are 2 procedurally different modes of RA: recipient oriented extended allocation (REAL) and competitive rescue allocation (CRA). The objective of this study was to evaluate the association of patient survival and graft failure with RA mode and whether or not it varied across the different ET countries. METHODS: The ET database was retrospectively analyzed for donor and recipient clinical and demographic characteristics in association with graft outcomes of deceased donor renal transplantation (DDRT) across all ET countries and centers from 2014 to 2021 using Cox proportional hazards methods. RESULTS: Seventeen thousand six hundred seventy-nine renal transplantations were included (SA 15 658 [89%], REAL 860 [4.9%], and CRA 1161 [6.6%]). In CRA, donors were older, cold ischemia times were longer, and HLA matches were worse in comparison with REAL and especially SA. Multivariable analyses showed comparable graft and recipient survival between SA and REAL; however, CRA was associated with shorter graft survival. Germany performed 76% of all DDRTs after REAL and CRA and the latter mode reduced waiting times by up to 2.9 y. CONCLUSIONS: REAL and CRA are used differently in the ET countries according to national donor rates. Both RA schemes optimize graft utilization, lead to acceptable outcomes, and help to stabilize national DDRT programs, especially in Germany.

Effect of Pre-Transplant Recipient Underweight on the Postoperative Outcome and Graft Survival in Primary Kidney Transplantation.

BACKGROUND: The objective of this study was to evaluate the influence of recipient underweight on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). PATIENTS AND METHODS: Three hundred thirty-three 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 underweight (BMI <18.5 kg/m2; N = 29) and normal weight (BMI 18.5-24.9 kg/m2; N = 304) groups. Clinicopathological characteristics, postoperative outcomes, and graft and patient survival were analyzed retrospectively. RESULTS: The postoperative rate of surgical complications and renal function were comparable between the groups. One year and 3 years after KT, 70% and 92.9%, respectively, of the pre-transplant underweight patients reached a normal BMI (≥18.5 kg/m2). The mean death-censored graft survival was significantly lower in pre-transplant underweight patients than in pre-transplant normal-weight patients (11.5 ± 1.6 years vs 16.3 ± 0.6 years, respectively; P = .045). Especially KT recipients with a moderate or severe pre-transplant underweight (BMI <17 kg/m2; N = 8) showed an increased rate of graft loss (5- and 10-year graft survival: 21.4% each). No statistical difference could be observed between the 2 groups regarding causes of graft loss. In multivariate analysis, recipient underweight (P = .024) remained an independent prognostic factor for graft survival. CONCLUSION: Being underweight did not affect the early postoperative outcome after primary KT. However, underweight, and especially moderate and severe thinness, is associated with reduced long-term kidney graft survival, and therefore this group of patients should be monitored with special attention.

Prediction of the Postoperative Outcome in Liver Resection Using Perioperative Serum Lactate Levels.

BACKGROUND: The aim of our study was to analyze perioperative lactate levels and their predictive value for postoperative mortality and morbidity after liver resection. METHODS: The clinicopathological characteristics and outcomes of 152 patients who underwent liver resection for benign and malign diagnoses were analyzed retrospectively. Lactate concentrations at three different time points, (1) before liver resection (LAC-PRE), (2) after liver resection on day 0 (LAC-POST), and (3) on day one after the operation (LAC-POD1) were assessed regarding the prognostic value in predicting postoperative complications and mortality according to the Clavien-Dindo (CD) classification. RESULTS: The rates of postoperative complications (CD ≥ IIIb) and mortality rates were 19.7% (N = 30) and 4.6% (N = 7), respectively. The LAC-PRE levels showed no correlation with the postoperative outcome. The ROC curve analysis showed that LCT-POST and LCT-POD1 values were moderately strong in predicting postoperative morbidity (0.681 and 0.768, respectively) and had strong predictive accuracies regarding postoperative mortality (0.800 and 0.838, respectively). The multivariate analysis revealed LAC-POST as a significant predictor of postoperative complications (CD ≥ IIIb: OR 9.28; 95% CI: 2.88-29.9; p < 0.001) and mortality (OR 11.69; 95% CI: 1.76-77.7; p = 0.011). CONCLUSION: Early postoperative lactate levels are a useful and easily practicable predictor of postoperative morbidity and mortality in patients after liver resection.

