Lung Ultrasound Score on Postoperative Day 1 Is Predictive of the Occurrence of Pulmonary Complications after Major Abdominal Surgery: A Multicenter Prospective Observational Study.

BACKGROUND: Postoperative pulmonary complications after major abdominal surgery are frequent and carry high morbidity and mortality. Early identification of patients at risk of pulmonary complications by lung ultrasound may allow the implementation of preemptive strategies. The authors hypothesized that lung ultrasound score would be associated with pulmonary postoperative complications. The main objective of the study was to evaluate the performance of lung ultrasound score on postoperative day 1 in predicting pulmonary complications after major abdominal surgery. Secondary objectives included the evaluation of other related measures for their potential prediction accuracy. METHODS: A total of 149 patients scheduled for major abdominal surgery were enrolled in a bicenter observational study. Lung ultrasound score was performed before the surgery and on days 1, 4, and 7 after surgery. Pulmonary complications occurring before postoperative day 10 were recorded. RESULTS: Lung ultrasound score on postoperative day 1 was higher in patients developing pulmonary complications before day 10 (median, 13; interquartile range, 8.25 to 18; vs. median, 10; interquartile range, 6.5 to 12; Mann-Whitney P = 0.002). The area under the curve for predicting postoperative pulmonary complications before day 10 was 0.65 (95% CI, 0.55 to 0.75; P = 0.003). Lung ultrasound score greater than 12 had a sensitivity of 0.54 (95% CI, 0.40 to 0.67), specificity of 0.77 (95% CI, 0.67 to 0.85), and negative predictive value of 0.74 (95% CI, 0.65 to 0.83). Lung ultrasound score greater than 17 had sensitivity of 0.33 (95% CI, 0.21 to 0.47), specificity of 0.95 (95% CI, 0.88 to 0.98), and positive predictive value of 0.78 (95% CI, 0.56 to 0.93). Anterolateral lung ultrasound score and composite scores using lung ultrasound score and other patient characteristics showed similar predictive accuracies. CONCLUSIONS: An elevated lung ultrasound score on postoperative day 1 is associated with the occurrence of pulmonary complications within the first 10 days after major abdominal surgery.

Restrictive intraoperative fluid intake in liver surgery and postoperative renal function: A propensity score matched study.

BACKGROUND: Postoperative acute kidney injury (AKI) is a common complication in hepatic surgery. In hepatic surgery, relative hypovolemia may help to limit blood loss, but the consequences of restrictive fluid intake are unknown. The goal of this study was to determine the influence of intraoperative fluid intake on the incidence of AKI and its consequences. METHODS: Data from 397 consecutive patients who underwent liver resection were prospectively recorded and retrospectively analyszed. We compared the incidence of postoperative acute kidney failure in patients given restrictive (≤ 5 mL/kg/h) versus liberal (> 5 mL/kg/h) fluid therapy. We calculated a 1:1 match propensity score using logistic regression to estimate the likelihood of patients receiving restrictive or liberal intraoperative fluid intakes. The association between the intraoperative fluid intake strategy and occurrence of postoperative AKI were tested using a Cox frailty model on the database of matched patients. RESULTS: Postoperative AKI was diagnosed in 133 of the 397 patients. Fluid intake strategy was restrictive for 121 patients and liberal for 276 patients. After propensity score matching to balance confounding factors, the liberal strategy was associated with a significantly lower risk for postoperative AKI compared to the restrictive strategy (Hazard Ratio 0.40 [0.29; 0.56], P<0.001). Patients with postoperative AKI had longer hospital stays and higher mortality. There were no cases of further blood loss in the liberal fluid intake group. CONCLUSIONS: A restrictive fluid intake strategy is a risk factor for developing postoperative AKI, with serious consequences, without reducing blood loss in liver surgery.

Pulmonary infection after hepatic resection: Associated factors and impact on outcomes.

