Prevalence of Steatosis Hepatis in the Eurotransplant Region: Impact on Graft Acceptance Rates

Due to the shortage of liver allografts and the rising prevalence of fatty liver disease in the general population, steatotic liver grafts are considered for transplantation. This condition is an important risk factor for the outcome after transplantation. We here analyze the characteristics of the donor pool offered to the Charité – Universitätsmedizin Berlin from 2010 to 2016 with respect to liver allograft nonacceptance and steatosis hepatis. Of the 2653 organs offered to our center, 19.9% (n=527) were accepted for transplantation, 58.8% (n=1561) were allocated to other centers, and 21.3% (n = 565) were eventually discarded from transplantation. In parallel to an increase of the incidence of steatosis hepatis in the donor pool from 20% in 2010 to 30% in 2016, the acceptance rates for steatotic organs increased in our center from 22.3% to 51.5% in 2016 (p < 0.001), with the majority (86.9%; p > 0.001) having less than 30% macrovesicular steatosis hepatis. However, by 2016, the number of canceled transplantations due to higher grades of steatosis hepatis had significantly increased from 14.7% (n = 15) to 63.6% (42; p < 0.001). The rising prevalence of steatosis hepatis in the donor pool has led to higher acceptance rates of steatotic allografts. Nonetheless, steatosis hepatis remains a predominant phenomenon in discarded organs necessitating future concepts such as organ reconditioning to increase graft utilization.

Proposal of Two Prognostic Models for the Prediction of 10-Year Survival after Liver Resection for Colorectal Metastases

Background. One-third of 5-year survivors after liver resection for colorectal liver metastases (CLM) develop recurrence or tumor-related death. Therefore 10-year survival appears more adequate in defining permanent cure. The aim of this study was to develop prognostic models for the prediction of 10-year survival after liver resection for colorectal liver metastases. Methods. N=965 cases of liver resection for CLM were retrospectively analyzed using univariable and multivariable regression analyses. Receiver operating curve analyses were used to assess the sensitivity and specificity of developed prognostic models and their potential clinical usefulness. Results. The 10-year survival rate was 15.2%. Age at liver resection, application of chemotherapies of the primary tumor, preoperative Quick’s value, hemoglobin level, and grading of the primary colorectal tumor were independent significant predictors for 10-year patient survival. The generated formula to predict 10-year survival based on these preoperative factors displayed an area under the receiver operating curve (AUROC) of 0.716. In regard to perioperative variables, the distance of resection margins and performance of right segmental liver resection were additional independent predictors for 10-year survival. The logit link formula generated with pre- and perioperative variables showed an AUROC of 0.761. Conclusion. Both prognostic models are potentially clinically useful (AUROCs >0.700) for the prediction of 10-year survival. External validation is required prior to the introduction of these models in clinical patient counselling.

The Falciform Ligament for Mesenteric and Portal Vein Reconstruction in Local Advanced Pancreatic Tumor: A Surgical Guide and Single-Center Experience

Background. Since local tumor infiltration to the mesenteric-portal axis might represent a challenging assignment for curative intended resectability during pancreatic surgery, appropriate techniques for venous reconstruction are essential. In this study, we acknowledge the falciform ligament as a feasible and convenient substitute for mesenteric and portal vein reconstruction with high reliability and patency for local advanced pancreatic tumor. Methods. A retrospective single-center analysis. Between June 2017 and January 2018, a total of eleven consecutive patients underwent pancreatic resections with venous reconstruction using falciform ligament. Among them, venous resection was performed in nine cases by wedge and in two cases by full segment. Patency rates and perioperative details were reviewed. Results. Mean clamping time of the mesenteric-portal blood flow was 34 min, while perioperative mortality rate was 0%. By means of Duplex ultrasonography, nine patients were shown to be patent on the day of discharge, while two cases revealed an entire occlusion of the mesenteric-portal axis. Orthograde flow demonstrated a mean value of 34 cm/s. All patent grafts on discharge revealed persistent patency within various follow-up assessments. Conclusion. The falciform ligament appears to be a feasible and reliable autologous tissue for venous blood flow reconstruction with high postoperative patency. Especially the possibility of customizing graft dimensions to the individual needs based on local findings allows an optimal size matching of the conduit. The risk of stenosis and/or segmental occlusion may thus be further reduced.

