Sarcopenic obesity may predict worse liver regeneration after right graft living donor liver transplantation.

Sarcopenic obesity impairs the outcome after liver transplantation. The effect of this on liver regeneration has not yet been studied. The aim of this study was to evaluate the potential effect of body composition changes on liver volume gain after living donor liver transplantation. We observed liver regeneration in 100 patients who underwent living donor liver transplantation using right lobe grafts (Segments V-VIII). Liver volumetry and body composition analysis were performed based on CT images with special software. The gain of liver volume was calculated between 2 points in time considering the absolute and percentage values: before surgery and early after surgery, with a median time of 10 days. Pearson's correlation and multivariate analysis using stepwise multiple regression were used to examine the potential correlation between body composition and liver volume gain. The liver volume increase was significantly negatively correlated with adipose tissue in the body stem ( r = -0.4, p < 0.001) and positively correlated with psoas mass ( r = 0.24, p = 0.02). These results correspond with those of the multiple regression analysis, which indicated adipose tissue (ß = -1.0, p < 0.001) and psoas mass (ß = 0.12, p < 0.001). The presence of malignancy as an indication for liver transplantation was another significant independent factor negatively affecting liver growth (ß = -13.1, p = 0.046). Sarcopenic obesity predicts an impaired liver volume increase after living donation. This could worsen the postoperative outcome. The role of alimentary interventions and exercises in improving body composition and thus postoperative outcome should be evaluated through prospective interventional studies.

Auxilliary Liver Transplantation According to the RAPID Procedure in Noncirrhotic Patients: Technical Aspects and Early Outcomes.

OBJECTIVE: To present technical details and short-term experiences of liver transplantation as a 2-stage procedure using small for size grafts in a multicenter cohort study. BACKGROUND: Two-stage liver transplantation using small for size grafts should be a feasible procedure with lower morbidity and mortality rates. Retrospective cohort study between 2015 and 2022 with multicenter experience. Twenty-three resection and partial liver transplantation with delayed total hepatectomy procedures for noncirrhotic indications were performed in 6 European centers (20 with grafts from living donors and 3 after deceased donation). Procedure's feasibility, graft volumetric changes, morbidity, and mortality of donor and recipient were explored. RESULTS: There was a low donor morbidity (4.3%) in our cohort. Hypertrophy of the graft was rapid (mean graft volume increases 107% between both stages) and offered the opportunity for remnant hepatectomy after a median of 14 days. In all cases, portomesenteric flow was routed to the graft by right remnant portal vein ligation. Portal vein inflow modulation to alleviate transient harmful portal hypertension was not needed in any case. Early postoperative mortality (4.3%) of the recipients were low. Ten patients suffered from complications ≥IIIb according to the Clavien-Dindo classification. CONCLUSIONS: Two-stage liver transplantation is a feasible option for noncirrhotic patients allowing the safe use of small for size grafts and could possibly be extended with caution to liver diseases with portal hypertension and cirrhosis. The resection and partial liver transplantation with delayed total hepatectomy technique might be a viable option for expanding the donor pool given the current organ shortage especially for low-model of end stage liver disease patients.

Value of palliative surgery in perihilar cholangiocarcinoma.

PURPOSE: The survival rate of patients with irresectable perihilar cholangiocarcinoma is remarkably poor. An essential part of palliation is treatment of obstructive cholestasis caused by the tumor. Currently, this is mainly performed endoscopically by stent or via PTBD, requiring frequent changes of the stents and limiting health-related quality of life due to the multiple hospital stays needed. The aim of this study was to evaluate surgical palliation via extrahepatic bile duct resection as an option for palliative treatment. METHODS: Between 2005 and 2016, we treated 120 pCCC patients with primary palliative care. Three treatment strategies were retrospectively considered: extrahepatic bile duct resection (EBR), exploratory laparotomy (EL), and primary palliative (PP) therapy. RESULTS: The EBR group required significantly less stenting postoperatively, and the overall morbidity was 29.4% (EBR). After the surgical procedure, fewer subsequent endoscopic treatments for stenting or PTBD were necessary in the EBR group over time. The 30-day mortality was 5.9% (EBR) and 3.4% (EL). The median overall survival averaged 570 (EBR), 392 (EL), and 247 (PP) days. CONCLUSIONS: In selected pCCC patients, palliative extrahepatic bile duct resection is a feasible option for treatment of obstructive cholestasis and should be reconsidered as a therapy option for these patients even in a palliative setting.

