Practical model to identify liver transplant recipients at low risk of postoperative haemorrhage, bile leakage and ascites.

BACKGROUND: This study aimed to identify a subgroup of recipients at low risk of haemorrhage, bile leakage and ascites following liver transplantation (LT). METHODS: Factors associated with significant postoperative ascites (more than 10 ml/kg on postoperative day 5), bile leakage and haemorrhage after LT were identified using three separate multivariable analyses in patients who had LT in 2010-2019. A model predicting the absence of all three outcomes was created and validated internally using bootstrap procedure. RESULTS: Overall, 944 recipients underwent LT. Rates of ascites, bile leakage and haemorrhage were 34.9, 7.7 and 6.0 per cent respectively. The 90-day mortality rate was 7.0 per cent. Partial liver graft (relative risk (RR) 1.31; P = 0.021), intraoperative ascites (more than 10 ml/kg suctioned after laparotomy) (RR 2.05; P = 0.001), malnutrition (RR 1.27; P = 0.006), portal vein thrombosis (RR 1.56; P = 0.024) and intraoperative blood loss greater than 1000 ml (RR 1.39; P = 0.003) were independently associated with postoperative ascites and/or bile leak and/or haemorrhage, and were introduced in the model. The model was well calibrated and predicted the absence of all three outcomes with an area under the curve of 0.76 (P = 0.001). Of the 944 patients, 218 (23.1 per cent) fulfilled the five criteria of the model, and 9.6 per cent experienced postoperative ascites (RR 0.22; P = 0.001), 1.8 per cent haemorrhage (RR 0.21; P = 0.033), 4.1 per cent bile leak (RR 0.54; P = 0.048), 40.4 per cent severe complications (RR 0.70; P = 0.001) and 1.4 per cent 90-day mortality (RR 0.13; P = 0.004). CONCLUSION: A practical model has been provided to identify patients at low risk of ascites, bile leakage and haemorrhage after LT; these patients could potentially qualify for inclusion in non-abdominal drainage protocols.

Treatment of polycystic liver disease. Update on the management.

Polycystic liver disease (PLD) may consist of autosomal dominant PLD or isolated PLD without renal impairment. The natural history of liver cysts is to increase in size and number, causing progressive disease that can lead to very large and incapacitating hepatomegaly. Only symptomatic hepatomegaly (pain, inability to eat, weight loss, dyspnea) or cystic complications such as infection or intracystic hemorrhage should be treated. The treatment of PLD thus covers a wide range of therapeutic options, ranging from non-intervention to liver transplantation, including needle aspiration evacuation with injection of sclerosant, laparoscopic fenestration and fenestration by laparotomy combined with liver resection. The choice between these different treatments depends on the symptomatology, the intrahepatic extension of the lesions and the patient's general condition. Hepatic resection is commonly chosen since the vast majority of PLD consists of multiple small cysts that are impossible or difficult to fenestrate. Since cysts are inhomogeneously distributed in the hepatic parenchyma with most areas less affected, the preservation of this less-involved territory allows liver regeneration relatively free of cysts. Hepatectomies for PLD are technically difficult because the planes and the vascular and biliary structures are compressed by the cysts. Liver transplantation, whether isolated or associated with renal transplantation, is indicated in cases of severe malnutrition and/or end-stage renal disease or if the volume of remnant parenchyma is insufficient and suggests failure of a partial hepatectomy.

Multibiomarker response in the earthworm Eisenia fetida as tool for assessing multi-walled carbon nanotube ecotoxicity.