BACKGROUND AND AIMS: Postoperative pulmonary complications are frequent after hepatectomy. The aim of this retrospective study was to use preoperative and intraoperative data to establish specific factors associated with post-hepatectomy pneumonia (PHPN). METHODS: Patients underwent minor or major hepatectomy for cancer or non-cancer treatment. Surgical procedure was performed by laparoscopy or laparotomy. PHPN was defined as a new radiologic finding associated with fever, leucocytosis and purulent bronchial secretions. The incidence, associated factors and prognosis of PHPN were investigated. RESULTS: In 399 patients undergoing planned hepatectomy, 49 (12.3%) developed pneumonia. Of 81 patients (20.3%) with cirrhosis, 77 were Child-Pugh A and 4 were Child-Pugh B. Hepatectomy indication was cancer in 331 patients (of which metastasis in 213). Laparoscopy rate was 31.3%. In multivariate analysis, the main factors statistically associated with PHPN were: chronic obstructive pulmonary disease (COPD) (odds ratio [OR] = 4.17; 95% confidence interval [CI], 1.60-10.84; P = 0.003), intraoperative blood transfusion (OR = 2.46; 95% CI 1.01-5.70; P = 0.001), laparotomy (OR = 3.01; 95% CI 1.09-8.27; P = 0.03), and nasogastric tube maintained at day 1 (OR = 2.09; 95% CI 1.03-4.22; P = 0.04). Length of stay was significantly different between groups without PHPN (10.2 days) versus with PHPN (26.4 days; P < 0.001). Intra-hospital and one-year mortality were greater in the PHPN group than the pneumonia-free group (8.16 vs 0% and 18.4 vs 3.4%, respectively; P < 0.001). CONCLUSIONS: COPD, transfusion and laparotomy (versus laparoscopy) are factors associated with PHPN and impaired survival.

Time to Conversion to an Everolimus-Based Regimen: Renal Outcomes in Liver Transplant Recipients From the EVEROLIVER Registry.

Longterm use of a calcineurin inhibitor (CNI)-based regimen is one of the major reasons for chronic renal failure in liver transplantation recipients (LTRs). The Everolimus Liver registry (EVEROLIVER) evaluated renal function in LTRs who were converted to everolimus (EVR). This observational registry included all LTRs receiving EVR across 9 centers from France. Data are being collected in an electronic database over 10 years (12 visits/patient) to evaluate efficacy, renal function (estimated glomerular filtration rate [eGFR]), and safety of EVR use in clinical practice, and the current analysis is reporting up to 60 months of findings. Until September 2017, 1045 patients received EVR after a mean time of 3.6 ± 5.1 years. CNI withdrawal was feasible in 57.7% of patients as of month 60. Mean eGFR improved in patients with baseline eGFR <60 mL/minute/1.73 m2 and was maintained in those with baseline eGFR ≥60 mL/minute/1.73 m2 . Among patients with chronic kidney disease (CKD; baseline eGFR <60 mL/minute/1.73 m2 ), 55% converted to EVR within 3 months (early conversion) and 39.4% converted between 4 and 12 months after transplantation (mid-conversion) experienced improvement in eGFR (≥60 mL/minute/1.73 m2 ) at month 36. Only 20.9% and 17.4% among those converted beyond 12 months (late conversion) experienced improvement respectively at month 36 and 60. A logistic regression analysis in patients with CKD stage ≥3 demonstrated that late conversion, age, and female sex were associated with nonimprovement of eGFR (≥60 mL/minute/1.73 m2 ). Data from this real-life use of EVR indicate that renal function was maintained from the preconversion period until month 36 even in patients with advanced CKD. However, early rather than late conversion appears to be a safe approach to preserve longterm renal function in LTRs.