Pathogen detection in patients with perihilar cholangiocarcinoma: Implications for targeted perioperative antibiotic therapy.

BACKGROUND: Cholestasis should be relieved by biliary drainage prior to major liver resection. This condition is often associated with bacterial colonization of the otherwise sterile biliary system. Cholangitis reduces the regenerative capacity of the remaining liver. Therefore, targeted antibiotic therapy is a key feature in perioperative treatment in patients with perihilar cholangiocarcinoma (pCCC). METHODS: Between December 1999 and December 2017, 251 pCCC patients were treated in our center. In total, 115 patients underwent a microbiological analysis. In addition to the characterization of the specific microorganisms and antibiotic resistance, we analyzed subgroups according to preoperative intervention. RESULTS: Enterococci (87/254, 34%) and Enterobacteria (65/254, 26%) were the most frequently detected genera. In 43% (50/115) of patients, Enterococcus faecalis was found in the bile duct sample. Enterococcus faecium (29/115) and Escherichia coli (29/115) were detected in 25% of patients. In patients with percutaneous transhepatic biliary drainage (3/8, 38%) or stents (24/79, 30%), Enterococcus faecium was diagnosed most frequently (P < 0.05). Enterococcus faecium and Klebsiella oxytoca were significantly more frequently noted in the time period after 2012 (P < 0.05). With regard to fungal colonization, the focus was on various Candida strains, but these strains generally lacked resistance. CONCLUSIONS: pCCC patients exhibit specific bacterial colonization features depending on the type of preoperative biliary intervention. Specifically, targeted antibiosis should be applied in this patient cohort to minimize the risk of biliary complications after major liver resection. In our cohort, the combination of meropenem and vancomycin represents an effective perioperative medical approach.

Liver growth prediction in ALPPS - A multicenter analysis from the international ALPPS registry.

BACKGROUND: While ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR). METHODS: This cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018. We analyse the influence of demographic, tumour type and perioperative data on the growth of the FLR. The volume of the FLR was calculated in millilitre and percentage using computed-tomography (CT) scans before and after stage 1, both according to Vauthey formula. RESULTS: A total of 734 patients were included from 99 centres. The median sFLR at stage 1 and stage 2 was 0.23 (IQR, 0.18-0.28) and 0.39 (IQR: 0.31-0.46), respectively. The variables associated with a lower increase from sFLR1 to sFLR2 were age˃68 years (p = .02), height ˃1.76 m (p ˂ .01), weight ˃83 kg (p ˂ .01), BMI˃28 (p ˂ .01), male gender (p ˂ .01), antihypertensive therapy (p ˂ .01), operation time ˃370 minutes (p ˂ .01) and hospital stay˃14 days (p ˂ .01). The time required to reach sufficient volume for stage 2, male gender accounts 40.3% in group ˂7 days, compared with 50% of female, and female present 15.3% in group ˃14 days compared with 20.6% of male. CONCLUSIONS: Height, weight, FLR size and gender could be the variables that most constantly influence both daily growths, the interstage increase and the standardized FLR before the second stage.

Simultaneous right-sided nephrectomy with orthotopic liver and kidney transplantation-An alternative method for patients with autosomal dominant polycystic liver and kidney disease.