Carbon nanotubes have received a great attention in the last years thanks to their remarkable structural, electrical, and chemical properties. Nowadays carbon nanotubes are increasingly found in terrestrial and aquatic environment and potential harmful impacts of these nanoparticles on humans and wildlife are attracting increasing research and public attention. The effects of carbon nanotubes on aquatic organisms have been explored by several authors, but comparatively the information available on the impact of these particles on soil organisms is much less. Earthworms have traditionally been considered to be convenient indicators of land use impact and soil fertility. The aim of this work was to study the integrated response of a suite of biomarkers covering molecular to whole organism endpoints for the assessment of multi-walled carbon nanotube (MWCNTs) effects on earthworms (Eisenia fetida) exposed to spiked soil. Results showed that cellular and biochemical responses, such as immune cells morphometric alterations and lysosomal membrane destabilization, acetylcholinesterase inhibition and metallothionein tissue concentration changes, showed high sensitivity to MWCNTs exposure. They can improve our understanding and ability to predict chronic toxicity outcomes of MWCNTs exposure such as reproductive alterations. In this context although more investigation is needed to understand the mechanistic pathway relating the biochemical and cellular biomarker analyzed to reproductive alterations, the obtained results give an early contribution to the future development of an adverse outcomes pathways for MWCNTs exposure.

French survey of the first three-years of liver transplantation activity from uncontrolled donors deceased after cardiac death.

OBJECTIVE: To assess the first three years of French activity related to liver transplantation from uncontrolled donation after cardiac death (uDCD). STUDY DESIGN: Prospective and observational study in the three active centres authorized by the French Biomedicine Agency. PATIENTS AND METHODS: All patients deceased between 2010 and 2012 after an uncontrolled cardiac arrest admitted to one of three centres (Pitié-Salpêtrière, Saint-Louis or Bicêtre hospitals, AP-HP, Paris, France) and potentially eligible for liver recovery were included. Abdominal normothermic oxygenated recirculation (ANOR) was used for graft preservation. RESULTS: One hundred twenty-six potential uDCD donors were identified as eligible for liver recovery after hospital admission. The main causes of organ recovery failure were technical failure related to ANOR (29 patients, 23%), refusal of consent (39 patients, 31% of potential uDCD donors and 40% of asked relatives) and abnormal hepatic transaminases up to 200 UI.L(-1) during ANOR (24 patients, 19%). Finally, 11 livers were transplanted. Process efficiency was 9% [95% CI: 4-15%]. One-year recipient survival was 82%, [95% CI: 48-98%] and one-year graft survival was 64% [95% CI: 31-89%]. CONCLUSION: Liver transplantation from uDCD donors is achievable in France, despite low process efficiency.

Risk factors associated with preoperative fecal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae in liver transplant recipients.

OBJECTIVE: The aim of the study was to identify risk factors associated with pre-transplant fecal carriage of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae in liver transplant recipients. PATIENTS AND METHODS: Over a 3-year period (January 2009-December 2011), 317 patients who underwent liver transplantation were screened preoperatively for fecal carriage of ESBL-producing Enterobacteriaceae. Risk factors for fecal carriage were investigated by univariate analysis and stepwise logistic regression. RESULTS: Of the 317 patients screened, 50 (15.7%) harbored an ESBL-producing isolate. Previous infection with an ESBL-producing organism had developed during the last 6 months in 20% of fecal carriers versus in none of the non-carriers. Other variables associated with fecal carriage were a model for end-stage liver disease score ≥25, pre-transplant stay in the intensive care unit ≥48 h, hospital stay ≥10 days in the last 6 months, a history of spontaneous bacterial peritonitis (SBP), exposure to a ß-lactam agent in the last month, and prophylaxis with norfloxacin. Independent predictors of fecal carriage in the multivariate logistic regression model were exposure to a ß-lactam agent in the month preceding transplantation (odds ratio [OR] = 7.8, confidence interval [CI] = 4-15.5, P < 0.001), and a history of SBP (OR = 2.4, CI = 1.1-4.9, P = 0.02). CONCLUSIONS: Previous infection with an ESBL-producing isolate, recent exposure to a ß-lactam agent, and a history of SBP are risk factors for preoperative fecal carriage of ESBL-producing Enterobacteriaceae in liver transplant recipients. Patients at risk of fecal carriage should receive intraoperative prophylaxis and, when necessary, empiric postoperative antimicrobial treatment that includes coverage for these organisms.

Liver resection in transplanted patients: a single-center Western experience.

