TICACOS international: A multi-center, randomized, prospective controlled study comparing tight calorie control versus Liberal calorie administration study.

Since the first TICACOS study, 3 additional studies have been published comparing a medical nutrition therapy guided by indirect calorimetry to a regimen prescribed on the basis of predictive equations. A recent guidelines document included a meta-analysis including these 4 papers and found a trend for improvement (OR 0.98-1.48) in favor of medical nutrition therapy guided by indirect calorimetry in terms of survival. The aim of our study was to perform a multicenter prospective, randomized, controlled non blinded study in critically patients to assess the added value for measuring daily resting energy expenditure as a guide for nutritional support. The primary objective was to decrease infectious rate of these critically ill patients. MATERIAL AND METHODS: This phase III, multi-center, randomized, controlled non blinded study was planned to include 580 newly-admitted, adult ventilated ICU patients that were planned to stay more than 48 h in the ICU departments. The nutritional support was aimed to meet 80-100% of energy requirement measured by indirect calorimetry. The calorie needs were determined by IC in the Study group and by an equation (20-25 kcal/kg ideal body weight/day) in the Control Group. The ICU staff was trained to strive to supply 80-100% of a patient's energy requirements through artificial nutrition, preferably enteral feeding. Primary endpoint was infection rate and secondary endpoints included other morbidities and mortality during ICU, at 90 and 180 days. Comparison between the study and the control group was performed using T test for equality of means (independent samples test). Correlations were performed using the Pearson correlation test. A p level of 0.05 or below was considered as significant. Cross tabs procedure used Chi-square test for testing differences in complication rates, length of stay and length of ventilation. Correlations between energy balances and complications was also be tested using one way analysis as well as ANOVA analysis between groups and within groups. Kaplan Meir curves assessed the proportion of surviving patients in the 2 groups. RESULTS: Seven centers with a calorimeter available participated to the study. Due to slow inclusion rate, the study was stopped after 6 years and after inclusion of 417 patients only. From the 417 intended to treat patients, 339 followed the protocol. There was no differences between control and study groups in terms of age, sex BMI, SOFA (7.1 ± 3.1 vs 7.4 ± 3.3) and APACHE II scores (22.4 ± 7.9 vs 22.2 ± 7.4). The rate of infection (40 vs 31), including pneumonia rate, need for surgery, dialysis requirement, length of ventilation, ICU length of stay, and hospital length of stay were not different between groups. Mortality (30 in the control vs 21 in the study group) was not significantly different between groups. The decreased mortality observed in the study group when added to previous studies may have a positive effect on the meta-analysis previously published. CONCLUSION: Tight Calorie Control guided by indirect calorimetry decreased the rate of infection and mortality but not significantly. This may be explained by the not relatively small sample size. There results together with the previous 4 prospective randomized studies, may improve the results of the meta-analysis exploring the effects of IC guided nutrition on mortality.

Toll-like receptor 4 modulation as a strategy to treat sepsis.

Despite a decrease in mortality over the last decade, sepsis remains the tenth leading causes of death in western countries and one of the most common cause of death in intensive care units. The recent discovery of Toll-like receptors and their downstream signalling pathways allowed us to better understand the pathophysiology of sepsis-related disorders. Particular attention has been paid to Toll-like receptor 4, the receptor for Gram-negative bacteria outer membrane lipopolysaccharide or endotoxin. Since most of the clinical trial targeting single inflammatory cytokine in the treatment of sepsis failed, therapeutic targeting of Toll-like receptor 4, because of its central role, looks promising. The purpose of this paper is to focus on the recent data of various drugs targeting TLR4 expression and pathway and their potential role as adjunctive therapy in severe sepsis and septic shock.

Color Doppler sonography of small bowel wall changes in 21 consecutive cases of acute mesenteric ischemia.