PURPOSE: In patients suffering from autosomal dominant polycystic liver and kidney disease (ADPLKD), combined organ transplantation often poses a technical challenge due to the large volume of both organs. To simplify the transplantation procedure by improving the exposure of anatomical structures, we introduce a novel surgical technique of orthotopic liver and kidney transplantation. METHODS: The modified simultaneous liver and kidney transplantation technique via a right-sided L-incision included three steps: (1) right-sided nephrectomy in the recipient followed by (2) orthotopic liver transplantation in cava replacement technique and (3) the orthotopic kidney transplantation with arterial reconstruction to the right common iliac artery. RESULTS: In total, seven patients with ADPLKD were transplanted by using the modified transplantation technique. The mean operation time was 342.43 min (±68.77). Postoperative patients were treated for 6.28 days (±2.50) in the intensive care unit and were discharged from the surgical ward approximately 28 days (±5.66) after the operation with normal graft function. Complications associated with the use of the modified technique, such as bleeding, anastomotic stenosis, biloma, or urinoma, did not occur. CONCLUSION: Modified simultaneous liver and kidney transplantation is a safe alternative for patients with ADPLKD. By combining right-sided nephrectomy and orthotopic graft transplantation, the approach optimizes the exposure of anatomical structures and simplifies the transplantation procedure. Additionally, the modified transplantation technique does not require a particular organ explantation procedure and can be applied for all liver and kidney grafts.

Acceptance of SARS-CoV-2 vaccines by liver transplant recipients and candidates.

Guidelines recommend vaccination against SARS-CoV-2 in transplant recipients, candidates, and their household contacts. However, little is known about the acceptance of COVID-19 vaccines in these groups.In March 2021, we surveyed 826 liver transplant recipients, candidates, and their household contacts to determine acceptance rates and factors influencing the acceptance of the COVID-19 vaccine; 341 patients (40%) and 237 household contacts (28%) returned the questionnaire. Ninety percent of patients returning the survey reported they were willing to receive the vaccine within the next 6 months or had already started vaccination. Only 2% of patients and 4% of household contacts reported refusing the vaccine, and 8% of patients and 9% of household contacts wanted to postpone vaccination because of concerns about side effects. Having received the influenza vaccine in the last 2 seasons was the strongest indicator of acceptance to receive the SARS-CoV-2 vaccine within 6 months (odds ratio 5.11; 95% confidence interval 2.43-10.74; p < 0.001). Thirty-two percent of responding patients reported fear of side effects as a reason for having refused vaccination before.Although the acceptance of the SARS-CoV-2 vaccine was particularly high among German liver transplant recipients, candidates, and household contacts in this survey, transplant physicians are encouraged to discuss safety concerns with patients who have refused the seasonal influenza vaccine in the past.

[Education of Abdominal Organ Procurement Surgeons in Germany - Challenges and Possible Solutions]. / Ausbildung von Entnahmechirurgen abdomineller Organe in Deutschland ­ Herausforderungen und Lösungsansätze.

The procurement of abdominal organs is a highly specialised operation, which marks the first important step for a successful transplantation. The article gives an overview of the organisation and the current state of the education of procurement surgeons in Germany. We comment on current challenges and discuss these in an international context.

Between fear and courage: Attitudes, beliefs, and behavior of liver transplantation recipients and waiting list candidates during the COVID-19 pandemic.

Patients with chronic liver disease and patients after solid organ transplantation (SOT) are vulnerable to severe coronavirus disease 2019 (COVID-19). We evaluated fears, attitudes, and opinions associated with COVID-19 in 365 SOT recipients (95% liver, 5% pancreas/kidney), 112 SOT candidates, and 394 immediate household contacts in 2 German transplant centers. Seven (1.5%) patients and 10 (2.5%) controls had contact with confirmed COVID-19 cases. Fear of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was expressed by 65% of SOT recipients and by 55% of SOT candidates. SOT recipients had higher levels of fear of infection and more often wore personal protective gear than household controls. Female sex, steroid treatment, and using the local newspaper as a primary source of information were independently associated with expressed fear of infection in SOT recipients. Younger age and more recent transplantation correlated with concerns about severe COVID-19 expressed by patients and with concerns about worse medical care expressed by household controls. One third of the patients expressed fear that immunosuppression could worsen COVID-19 but only 15% used the transplantation center as a source of information. These data show that fears associated with the SARS-CoV-2 pandemic are frequently expressed but measures to prevent infection are regularly followed by patients before and after SOT.

Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis.

