Crystalloid volume versus catecholamines for management of hemorrhagic shock during esophagectomy - assessment of microcirculatory tissue oxygenation of the gastric conduit in a porcine model using hyperspectral imaging - an experimental study.

INTRODUCTION: Oncologic esophagectomy is a two-cavity procedure with considerable morbidity and mortality. Complex anatomy and the proximity to major vessels constitute a risk for massive intraoperative hemorrhage. Currently, there is no conclusive consensus on the ideal anesthesiologic countermeasure in case of such immense blood loss. The objective of this work was to identify the most promising anesthesiologic management in case of intraoperative hemorrhage with regards to tissue perfusion of the gastric conduit during esophagectomy using hyperspectral imaging (HSI). MATERIAL AND METHODS: An established live porcine model (n=32) for esophagectomy was used with gastric conduit formation and simulation of a linear stapled side-to-side esophagogastrostomy. After a standardized procedure of controlled blood loss of about 1 L per pig, the four experimental groups (n=8 each) differed in anesthesiologic intervention i.e. (I) permissive hypotension, (II) catecholamine therapy using noradrenaline, (III) crystalloid volume supplementation and (IV) combined crystalloid volume supplementation with noradrenaline therapy. HSI tissue oxygenation (StO2) of the gastric conduit was evaluated and correlated with systemic perfusion parameters. Measurements were conducted before (T0) and after (T1) laparotomy, after hemorrhage (T2) and 60 minutes (T3) and 120 minutes (T4) after anesthesiologic intervention. RESULTS: StO2 values of the gastric conduit showed significantly different results between the four experimental groups with 63.3% (±7.6%) after permissive hypotension (I), 45.9% (±6.4%) after catecholamine therapy (II), 70.5% (±6.1%) after crystalloid volume supplementation (III) and 69.0% (±3.7%) after combined therapy (IV). StO2 values correlated strongly with systemic lactate values (r=-0.67; CI -0.77 to -0.54), which is an established prognostic factor. CONCLUSION: Crystalloid volume supplementation (III) yields the highest StO2 values and lowest systemic lactate values and therefore appears to be the superior primary treatment strategy after hemorrhage during esophagectomy with regards to microcirculatory tissue oxygenation of the gastric conduit.

Robotic colectomy with CME versus laparoscopic colon resection with or without CME for colon cancer: a systematic review and meta-analysis.

INTRODUCTION: This systematic review with meta-analysis aimed to compare the robotic complete mesocolon excision (RCME) to laparoscopic colectomy (LC) with (LCME) or without CME (LC non-CME) in postoperative outcomes, harvested lymph nodes and disease-free survival. METHODS: We performed a systematic review with meta-analysis according to PRISMA 2020 and AMSTAR 2 guidelines. RESULTS: The literature search yielded seven comparative studies including 677 patients: 269 patients in the RCME group and 408 in the LC group. The pooled analysis concluded to a lower conversion rate in the RCME group (OR=0.17; 95% CI [0.04, 0.74], p=0.02). There was no difference between the two groups in terms of morbidity (OR=1.03; 95% CI [0.70, 1.53], p=0.87), anastomosis leakage (OR=0.83; 95% CI [0.18, 3.72], p=0.81), bleeding (OR=1.90; 95% CI [0.64, 5.58], p=0.25), wound infection (OR=1.37; 95% CI [0.51, 3.68], p=0.53), operative time (mean difference (MD)=36.32; 95% CI [-24.30, 96.93], p=0.24), hospital stay (MD=-0.94; 95% CI [-2.03, 0.15], p=0.09) and disease-free survival (OR=1.29; 95% CI [0.71, 2.35], p=0.41). In the subgroup analysis, the operative time was significantly shorter in the LCME group than RCME group (MD=50.93; 95% CI [40.05, 61.81], p<0.01) and we noticed a greater number of harvested lymph nodes in the RCME group compared with LC non-CME group (MD=8.96; 95% CI [5.98, 11.93], p<0.01). CONCLUSIONS: The robotic approach for CME ensures a lower conversion rate than the LC. RCME had a longer operative time than the LCME subgroup and a higher number of harvested lymph nodes than the LC non-CME group.

Delayed Surgery for Perforated Appendicitis is Feasible in Children Without Compromising the Outcome in Selected Cases.