Enhanced Recovery in Liver Transplantation: A Feasibility Study.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) programmes after surgery are effective in reducing length of stay, functional recovery and complication rates in liver surgery (LS) with the indirect advantage of reducing hospitalisation costs. Preoperative comorbidities, challenging surgical procedures and complex post-operative management are the points that liver transplantation (LT) shares with LS. Nevertheless, there is little evidence regarding the feasibility and safety of ERAS programmes in LT. METHODS: We designed a pilot, small-scale, feasibility study to assess the impact on hospital stay, protocol compliance and safety of an ERAS programme tailored for LT. The ERAS arm was compared with a 1:2 match paired control arm with similar characteristics. All patients with MELD <25 were included. A dedicated LT-tailored protocol was derived from publications on ERAS liver surgery. RESULTS: Ten patients were included in the Fast-Trans arm. It was observed a 47% reduction of the total LOS, as compared to the control arm: 9.5 (9.0-10.5) days versus 18.0 (14.3-24.3) days, respectively, p <0.001. The protocol achieved 72.9% compliance. No differences were observed in terms of post-operative complications or readmission rates after discharge between the two arms. Overall, it was observed a reduction of length of stay in ICU and surgical ward in the Fast-Trans arm compared with the control arm. CONCLUSION: Considered the main points in common between LS and LT, this small-scale study suggests that the application of an ERAS programme tailored to the LT setting is feasible. Further testing will be appropriate to generalise these findings.

LCR1 and LCR2, two multi-analyte blood tests to assess liver cancer risk in patients without or with cirrhosis.

BACKGROUND: No blood test has been shown to be effective in the prediction of primary liver cancer in patients without cirrhosis. AIM: To construct and internally validate two sequential tests for early prediction of liver cancer. These tests enable an algorithm which could improve the performance of the standard surveillance protocol recommended (imaging with or without AFP), limited to patients with cirrhosis. METHODS: We performed a retrospective analysis in prospectively collected specimens from an ongoing cohort. We designed an early sensitive high-risk test (LCR1) that combined (using Cox model) hepatoprotective proteins (apolipoproteinA1, haptoglobin) with known risk factors (gender, age, gammaglutamyltranspeptidase), and a marker of fibrosis (alpha2-macroglobulin). To increase the specificity, we then combined (LCR2) these components with alpha-fetoprotein. RESULTS: A total of 9892 patients, 85.9% without cirrhosis, were followed up for 5.9 years [IQR: 4.3-9.4]. LCR1 and LCR2 time-dependent AUROCs were not different in construction and validation randomised subsets. Among 2027 patients with high-LCR1 then high-LCR2, 167 cancers (113 with cirrhosis, 54 without cirrhosis) were detected, that is 12 patients needed to screen one cancer. The negative predictive value was 99.5% (95% CI 99.0-99.7) in the 2026 not screened patients (11 cancers without cirrhosis) higher than the standard surveillance, which detected 113 cancers in 755 patients screened, that is seven patients needed to screen one cancer, but with a lower negative predictive value 98.0% (97.5-98.5; Z = 4.3; P < 0.001) in 3298 not screened patients (42 cancers without cirrhosis). CONCLUSIONS: In patients with chronic liver disease the LCR1 and LCR2 tests identify those with a high risk of liver cancer, including in those without cirrhosis. NCT01927133.

Immunological environment in colorectal cancer: a computer-aided morphometric study of whole slide digital images derived from tissue microarray.

Cancer research has moved from investigating tumour cells to including analysis of the tumour microenvironment as well. The aim of this study was to assess the cellular infiltrate of colorectal cancer (CRC) using computer-aided analysis of whole slide digital image derived from tissue microarray (TMA). TMA slides from 31 CRC patients were immunostained for forkhead box protein 3 (FOXP3) and immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) at four sites: centre (C) and invasive front (F) of the tumour, proximal non-metastatic draining lymph node (N-), tumour-draining lymph node with metastasis (N+) and healthy mucosa at 10 cm from the cancer (M). We analysed the proportion of IDO+ tissue areas in the lamina propria or in the non-epithelial area of the lymph node and in epithelial cells in each site. The normal mucosa of patients operated on for benign disease was also analysed. The proportion (%) of FOXP3+ tissue area in C, F, N-, N+ and M were 2.3 ± 1.8, 2.6 ± 2.9, 6.0 ± 2.9, 14.2 ± 5.8 and 1.2 ± 0.8 (p < 0.001). The proportion (%) of IDO+ tissue area in the lamina propria of C, F, N-, N+ and M were 1.6 ± 3.1, 1.1 ± 1.3, 3.4 ± 2.5, 9.1 ± 8.5 and 6.7 ± 5.4 (p < 0.001). IDO+ tissue area in the lamina propria was not significantly different between healthy mucosa of patients with cancer than without (1.8 ± 3 vs 1.1 ± 0.95). The proportion of IDO positive tissue area in the epithelium was significantly higher in healthy mucosa of patients with cancer than without (5.4 ± 13.8 vs 2.1 ± 2.4). The FOXP3+ tissue area was increased in healthy mucosa of CRC patients in comparison with healthy mucosa of patients with colorectal resection for disease other than cancer: 1.20 ± 1.81 versus 0.81 ± 0.51 (p < 0.05). The proportion of IDO+ tissue area in lymph node (N-) was correlated with the proportion of FOXP3+ tissue area in tumour area (r = 0.44, p < 0.01). TMA technique permits simultaneous analysis of FOXP3+ and IDO+ cells at different sites including tumour, draining non-metastatic lymph node, metastatic lymph node and normal mucosa.