BACKGROUND & AIMS: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. METHODS: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983-2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10-15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. RESULTS: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28-0.61; p <0.0001), graft loss (aHR 0.33; 95% CI 0.13-0.82; p <0.05), liver-related death (aHR 0.46; 95% CI 0.22-0.98; p <0.05), and all-cause death (aHR 0.69; 95% CI 0.49-0.96; p <0.05). On RMST analysis, preventive UDCA led to a survival gain of 2.26 years (95% CI 1.28-3.25) over a period of 20 years. Exposure to cyclosporine rather than tacrolimus had a complementary protective effect alongside preventive UDCA, reducing the cumulative incidence of PBC recurrence and all-cause death. CONCLUSIONS: Preventive UDCA after LT for PBC is associated with a reduced risk of disease recurrence, graft loss, and death. A regimen combining cyclosporine and preventive UDCA is associated with the lowest risk of PBC recurrence and mortality. LAY SUMMARY: Recurrence of primary biliary cholangitis after liver transplantation is frequent and can impair graft and patient survival. We performed the largest international study of transplanted patients with primary biliary cholangitis to date. Preventive administration of ursodeoxycholic acid after liver transplantation was associated with reduced risk of disease recurrence, graft loss, liver-related and all-cause mortality. A regimen combining cyclosporine and preventive ursodeoxycholic acid was associated with the best outcomes.

The MEGNA Score and Preoperative Anemia are Major Prognostic Factors After Resection in the German Intrahepatic Cholangiocarcinoma Cohort.

BACKGROUND: Surgical resection is associated with the best long-term results for intrahepatic cholangiocarcinoma (ICC); however, long-term outcomes are still poor. OBJECTIVE: The primary aim of this study was to validate the recently proposed MEGNA score and to identify additional prognostic factors influencing short- and long-term survival. PATIENTS AND METHODS: This was a retrospective analysis of a German multicenter cohort operated at 10 tertiary centers from 2004 to 2013. Patients were clustered using the MEGNA score and overall survival was analyzed. Cox regression analysis was used to identify prognostic factors for both overall and 90-day survival. RESULTS: A total of 488 patients undergoing liver resection for ICC fulfilled the inclusion criteria and underwent analysis. Median age was 67 years, 72.5% of patients underwent major hepatic resection, and the lymphadenectomy rate was 86.9%. Median overall survival was 32.2 months. The MEGNA score significantly discriminated the long-term overall survival: 0 (68%), I (48%), II (32%), and III (19%) [p <0.001]. In addition, anemia was an independent prognostic factor for overall survival (hazard ratio 1.78, 95% confidence interval 1.29-2.45; p <0.01). CONCLUSION: Hepatic resection provides the best long-term survival in all risk groups (19-65% overall survival). The MEGNA score is a good discriminator using histopathologic items and age for stratification. Correction of anemia should be attempted in every patient who responds to treatment. Perioperative liver failure remains a clinical challenge and contributes to a relevant number of perioperative deaths.

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

BACKGROUND: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). METHODS: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. RESULTS: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. CONCLUSION: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Living donor liver transplantation with two-stage hepatectomy for patients with isolated, irresectable colorectal liver-the LIVER-T(W)O-HEAL study.

BACKGROUND: Colorectal cancer is the third most common malignancy worldwide. The occurrence of liver metastases worsens the prognosis of the patient significantly if the tumor burden is not resectable. Liver transplantation might be an option for otherwise irresectable colorectal liver metastases. In this study, we evaluate the role of two-stage hepatectomy in combination with a left-lateral living donor liver transplantation. METHODS: Patients with irresectable liver metastases having a stable disease or tumor regression after at least 8 weeks of systemic chemotherapy without an extrahepatic tumor burden (except resectable lung metastases) are suitable for study inclusion. A randomization is not planned since the control arm (systemic chemotherapy) is well established and the superiority of the transplantation procedure has to be expected. The surgical treatment consists of two steps: in a first operation, a left hemihepatectomy in the recipient will be performed. At this place, the left lateral liver lobe (segments II and III) of a living donor will be transplanted. To induce a growth of the graft, a portal vein ligation will be performed. Approximately after 2 weeks, the removal of the right hemiliver will be conducted if the control imaging shows a sufficient growth of the graft. RESULTS: The patient recruitment is ongoing. In total, three patients have been already transplanted with this protocol. Up to now, they are tumor-free and in good clinical health. DISCUSSION: With the design of the LIVER-T(W)O-HEAL study, it might be possible to offer patients with otherwise irresectable colorectal liver metastases a curative treatment option. The key point of this study will be, most probably, the patient's selection. TRIAL REGISTRATION: Registered at Clinical Trials; NCT03488953 ; registered on April 5, 2018.