BACKGROUND AND AIM: The relationship between time to surgery and risk of postoperative complications and re-intervention has not been conclusively investigated in pediatric perforated appendicitis (PA). The aim of this study was to determine whether time to appendectomy (TTA) is a risk factor for postoperative complications and re-intervention in a cohort of children undergoing appendectomy for PA. METHODS: A total of 254 children (age: 8.7 ± 3.7 years) undergoing appendectomy for PA were retrospectively evaluated and stratified into Group I-III according to the Clavien-Dindo classification for postoperative complications (Group I n = 218, 86%; Group II n = 7, 3%; Group III n = 29, 11%). RESULTS: The TTA was comparable between all groups (group I: 8.8 ± 9.2 h; group II: 7.8 ± 5.3 h; group III: 9.5 ± 9.6 h; overall: 8.8 ± 9.1 h; p = 0.885). A C-reactive protein (CRP) value at admission of ≥128.6 mg/l indicated a higher risk for developing Grade II complications with no need for re-intervention (OR: 3.963; 95% CI: 1.810-8.678; p = 0.001) and Grade III complications with the need for re-intervention (OR: 3.346; 95% CI: 1.456-7.690; p = 0.004). This risk was independent of the TTA (OR: 1.007; 95% CI: 0.980-1.035; p = 0.613). CONCLUSIONS: Appendectomy can be delayed by an average time delay of about 9 h in children with PA without increasing the risk of postoperative complications and re-intervention, also in patients at high risk defined by the initial CRP level ≥ 128.6 mg/l. This data may support the correct risk-adjusted scheduling of surgical interventions in times of limited capacity.

Learning Curves in Open, Laparoscopic, and Robotic Pancreatic Surgery: A Systematic Review and Proposal of a Standardization.

Objective: To depict and analyze learning curves for open, laparoscopic, and robotic pancreatoduodenectomy (PD) and distal pancreatectomy (DP). Background: Formal training is recommended for safe introduction of pancreatic surgery but definitions of learning curves vary and have not been standardized. Methods: A systematic search on PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in pancreatic surgery. Primary outcome was the number needed to reach the learning curve as defined by the included studies. Secondary outcomes included endpoints defining learning curves, methods of analysis (statistical/arbitrary), and classification of learning phases. Results: Out of 1115 articles, 66 studies with 14,206 patients were included. Thirty-five studies (53%) based the learning curve analysis on statistical calculations. Most often used parameters to define learning curves were operative time (n = 51), blood loss (n = 17), and complications (n = 10). The number of procedures to surpass a first phase of learning curve was 30 (20-50) for open PD, 39 (11-60) for laparoscopic PD, 25 (8-100) for robotic PD (P = 0.521), 16 (3-17) for laparoscopic DP, and 15 (5-37) for robotic DP (P = 0.914). In a three-phase model, intraoperative parameters improved earlier (first to second phase: operating time -15%, blood loss -29%) whereas postoperative parameters improved later (second to third phase: complications -46%, postoperative pancreatic fistula -48%). Studies with higher sample sizes showed higher numbers of procedures needed to overcome the learning curve (rho = 0.64, P < 0.001). Conclusions: This study summarizes learning curves for open-, laparoscopic-, and robotic pancreatic surgery with different definitions, analysis methods, and confounding factors. A standardized reporting of learning curves and definition of phases (competency, proficiency, mastery) is desirable and proposed.

Consensus on definition and severity grading of lymphatic complications after kidney transplantation.

BACKGROUND: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy. METHODS: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres. RESULTS: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention. CONCLUSION: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.