AIM OF THE STUDY: To describe the small bowel wall changes observed with color Doppler sonography in acute mesenteric ischemia with comparison with its outcome. MATERIAL AND METHODS: We reviewed the sonographic findings of 21 patients with a final diagnosis of acute mesenteric ischemia (12 acute arterial forms and 9 acute venous forms). These examinations included identification of non peristaltic thin-walled fluid-filled intestinal loops (with or without pneumatosis), thickened intestinal wall (> 3 mm) (noted as stratified or not), and preserved or absent mural flow assessed with color Doppler. Sonographic findings were compared with the surgical data (n = 16) or with the clinical outcome (n = 5). RESULTS: In acute arterial ischemia, non-peristaltic thin-walled intestinal loops were detected with sonography in five cases, with visualization of pneumatosis in one. Bowel infarction was diagnosed in four of these five patients including one patient with pneumatosis. Thickened bowel loops were sonographically detected in four cases, of which 3 required resection. Conservative therapy was performed in the remaining case having preserved wall stratification and mural flow with color Doppler. In acute venous ischemia, thickened bowel loops were detected with sonography in six cases. Conservative therapy was performed in three cases for whom preserved mural flow was noted. Stratification was present in two of these three cases. CONCLUSION: In acute arterial ischemia, intestinal resection is frequently required when non-peristaltic, thin-walled, fluid-filled loops are detected with sonography. In arterial and venous ischemia, absence of wall stratification and mural flow are frequently associated with ischemia requiring surgery.

90-day follow-up of patients treated with Drotrecogin Alfa (activated) for severe sepsis: a Belgian open label study.

INTRODUCTION: Severe sepsis is the major cause of mortality in intensive care units (ICUs). The BOOST study (= B (Belgian) OO (Open Label) ST (Study)) is a Belgian open-label trial designed to pragmatically assess the safety and efficacy of Drotrecogin Alfa (activated) (DAA), the only registered treatment in this indication with favourable ratio benefit/risk. METHODOLOGY: Adult patients with severe sepsis and 2 or more sepsis-induced organ dysfunctions (OD) within the 48-hour period preceding the treatment (DAA at 24 microg/kg/h for 96 hours), were included between January 2003 and October 2003. Platelet count < 30 000/mm3 and increased risk for bleeding were exclusion criteria. Mortality and location were evaluated at 28 and 90 days. RESULTS: Of the 100 included patients, 97 (median age: 66 years; men/women: 57/40) were treated and completed the study. The predominant infection sites were lung (49%) and abdomen (29%) and 35% had had recent surgery. The mean and median numbers of OD were 3.4 and 3.0, respectively, and most patients (80 %; 77/97) had 3 or more organ failures at baseline, predominantly respiratory (95%) and cardiovascular (87%). The mean APACHE II score was 25.3 (range: 6-53). The 28-day mortality rate was 32.0% (90% CI: 24.2-39.7) and increased with the number of OD: from 15% (1.9-28.1) for2 ODs, to 71% (52.4-88.8) for 5 ODs. At day 28, the 66 surviving patients were located in general ward (35%), in the ICU (32%) or at home (30%). The 90-day mortality rate was 42% (90% CI: 34.0-50.5), with most of the survivors (73%) staying at home. Eight serious adverse events, including 4 bleedings, were reported between study days 2 and 5, in 5 patients (5.2%) and led to death in 2 patients (2.1%). CONCLUSION: Despite a higher severity of illness at baseline, this phase IV open-label long-term study in Belgian ICUs shows consistent results with previous studies with DAA. Importantly, most of the surviving patients at day 90 were staying at home.

Current surgical management of acute pancreatitis.

BACKGROUND: About 20% of the patients with acute pancreatitis may run a rapidly progressive or fulminant course resulting in the multiple organ dysfunction syndrome with or without accompanying sepsis. In this subset of patients, the mortality rate still ranges from less than 10% with sterile to over 30% with infected pancreatic necrosis. The goal of this review is to assess the available treatment strategies to allow the development of a formalized surgical approach to those patients. METHODS: A literature review of management of acute pancreatitis. RESULTS AND CONCLUSION: Over the past 20 years, there has been a substantial change in the surgical management of severe acute pancreatitis. This change has been away from a preventive surgery based on early major interventions towards a surgery of complications based increasingly on less aggressive options that take place at a later stage of the attack with specific criteria governing the timing of surgical therapy. Non-surgical options remain more than ever the cornerstone of management in many of these patients.