Auxiliary living donor liver transplantation combined with two-stage hepatectomy for unresectable colorectal liver metastases.

PURPOSE OF REVIEW: To review the role of liver transplantation for unresectable colorectal liver metastases (u-CRLM) and to describe the intial experience with auxiliary living donor liver transplantation combined with two-stage hepatectomy for u-CRLM (i.e. living donor RAPID). RECENT FINDINGS: Patients affected with u-CRLM have a poor prognosis with 5 years overall survival (OS) rate less than 10% under standard modern chemotherapy.There is an actual international consensus that liver transplantation for u-CRLM represents a viable option in highly selected patients with OS rate at 5 years up to 80% notwithstanding high recurrence rates. Due to the scarcity of whole liver graft from deceased donors, the RAPID procedure (i.e. resection and partial liver segment 2-3 transplantation from deceased donors with delayed total hepatectomy) has been introduced as possible alternative. The RAPID procedure represents the most actual and modern fusion of the two most challenging procedures of modern hepatobiliary and liver transplant surgery: that is auxiliary partial orthotopic liver transplantation and associating liver partition and portal vein ligation for staged hepatectomy. Although the deceased donor-RAPID procedure may show promising results, the basic problem of scarcity of organs from deceased donors and mainly the lack of splittable organs still remains. SUMMARY: The living donor RAPID, based on transplantation of left lateral segments from living donor, may represent the way out to this problem. It is feasible and safe (for both donor and recipient), but characterized by a very challenging high-end transplantological procedure.

Posttraumatic venous gas in the liver - a case report and review of the current literature.

BACKGROUND: There are numerous causes of hepatic gas formation that range from serious pathologies to incidental findings, including mesenteric infarction, liver abscess, inflammatory bowel disease or minimally invasive hepatic interventions. CASE PRESENTATION: We report a case of a 50-year-old man who was admitted to the emergency room after a car accident. The clinical examination and further diagnostics revealed a craniocerebral injury with a fracture of the skull, concomitant soft tissue lesions and subarachnoidal bleeding. Furthermore, a blunt thoracic trauma with hemopneumothorax due to rib fractures was treated with a chest tube. No obvious abdominal pathology was seen. While in the operating theatre for the surgical revision of the cranial soft tissue lesions, a femoral venous catheter was inserted without any complications. A routine ultrasound of the abdomen six hours after the trauma revealed unclear hepatic gas formation. A contrast-enhanced computer tomography (CT) scan of the abdomen was performed, and the gas formation was found to be localized within the left hepatic vein. Afterwards, there was no specific treatment of the hepatic venous gas formation, as no alterations of liver function or liver enzymes were seen. The further course of the patient was uneventful regarding the gas formation in the liver, and another ultrasound two days later revealed no further gas in the liver. CONCLUSIONS: The placement of a femoral venous catheter is a risk factor for gas formation in liver veins. No further treatment is needed in cases with stable liver function. To rule out serious pathologies, diagnostic findings (e.g., ultrasound, CT), clinical history and underlying diseases need to be analyzed carefully after the detection of intrahepatic gas formation. With contrast-enhanced CT, the localization of the gas and its potential causes might be detectable.

Experiences with surgically treated primary or secondary hepatic sarcoma.