Evolution of platelet functions in cirrhotic patients undergoing liver transplantation: A prospective exploration over a month.

This prospective observational study was designed to analyze platelet functions across time in 50 patients scheduled for liver transplantation (LT) secondary to decompensated cirrhosis or hepatocellular carcinoma. Platelet functions were assessed before LT (pre-LT), one week (D7) and 1 month (D28) after LT. Platelet count significantly increased from pre-LT time to day 28 as well as circulating CD34+hematopoietic stem cells. To avoid any influence of platelet count on assays, platelet function was evaluated on platelet-rich-plasma adjusted to pre-LT platelet count. Although platelet secretion potential did not differ between time-points, as evaluated by the expression of CD62P upon strong activation, platelet aggregation in response to various agonists significantly increased along time, however with no concomitant increase of circulating markers of platelet activation: platelet microvesicles, platelet-leukocyte complexes, soluble CD40L and soluble CD62P. In the multivariate analysis, hepatic function was associated with platelet count and function. A lower platelet aggregation recovery was correlated with Child C score. History of thrombosis or bleeding was associated with respective higher or lower values of platelet aggregation. This longitudinal analysis of platelet functions in LT patients showed an improvement of platelet functions along time together with platelet count increase, with no evidence of platelet hyperactivation at any time-point.

Risk factors for pulmonary complications after hepatic resection: role of intraoperative hemodynamic instability and hepatic ischemia.

BACKGROUND: Postoperative operative pulmonary complications (PPCs) after hepatic surgery are associated with increased length of hospital stays. Intraoperative blood transfusion, extensive resection and different comorbidities have been identified. Other parameters, like time of hepatic ischemia, have neither been clinically studied, though experimental studies show that hepatic ischemia can provide lung injury. The objective of this study was to determinate the risk factors of postoperative pulmonary complications (PPCs) after hepatic resection within 7 postoperative days. METHOD: Ninety-four patients consecutively who underwent elective hepatectomy between January and December 2013. Demographic data, pathological variables, and preoperative, intraoperative, and postoperative variables had been prospectively collected in a data base. The dependant variables studied were the occurrence of PPCs, defined before analysis of the data. RESULTS: PPCs occurred in 32 (34%) patients. A multivariate analysis allowed identifying the risk factors for PPCs. On multivariate analysis, preoperative gamma-glutamyltransferase (GGT) elevation OR =5,12 [1,85-15,69] p = 0,002, liver ischemia duration OR = 1,03 [1,01-1,06] p = 0,01 and the intraoperative use of vasopressor OR = 4,40 [1,58-13,36] p = 0,006 were independently associated with PPCs. For every 10 min added in ischemia duration, the OR of the risk of PPCs was estimated to be 1.37 (CI95% = [1.08-1.81], p = 0.01). CONCLUSION: Three risk factors for PPCs have been identified in a population undergoing liver resection: preoperative GGT elevation, ischemia duration and the intraoperative use of vasopressor. PPCs after liver surgery could be related to lung injury induced by liver ischemia reperfusion and not solely by direct infectious process. That could explain why factors influencing directly or indirectly liver ischemia were independently associated with PPCs.