ANTECEDENTES: La incidencia de complicaciones linfáticas tras el trasplante renal (post-kidney-transplantation lymphatic, PKTL) varía considerablemente en la literatura. Esto se debe en parte a que no se ha establecido una definición universalmente aceptada. Este estudio tuvo como objetivo proponer una definición aceptable para las complicaciones PKTL y un sistema de clasificación de la gravedad basado en la estrategia de tratamiento. MÉTODOS: Se realizó una búsqueda sistemática de la literatura relevante en MEDLINE y Web of Science. Se logró un consenso para la definición y la clasificación de gravedad de las PKTL entre veinte centros de trasplante de alto volumen. RESULTADOS: En 32 de los 87 estudios incluidos se definía la linforrea/linfocele. Sesenta y tres artículos describían como se trataban las PKTL, pero ninguno calificó la gravedad de las mismas. La definición propuesta para la linforrea fue la de un débito diario superior a 50 ml de líquido (no orina, sangre o pus) a través del drenaje o del orificio cutáneo tras su retirada, más allá del 7º día postoperatorio del trasplante renal. La definición propuesta para linfocele fue la de una colección de líquido de tamaño variable adyacente al riñón trasplantado, tras haber descartado un urinoma, hematoma o absceso. Las PKTL de grado A fueron aquellas con escaso impacto o que no requirieron tratamiento invasivo; las PKTL de grado B fueron aquellas que precisaron intervención no quirúrgica y las PKTL de grado C aquellas en que fue necesaria la reintervención quirúrgica. CONCLUSIÓN: Se propone una definición clara y una clasificación de gravedad basada en la estrategia de tratamiento de las PKTLs. La definición propuesta y el sistema de calificación en 3 grados son razonables, sencillos y fáciles de comprender, y servirán para estandarizar los resultados de las PKTL y facilitar las comparaciones entre los diferentes estudios.

Does vancomycin resistance increase mortality in Enterococcus faecium bacteraemia after orthotopic liver transplantation? A retrospective study.

BACKGROUND: The relevance of vancomycin resistance in enterococcal blood stream infections (BSI) is still controversial. Aim of this study was to outline the effect of vancomycin resistance of Enterococcus faecium on the outcome of patients with BSI after orthotopic liver transplantation (OLT). METHODS: The outcome of OLT recipients developing BSI with vancomycin-resistant (VRE) versus vancomycin-susceptible Enterococcus faecium (VSE) was compared based on data extraction from medical records. Multivariate regression analyses identified risk factors for mortality and unfavourable outcomes (defined as death or prolonged intensive care stay) after 30 and 90 days. RESULTS: Mortality was similar between VRE- (n = 39) and VSE- (n = 138) group after 30 (p = 0.44) or 90 days (p = 0.39). Comparable results occurred regarding unfavourable outcomes. Mean SOFANon-GCS score during the 7-day-period before BSI onset was the independent predictor for mortality at both timepoints (HR 1.32; CI 1.14-1.53; and HR 1.18; CI 1.08-1.28). Timely appropriate antibiotic therapy, recent ICU stay and vancomycin resistance did not affect outcome after adjusting for confounders. CONCLUSION: Vancomycin resistance did not influence outcome among patients with Enterococcus faecium bacteraemia after OLT. Only underlying severity of disease predicted poor outcome among this homogenous patient population. TRIAL REGISTRATION: This study was registered at the German clinical trials register (DRKS-ID: DRKS00013285).

Effect of mycophenolic acid on inosine monophosphate dehydrogenase (IMPDH) activity in liver transplant patients.