Temporary CBD Stenting with a Nelaton Tube Is a More Practical and Safer Option Than T-Tube Drainage after Conventional CBD Exploration for Choledocholithiasis

Objective. We are trying to investigate the possibility, safety, and benefits of replacing the role of T-tube by another more safe and effective procedure for biliary decompression in the case of common bile duct (CBD) exploration. Methods. Our present study includes fifty consecutive patients who underwent a traditional CBD exploration due to choledocholithiasis. Patients were divided into 2 equal groups. In the 1st group, a spontaneously expelled Nelaton tube is placed in the CBD to aid in bile drainage to the duodenum, while in the 2nd group, a conventional T-tube is placed to decompress the CBD in the early postoperative (PO) days to a drainage bag. Operative and PO data as well as PO hospital stay time were recorded. All data were collected and statistically analyzed. Results. The mean operative time and PO hospital stay days were significantly low (p value < 0.05) in the Nelaton tube drainage group compared with the T-tube drainage group. On the other hand, the mean time needed for the abdominal drain removal was significantly higher in the T-tube drainage group (p value < 0.05). Conclusion. Nelaton tube with internal biliary drainage is effective and safer than T-tube drainage and it helps in reduction of the PO hospital stay time. In addition, it avoids all short-term complications of T-tube.

The Role of Normothermic Perfusion in Liver Transplantation (TRaNsIT Study): A Systematic Review of Preliminary Studies

Introduction. The success of liver transplantation has been limited by the unavailability of suitable donor livers. The current organ preservation technique, i.e., static cold storage (SCS), is not suitable for marginal organs. Alternatively, normothermic machine perfusion (NMP) promises to recreate the physiological environment and hence holds promise for the better organ preservation. The objective of this systematic review is to provide an overview of the safety, benefits, and insight into the other potential useful parameters of NMP in the liver preservation. Material and Methods. We searched the current literature following registration in the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42018086034 for prospective trials comparing the role of NMP device to SCS in liver transplant by searching the PubMed, EMBASE, Cochrane, BIOSIS, Crossref, and Scopus databases and clinical trial registry. Results. The literature search identified five prospective clinical trials (four being early phase single institutional and single randomized multi-institutional) comparing 187 donor livers on NMP device to 273 donor livers on SCS. The primary outcome of interest was to assess the safety and graft survival at day 30 after transplant following NMP of the donor liver. Secondary outcomes included were early allograft dysfunction (EAD) in the first seven days; serum measures of liver functions as bilirubin, aspartate aminotransferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), and international normalized ratio (INR) on days 1–7; major complications as defined by a Clavien-Dindo score ≥ 3; and patient and graft survival and biliary complications at six months. The peaked median AST level between days 1 and 7 in the five trials was 417–1252 U/L (range 84–15009 U/L) while on NMP and 839–1474 U/L (range 153–8786 U/L) in SCS group. The median bilirubin level on day 7 ranged within 25–79 µmol/L (range 8–344 µmol/l) and 30–47.53 µmol/l (range 9–340 µmol/l) in NMP and SCS groups, respectively. A single case of PNF was reported in NMP group in the randomized trial while none of the other preliminary studies reported any in either group. There was intertrial variability in EAD which ranged within 15–56% in NMP group while being within 23–37% in SCS group. Biliary complications observed in NMP group ranged from 0 to 20%. Single device malfunction was reported in randomized controlled trial leading to renouncement of transplant while none of the other trials reported any machine failure, although two user related device errors inadvertent were reported. Conclusion. This review outlines that NMP not only demonstrated safety and efficacy but also provided the favourable environment of organ preservation, repair, and viability assessment to donor liver prior to the transplantation with low rate of posttransplantation complication as PNF, EAD, and biliary complication; however further studies are needed to broaden our horizon.

Normothermic Ex Vivo Machine Perfusion for Liver Grafts Recovered from Donors after Circulatory Death: A Systematic Review and Meta-Analysis

As a result of donation after circulatory death liver grafts’ poor tolerance to cold storage, there has been increasing research interest in normothermic machine perfusion. This study aims to systematically review the current literature comparing normothermic perfusion to cold storage in donation after circulatory death liver grafts and complete a meta-analysis of published large animal and human studies. A total of nine porcine studies comparing cold storage to normothermic machine perfusion for donation after circulatory death grafts were included for analysis. There was a significant reduction in AST (mean difference −2291 U/L, CI (−3019, −1563); P ≤ 0.00001) and ALT (mean difference −175 U/L, CI (−266, −85); P=0.0001), for normothermic perfusion relative to static cold storage, with moderate (I2 = 61%) and high (I2 = 96%) heterogeneity, respectively. Total bile production was also significantly higher (mean difference = 174 ml, CI (155, 193); P≤0.00001). Further research focusing on standardization, performance of this technology following periods of cold storage, economic implications, and clinical trial data focused on donation after circulatory death grafts will be helpful to advance this technology toward routine clinical utilization for these grafts.