Rate of employment after liver transplantation in France: a single-centre study.

BACKGROUND: A return to gainful employment is an important outcome parameter after liver transplantation (LT). A recent study in the USA has shown a very high rate of unemployment after LT (75%). To date, there are no available data in France, where the public health insurance programme guarantees financial protection for everyone. AIMS: The aim of this study was to assess the employment rate after LT in a French LT centre and to determine factors associated with employment after LT. METHODS: All patients who had undergone liver transplantation at our centre between January 2000 and April 2011 and who met the following criteria responded to a questionnaire: (i) between 18 and 65 years old at the time of LT, (ii) alive 1 year after LT, (iii) alive, not retired and released from the hospital at the time of survey, (iv) French residents who were affiliated with French national health insurance. RESULTS: A total of 345 LTs were performed in 314 patients during the study period. Of the patients, 109 were excluded from the study: 23 had died within the first year after LT, 28 had died at the time of the survey, three were still in the hospital, seven were living in a foreign country, 11 had retired and 37 were older than 65 years after LT. Two hundred five patients were included in the study. The response rate was 76.6% (157/205). Patients responded a mean 6.1 ± 0.9 years after LT, 77.7% were French nationals, 73.2% were men, and the mean age at LT was 48.8 ± 9.9 years. The aetiologies of liver disease were as follows: alcohol 32.5%, hepatitis C 26.1%, alcohol and hepatitis C 3.8%, hepatitis B 15.3%, biliary cirrhosis 5.1%, autoimmune 2.5% and other causes 14.7%. Two years after LT, 43.3% of patients were employed. The demographic variables associated with post-LT employment were male sex (P<0.001), age under 40 years at LT (P=0.02), a sedentary job (P=0.007), raising children under the age of 18 years at the time of LT (P=0.01), a high level of education (P=0.001), not being affiliated with the French universal health coverage or 'CMU' (P=0.001). Only 53.3% of the patients who did not return to work after LT stated that they felt like they had a physical disability. CONCLUSION: The rate of return to work after LT in France was 43.1%, which was higher than that reported in the US study. However, this rate remains low and policies supporting return to work are needed to help liver recipients who wish to work after LT.

First experience of liver transplantation with type 2 donation after cardiac death in France.

Organ donation after unexpected cardiac death [type 2 donation after cardiac death (DCD)] is currently authorized in France and has been since 2006. Following the Spanish experience, a national protocol was established to perform liver transplantation (LT) with type 2 DCD donors. After the declaration of death, abdominal normothermic oxygenated recirculation was used to perfuse and oxygenate the abdominal organs until harvesting and cold storage. Such grafts were proposed to consenting patients < 65 years old with liver cancer and without any hepatic insufficiency. Between 2010 and 2013, 13 LTs were performed in 3 French centers. Six patients had a rapid and uneventful postoperative recovery. However, primary nonfunction occurred in 3 patients, with each requiring urgent retransplantation, and 4 early allograft dysfunctions were observed. One patient developed a nonanastomotic biliary stricture after 3 months, whereas 8 patients showed no sign of ischemic cholangiopathy at their 1-year follow-up. In comparison with a control group of patients receiving grafts from brain-dead donors (n = 41), donor age and cold ischemia time were significantly lower in the type 2 DCD group. Time spent on the national organ wait list tended to be shorter in the type 2 DCD group: 7.5 months [interquartile range (IQR), 4.0-11.0 months] versus 12.0 months (IQR, 6.8-16.7 months; P = 0.08. The 1-year patient survival rates were similar (85% in the type 2 DCD group versus 93% in the control group), but the 1-year graft survival rate was significantly lower in the type 2 DCD group (69% versus 93%; P = 0.03). In conclusion, to treat borderline hepatocellular carcinoma, LT with type 2 DCD donors is possible as long as strict donor selection is observed.

Nonalcoholic fatty liver disease increases the risk of hepatocellular carcinoma in patients with alcohol-associated cirrhosis awaiting liver transplants.