BACKGROUND: Liver resection (LR) in liver transplant (OLT) recipients, an extremely rare situation, who performed on 8 recipients. METHODS: This retrospective analysis of prospectively collected data concerned 8 (0.66%) 1198 LR cases among OLT performed from 1997 to 2011. We analyzed demographic data, surgical indications, and postoperative courses. RESULTS: The indications were resectable recurrent hepatocellular carcinomas (HCC, n = 3), persistent fistula from a posterior sectorial duct (n = 1), recurrent cholangitis due to anastomotic stricture on the posterior sectorial duct (n = l), hydatid cyst (n = l), left arterial hepatic thrombosis with secondary ischemic cholangitis (n = 1), and a large symptomatic biliary cyst (n = 1). The mean interval time to liver resection was 23.7 months (range, 5-47). LR included right hepatectomy (n = 1), right posterior hepatectomy (n = 1), left lobectomy (n = 4), pericystectomy (n = 1), or biliary fenestration (n = 1). Which there was no postoperative mortality, the global morbidity rate was 62% (5/8). The mean follow-up after LR was 92 months (range, 11-156). No patients required retransplantation. None of the 3 patients who underwent LR for HCC showed a recurrence. CONCLUSIONS: LR in OLT recipients is safe, but associated with a high morbidity rate. This procedure can avoid retransplantation in highly selected patients, presenting a possible option particularly for transplanted patients with a resectable, recurrent HCC.

Fatal Escherichia coli skin and soft tissue infections in liver transplant recipients: report of three cases.

Gram-negative bacilli are unusual agents of skin and soft tissue infections. Most previous cases have been reported in cirrhotic or immunocompromised patients, including a single case in a liver transplant recipient. The present report describes 3 cases of fatal skin or soft tissue infections caused by Escherichia coli that occurred in the postoperative course of liver transplantation. The 3 patients were profoundly immunosuppressed as a result of pre-transplant cirrhosis and the postoperative administration of a potent immunosuppressive therapy. Skin and soft tissue infections developed within the first week after liver transplantation, while graft liver function was satisfactory. The 3 patients presented with fever and skin lesions with or without bullae. Despite prompt appropriate antibiotic therapy and surgical debridement, the outcome was rapidly fatal (24 h on average). E. coli was isolated from subcutaneous tissues in 2 cases and from several blood cultures in the third one. The 3 isolates belonged to distinct phylogenetic groups, and did not harbor most of the virulence factors usually reported in extraintestinal pathogenic E. coli isolates. Our report suggests that E. coli can cause severe skin or soft tissue infection in the postoperative course of liver transplantation. The onset of infection is very early and the outcome is extremely poor, despite prompt adapted medical and surgical treatment. Host factors, rather than E. coli bacterial virulence potential, appear to be the major determinants of severity in these patients.

Simultaneous surgical repair for combined biliary and arterial stenoses after liver transplantation.

After orthotopic liver transplantation (OLT), hepatic artery stenoses (HAS) and biliary strictures (BS) are frequent. These complications remain a significant cause of graft loss and patient death. The present study reported a group of 7 patients in whom both HAS and BS were identified and treated surgically in the same surgical session. The median times to diagnosis were 42 (range, 5-120) and 84 (range, 15-280) days after OLT for biliary and arterial stenosis, respectively. The mortality was nil. Two patients (28%) developed postoperative complications. The median hospital stay was 16 days (range, 10-42). All patients are alive; there was no graft loss. With a median of 76 months' follow-up (range, 38-132), only 1 patient (14%) developed recurrence of both BS and HAS. In patients with coincident biliary and artery stenosis, concomitant surgical repair is feasible, offering good long-term results.

Integration of biochemical, histochemical and toxicogenomic indices for the assessment of health status of mussels from the Tamar Estuary, U.K.