PURPOSE: Liver resection in hepatic sarcoma is rare, but other alternative treatment options are scarce. Surgery offers the only aggressive approach to achieve a tumour-free state. The aim of this investigation was to evaluate the outcome and survival of these patients at a single hepato-biliary university hospital. METHODS: Between January 2004 and July 2013, 896 anatomical liver resections were performed. Eleven liver resections (1.2%) were performed due to primary hepatic sarcoma or hepatic sarcoma metastases. The demographic and clinical parameters were collected from the institutional patients' records. RESULTS: In eight patients (83%), liver resection was performed due to hepatic sarcoma metastases. The surgical procedures were as follows: two patients (18%) had segmentectomy, six patients (55%) had hemihepatectomy or extended hemihepatectomy and three patients (27%) had multivisceral resections. In nine patients (82%), the resection margins were tumour free. In 55% (n = 6) of the patients, the maximal tumour diameter was greater than 10 cm. The postoperative morbidity was low with a Clavien-Dindo score of 2 (range 0-5). One patient died on postoperative day 2 after multivisceral resection. During the follow-up of 932 days (range 2-2.220 days) the 1-, 2- and 3-year survival rates were 91, 63 and 45%, respectively. Tumour recurrence was detected in seven patients (63%). CONCLUSIONS: Liver resections in patients with primary or secondary hepatic sarcoma are rare. The main goal in these patients is to achieve complete tumour resection because chemotherapy offers no suitable alternative, but the long-term survival rates are limited because of high a recurrence rate even after aggressive surgical approaches.

Long-term follow-up of five yr shows superior renal function with everolimus plus early calcineurin inhibitor withdrawal in the PROTECT randomized liver transplantation study.

BACKGROUND: The 12-month (M) PROTECT study showed that de novo liver transplant recipients (LTxR) who switched from a calcineurin inhibitor (CNI)-based immunosuppression to a CNI-free everolimus (EVR)-based regimen showed numerically better renal function. Here, we present the five-yr follow-up data. METHODS: PROTECT was a randomized controlled study in which LTxR received basiliximab and CNI-based immunosuppression ± corticosteroids. Patients were randomized 1:1 to receive EVR or continue CNI. Patients completing the core study could enter the extension study on their randomized treatment. RESULTS: A total of 81 patients entered the extension study (41, EVR; 40, CNI). At M59 post-randomization, the adjusted mean eGFR was significantly higher in the EVR group, with a benefit of 12.4 mL/min using Cockcroft-Gault (95% CI: 1.2; 23.6; p = 0.0301). Also, there was a significant benefit for adjusted and unadjusted eGFR using the four-variable Modification of Diet in Renal Disease (MDRD4) or Nankivell formula. During the extension period, treatment failure rates were similar. SAEs occurred in 26 (63.4%) and 28 (70.0%) of the patients in EVR and CNI groups, respectively. CONCLUSION: Compared with the CNI-based treatment, EVR-based CNI-free immunosuppression resulted in significantly better renal function and comparable patient and graft outcomes after five-yr follow-up.

Chemerin in peritoneal sepsis and its associations with glucose metabolism and prognosis: a translational cross-sectional study.

BACKGROUND: Stress hyperglycaemia (SHG) is a common complication in sepsis associated with poor outcome. Chemerin is an adipocytokine associated with inflammation and impaired glucose homeostasis in metabolic diseases such as type 2 diabetes (T2D). We aimed to investigate how alterations of circulating chemerin levels and corresponding visceral adipose tissue (VAT) expression are linked to glucose metabolism and prognosis in sepsis. METHODS: Clinical data and tissue samples were taken from a cross-sectional study including control, T2D and sepsis patients, all undergoing laparotomy. A second independent patient cohort of patients with sepsis was included to evaluate associations with prognosis. This was complemented by a murine model of peritoneal infection and a high-fat diet. We analysed circulating chemerin by enzyme-linked immunosorbent assay and VAT messenger RNA (mRNA) expression by real-time polymerase chain reaction. RESULTS: Circulating chemerin was increased in sepsis 1.69-fold compared with controls (p = 0.012) and 1.47-fold compared with T2D (p = 0.03). Otherwise, chemerin VAT mRNA expression was decreased in patients with sepsis (p = 0.006) and in septic diabetic animals (p = 0.009). Circulating chemerin correlated significantly with intra-operative glucose (r = 0.662; p = 0.01) and in trend with fasting glucose (r = 0.528; p = 0.052). After adjusting for body mass index or haemoglobin A1c, chemerin correlated in trend with insulin resistance evaluated using the logarithmised homeostasis model assessment of insulin resistance (r = 0.539, p = 0.071; r = 0.553, p = 0.062). Chemerin was positively associated with Acute Physiology and Chronic Health Evaluation II score in patients with sepsis (p = 0.036) and with clinical severity in septic mice (p = 0.031). In an independent study population, we confirmed association of chemerin with glucose levels in multivariate linear regression analysis (ß = 0.556, p = 0.013). In patients with sepsis with SHG, non-survivors had significantly lower chemerin levels than survivors (0.38-fold, p = 0.006), while in patients without SHG, non-survivors had higher chemerin levels, not reaching significance (1.64-fold, p = 0.089). No difference was apparent in patients with pre-existing T2D (p = 0.44). CONCLUSIONS: We show, for the first time to our knowledge, that chemerin is increased in sepsis and that it associates with impaired glucose metabolism and survival in these patients. It could be further evaluated as a biomarker to stratify mortality risk of patients with SHG.