BACKGROUND & AIMS: Many patients with alcohol-associated cirrhosis also have diabetes, obesity, or insulin resistance-mediated steatosis, but little is known about how these disorders affect the severity of liver disease. We analyzed the prevalence and prognostic implications of metabolic risk factors (MRFs) such as overweight, diabetes, dyslipidemia, and hypertension in patients with alcohol-associated cirrhosis awaiting liver transplants. METHODS: We performed a retrospective study of 110 patients with alcohol-associated cirrhosis (77% male; mean age, 55 y; 71% with >6 mo of abstinence) who received liver transplants at a single center in Paris, France, from 2000 through 2013. We collected data on previous exposure to MRFs, steatosis (>10% in the explant), and histologically confirmed hepatocellular carcinoma (HCC). RESULTS: HCC was detected in explants from 29 patients (26%). Steatosis was detected in explants from 47 patients (70% were abstinent for ≥6 mo); 50% had a history of overweight or type 2 diabetes. Fifty-two patients (47%) had a history of MRFs and therefore were at risk for nonalcoholic fatty liver disease. A higher proportion of patients with MRF had HCC than those without MRF (46% vs 9%; P < .001). A previous history of overweight or type 2 diabetes significantly increased the risk for HCC (odds ratio, 6.23; 95% confidence interval [CI], 2.47-15.76, and odds ratio, 4.63; 95% CI, 1.87-11.47, respectively; P < .001). MRF, but not steatosis, was associated with the development of HCC (odds ratio, 11.76; 95% CI, 2.60-53; P = .001) independent of age, sex, amount of alcohol intake, or severity of liver disease. CONCLUSIONS: Patients with alcohol-associated cirrhosis who received transplants frequently also had nonalcoholic fatty liver disease. MRFs, particularly overweight, obesity, and type 2 diabetes, significantly increase the risk of HCC.

Liver biopsy analysis has a low level of performance for diagnosis of intermediate stages of fibrosis.

BACKGROUND & AIMS: There is controversy about the performance of noninvasive tests such as FibroTest in diagnosing intermediate stages of fibrosis. We investigated whether this controversy results from limitations of biopsy analysis for intermediate-stage fibrosis and inappropriate determination of the standard area under the receiver-operator characteristic curve (AUROC). METHODS: To determine whether biopsy has a lower diagnostic performance for fibrosis stage F2 (few septa) vs F1 (fibrosis without septa), compared with its performance for F1 vs F0 or F4 vs F3, we determined the fibrotic areas of large surgical samples collected from 20 consecutive patients with chronic liver disease or normal liver tissue that surrounded tumors. We analyzed digitized images of 27,869 virtual biopsies of increasing length and also analyzed data from 6500 patients with interpretable FibroTest results who also underwent biopsy analysis. RESULTS: The overall performance of biopsy analysis (by Obuchowski measure) increased with biopsy length from 0.885 for 5-mm to 0.912 for 30-mm samples (P < .0001). The performance of biopsy was lower for the diagnosis of F2 vs F1 samples (weighted AUROC [wAUROC] = 0.505) than for F1 vs F0 (wAUROC = 0.773; 53% difference; P < .0001) or F4 vs F3 (wAUROC = 0.700; 39% difference; P < .0001), even when 30-mm biopsy samples were used. The performance of FibroTest was also lower for the diagnosis of F2 vs F1 samples (wAUROC = 0.512) than for F1 vs F0 samples (wAUROC = 0.626; 22% difference; P < .0001) or F4 vs F3 (wAUROC = 0.628; 23% difference; P < .0001). However, the FibroTest had smaller percentage differences among wAUROC values than biopsy. CONCLUSIONS: Biopsy has a low level of diagnostic performance for fibrosis stages F2 and F1. The recommendation for biopsy analysis, instead of a validated biomarker panel such as FibroTest, for the diagnosis of intermediate stages of fibrosis is therefore misleading.

Thrombocytopenia, splenomegaly, and portal blood flow in patients who have undergone liver transplantation for cirrhosis.