The aim of this study was to examine whether a combination of biochemical, histopathological and toxicogenomic data could be used as a valuable tool for the assessment of biological risk associated with pollutants within the Tamar River and Estuary, S.W. England, U.K. Accordingly, biochemical and histopathological biomarkers (protein carbonyls, lipofuscin, neutral lipids, lysosomal stability [N-acetyl-ß-hexosaminidase and neutral red], lysosomal volume, ferric reducing antioxidant power [FRAP] and malonaldehyde [MDA]) and gene expression profiles were assessed in 5 sites from the Tamar River and Estuary (Neal Point, Town Quay, Wilcove, Cremyll Ferry and Whitsand; and a reference site, Trebarwith Strand, N. Cornwall). PAHs were measured in mussel tissue and sediment and metals were measured in mussel tissue only. Data from the biomarkers was integrated into a Mussel Expert System (MES) model to produce a simple assessment of mussel stress. Clear gradients of mussel toxicity were identified by the biomarkers (with the exception of neutral lipids) with the highest impacted animals found furthest up the Tamar, whilst the MES was unable to identify a gradient of effect. Gene expression profiles also indicated a gradient of stress with the greatest number of significantly up- or down- regulated genes found at the uppermost 2 sites. The MES did, however, determine that mussels from all sites, except the reference site, were highly stressed; a conclusion that could not be inferred from the biomarker data alone. It is concluded that the MES is a valuable tool that permits integration and interpretation of complex sets of biomarker data by identifying the biological meaning of biomarker changes.

Molecular epidemiology of Escherichia coli bacteremia in liver transplant recipients.

The characteristics of Escherichia coli strains causing bacteremia in profoundly immunosuppressed patients such as transplant recipients are undefined. The phylogenetic group and the virulence genotype of 57 distinct E. coli strains that caused bacteremia in 53 liver transplant recipients were investigated, and the association of these characteristics with host factors and in-hospital mortality was examined. Phylogenetic groups A, B1, B2, and D accounted for 39%, 10%, 25%, and 26% of the isolates, respectively. The most prevalent virulence genes were fyuA (yersiniabactin system: 70%) and iutA (aerobactin system: 63%), whereas hlyA (alpha-hemolysin) and cnf1 (cytotoxic necrotizing factor 1) occurred in only 14% and 12% of isolates, respectively. Most virulence genes were significantly more prevalent among group B2 and D isolates, vs. group A and B1 isolates. The overall rate of in-hospital mortality after E. coli bacteremia was 20%. Predictors of mortality included onset of bacteremia within 30 days of transplantation or during the intensive care unit stay, and non-urinary source and cutaneous source, but not E. coli phylogenetic group or virulence profile. Compared with historical E. coli bloodstream isolates from non-transplant patients, those from liver transplant recipients are characterized by a higher prevalence of groups A and B1 isolates and reduced virulence gene content. This finding can be explained by the severely immunocompromised status of the patients and the predominance of abdominal-source bacteremic episodes. Time of onset and source of bacteremia, not bacterial characteristics, predict mortality.

Microbiological findings of culture-positive preservation fluid in liver transplantation.

Bacterial and fungal infections are the leading cause of mortality in liver transplant (LT) recipients. Few studies have examined the incidence of culture-positive preservation fluid (PF) and the outcome of related recipients. The aim of this study was to determine the incidence and the microbiologic findings of PF positive cultures, and to evaluate the impact on morbidity and mortality of LT recipients. A retrospective analysis of PF cultures performed after 477 LTs from cadaveric grafts between January 2001 and February 2008 was conducted. Forty-five (9.5%) PFs were found to be positive with 1 or 2 pathogens. The demographic profiles of recipients of PF with positive or negative cultures were similar. Enterobacteriaceae species were the most frequent organisms (n = 30), followed by Staphylococcus aureus (n = 5), coagulase-negative staphylococci (n = 5), enterococci (n = 4), and yeasts (n = 3). Mortality rate at 1 month was not significantly different in recipients with positive or sterile PF cultures (88.1% vs. 87.7%, respectively). The rate of bacteremia among LT recipients with positive or negative PF cultures was not statistically different. Systemic infections caused by the pathogen cultured from the PF occurred in 8 (18%) of the 45 recipients, including bacteremia (4/8) or intra-abdominal sepsis (5/8). Causative organisms were Enterobacteriaceae species (n = 5), Candida species (n = 2), and Enterococcus faecium (n = 1). Among the 8 patients who developed infection with the PF organism, 4 (50%) died in the intensive care unit (ICU) vs. an ICU mortality rate of 8% (3/37) in those who did not develop infection with the PF organism (P < 0.05). Infection occurred less frequently in recipients who received antimicrobial therapy with activity against the PF isolate than in those without appropriate treatment (41% vs. 3.8%, P < 0.005). Those who develop infection with organisms recovered from PF cultures appear to have high early mortality rates; therefore, appropriate antimicrobial therapy against organisms cultured from PF should be given.