Nonoperative Management May Be a Viable Approach to Plexiform Neurofibroma of the Porta Hepatis in Patients with Neurofibromatosis-1

Background. Plexiform neurofibroma (PNF) in the porta hepatis (PH) is an unusual manifestation of neurofibromatosis-1 (NF-1). Resection is often recommended given the risk of malignant transformation. We encountered a challenging case in clinical practice which prompted us to report our findings and perform a systematic review on the management of these tumors. Methods. We reported the case of a 31-year-old woman with NF-1 and PNF of the PH. PRISMA 2009 guidelines were followed for systematic review. Results. Our patient was found to have unresectable disease at exploration. After >5 years of follow-up, she continued to have stable disease on imaging. We identified 12 studies/case reports including 10 adult and 6 pediatric patients with PNF of PH. None of the 7 adult patients with NF-1 and PNF of PH underwent a successful tumor resection. All pediatric patients were managed with surveillance alone. All but one pediatric patient had NF-1. None of the reported cases of PNF of PH had malignant transformation. Conclusion. Our findings suggest that PNFs of PH in the setting of NF-1 are often unresectable and may have an indolent course. Surveillance alone may be a reasonable option in some patients; however, further studies are needed.

Child-Pugh Parameters and Platelet Count as an Alternative to ICG Test for Assessing Liver Function for Major Hepatectomy

Objective. To study the correlations and discrepancies between Child-Pugh system and indocyanine green (ICG) clearance test in assessing liver function reserve and explore the possibility of combining two systems to gain an overall liver function assessment. Design. Retrospective analysis of 2832 hepatocellular carcinoma (HCC) patients graded as Child-Pugh A and Child-Pugh B with ICG clearance test being performed was conducted. Results. ICG retention rate at 15 minutes (ICG15) correlates with Child-Pugh score, however, with a large variance. Platelet count improves the correlation between Child-Pugh score and ICG15. ICG15 can be estimated using the following regression formula: estimated ICG15 (eICG15) = 45.1 + 0.435 × bilirubin − 0.917 × albumin + 0.491 × prothrombin time − 0.0283 × platelet (R2=0.455). Patients with eICG15 >20.0% who underwent major hepatectomy had a tendency towards more posthepatectomy liver failure (4.1% versus 8.0%, p=0.09) and higher in-hospital mortality (3.7% versus 8.0%, p=0.052). They also had shorter median overall survival (5.10±0.553 versus 3.01±0.878 years, p=0.015) and disease-free survival (1.37±0.215 versus 0.707±0.183 years, p=0.018). Conclusion. eICG15 can be predicted from Child-Pugh parameters and platelet count. eICG15 correlates with in-hospital mortality after major hepatectomy and predicts long-term survival.

Gallbladder Carcinoma in the United States: A Population Based Clinical Outcomes Study Involving 22,343 Patients from the Surveillance, Epidemiology, and End Result Database (1973–2013)

Introduction. Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract and the third most common gastrointestinal tract malignancy. This study examines a large cohort of GBC patients in the United States in an effort to define demographics, clinical, and pathologic features impacting clinical outcomes. Methods. Demographic and clinical data on 22,343 GBC patients was abstracted from the SEER database (1973–2013). Results. GBC was presented most often among Caucasian (63.9%) females (70.7%) as poorly or moderately differentiated (42.5% and 38.2%) tumors, with lymph node involvement (88.2%). Surgery alone was the most common treatment modality for GBC patients (55.0%). Combination surgery and radiation (10.6%) achieved significantly longer survival rates compared to surgery alone (4.0±0.2 versus 3.7±0.1 years, p=0.004). Overall mortality was 87.0% and cancer-specific mortality was 75.4%. Conclusions. GBC is an uncommon malignancy that presents most often among females in their 8th decade of life, with over a third of cases presenting with distant metastasis. The incidence of GBC has doubled in the last decade concurrent with increases in cholecystectomy rates attributable in part to improved histopathological detection, as well as laparoscopic advances and enhanced endoscopic techniques. Surgical resection confers significant survival benefit in GBC patients.

Mediastinal Pseudocyst: Varied Presentations and Management—Experience from a Tertiary Referral Care Centre in India

Pseudocysts are a recognised complication following acute or chronic pancreatitis. Usually located in peripancreatic areas, they have also been reported to occur in atypical regions like liver, pelvis, spleen, and mediastinum. Mediastinal pseudocysts are a rare entity and present with myriad of symptoms due to their unique location. They are a clinical challenge to diagnose and manage. In this paper, we describe the clinical and radiological characteristics of mediastinal pseudocysts in 7 of our patients, as well as our experience in managing these patients along with their clinical outcome.