The platelet count (PC), the spleen size (SS), and the portal blood flow (PBF) have been independently studied in the perioperative period after orthotopic liver transplantation (OLT) for cirrhosis, but these parameters have not been described and analyzed in combination. We analyzed PC data and Doppler sonography measurements of SS and PBF from 125 adult patients before OLT and 1, 3, 6, 9, and 12 months after transplantation. A linear mixed model with fixed subject random intercepts was used. PCs increased significantly from 101.5 ± 68.5 × 10(9) /L before OLT to 162.4 ± 86 × 10(9) /L 1 month after OLT and remained stable for 1 year after the operation. PBF increased significantly from 619 ± 239 mL/minute before OLT to 1379 ± 491 mL/minute after OLT and remained stable during the first year. SS slowly decreased after OLT, but the decrease became significant only 9 months after the operation (13.8 ± 4.2 cm before OLT versus 11.7 ± 3.7 cm at 9 months, P < 0.05). The cirrhosis etiology did not influence the evolution of the parameters. With or without replication or interferon treatment before OLT, the hepatitis C group viruses did not influence PCs postoperatively. The evolution of SS was correlated to the evolution of PCs in the year after transplantation. In conclusion, PCs and PBF increase rapidly after OLT, whereas SS slowly decreases. The cirrhosis etiology does not influence the evolution of PCs. Thrombocytopenia and splenomegaly are 2 results of portal hypertension, but the rapid normalization of PBF does not completely or rapidly reverse these 2 phenomena.

Extracorporeal membrane oxygenation as a bridge to liver transplantation for acute respiratory distress syndrome-induced life-threatening hypoxaemia aggravated by hepatopulmonary syndrome.

INTRODUCTION: Combined with massive lung aeration loss resulting from acute respiratory distress syndrome, hepatopulmonary syndrome, a liver-induced vascular lung disorder characterized by diffuse or localized dilated pulmonary capillaries, may induce hypoxaemia and death in patients with end-stage liver disease. METHODS: The case of such a patient presenting with both disorders and in whom an extracorporeal membrane oxygenation was used is described. RESULTS: A 51-year-old man with a five-year history of alcoholic cirrhosis was admitted for acute respiratory failure, platypnoea and severe hypoxaemia requiring emergency tracheal intubation. Following mechanical ventilation, hypoxaemia remained refractory to positive end-expiratory pressure, 100% of inspired oxygen and inhaled nitric oxide. Two-dimensional contrast-enhanced (agitated saline) transthoracic echocardiography disclosed a massive right-to-left extracardiac shunt, without patent foramen ovale. Contrast computed tomography (CT) of the thorax using quantitative analysis and colour encoding system established the diagnosis of acute respiratory distress syndrome aggravated by hepatopulmonary syndrome. According to the severity of the respiratory condition, a veno-venous extracorporeal membrane oxygenation was implemented and the patient was listed for emergency liver transplantation. Orthotopic liver transplantation was performed at Day 13. At the end of the surgical procedure, the improvement in oxygenation allowed removal of extracorporeal membrane oxygenation (Day 5). The patient was discharged from hospital at Day 48. Three months after hospital discharge, the patient recovered a correct physical autonomy status without supplemental O2. CONCLUSIONS: In a cirrhotic patient, acute respiratory distress syndrome was aggravated by hepatopulmonary syndrome causing life-threatening hypoxaemia not controlled by standard supportive measures. The use of extracorporeal membrane oxygenation, by controlling gas exchange, allowed the performing of a successful liver transplantation and final recovery.

Intractable ascites without mechanical vascular obstruction after orthotopic liver transplantation: etiology and clinical outcome of sinusoidal obstruction syndrome.

Intractable ascites after orthotopic liver transplantation (OLT) is a relatively rare complication. However, it often takes a life threatening course, which requires re-transplantation. In previous studies, several reports gave hepatic sinusoidal obstruction syndrome (SOS) as one of the causes of refractory ascites. However, the detailed etiology of SOS after OLT and its association with clinical consequences remain unclear because there have been few studies to date. We report two recent cases with rapidly progressive refractory ascites associated with SOS, following completely different clinical courses. In case 1, the first episode of acute allograft rejection triggered SOS and subsequent intractable ascites, while the second acute rejection worsened his clinical status. A transjugular intrahepatic portosystemic stent-shunt (TIPS) was placed and this procedure resulted in complete disappearance of ascites and of renal dysfunction. In contrast, refractory ascites in case 2, who had neither rejection nor mechanical outlet obstruction, worsened despite TIPS stent placement, and re-transplantation was necessary. We speculate that the pre-existing diseased liver of the cadaver donor caused this serious complication, necessitating a second graft.

