Intestinal Bacteremia After Liver Transplantation Is a Risk Factor for Recurrence of Primary Sclerosing Cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic progressive pathological process, related to inflammatory bowel disease and subsequent bacterial translocation. Liver transplantation (LT) is the only curative therapy, but outcomes are compromised by recurrence of PSC (rPSC). The aim of the study was to investigate a potential link between intestinal bacteremia, fucosyltransferase-2 (FUT2), and rPSC after LT. METHODS: LT recipients with PSC (n = 81) or without PSC (n = 271) were analyzed for clinical outcomes and positive bacterial blood cultures. A link between bacteremia and the genetic variant of the FUT2 gene was investigated. RESULTS: The incidence of inflammatory bowel disease was significantly higher in PSC recipients but not associated with rPSC. Bacteremia occurred in 31% of PSC recipients. The incidence of rPSC was 37% and was significantly more common in patients with intestinal bacteremia versus no bacteremia (82% versus 30%; P = 0.003). The nonsecretor polymorphism of the FUT2 gene was identified as a genetic risk factor for both intestinal bacteremia and rPSC. Combined FUT2 genotype and intestinal bacteremia in recipients resulted in the highest risk for rPSC (hazard ratio, 15.3; P < 0.001). CONCLUSIONS: Thus, in this article, we showed that bacterial translocation is associated with rPSC after LT and related to the FUT2 nonsecretor status.

Cell-free microRNAs as early predictors of graft viability during ex vivo normothermic machine perfusion of human donor livers.

BACKGROUND: Cell-free microRNAs (miRs) have emerged as early and sensitive biomarkers for tissue injury and function. This study aimed to investigate whether the release of hepatocyte-derived microRNAs (HDmiRs) and cholangiocyte-derived miRs (CDmiRs) correlates with hepato-cholangiocellular injury and function during oxygenated, normothermic machine perfusion (NMP) of human liver grafts. METHODS: Donor livers (n = 12), declined for transplantation, were subjected to oxygenated NMP (6 hours) after a period of static cold storage (median 544 minutes (IQR 421-674)). Perfusate and bile samples were analyzed by qRT-PCR for HDmiR-122 and CDmiR-222. Spearman correlations were performed between miR levels and currently available indicators and classic markers. RESULTS: Both HDmiR-122 and CDmiR-222 levels in perfusate at 30 minutes of NMP strongly correlated with hepatocyte injury (peak perfusate AST) and cholangiocyte injury (peak biliary LDH). In bile, only CDmiR-222 correlated with these injury markers. For hepato-cholangiocellular function, both miRs in perfusate correlated with total bilirubin, while HDmiR-122 (in perfusate) and CDmiR-222 (in bile) correlated with bicarbonate secretion. Both the relative ratio of HDmiR-122/CDmiR-222 and AST in perfusate at 30 minutes significantly correlated with cumulative bile production, but only the relative ratio was predictive of histopathological injury after 6 hours NMP. CONCLUSION: Early levels of HDmiR-122 and CDmiR-222, in perfusate and/or bile, are predictive of excretory functions and hepato-cholangiocellular injury after 6 hours NMP. These miRs may represent new biomarkers for graft viability and function during machine perfusion.

Suitability of livers for transplantation when treated by normothermic machine perfusion.

BACKGROUND: Many factors may compromise the functional recovery of a harvested potential liver for engraftment. Normothermic machine perfusion (NMP) can revive hepatic metabolism ex vivo enabling subsequent transplantation. In this study, we evaluated the recovery of 11 discarded livers' function utilizing NMP. MATERIALS AND METHODS: Eleven consecutive discarded livers underwent NMP for 6 hours. Liver function recovery was defined by lactate levels of ≤3 mmol/L and continuous bile production. RESULTS: Ten of 11 livers perfused were fatty. The median percentage of macrosteatosis (MaS) and microsteatosis (MiS) was 40% (10%-90%) and 40% (20%-50%), respectively, based on a review of paraffin-embedded sections of preperfusion biopsies. A discarded "amyloid" liver from an HIV-positive donor was also studied. Recovery of liver function was observed in 4 livers, including that with the amyloid deposition. These livers sustained shorter cold ischemia times and seemed to have increased portal and arterial blood flow. No significant change in MiS or MaS was observed before and after perfusion. CONCLUSION: Our results suggest that some discarded grafts might have been salvaged for transplantation. Further studies utilizing NMP with subsequent transplantation would validate this strategy.

Hypo- and normothermic perfusion of the liver: Which way to go?