Dickkopf-Related Protein 1 as Response Marker for Transarterial Chemoembolization of Hepatocellular Carcinomas.

Background and Aims: In the treatment of hepatocellular carcinoma (HCC), response prediction to transarterial chemoembolization (TACE) based on serum biomarkers is not established. We have studied the association of circulating Dickkopf-related protein 1 (DKK-1) with baseline characteristics and response to TACE in European HCC patients. Methods: Patients with HCC treated with TACE from 2010 to 2018 at a tertiary referral hospital were retrospectively enrolled. Levels of DKK-1 were measured in serum samples collected before TACE. Response was assessed according to mRECIST criteria at week 12 after TACE. Results: Ninety-seven patients were enrolled, including seventy-nine responders and eighteen refractory. Before TACE, median DKK-1 serum levels were 922 [range, 199−4514] pg/mL. DKK-1 levels were lower in patients with liver cirrhosis (p = 0.002) and showed a strong correlation with total radiologic tumor size (r = 0.593; p < 0.001) and with Barcelona Clinic Liver Cancer stages (p = 0.032). Median DKK-1 levels were significantly higher in refractory patients as compared to responders (1471 pg/mL [range, 546−2492 pg/mL] versus 837 pg/mL [range, 199−4515 pg/mL]; p < 0.001), and DKK-1 could better identify responders than AFP (AUC = 0.798 vs. AUC = 0.679; p < 0.001). A DKK-1 cutoff of ≤1150 pg/mL was defined to identify responders to TACE with a sensitivity of 78% and specificity of 77%. DKK-1 levels were suitable to determine response to TACE in patients with low AFP serum levels (AFP levels < 20 ng/mL; AUC = 0.843; 95% CI [0.721−0.965]; p = 0.003). Conclusion: DKK-1 levels in serum are strongly associated tumor size and with response to TACE in European HCC patients, including those patients with low AFP levels.

Predictive Value of HAS-BLED Score Regarding Bleeding Events and Graft Survival following Renal Transplantation.

Objective: Due to the high prevalence and incidence of cardio- and cerebrovascular diseases among dialysis-dependent patients with end-stage renal disease (ERSD) scheduled for kidney transplantation (KT), the use of antiplatelet therapy (APT) and/or anticoagulant drugs in this patient population is common. However, these patients share a high risk of complications, either due to thromboembolic or bleeding events, which makes adequate peri- and post-transplant anticoagulation management challenging. Predictive clinical models, such as the HAS-BLED score developed for predicting major bleeding events in patients under anticoagulation therapy, could be helpful tools for the optimization of antithrombotic management and could reduce peri- and postoperative morbidity and mortality. Methods: Data from 204 patients undergoing kidney transplantation (KT) between 2011 and 2018 at the University Hospital Leipzig were retrospectively analyzed. Patients were stratified and categorized postoperatively into the prophylaxis group (group A)­patients without pretransplant anticoagulation/antiplatelet therapy and receiving postoperative heparin in prophylactic doses­and into the (sub)therapeutic group (group B)­patients with postoperative continued use of pretransplant antithrombotic medication used (sub)therapeutically. The primary outcome was the incidence of postoperative bleeding events, which was evaluated for a possible association with the use of antithrombotic therapy. Secondary analyses were conducted for the associations of other potential risk factors, specifically the HAS-BLED score, with allograft outcome. Univariate and multivariate logistic regression as well as a Cox proportional hazard model were used to identify risk factors for long-term allograft function, outcome and survival. The calibration and prognostic accuracy of the risk models were evaluated using the Hosmer−Lemshow test (HLT) and the area under the receiver operating characteristic curve (AUC) model. Results: In total, 94 of 204 (47%) patients received (sub)therapeutic antithrombotic therapy after transplantation and 108 (53%) patients received prophylactic antithrombotic therapy. A total of 61 (29%) patients showed signs of postoperative bleeding. The incidence (p < 0.01) and timepoint of bleeding (p < 0.01) varied significantly between the different antithrombotic treatment groups. After applying multivariate analyses, pre-existing cardiovascular disease (CVD) (OR 2.89 (95% CI: 1.02−8.21); p = 0.04), procedure-specific complications (blood loss (OR 1.03 (95% CI: 1.0−1.05); p = 0.014), Clavien−Dindo classification > grade II (OR 1.03 (95% CI: 1.0−1.05); p = 0.018)), HAS-BLED score (OR 1.49 (95% CI: 1.08−2.07); p = 0.018), vit K antagonists (VKA) (OR 5.89 (95% CI: 1.10−31.28); p = 0.037), the combination of APT and therapeutic heparin (OR 5.44 (95% CI: 1.33−22.31); p = 0.018) as well as postoperative therapeutic heparin (OR 3.37 (95% CI: 1.37−8.26); p < 0.01) were independently associated with an increased risk for bleeding. The intraoperative use of heparin, prior antiplatelet therapy and APT in combination with prophylactic heparin was not associated with increased bleeding risk. Higher recipient body mass index (BMI) (OR 0.32 per 10 kg/m2 increase in BMI (95% CI: 0.12−0.91); p = 0.023) as well as living donor KT (OR 0.43 (95% CI: 0.18−0.94); p = 0.036) were associated with a decreased risk for bleeding. Regarding bleeding events and graft failure, the HAS-BLED risk model demonstrated good calibration (bleeding and graft failure: HLT: chi-square: 4.572, p = 0.802, versus chi-square: 6.52, p = 0.18, respectively) and moderate predictive performance (bleeding AUC: 0.72 (0.63−0.79); graft failure: AUC: 0.7 (0.6−0.78)). Conclusions: In our current study, we could demonstrate the HAS-BLED risk score as a helpful tool with acceptable predictive accuracy regarding bleeding events and graft failure following KT. The intensified monitoring and precise stratification/assessment of bleeding risk factors may be helpful in identifying patients at higher risks of bleeding, improved individualized anticoagulation decisions and choices of antithrombotic therapy in order to optimize outcome after kidney transplantation.