BACKGROUND: Due to the development of immunosuppressants, the focus in transplanted patients has shifted from short-term to long-term survival as well as a better adjustment of these drugs in order to prevent over- and under-immunosuppression. Mycophenolic acid (MPA) is a noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH) and approved for prophylaxis of acute rejection after kidney, heart, and liver transplantation, where it has become a part of the standard therapy. Targeting inosine monophosphate IMPDH activity as a surrogate pharmacodynamic marker of MPA-induced immunosuppression may allow a more accurate assessment of efficacy and aid in limiting toxicity in liver transplanted patients. AIM: Assess IMPDH-inhibition in liver transplant recipients and its impact on biliary/infectious complications, acute cellular rejection (ACR) and liver dependent survival. METHODS: This observational cohort study comprises 117 liver transplanted patients that were treated with mycophenolate mofetil (MMF) for at least 3 months. Blood samples (BS) were collected and MPA serum level and IMPDH activity were measured before (t(0)), 30minutes (t(30)) and 2h after (t(120)) MMF morning dose administration. Regarding MPA, we assessed the area under the curve (AUC). Patients were prospectively followed up for one year and assessed for infectious and biliary complications, episodes of ACR and liver dependent survival. RESULTS: The MPA levels showed a broad interindividual variability at t(0) (2.0±1.8ng/ml), t(30) (12.7±9.0ng/ml) and t(120) (7.5±4.3ng/ml). Corresponding IMPDH activity was at t(o) (23.2±9.5 nmol/h/mg), at t(30) (16.3±8.8 nmol/h/mg) and t(120) (18.2±8.7 nmol/h/mg). With regard to MPA level we found no correlation with infectious or biliary complications within the follow-up period. Patients with baseline IMPDH(a) below the median had significant more viral infections (6 (10.2%) vs. 17 (29.3%); P=0.009) with especially more cytomegalovirus (CMV) infections (1 (3.4%) vs. 6 (21.4%); P=0.03)). Furthermore, patients with baseline IMPDH(a) above the median developed more often non-anastomotic biliary strictures (8 (13.6%) vs. 1 (1.7%), P=0.03). We found the group reaching the combined clinical endpoint of death and re-transplantation showing significantly lower MPA baseline values (t(0) 0.9±0.7 vs. 2.1±1.8µg/ml Mann-Whitney-U: P=0.02). We calculated a simplified MPA(AUC) with the MPA level at baseline, 30 and 120minutes after MPA administration. Whereas we found no differences with regard to baseline characteristics at entry into the study patients with MPA (AUC) below the median experienced significantly more often the combined clinical endpoint (12.1% (7/58) vs. 0.0% (0/57); P=0.002) and had a reduced actuarial re-transplantation-free survival (1.0 year vs. 0.58 years; Log-rank: P=0.007) during the prospective one-year follow-up period. In univariate and multivariate analysis including gender, age, BMI, ACR, MPA (AUC) and IMPDH(a) only BMI, MPA (AUC) and IMPDH(a) were independently associated with reduced actuarial re-transplantation-free survival. CONCLUSION: MPA-levels and IMPDH-activity in liver transplanted patients allows individual risk assessment. Patients with higher IMPDH inhibition acquire more often viral infections. Insufficient IMPDH inhibition is associated with development of non-anastomotic bile duct strictures and reduced re-transplantation-free survival.

Outcome after liver resection for primary and recurrent intrahepatic cholangiocarcinoma.

Background: Liver resection is the only curative therapeutic option for intrahepatic cholangiocarcinoma (ICC), but the approach to recurrent ICC is controversial. This study analysed the outcome of liver resection in patients with recurrent ICC. Methods: Demographic, radiological, clinical, operative, surgical pathological and follow-up data for all patients with a final surgical pathological diagnosis of ICC treated in a tertiary referral centre between 2001 and 2015 were collected retrospectively and analysed. Results: A total of 190 patients had liver resection for primary ICC. The 1-, 3- and 5-year overall survival (OS) rates were 74·8, 56·6 and 37·9 per cent respectively. Independent determinants of OS were age 65 years or above (hazard ratio (HR) 2·18, 95 per cent c.i. 1·18 to 4·0; P = 0·012), median tumour diameter 5 cm or greater (HR 2·87, 1·37 to 6·00; P = 0·005), preoperative biliary drainage (HR 2·65, 1·13 to 6·20; P = 0·025) and local R1-2 status (HR 1·90, 1·02 to 3·53; P = 0·043). Recurrence was documented in 87 patients (45·8 per cent). The mean(s.d.) survival time after recurrence was 16(17) months. Independent determinants of recurrence were median tumour diameter 5 cm or more (HR 1·71, 1·09 to 2·68; P = 0·020), high-grade (G3-4) tumour (HR 1·63, 1·04 to 2·55; P = 0·034) and local R1 status (HR 1·70, 1·09 to 2·65; P = 0·020). Repeat resection with curative intent was performed in 25 patients for recurrent ICC, achieving a mean survival of 25 (95 per cent c.i. 16 to 34) months after the diagnosis of recurrence. Patients deemed to have unresectable disease after recurrence received chemotherapy or chemoradiotherapy alone, and had significantly poorer survival. Conclusion: Patients with recurrent ICC may benefit from repeat surgical resection.