The demand of donor livers for transplantation exceeds the supply. In an attempt to maximize the number of potentially usable donor livers, several centers are exploring the role of machine perfusion. This review provides an update on machine perfusion strategies and basic concepts, based on current clinical issues, and discuss challenges, including currently used biomarkers for assessing the quality and viability of perfused organs. The potential benefits of machine perfusion on immunogenicity and the consequences on post-operative immunosuppression management are discussed.

The release of microRNA-122 during liver preservation is associated with early allograft dysfunction and graft survival after transplantation.

Early allograft dysfunction (EAD) after liver transplantation (LT) is associated with inferior graft survival. EAD is more prevalent in grafts from donation after circulatory death (DCD). However, accurate prediction of liver function remains difficult because of the lack of specific biomarkers. Recent experimental and clinical studies highlight the potential of hepatocyte-derived microRNAs (miRNAs) as sensitive, stable, and specific biomarkers of liver injury. The aim of this study was to determine whether miRNAs in graft preservation fluid are predictive for EAD after clinical LT and in an experimental DCD model. Graft preservation solutions of 83 liver grafts at the end of cold ischemia were analyzed for miRNAs by reverse transcription polymerase chain reaction. Of these grafts, 42% developed EAD after transplantation. Results were verified in pig livers (n = 36) exposed to different lengths of warm ischemia time (WIT). The absolute miR-122 levels and miR-122/miR-222 ratios in preservation fluids were significantly higher in DCD grafts (P = 0.001) and grafts developing EAD (P = 0.004). In concordance, the miR-122/miR-222 ratios in perfusion fluid correlate with serum transaminase levels within the first 24 hours after transplantation. Longterm graft survival was significantly diminished in grafts with high miR-122/miR-222 ratios (P = 0.02). In the porcine DCD model, increased WIT lead to higher absolute miR-122 levels and relative miR-122/miR-222 ratios in graft perfusion fluid (P = 0.01 and P = 0.02, respectively). High miR-122/miR-222 ratios in pig livers were also associated with high aspartate aminotransferase levels after warm oxygenated reperfusion. In conclusion, both absolute and relative miR-122 levels in graft preservation solution are associated with DCD, EAD, and early graft loss after LT. As shown in a porcine DCD model, miRNA release correlated with the length of WITs. Liver Transplantation 23 946-956 2017 AASLD.

Recurrence of hepatocellular carcinoma after liver transplantation: Is there a place for resection?

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is widely considered as a terminal condition. Therefore, the role of surgery is uncertain in this case. The purpose of this study was to identify the prognostic factors of survival after post-LT HCC recurrence and to evaluate the impact of surgery in this setting. All patients transplanted for HCC between 1991 and 2013 in a single institution and who further developed a post-LT recurrence were included in this study. Univariate and multivariate analyses were performed to identify factors affecting postrecurrence survival. Of the 493 patients transplanted for HCC, a total of 70 (14.2%) consecutive patients developed a recurrence after a median disease-free interval of 17 months. Median survival (MS) from the time of recurrence was 19 months, with a 3-year postrecurrence survival of 26%. Most recurrences were extrahepatic (lung, lymph node, and bone; n = 51; 72.9%), whereas only intrahepatic recurrences were observed in 2 (2.8%) patients. Both intrahepatic and extrahepatic locations were found in 17 (24.3%) patients. A total of 22 (31.4%) patients underwent macroscopically complete resection of the recurrence (intrahepatic [n = 2] and extrahepatic [n = 20]). The MS for resected patients after transplantation was 35 months compared with 15 months for nonresected patients (P < 0.001). In multivariate analysis, the independent unfavorable factors of postrecurrence survival were alpha-fetoprotein level > 100 ng/mL at relapse (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.1; P = 0.03), intrahepatic location (HR, 1.8; 95% CI, 1.0-3.2; P = 0.05), and multifocal recurrence (HR, 1.8; 95% CI, 1.1-3.1; P = 0.04). The management including surgery (HR, 0.4; 95% CI, 0.2-0.7; P = 0.004) was identified as an independent favorable factor. In conclusion, recurrence of HCC after LT is associated with a poor prognosis. However, resection is associated with improved survival and should therefore be considered when feasible. Liver Transplantation 23 440-447 2017 AASLD.

Radiological and clinical predictors of long-term outcome in rotator cuff calcific tendinitis.