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

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

[Cholangiocarcinoma-Intrahepatic to hilar bile duct cancer]. / Cholangiokarzinome ­ intrahepatisches bis hiläres Gallengangkarzinom.

BACKGROUND: In addition to conditioning measures in liver surgery, perioperative anti-tumor therapy is becoming increasingly more important in cholangiocarcinoma (CCA). OBJECTIVE: Systematic literature review on the status of multimodal and in particular neoadjuvant therapy for CCA. MATERIAL AND METHODS: Literature overview of the current scientific original and review articles. RESULTS: Resection and rarely also liver transplantation are still the only curative treatment approaches for CCA in the non-distant metastatic stage; however, long-term results, e.g. in node positive tumors, are still unsatisfactory. Adjuvant chemotherapy is now standard but cannot be used in many patients. Neoadjuvant concepts include chemotherapy and local and locoregional procedures, such as radioembolization. Both are increasingly used in intrahepatic CCA (iCCA) but rarely in perihilar CCA. Initial data show that this is very effective in iCCA to achieve secondary operability in primarily inoperable cases. In addition, based on the current literature, neoadjuvant therapy also seems justified in operable intrahepatic CCA with a high risk of recurrence (e.g. lymph node metastases). CONCLUSION: There is a high potential for the use of multimodal therapy in CCA, which could further increase in the near future as a result of new therapeutic agents. Due to the lack of evidence clear recommendations cannot be given; however, it is becoming apparent that neoadjuvant therapy is gaining importance in iCCA and is already increasingly used as part of individual concepts in patients with a high risk of recurrence.

Correlation of Different Serum Biomarkers with Prediction of Early Pancreatic Graft Dysfunction Following Simultaneous Pancreas and Kidney Transplantation.