Antimicrobial therapy for intra-abdominal infections: guidelines from the Infectious Disease Advisory Board (IDAB).

Intra-abdominal infection is a common cause of severe sepsis in a hospital setting and remains associated with a significant morbidity, mortality and resource use. Early adequate surgery or drainage remain the cornerstones of intra-abdominal infection management and impact on patients outcome. Concomitant early and adequate empiric antimicrobial therapy further influences patients morbidity and mortality. Multiple empirical regimens have been proposed in this setting, but rarely supported by well designed, randomized-controlled studies. The current manuscript summarizes the recommendations of the Infection Disease Advisory Board on the management of intra-abdominal infections. Empiric antimicrobial therapy for the most common causes of abdominal infections is proposed. In addition, particular attention has been paid on antibiotic treatment duration.

Focal bowel wall changes detected with colour Doppler ultrasound: diagnostic value in acute non-diverticular diseases of the colon.

We performed a study to determine if colour Doppler findings may help to identify the cause of wall thickening in acute non-diverticular diseases of the colon. The study group included 66 patients admitted to the emergency department with a final diagnosis of infectious colitis (n=23), inflammatory colitis (n=10), ischaemic colitis (n=23) and malignant tumours (n=10). The following ultrasound features were assessed: maximal wall thickness, wall stratification, arterial flow in the colonic wall and arteriolar resistive index. Higher values of wall thickness were observed in malignant tumour (18.2+/-6.2 mm, p<0.001). Moderately thickened wall (6.6+/-1.3 mm, p< or =0.06), preserved stratification (90% versus 46% in the remainder of the study population) and lower resistive index (0.51+/-0.10, p< or =0.05) were significantly related to inflammatory colitis. Absence of arterial flow was more frequently observed in ischaemia (43% versus 12% in the remainder of the study population). In conclusion, despite some overlap, both ultrasound and colour Doppler features are helpful in the differential diagnosis of colonic thickening related to non-diverticular colonic lesions.

Adult liver transplantation at UCL: update 2002.

The authors present the results of a single centre study of 587 liver transplants performed in 522 adults during the period 1984-2002. Results have improved significantly over time due to better pre-, peri- and post-transplant care. One, five, ten and fifteen year actuarial survivals for the whole patient group are 81.2; 69.8; 58.9 and 51.2%. The high incidence of de novo tumors (12.3%), of cardiovascular diseases (7.5%) and of end-stage renal function (3.6%) should be further incentives to tailor the immunosuppression to the individual patient and to direct the attention of the transplant physician to the long-term quality of life of the liver recipient.

Early multi-system organ failure associated with acute pancreatitis: a plea for a conservative therapeutic strategy.

The mortality of severe acute pancreatitis still ranges between 10 and 20%. Nowadays, infected pancreatic necrosis is the leading cause of death. Despite advances in intensive care therapy, however, early and worsening multi-system organ failure remains a source of substantial morbidity and still accounts for 20 to 50% of the deaths. In recent years, the systemic inflammatory response syndrome and the relevant cascades of inflammatory mediators have been implicated as the key factor in the emergence of remote tissue damage. Early multi-system organ failure that supervenes in the first week is typically associated with a sterile necrotizing process. There are no pathophysiological, clinical or economical data to support the practice of debridement of sterile necrosis to prevent or to control early multi-system organ failure. This issue has never been addressed in a controlled study. Besides intensive care support, non-surgical therapeutic modalities including urgent endoscopic sphincterotomy for impacted stones, antibiotic prophylaxis for the prevention of pancreatic infection and early jejunal nutrition have been specifically developed hopefully to attenuate multiple organ failure, to obviate the need of surgical drainage and to improve survival. Fine needle aspiration of necrotic areas must be incorporated in any conservative therapeutic strategy in order to identify and not to jeopardize those with infected necrosis that remains an absolute indication for drainage. A specific treatment of acute pancreatitis is still lacking, so far. However, there is ample experimental and pathophysiological evidence in favour of immunomodulatory therapy in severe acute pancreatitis. The administration of one or several antagonists of inflammatory mediators possibly combined with a protease inhibitor may at last provide the opportunity to interfere with the two major determinants of prognosis: the severity of multiple organ failure and the extent of necrotic areas that creates the culture medium for bacterial superinfection. These benefits remain to be substantiated in a controlled study, however.