Antecedentes: La resección hepática es la única opción terapéutica curativa para el colangiocarcinoma intrahepático (intrahepatic colangiocarcinoma, iCCA), pero el enfoque terapéutico de la recidiva del iCCA es controvertido. En este estudio se analizaron los resultados de la resección hepática en pacientes con recidiva de un iCCA. Métodos: Se recopilaron de forma retrospectiva y se analizaron los datos demográficos, radiológicos, clínicos, quirúrgicos, de anatomía patológica y de seguimiento de todos los pacientes con diagnóstico anatomopatológico definitivo de iCCA en un centro de referencia terciario entre 2001 y 2015. Resultados: En total, 190 pacientes se sometieron a resección hepática por iCCA primario. La supervivencia global (overall survival, OS) a 1, 3 y 5 años fue del 75%, 57% y 38%, respectivamente. La edad de ≥ 65 años (cociente de riesgos instantáneos, hazard ratio, HR 2,2, i.c. del 95% 1,2­4,0, P = 0,012), la mediana del diámetro del tumor ≥ 5 cm (HR 2,9, i.c. del 95% 1,4­6,0, P = 0,005), el drenaje biliar preoperatorio (HR 2,6, i.c. del 95% 1,3­6,2, P = 0.025) y el estado local R1/2 (HR 1,9, i.c. del 95% 1,0­3,5, P = 0,043) fueron factores pronósticos independientes de la OS. La recidiva se documentó en 87 (45,8%) pacientes. El tiempo medio de supervivencia después de la recidiva fue de 16 ± 2 meses. Los factores pronósticos independientes de recidiva fueron la mediana del diámetro del tumor ≥ 5 cm (HR 1,7, i.c. del 95% 1,1­2,7, P = 0,020), el tumor de alto grado (G3­G4) (HR 1,6, i.c. del 95% 1,0­2,5, P = 0,034) y el estado local R1 (HR 1,7, i.c. del 95% 1,1­2,6, P = 0,020). La resección repetida con intención curativa se realizó en 25 pacientes con iCCA recidivado, con una supervivencia media de 25 meses (i.c. del 95% 16­34 meses) tras el diagnóstico de recidiva. Los pacientes que se consideraron no resecables después de la recidiva se sometieron a quimioterapia o quimiorradioterapia y presentaron una supervivencia significativamente peor. Conclusión: Los pacientes con recidiva de un iCCA pueden beneficiarse de la resección quirúrgica repetida.

Surgical outcomes after pediatric kidney transplantation at the University of Heidelberg.

BACKGROUND: Kidney transplantation (KTx) is the treatment of choice for children with end-stage renal disease (ESRD). OBJECTIVE: An update of 48 years of surgical experience with pediatric KTx (PKTx) is presented, and the results between recipients of organs from deceased donors (DDs) and living donors (LDs) are compared. STUDY DESIGN: All patients younger than 18 years who underwent KTx between 1967 and 2015 were evaluated. Data from 540 PKTx operations (409 DD and 131 LD) were obtained from the transplant center database. Peri-operative data and graft and patient survival were analyzed in the DD and LD groups. RESULTS: Fewer recipients in the LD group underwent dialysis before PKTx than those in the DD group (50.8% in LD vs. 94.9% in DD, P < 0.001). The mean duration of dialysis (DD: 798 ± 525 days vs. LD: 625 ± 650 days, P = 0.03), time on the waiting list (DD: 472 ± 435 days vs. LD: 120 ± 243 days, P < 0.001), cold ischemia time (CIT) (DD: 1206 ± 368 min vs. LD: 140 ± 63 min, P < 0.001), operation time, and hospital stay were lower in the LD group. Except for arterial stenosis, the rates of postoperative vascular and urological complications were not different between the two groups. The cumulative 25-year graft and patient survival rates were 46.4% and 84.1% in the DD group and 76.5% and 96.1% in the LD group, respectively. DISCUSSION: PKTx is the treatment of choice for children with ESRD. Graft quality has a direct impact on KTx outcome and rate of graft failure. Better HLA compatibility and shorter CIT reduce the impairment of graft function after LD PKTx. In addition, Establishment of an interdisciplinary approach using an individualized risk assessment and prevention model can improve PKTx outcomes. CONCLUSION: Compared with DD PKTx, LD PKTx has better graft survival associated with a shorter duration of preceding dialysis, waiting time, and CIT and seems to be more beneficial for children.

Randomized clinical trial of stapler hepatectomy versus LigaSure™ transection in elective hepatic resection.