OBJECTIVES: Knowledge on the epidemiology and long-term course of rotator cuff calcific tendinitis (RCCT) is scarce. We assessed demographics, radiological characteristics, and their association with long-term outcomes in a large patient group. METHODS: Baseline demographics, radiological characteristics and treatment were recorded in 342 patients. Interobserver agreement of radiological measures was analyzed. Long-term outcome was evaluated with questionnaires (WORC, DASH). The association of baseline characteristics with outcome was assessed. RESULTS: Mean age was 49.0 (SD = 10.0), and 59.5 % were female. The dominant arm was affected in 66.0 %, and 21.3 % had bilateral disease. Calcifications were on average 18.7 mm (SD = 10.1, ICC = 0.84 (p < 0.001)) and located 10.1 mm (SD = 11.8) medially to the acromion (ICC = 0.77 (p < 0.001)). Gärtner type I calcifications were found in 32.1 % (Kappa = 0.47 (p < 0.001)). After 14 years (SD = 7.1) of follow-up, median WORC was 72.5 (range, 3.0-100.0; WORC < 60 in 42 %) and median DASH 17.0 (range, 0.0-82.0). Female gender, dominant arm involvement, bilateral disease, longer duration of symptoms, and multiple calcifications were associated with inferior WORC. DASH results were similar. CONCLUSIONS: Many subjects have persisting shoulder complaints years after diagnosis, regardless of treatment. Female gender, dominant arm involvement, bilateral disease, longer duration of symptoms, and multiple calcifications were associated with inferior outcome. Radiological measures had moderate-to-good reliability and no prognostic value. KEY POINTS: • Most RCCT studies report on short-term outcome and/or small patients groups. • In this large, long-term observational study, RCCT appeared to not be self-limiting in many subjects. • Negative prognostic factors included female gender, more calcifications, dominant arm affected, and longer duration of symptoms. • Interobserver agreement of general radiological RCCT measures is moderate to good. • More rigorous diagnostics and treatment might be needed in specific RCCT cases.

Perforation of the gallbladder: a rare cause of acute abdominal pain.

An 82-year-old woman without any previous medical history arrived in the emergency department with severe pain in the entire abdomen since 5 h. Blood tests showed, apart from a CRP of 28 mg/l, no abnormalities. We decided to perform an abdominal ultrasound, which showed an easily compressible gallbladder, containing a small, mobile gallstone and free fluid in the abdomen. During ultrasound-guided punction of this fluid, bile is aspirated. We performed laparoscopy and confirmed a large amount of intraperitoneal bile. Upon inspecting the gallbladder a perforation is seen in the anti-hepatic side of the gallbladder. After performing a cholecystectomy, we opened the gallbladder and detected a dissection-like lesion, which provided access to the peritoneal cavity. The confirmed diagnosis was acute onset free perforation of the gallbladder. The perforation was probably caused by the small obstructing gallstone seen on ultrasound or by another small stone, which could not be visualized.

Calcific tendinitis of the rotator cuff: a randomized controlled trial of ultrasound-guided needling and lavage versus subacromial corticosteroids.

BACKGROUND: Calcific tendinitis of the rotator cuff (RCCT) is frequently diagnosed in patients with shoulder pain, but there is no consensus on its treatment. PURPOSE: To compare 2 regularly applied RCCT treatments: ultrasound (US)-guided needling and lavage (barbotage) combined with a US-guided corticosteroid injection in the subacromial bursa (subacromial bursa injection [SAI]) (group 1) versus an isolated SAI (group 2). STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Patients were randomly assigned to the 2 groups. Shoulder function was assessed before treatment and at regular follow-up intervals (6 weeks and 3, 6, and 12 months) using the Constant shoulder score (CS, primary outcome), the Western Ontario Rotator Cuff Index (WORC), and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). Additionally, calcification location, size, and Gärtner classification were assessed on radiographs. Results were analyzed using the t test, linear regression, and a mixed model for repeated measures. RESULTS: This study included 48 patients (25 female, 52.1%; mean age, 52.0 ± 7.3 years; 23 patients in group 1) with a mean baseline CS of 68.7 ± 11.9. No patients were lost to follow-up. Four patients in group 1 and 11 in group 2 (P = .06) had an additional barbotage procedure or surgery during the follow-up period because of persisting symptoms and no resorption. At 1-year follow-up, the mean CS in group 1 was 86.0 (95% CI, 80.3-91.6) versus 73.9 (95% CI, 67.7-80.1) in group 2 (P = .005). The mean calcification size decreased by 11.6 ± 6.4 mm in group 1 and 5.1 ± 5.7 mm in group 2 (P = .001). There was total resorption in 13 patients in group 1 and 6 patients in group 2 (P = .07). With regression analyses, correcting for baseline CS and Gärtner type, the mean treatment effect was 20.5 points (P = .05) in favor of barbotage. Follow-up scores were significantly influenced by baseline scores. Results for the DASH and WORC were similar. CONCLUSION: On average, there was improvement at 1-year follow-up in both treatment groups, but clinical and radiographic results were significantly better in the barbotage group.