Background: Despite recent advances and refinements in perioperative management of simultaneous pancreas−kidney transplantation (SPKT) early pancreatic graft dysfunction (ePGD) remains a critical problem with serious impairment of early and long-term graft function and outcome. Hence, we evaluated a panel of classical blood serum markers for their value in predicting early graft dysfunction in patients undergoing SPKT. Methods: From a prospectively collected database medical data of 105 patients undergoing SPKT between 1998 and 2018 at our center were retrospectively analyzed. The primary study outcome was the detection of occurrence of early pancreatic graft dysfunction (ePGD), the secondary study outcome was early renal graft dysfunction (eRGD) as well as all other outcome parameters associated with the graft function. In this context, ePGD was defined as pancreas graft-related complications including graft pancreatitis, pancreatic abscess/peritonitis, delayed graft function, graft thrombosis, bleeding, rejection and the consecutive need for re-laparotomy due to graft-related complications within 3 months. With regard to analyzing ePGD, serum levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), pancreatic lipase as well as neutrophil−lymphocyte ratio (NLR) and platelet−lymphocyte ratio (PLR) were measured preoperatively and at postoperative days (POD) 1, 2, 3 and 5. Further, peak serum levels of CRP and lipase during the first 72 h were evaluated. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for ePGD and eRGD. Cut-off levels were calculated with the Youden index. Significant diagnostic biochemical cut-offs as well as other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 105 patients included, 43 patients (41%) and 28 patients (27%) developed ePGD and eRGD following SPKT, respectively. The mean WBC, PCT, NLR, PLR, CRP and lipase levels were significantly higher on most PODs in the ePGD group compared to the non-ePGD group. ROC analysis indicated that peak lipase (AUC: 0.82) and peak CRP levels (AUC: 0.89) were highly predictive for ePGD after SPKT. The combination of both achieved the highest AUC (0.92; p < 0.01) in predicting ePGD. Concerning eRGD, predictive accuracy of all analyzed serological markers was moderate (all AUC < 0.8). Additionally, multivariable analysis identified previous dialysis/no preemptive transplantation (OR 2.4 (95% CI: 1.41−4.01), p = 0.021), donor age (OR 1.07 (95% CI: 1.03−1.14), p < 0.010), donor body mass index (OR 1.32 (95% CI: 1.01−1.072), p = 0.04), donors cerebrovascular cause of death (OR 7.8 (95% CI: 2.21−26.9), p < 0.010), donor length of ICU stay (OR 1.27 (95% CI: 1.08−1.49), p < 0.010), as well as CIT pancreas (OR 1.07 (95% CI: 1.03−1.14), p < 0.010) as clinical relevant prognostic predictors for ePGD. Further, a peak of lipase (OR 1.04 (95% CI: 1.02−1.07), p < 0.010), peak of CRP levels (OR 1.12 (95% CI: 1.02−1.23), p < 0.010), pancreatic serum lipase concentration on POD 2 > 150 IU/L (OR 2.9 (95% CI: 1.2−7.13), p = 0.021) and CRP levels of ≥ 180 ng/mL on POD 2 (OR 3.6 (95% CI: 1.54−8.34), p < 0.01) and CRP levels > 150 ng/mL on POD 3 (OR 4.5 (95% CI: 1.7−11.4), p < 0.01) were revealed as independent biochemical predictive variables for ePGD after transplantation. Conclusions: In the current study, the combination of peak lipase and CRP levels were highly effective in predicting early pancreatic graft dysfunction development following SPKT. In contrast, for early renal graft dysfunction the predictive value of this parameter was less sensitive. Intensified monitoring of these parameters may be helpful for identifying patients at a higher risk of pancreatic ischemia reperfusion injury and various IRI- associated postoperative complications leading to ePGD and thus deteriorated outcome.

Influence of Intraoperative Hemodynamic Parameters on Outcome in Simultaneous Pancreas-Kidney Transplant Recipients.

Objectives: Adequate organ perfusion, as well as appropriate blood pressure levels at the time of unclamping, is crucial for early and long-term graft function and outcome in simultaneous pancreas−kidney transplantation (SPKT). However, the optimal intraoperative mean arterial pressure (MAP) level has not well been defined. Methods: From a prospectively collected database, the medical data of 105 patients undergoing SPKT at our center were retrospectively analyzed. A receiver operating characteristic (ROC) analysis was preliminarily performed for optimal cut-off value for MAP at reperfusion, to predict early pancreatic graft function. Due to these results, we divided the patients according to their MAP values at reperfusion into <91 mmHg (n = 47 patients) and >91 mmHg (n = 58 patients) groups. Clinicopathological characteristics and outcomes, as well as early graft function and long-term survival, were retrospectively analyzed. Results: Donor and recipient characteristics were comparable between both groups. Rates of postoperative complications were significantly higher in the <91 mmHg group than those in the >91 mmHg group (vascular thrombosis of the pancreas: 7 (14%) versus 2 (3%); p = 0.03; pancreatitis/intraabdominal abscess: 10 (21%) versus 4 (7%); p = 0.03; renal delayed graft function (DGF): 11 (23%) versus 5 (9%); p = 0.03; postreperfusion urine output: 106 ± 50 mL versus 195 ± 45 mL; p = 0.04). There were no significant differences in intraoperative volume repletion, central venous pressure (CVP), use of vasoactive inotropic agents, and the metabolic outcome. Five-year pancreas graft survival was significantly higher in the >91 mmHg group (>91 mmHg: 82% versus <91 mmHg: 61%; p < 0.01). No significant differences were observed in patient and kidney graft survival at 5 years between both groups. Multivariate Cox regression analysis affirmed MAP < 91 mmHg as an independent prognostic predictor for renal DGF (HR 3.49, 1.1−10.8, p = 0.03) and pancreas allograft failure (HR 2.26, 1.0−4.8, p = 0.01). Conclusions: A MAP > 91 mmHg at the time point of reperfusion was associated with a reduced rate of postoperative complications, enhancing and recovering long-term graft function and outcome and thus increasing long-term survival in SPKT recipients.