BACKGROUND: Previous studies have demonstrated stapler hepatectomy and use of various energy devices to be safe alternatives to the clamp-crushing technique in elective hepatic resection. In this randomized trial, the effectiveness and safety of stapler hepatectomy were compared with those of parenchymal transection with the LigaSure™ vessel sealing system. METHOD: Patients scheduled for elective liver resection at two tertiary-care centres were randomized during surgery to stapler hepatectomy or transection with the LigaSure™ device. Total intraoperative blood loss was the primary efficacy endpoint. Transection time, duration of operation, perioperative complications and length of hospital stay were recorded as secondary endpoints. RESULTS: A total of 138 patients were analysed, 69 in the LigaSure™ and 69 in the stapler hepatectomy group. Baseline characteristics were well balanced between the groups. Mean intraoperative blood loss was significantly higher in the LigaSure™ group than the stapler hepatectomy group: 1101 (95 per cent c.i. 915 to 1287) versus 961 (752 to 1170) ml (P = 0·028). The parenchymal transection time was significantly shorter in the stapler group (P = 0·005), as was the total duration of operation (P = 0·027). Surgical morbidity did not differ between the groups, nor did the grade of complications. CONCLUSION: Stapler hepatectomy was associated with reduced blood loss and a shorter duration of operation than the LigaSure™ device for parenchymal transection in elective partial hepatectomy. Registration number: NCT01858987 (http://www.clinicaltrials.gov).

Meta-analysis of the prognostic role of perioperative platelet count in posthepatectomy liver failure and mortality.

BACKGROUND: Emerging evidence suggests that the perioperative platelet count (PLT) can predict posthepatectomy liver failure (PHLF). In this systematic review and meta-analysis, the impact of perioperative PLT on PHLF and mortality was evaluated. METHODS: MEDLINE and Web of Science databases were searched systematically for relevant literature up to January 2018. All studies comparing PHLF or mortality in patients with a low versus high perioperative PLT were included. Study quality was assessed using methodological index for non-randomized studies (MINORS) criteria. Meta-analyses were performed using Mantel-Haenszel tests with a random-effects model, and presented as odds ratios (ORs) with 95 per cent confidence intervals. RESULTS: Thirteen studies containing 5260 patients were included in the meta-analysis. Two different cut-off values for PLT were used: 150 and 100/nl. Patients with a perioperative PLT below 150/nl had higher PHLF (4 studies, 817 patients; OR 4·79, 95 per cent c.i. 2·89 to 7·94) and mortality (4 studies, 3307 patients; OR 3·78, 1·48 to 9·62) rates than patients with a perioperative PLT of 150/nl or more. Similarly, patients with a PLT below 100/nl had a significantly higher risk of PHLF (4 studies, 949 patients; OR 4·65, 2·60 to 8·31) and higher mortality rates (7 studies, 3487 patients; OR 6·35, 2·99 to 13·47) than patients with a PLT of 100/nl or greater. CONCLUSION: A low perioperative PLT correlates with higher PHLF and mortality rates after hepatectomy.

Association of pre- and early post-transplant serum amino acids and metabolites of amino acids and liver transplant outcome.

The aim of the present study was to investigate association of serum amino (AA) acids and metabolites of AAs with post-transplant outcome in liver transplant recipients. Eighty-nine patients with end-stage liver diseases and available pre- and early post-transplant serum were characterised as patients with (GI) and without one-year mortality (GII) and patients with and without early graft dysfunction (EAD). A panel of pre- and early post-transplant serum levels of AAs and early and metabolites of tryptophan were measured using tandem mass spectrometry. Patient groups had significantly higher pre-transplant serum levels of phenylalanine, tryptophan, and tryptophan metabolites than healthy controls (for all p<0.001). Pre-transplant serum levels of all these parameters were significantly higher in GI than in GII (for all p<0.001). GI had a higher MELD score and re-transplantation number than GII (p≤0.005 for both investigations). Serum bilirubin on day 5 and serum phenylalanine on day 10 post-transplant were associated parameters of mortality, whereas day 1post-transplant phenylalanine and kynurenine and female gender were associated parameters of EAD. Our results indicate that pre- and early post-transplant levels of phenylalanine, tryptophan and metabolites of tryptophan are increased in patients and are associated with EAD and one-year mortality in liver transplant recipients.

Analysis of the biliostatic potential of two sealants in a standardized porcine model of liver resection.