Long-term survival after portal vein arterialization for portal vein thrombosis in orthotopic liver transplantation.

Portal vein thrombosis is a relatively common finding during liver transplantation. The management of portal vein thrombosis during liver transplantation is technically demanding and ensures adequate portal flow to the liver graft. Eversion thromboendovenectomy and bypass using a patent splanchnic vein and cavoportal hemitransposition are the most often used procedures to treat portal vein thrombosis. There have been anecdotal reports of portal vein arterialization. We report a case of portal vein arterialization during orthotopic liver transplantation for decompensated cirrhosis. When thromboendovenectomy failed to restore sufficient portal flow and completion of arterial anastomosis between the recipient hepatic artery and the donor celiac trunk, a calibrated end-to-side anastomosis between the donor splenic artery and the donor portal vein was performed. With a 6-year follow-up, there are no symptoms related to portal hypertension, liver function is normal. However, an aneurismal dilatation of the portal branches has progressively developed. Calibrated portal vein arterialization is a possible option for portal vein thrombosis in liver transplantation, allowing long-term patient and graft survival.

A biomonitoring study assessing the residual biological effects of pollution caused by the HAVEN wreck on marine organisms in the Ligurian Sea (Italy).

Residual biological effects of the 1991 HAVEN oil spill off the Ligurian (Arenzano) coast were assessed in this study. Samples of the fish species Boops boops, Mullus barbatus, and Uranoscupus scaber were collected from two polluted sites near the HAVEN wreck and from an uncontaminated area. In addition to this, mussels were caged along the coast affected by the HAVEN disaster. The physiological status of fish and mussels was assessed using a battery of stress and exposure biomarkers. The PAH content of mussel and fish tissues was also analyzed. Significant biological responses were observed in lysosomal membrane stability, neutral lipid and lipofuscin accumulation and micronucleus frequency for mussels caged at two sites close to the HAVEN wreck. Chemical analyses indicated, however, that these effects are not caused by aromatic hydrocarbons. For this reason, we suggest that the aftermath of the HAVEN disaster contributes very little to coastal ecosystem pollution. This was also confirmed by the few biological effects observed in fish specimens (Boops boops) collected from surface waters. Nevertheless, it is important to point out that benthic fish displayed a stress syndrome potentially caused by aromatic hydrocarbons released from the oil tanker, as witnessed by an enhanced EROD activity and increased lipofuscin and neutral lipid lysosomal contents.

Assessment of heavy metal contamination using real-time PCR analysis of mussel metallothionein mt10 and mt20 expression: a validation along the Tunisian coast.

In mussel Mytilus galloprovincialis tissues, metallothionein belongs to two different gene classes, mt10 and mt20, showing differential expression at both basal conditions and under heavy metal challenge. In this study, a new more highly sensitive technique, expression analysis of mt10 and mt20 mRNA levels by quantitative reverse transcription polymerase chain reaction, was used to assess the effects of heavy metal contamination in the digestive glands of mussels caged along the Tunisian coast. To validate the new assay, total metallothionein protein, amount of heavy metals (zinc, copper, cadmium), and a biomarker of oxidative stress such as malondialdehyde content, were assessed in the same tissues. At the investigated sites, the molecular assay showed variations of mt20 relative gene expression levels within one or two orders of magnitude, with maximum values at two sites severely polluted with cadmium, Mahres (100-fold) and Menzel Jemile (165-fold). Changes in mt10 expression were recorded at all sites where copper had significantly accumulated, although fold induction levels were less pronounced than those of mt20. In this paper, gene expression data are discussed in relation to the studied biomarkers, demonstrating that the molecular technique based on the differential expression of mt10 and mt20 genes represents (i) a useful and robust tool for studying and monitoring heavy metal pollution under field conditions, and (ii) an improvement in the application of metallothionein as a biomarker of response to exposure to heavy metals in marine mussels.