Skeletonizing en bloc esophagectomy for cancer.

OBJECTIVE: To evaluate the long-term outcome of patients with esophageal cancer after resection of the extraesophageal component of the neoplastic process en bloc with the esophageal tube. SUMMARY BACKGROUND DATA: Opinions are conflicting about the addition of extended resection of locoregional lymph nodes and soft tissue to removal of the esophageal tube. METHODS: Esophagectomy performed en bloc with locoregional lymph nodes and resulting in a real skeletonization of the nonresectable anatomical structures adjacent to the esophagus was attempted in 324 patients. The esophagus was removed using a right thoracic (n = 208), transdiaphragmatic (n = 39), or left thoracic (n = 77) approach. Lymphadenectomy was performed in the upper abdomen and lower mediastinum in all patients. It was extended over the upper mediastinum when a right thoracic approach was used and up to the neck in 17 patients. Esophagectomy was carried out flush with the esophageal wall as soon as it became obvious that a macroscopically complete resection was not feasible. Neoplastic processes were classified according to completeness of the resection, depth of wall penetration, and lymph node involvement. RESULTS: Skeletonizing en bloc esophagectomy was feasible in 235 of the 324 patients (73%). The 5-year survival rate, including in-hospital deaths (5%), was 35% (324 patients); it was 64% in the 117 patients with an intramural neoplastic process versus 19% in the 207 patients having neoplastic tissue outside the esophageal wall or surgical margins (P <.0001). The latter 19% represented 12% of the whole series. The 5-year survival rate after skeletonizing en bloc esophagectomy was 49% (235 patients), 49% for squamous cell versus 47% for glandular carcinomas (P =.4599), 64% for patients with an intramural tumor versus 34% for those with extraesophageal neoplastic tissue (P <.0001), and 43% for patients with fewer than five metastatic nodes versus 11% for those with involvement of five or more lymph nodes (P =.0001). CONCLUSIONS: The strategy of attempting skeletonizing en bloc esophagectomy in all patients offers long-term survival to one third of the patients with resectable extraesophageal neoplastic tissues. These patients represent 12% of the patients with esophageal cancer suitable for esophagectomy and 19% of those having neoplastic tissue outside the esophageal wall or surgical margins.

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients.

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.

Efficacy and safety of recombinant human activated protein C for severe sepsis.

BACKGROUND: Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a previous study, drotrecogin alfa activated produced dose-dependent reductions in the levels of markers of coagulation and inflammation in patients with severe sepsis. In this phase 3 trial, we assessed whether treatment with drotrecogin alfa activated reduced the rate of death from any cause among patients with severe sepsis. METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter trial. Patients with systemic inflammation and organ failure due to acute infection were enrolled and assigned to receive an intravenous infusion of either placebo or drotrecogin alfa activated (24 microg per kilogram of body weight per hour) for a total duration of 96 hours. The prospectively defined primary end point was death from any cause and was assessed 28 days after the start of the infusion. Patients were monitored for adverse events; changes in vital signs, laboratory variables, and the results of microbiologic cultures; and the development of neutralizing antibodies against activated protein C. RESULTS: A total of 1690 randomized patients were treated (840 in the placebo group and 850 in the drotrecogin alfa activated group). The mortality rate was 30.8 percent in the placebo group and 24.7 percent in the drotrecogin alfa activated group. On the basis of the prospectively defined primary analysis, treatment with drotrecogin alfa activated was associated with a reduction in the relative risk of death of 19.4 percent (95 percent confidence interval, 6.6 to 30.5) and an absolute reduction in the risk of death of 6.1 percent (P=0.005). The incidence of serious bleeding was higher in the drotrecogin alfa activated group than in the placebo group (3.5 percent vs. 2.0 percent, P=0.06). CONCLUSIONS: Treatment with drotrecogin alfa activated significantly reduces mortality in patients with severe sepsis and may be associated with an increased risk of bleeding.