BACKGROUND: Improved resection techniques has decreased mortality rate following liver resections(LRx). Sealants are known as effective adjuncts for haemostasis after LRx. We compared biliostatic effectiveness of two sealants in a standardized porcine model of LRx. MATERIAL AND METHODS: We accomplished left hemihepatectomy on 27 pigs. The animals were randomized in control group(n = 9) with no sealant and treatment groups (each n = 9), in which resection surfaces were covered with TachoSil® and TissuFleece®/Tissucol Duo®. After 5 days the volume of ascites(ml), bilioma and/or bile leakages and degree of intra-abdominal adhesions were analysed. RESULTS: Proportion of ascites was lower in TissuFleece/Tissucol Duo® group. The ascites volume was lower in TachoSil® group. In sealant groups, increased adhesion specially in the TachoSil® group was seen. A reduction of the "bilioma rate" was seen in sealant groups, which was significantly lower in TissuFleece®/Tissucol Duo® group. CONCLUSION: In a standardized condition sealants have a good biliostatic effect but with heterogeneous potentials. This property in combination with the cost-benefit analysis should be the focus of future prospective studies.

Treatment-related Death in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

AIMS: We carried out a meta-analysis to determine the risk of treatment-related death associated with immune checkpoint inhibitor use in cancer patients. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, pembrolizumab; nivolumab; tremelimumab and atezolizumab. The authors extracted relevant information on participants, characteristics, treatment-related death and information on the methodology of the studies. RESULTS: After exclusion of ineligible records, 18 clinical trials were included in the analysis. The odds ratio for treatment-related death for CTLA-4 inhibitors (ipilimumab and tremelimumab) was 1.80 (95% confidence interval 1.25, 2.59; P=0.002) and for PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) was 0.63 (95% confidence interval 0.31, 1.30; P=0.22). Treated cancer seems to have no effect on the risk of treatment-related death. CONCLUSIONS: Analysis of our data showed that CTLA-4 inhibitors (ipilimumab and tremelimumab) in a higher dose (10 mg/kg) seem to be associated with a higher risk of treatment-related death compared with control regimens, whereas PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) do not cause the same risk. Clinicians have to be fully aware of these differential risks and council their patients appropriately.

Treatment-associated Fatigue in Cancer Patients Treated with Immune Checkpoint Inhibitors; a Systematic Review and Meta-analysis.

AIMS: Fatigue is one of the most prominent side-effects of immune checkpoint inhibition. Therefore, we assessed the risk of fatigue associated with inhibitors of the immune checkpoints. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, nivolumab, pembrolizumab and tremelimumab. The authors extracted relevant information on participants(') characteristics, all-grade and high-grade fatigue and information on the methodology of the studies. RESULTS: In total, 17 trials were considered eligible for the meta-analysis. The odds ratio for all-grade fatigue for CTLA-4 inhibitors was 1.23 (95% confidence interval 1.07, 1.41; P = 0.003) and for high-grade fatigue was 1.72 (95% confidence interval 1.26, 2.33; P = 0.0005). Moreover, the odds ratio for all-grade fatigue for PD-1 inhibitors was 0.72 (95% confidence interval 0.62, 0.84; P < 0.0001) and for high-grade fatigue was 0.36 (95% confidence interval 0.23, 0.56; P < 0.00001). CONCLUSIONS: The analysis of data showed that CTLA-4 inhibitors seem to be associated with a higher risk of all- and high-grade fatigue compared with control regimens, whereas PD-1 inhibitors seem to be associated with a lower risk of all- and high-grade fatigue compared with control regimens.

Predicting Postoperative Complications After Pediatric Perforated Appendicitis.

PURPOSE: Assessment of risk factors for postoperative complications following surgical treatment of pediatric perforated appendicitis (PA) is necessary to identify those patients in need of closer monitoring. In this study, we have investigated the impact of different risk factors on the occurrence of complications after an appendectomy in children with PA. MATERIAL AND METHODS: The study was a retrospective, single-centre analysis of all pediatric PA conducted over a 10-year period. Preoperative clinical and laboratory results, intraoperative findings, and postoperative complications were analyzed. Risk factors were defined and a risk score was determined for postoperative complications and reinterventions. RESULTS: Surgical treatment for appendicitis was performed in 840 pediatric patients during the observation period. 163 of the included patients were diagnosed with PA (mean age 8.9 ± 3.6 years). 19 (11.7%) patients developed postoperative complications, 17 (10.4%) of which required complication-related intervention. We identified five predictors of postoperative complications: the C-related protein value at admission, purulent peritonitis, open appendectomy (primary, secondary, or converted), placement of an abdominal drain, and administration of antibiotics not compliant to results from the subsequent antibiogram. The determined risk score was significantly higher in the complication group (p < .0001) and reintervention group (p < .001). CONCLUSIONS: Postoperative complications following pediatric PA can be predicted using specific preoperative, intraoperative, and postoperative risk factors. In the high-risk group, an active prevention, detection, and intervention of any occurring complication is necessary and we present a new specific pediatric risk score to define patients at risk for complications.