Intraoperative reperfusion assessment of human pancreas allografts using hyperspectral imaging (HSI).

Background: The most common causes of early graft loss in pancreas transplantation are insufficient blood supply and leakage of the intestinal anastomosis. Therefore, it is critical to monitor graft perfusion and oxygenation during the early post-transplant period. The goal of our pilot study was to evaluate the utility of hyperspectral imaging (HSI) in monitoring the microcirculation of the graft and adequate perfusion of the intestinal anastomosis during pancreatic allotransplantation. Methods: We imaged pancreatic grafts and intestinal anastomosis in real-time in three consecutive, simultaneous pancreas-kidney transplantations using the TIVITA® HSI system. Further, the intraoperative oxygen saturation (StO2), tissue perfusion (near-infrared perfusion index, NIR), organ hemoglobin index (OHI), and tissue water index (TWI) were measured 15 minutes after reperfusion by HSI. Results: All pancreas grafts showed a high and homogeneous StO2 (92.6%±10.45%). Intraoperative HSI analysis of the intestinal anastomosis displayed significant differences of StO2 (graft duodenum 67.46%±5.60% vs. recipient jejunum: 75.93%±4.71%, P<0.001) and TWI {graft duodenum: 0.63±0.09 [I (Index)] vs. recipient jejunum: 0.72±0.09 [I], P<0.001}. NIR and OHI did not display remarkable differences {NIR duodenum: 0.68±0.06 [I] vs. NIR jejunum: 0.69±0.04 [I], P=0.747; OHI duodenum: 0.70±0.12 [I] vs. OHI jejunum: 0.68±0.13 [I], P=0.449}. All 3 patients had an uneventful postoperative course with one displaying a Banff 1a rejection which was responsive to steroid treatment. Conclusions: Our study shows that contact-free HSI has potential utility as a novel tool for real-time monitoring of human pancreatic grafts after reperfusion, which could improve the outcome of pancreas transplantation. Further investigations are required to determine the predictive value of intraoperative HSI imaging.

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.

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.

Repeated percutaneous hepatic perfusion with melphalan can maintain long-term response in patients with liver cancers.

Chemosaturation (CS; CHEMOSAT®, Delcath Systems Inc.) temporarily administers melphalan into the liver by percutaneous hepatic perfusion (PHP). CS-PHP can effectively control growth in liver tumors, but efficacy and tolerability of sequential treatments are unclear. We analyzed outcomes of sequential CS-PHP treatment. Patients with either unresectable intrahepatic metastases of ocular melanoma (OM, n = 9), cholangiocarcinoma (CCA, n = 3), or hepatocellular carcinoma (HCC, n = 1) were recruited retrospectively. Response was assessed by tomography imaging. Ten patients (mean age 60 years) with more than one CS-PHP treatment were included. CS-PHP was administered 2-6 times in the OM patients, 3 times in the CCA, and the HCC patient received 6 treatments. Overall response rate (ORR) to CS-PHP was 80%, and stable disease was achieved in one patient. Median hepatic progression-free survival (hPFS) was 336 days (range 0-354) for OM, 251 days for the CCA patient, and 256 days for the HCC patient. At the end of observation (153-701 days after first CS-PHP), 6/10 patients were still alive (5/9 with OM, 0 with CCA, and 1 with HCC). Death cases were not related to CS-PHP. Adverse events were mostly hematologic, grade I-IV, and self-resolving. The liver function was not deteriorated by CS-PHP. We conclude that repeated CS-PHP treatments were effective and well tolerated in the long term.