Predictive factors for survival and recurrence rate in patients with node-negative gastric cancer--a European single-centre experience.

PURPOSE: Gastric cancer is a common disease with poor prognosis. Lymph node involvement is the strongest prognostic factor regarding survival in curatively (R0) resected patients. The aim of this study was to determine if a subgroup with higher risk for tumour recurrence exists in patients with node-negative gastric cancer. Furthermore, we aimed to identify prognostic factors and recurrence patterns for this subgroup. METHODS: We collected demographical, clinical, pathohistological and follow-up data from 1,074 patients with gastric cancer in a prospectively maintained database. In 228 cases, R0 resections for node-negative gastric cancer were performed. The median follow-up period was 59 months. Statistical analysis was performed using SPSS 19.0. RESULTS: The 5- , 10- and 15-year overall survival was 83, 75.5 and 73 %, respectively, with a disease-free survival of 78, 73 and 73 %. Tumour recurrence was observed in 18.9 % (43 cases), 14 % of which were diagnosed after more than 5 years. Gender, T-category , lymphangioinvasion, tumour differentiation, serosal infiltration, histological growth pattern, tumour size and classification according to Lauren were significant prognostic factors for overall survival in univariate analysis. Multivariate analysis showed tumour size and female sex to be independent prognostic factors. Non-exophytic tumour growth was a relevant factor for the development of local recurrence. Diffuse type gastric cancers as well as signet ring cells were significantly associated with the development of peritoneal carcinomatosis, and male gender with hematogenous metastases. CONCLUSIONS: Multimodal treatment and individual follow-up might be beneficial in patients with higher risk of recurrence after R0 resection of node-negative gastric cancer.

The influence of desmocollin 1-3 expression on prognosis after curative resection of colorectal liver metastases.

PURPOSE: Prognosis after curative resection of colorectal liver metastases is hard to determine based on clinical parameters; biomarkers are therefore needed. The purpose of this study was to determine the value of desmocollins (DSC) as potential biomarkers. Desmocollins are responsible for cell-cell adhesion in epithelial tissue; their loss may lead to reduced cellular adhesion and facilitate cellular migration, enabling tumor cells to form distant metastases. We analyzed DSC expression in colorectal liver metastases with respect to the risk of recurrence following liver resection. METHODS: Tissue microarrays from 257 consecutive patients who underwent R0-resection of colorectal liver metastases were constructed. RESULTS: Low expression of DSC 1, 2, and 3 was observed in 55, 54, and 79 % of liver metastases. There was no correlation between site or stage of the primary tumor, presence of extrahepatic tumor, grading, size or number of metastases, and desmocollin expression. Primary tumor stage I or II (p = 0.005) and no or few lymph node metastases (p < 0.001) were associated with a significantly better disease-free survival on univariate analysis. These parameters reached only marginal significance on multivariate analysis (p = 0.059 and p = 0.052, respectively), as did desmocollin 3 expression (p = 0.050). In the subgroup of patients with stages III-IV primary tumors, however, multivariate analysis showed a significant correlation between DSC 3 expression and disease-free survival after liver resection (p = 0.009). CONCLUSIONS: Reduced expression of DSC3 correlated with an increased risk of developing tumor recurrence after resection of liver metastases. These findings may be helpful in selecting high-risk patients who might benefit from multimodal therapy.