Long-term outcome in displaced lateral humeral condyle fractures following internal screw fixation in children.

BACKGROUND: The aim of this study was to investigate the long-term clinical outcome following open reduction and internal screw fixation of displaced lateral condyle fractures (LCFs) of the distal humerus and compare the outcome of primary and secondary LCFs. METHODS: The clinical outcome in 31 children (mean age 5.8±2.4 years) operated for primary or secondary LCFs was retrospectively analyzed by standardized clinical examination and compared using the Mayo score, Morger score, and Patients Satisfaction score. RESULTS: The scores did not differ significantly between the primary and secondary displacement groups (Mayo score: 99.3±3.3 vs. 100±0, p=0.852; Morger score: 3.8±0.5 vs. 3.9±0.3, p=0.852; Patients Satisfaction score: 3.7±0.6 vs. 3.9±0.3, p=0.546). Deficits in range of motion and joint axis deviation were minor (< 10°) and no elbow instabilities were observed. CONCLUSIONS: Surgical treatment of a secondary displaced LCF with open reduction and internal screw fixation leads to a favorable long-term outcome. The long-term outcome is similar between primary and secondary displaced LCFs.

A Single-center Experience on the Value of Pancreas Graft Biopsies and HLA Antibody Monitoring After Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: In simultaneous pancreas-kidney transplantation (SPKT), monitoring of the pancreas allograft is more complex than the kidney allograft due to difficulties in obtaining pancreas histology and weak clinical evidence supporting the role of donor-specific antibodies (DSA). METHODS: We performed a single-center retrospective analysis of all 17 SPKT recipients who underwent a total of 22 pancreas allograft indication biopsies from October 2009 to September 2012. Fifteen patients had at least 2 DSA measurements: pretransplantation and at the time of biopsy. RESULTS: All 7 patients (100%) with post-transplantation DSA-positivity (de novo: n = 6; persistent: n = 1) at biopsy had at least 1 rejection episode either of the pancreas (n = 4) or the kidney (n = 3), with 3 antibody-mediated rejections (AMR). In contrast, only 4 of 8 patients (50%) without post-transplantation DSA had evidence of rejection, with 1 AMR. Findings during pancreas allograft biopsy procedures led to a change of immunosuppressive therapy in 11 of 15 (73%) patients. Patient survival, graft survival, and function were not adversely affected by the presence of post-transplantation DSA. One major and 2 minor procedure-related complications occurred during the pancreas biopsies. CONCLUSIONS: In this small retrospective analysis, pancreas allograft histology provided the most therapeutically relevant information, rather than the kidney histology or DSA monitoring.

Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma.

BACKGROUND: Most hepatocellular carcinomas (HCCs) are diagnosed at an advanced stage. The prognostic value of serum tumour markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) is limited. The aim of our study is to evaluate the diagnostic value of serum growth factors, apoptotic and inflammatory mediators of cirrhotic patients with and without HCC. METHODS: Serum samples were collected from cirrhotic potential liver transplant patients (LTx) with (n=61) and without HCC (n=78) as well as from healthy controls (HCs; n=39). Serum concentrations of CRP, neopterin and IL-6 as markers of inflammation and thrombopoietin (TPO), GCSF, FGF basic and VEGF, HMGB1, CK-18 (M65) and CK18 fragment (M30) and a panel of proinflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CXCL5 and IL-8) were measured. Chi square, Fisher exact, Mann-Whitney U-tests, ROC curve analysis and forward stepwise logistic regression analyses were applied. RESULTS: Patients with HCC had higher serum TPO and chemokines (P<0.001 for TPO, CCL4, CCL5 and CXCL5) and lower CCL2 (P=0.008) levels than cirrhotic patients without HCC. Multivariate forward stepwise regression analysis for significant parameters showed that among the studied parameters CCL4 and CCL5 (P=0.001) are diagnostic markers of HCC. Serum levels of TPO and chemokines were lower, whereas M30 was significantly higher in cirrhotic patients than in HCs. CONCLUSIONS: High serum levels of inflammatory chemokines such as CCL4 and CCL5 in the serum of cirrhotic patients indicate the presence of HCC.