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

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

Influence of Multiple Donor Renal Arteries on the Outcome and Graft Survival in Deceased Donor Kidney Transplantation.

AIM: Complex arterial reconstruction in kidney transplantation (KT) using kidneys from deceased donors (DD) warrants additional study since little is known about the effects on the mid- and long-term outcome and graft survival. METHODS: A total of 451 patients receiving deceased donor KT in our department between 1993 and 2017 were included in our study. Patients were divided into three groups according to the number of arteries and anastomosis: (A) 1 renal artery, 1 arterial anastomosis (N = 369); (B) >1 renal artery, 1 arterial anastomosis (N = 47); and (C) >1 renal artery, >1 arterial anastomosis (N = 35). Furthermore, the influence of localization of the arterial anastomosis (common iliac artery (CIA), versus non-CIA) was analyzed. Clinicopathological characteristics, outcome, and graft and patient survival of all groups were compared retrospectively. RESULTS: With growing vascular complexity, the time of warm ischemia increased significantly (groups A, B, and C: 40 ± 19 min, 45 ± 19 min, and 50 ± 17 min, respectively; p = 0.006). Furthermore, the duration of operation was prolonged, although this did not reach significance (groups A, B, and C: 175 ± 98 min, 180 ± 35 min, and 210 ± 43 min, respectively; p = 0.352). There were no significant differences regarding surgical complications, post-transplant kidney function (delayed graft function, initial non-function, episodes of acute rejection), or long-term graft survival. Regarding the localization of the arterial anastomosis, non-CIA was an independent prognostic factor for deep vein thrombosis in multivariate analysis (CIA versus non-CIA: OR 11.551; 95% CI, 1.218-109.554; p = 0.033). CONCLUSION: Multiple-donor renal arteries should not be considered a contraindication to deceased KT, as morbidity rates and long-term outcomes seem to be comparable with grafts with single arteries and less complex anastomoses.

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.

Hyperspectral Imaging (HSI)-A New Tool to Estimate the Perfusion of Upper Abdominal Organs during Pancreatoduodenectomy.

Hyperspectral imaging (HSI) in abdominal surgery is a new non-invasive tool for the assessment of the perfusion and oxygenation of various tissues and organs. Its benefit in pancreatic surgery is still unknown. The aim of this study was to evaluate the key impact of using HSI during pancreatoduodenectomy (PD). In total, 20 consecutive patients were included. HSI was recorded during surgery as part of a pilot study approved by the local Ethics Committee. Data were collected prospectively with the TIVITA® Tissue System. Intraoperative HS images were recorded before and after gastroduodenal artery (GDA) clamping. We detected four patients with celiac artery stenosis (CAS) caused by a median arcuate ligament (MAL). In two of these patients, a reduction in liver oxygenation (StO2) was discovered 15 and 30 min after GDA clamping. The MAL was divided in these patients. HSI showed an improvement of liver StO2 after MAL division (from 61% to 73%) in one of these two patients. There was no obvious decrease in liver StO2 in the other two patients with CAS. HSI, as a non-invasive procedure, could be helpful in evaluating liver and gastric perfusion during PD, which might assist surgeons in choosing the best surgical approach and in improving patients' outcomes.

Profilin2 regulates actin rod assembly in neuronal cells.

Nuclear and cytoplasmic actin-cofilin rods are formed transiently under stress conditions to reduce actin filament turnover and ATP hydrolysis. The persistence of these structures has been implicated in disease pathology of several neurological disorders. Recently, the presence of actin rods has been discovered in Spinal Muscular Atrophy (SMA), a neurodegenerative disease affecting predominantly motoneurons leading to muscle weakness and atrophy. This finding underlined the importance of dysregulated actin dynamics in motoneuron loss in SMA. In this study, we characterized actin rods formed in a SMA cell culture model analyzing their composition by LC-MS-based proteomics. Besides actin and cofilin, we identified proteins involved in processes such as ubiquitination, translation or protein folding to be bound to actin rods. This suggests their sequestration to actin rods, thus impairing important cellular functions. Moreover, we showed the involvement of the cytoskeletal protein profilin2 and its upstream effectors RhoA/ROCK in actin rod assembly in SMA. These findings implicate that the formation of actin rods exerts detrimental effects on motoneuron homeostasis by affecting actin dynamics and disturbing essential cellular pathways.