Randomized clinical trial evaluating the need for routine nasogastric decompression after elective hepatic resection.

BACKGROUND: The value of routine nasogastric tube (NGT) decompression after elective hepatic resection has not been investigated. METHODS: Of 200 patients who had elective hepatic resection, including 68 who had previously had colorectal surgery, 100 were randomized to NGT decompression, where the NGT was left in place after surgery until the passage of flatus or stool, and 100 to no decompression, where the NGT was removed at the end of the operation. RESULTS: There was no difference between patients who had NGT decompression and those who did not in terms of overall surgical complications (15.0 versus 19.0 per cent respectively; P = 0.451) medical morbidity (61.0 versus 55.0 per cent; P = 0.391), in-hospital mortality (3.0 versus 2.0 per cent; P = 0.640), duration of ileus (mean(s.d.) 4.3(1.5) versus 4.5(1.7) days; P = 0.400) or length of hospital stay (14.2(8.5) versus 15.8(10.8) days; P = 0.220). Twelve patients randomized to no NGT decompression required reinsertion of the tube 3.9(1.9) days after surgery. Previous abdominal surgery had no influence on the need for NGT reinsertion. Severe discomfort was recorded in 21 patients in the NGT group and premature removal of the tube was required in 19. Pneumonia (13.0 versus 5.0 per cent; P = 0.047) and atelectasis (81 versus 67 per cent; P = 0.043) were significantly more common in the NGT group. CONCLUSION: Routine NGT decompression after elective hepatectomy had no advantages. Its use was associated with an increased risk of pulmonary complications.

Survival of micro-organisms in cryostorage of human sperm.

The authors describe the clinical application of semen cryostorage, survival of micro-organism during cryostorage procedures and the risk of cross-contamination.

Cryopreservation and sperm DNA integrity.

Cryopreservation of sperm is an extremely important issue in the field of male infertility as freezing can have detrimental effects on a variety of sperm functions, some of them not accessible to the traditional semen quality analysis. In this study, chromatin structure variations in human spermatozoa in semen were studied with the sperm chromatin structure assay (SCSA), both before and after cryopreservation. Samples were divided into two aliquots: the first was analysed without further treatment, while the second was stored in liquid nitrogen at -196 degrees C using standard cryopreservation techniques. The fresh and thawed aliquots were also assessed by light and fluorescence microscopy (after Acridine Orange staining, AO), and computer-assisted semen analysis (CASA) of motility. Overall sperm quality was found to deteriorate after cryopreservation. When thawed spermatozoa were subjected to an extra swim-up round, a general improvement in nuclear maturity was seen in post-rise spermatozoa.

Diagnosing erectile dysfunction: instruments for endocrine diagnosis.

Endocrine factors represent an important and potentially treatable cause of sexual dysfunction. The availability of a correct endocrinological diagnosis allows correct identification of most cases of sexual dysfunction in which the endocrine apparatus is involved. Not only the most frequent causes of endocrine sexual dysfunction, such as hypogonadism and hyperprolactinaemia, but almost all extra-gonadal endocrinopathies (hyper-and hypothyroidism, hyper- and hypocortisolism, steroidal secreting tumours, etc.) may have importance to a greater or lesser extent in sexual function. It is, therefore, necessary that the diagnostic process for sexual dysfunctions of an endocrine nature be as integrated and wide as possible, especially as such pathologies are normally extremely responsive to medical or surgical therapy.

Androgens and fertility.

Androgens play a pivotal role in the development of the male reproductive tract. The spermatogenesis requires high levels of intratesticular testosterone secreted by the Leydig cells. Testosterone exerts its action through the androgen receptor (AR), which is located both in the cytoplasm and in the nucleus of cells in the target tissue. Severe defects of the AR may result in abnormal male sexual development, while more subtle modifications can be a potential cause of male infertility. Low circulating levels of testosterone can be found in 20-30% of infertile men, but administration of testosterone or gonadotropins does not result in improved sperm production. Abuse of anabolic steroids is a frequent cause of male infertility, and substances such as endocrine disruptors can alter male fertility through an anti androgenic action.