Procalcitonin in liver transplantation: are high levels due to donors or recipients?

INTRODUCTION: To date, a specific marker to evaluate and predict the clinical course or complication of the liver-transplanted patient is not available in clinical practice. Increased procalcitonin (PCT) levels have been found in infectious inflammation; poor organ perfusion and high PCT levels in the cardiac donor appeared to predict early graft failure. We evaluated PCT as a predictor of early graft dysfunction and postoperative complications. METHODS: PCT serum concentrations were measured in samples collected before organ retrieval from 67 consecutive brain-dead donors and in corresponding recipients from day 0, before liver transplantation, up to day 7 after liver transplantation. The following parameters were recorded in donors: amount of vasopressive drug doses, cardiac arrest history 24 hours before retrieval, number of days in the intensive care unit, age of donor, and infection in donor, and the following parameters were recorded in recipients: cold and warm ischemia time, veno-venous bypass, transfusion amount during orthotopic liver transplantation (OLT), and occurrence of postoperative complication or hepatic dysfunction. RESULTS: In the donor, the preoperative level of PCT was associated with cardiac arrest and high doses of catecholamines before organ retrieval. In the recipient, elevated PCT levels were observed early after OLT, with a peak at day 1 or 2 after OLT, then a decrease until day 7. A postoperative peak of PCT levels was associated neither with preoperative PCT levels in the donor or the recipients nor with hepatic post-OLT dysfunction or other postoperative complications, but with two donor parameters: infection and cardiac arrest. CONCLUSION: PCT level in the donor and early PCT peak in the recipient are not predictive of post-OLT hepatic dysfunction or other complications. Cardiac arrest and infection in the donor, but not PCT level in the donor, are associated with high post-OLT PCT levels in the recipient.

Comparison of silver-impregnated with standard multi-lumen central venous catheters in critically ill patients.

OBJECTIVES: To evaluate a new silver-impregnated multi-lumen central venous catheter for reducing catheter-related colonization in intensive care patients. DESIGN: Multicenter, prospective, randomized, controlled clinical study. SETTING: Ten adult intensive care units (multidisciplinary, medical and surgical, university and nonuniversity hospitals) in eight institutions. PATIENTS: A total of 577 patients who required 617 multi-lumen central venous catheters between November 2002 and April 2004 were studied. INTERVENTIONS: Intensive care adult patients requiring multi-lumen central venous catheters expected to remain in place for >or=3 days were randomly assigned to undergo insertion of silver-impregnated catheters (silver group) or standard catheters (standard group). Catheter colonization was defined as the growth of >or=1,000 colony-forming units in culture of the intravascular tip of the catheter by the vortexing method. Diagnosis of catheter-related infection was performed by an independent and blinded expert committee. RESULTS: A total of 320 catheters were studied in the silver group and 297 in the standard group. Characteristics of the patients, insertion site, duration of catheterization (median, 11 vs. 10 days), and other risk factors for infection were similar in the two groups. Colonization of the catheter occurred in 47 (14.7%) vs. 36 (12.1%) catheters in the silver and the standard groups (p = .35), for an incidence of 11.2 and 9.4 per 1,000 catheter days, respectively. Catheter-related bloodstream infection was recorded in eight (2.5%) vs. eight (2.7%) catheters in the silver and the standard groups (p = .88), for an incidence of 1.9 and 2.1 per 1,000 catheter days, respectively. CONCLUSION: The use of silver-impregnated multi-lumen catheters in adult intensive care patients is not associated with a lower rate of colonization than the use of standard multi-lumen catheters.

Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy. METHODS: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities. RESULTS: The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04). CONCLUSIONS: Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.