Adult liver transplantation and steroid-azathioprine withdrawal in cyclosporine (Sandimmun)-based immunosuppression - 5 year results of a prospective study.

New immunosuppressants are said to be superior to cyclosporine due to their higher incidence of steroid sparing and to the reduced incidence of side-effects. From May 1992 to February 1995, 79 adults underwent primary liver transplantation using cyclosporine A (Sandimmun)-based triple drug immunosuppression. Nine patients who died early after liver transplantation due to reasons unrelated to immunological problems were excluded from this analysis. The long-term outcome of the remaining 70 patients was prospectively studied in relation to steroid and azathioprine withdrawal. They were re-evaluated 6-monthly in relation to liver and kidney function; cholesterolemia, infection, de novo diabetes mellitus and arterial hypertension, malignancy, ophthalmological and osteomuscular diseases. In case of rejection occurring during or after steroid tapering, patients were switched, by protocol, to tacrolimus therapy. Median follow-up was 81 months (range 60-96). Forty-four patients (62.8 %) were biopsied 5 years after transplant; 20 patients (28.6 %) were biopsied at a median follow-up of 32 months (range 7.8-47). Six patients (8.6 %) who refused biopsies more than 1 year after liver transplantation had normal liver values throughout the whole follow-up period. Five-year actual patient and graft survivals were 75 % and 65.8 %, respectively, for the whole group (n = 79) and 85.7 % and 74.3 % for the studied group (n = 70). Steroids could be withdrawn in all but two patients (97.1 %) at a median time of 7 months (range 3-42). Steroids were restarted in six patients (8.6 %) for extrahepatic reasons. Freedom from steroids was thus observed in 62 patients (88.6 %). Seven patients (10 %) had rejection after steroid tapering; six were switched to tacrolimus. Two patients (2.9 %) needed retransplantation because of acute and chronic rejection whilst still being on full immunosuppression. In total, three patients (4.3 %) had histological signs of chronic rejection during follow-up. At 5 years post-transplant, 66.6 % and 13.3 % of the 60 patients at risk were on cyclosporine and tacrolimus monotherapy, respectively; 93.3 % were steroid-free. Mean creatinine and cholesterol levels were 1.56 +/- 1.3 mg/dl and 193.5 +/- 56.6 mg/dl; incidences of de novo arterial hypertension, insulin dependent diabetes mellitus were 26.6 % and 13.3 %. Two patients (2.8 %) developed post-transplant lymphoproliferative disease, two (2.8 %) had skin cancer. Cyclosporine-based immunosuppression allows safe steroid withdrawal in most patients and cyclosporine monotherapy can be achieved in two-thirds without compromising graft and patient survival. Results of new immunosuppressive strategies should be approached with caution, especially when considering steroid sparing and the incidence of side-effects.

Prognosis of ischemic colitis: comparison of color doppler sonography with early clinical and laboratory findings.

OBJECTIVE: The objective of this study was to compare the value of color Doppler sonography with early clinical and laboratory findings in determining the prognosis of patients with ischemic colitis. SUBJECTS AND METHODS: We reviewed the early clinical, laboratory, and color Doppler sonographic data of 24 patients with ischemic colitis. The patients were divided into two groups on the basis of their outcome. The first group comprised the patients with transient ischemia who recovered uneventfully, and the second group included the patients who needed surgery because of symptomatic transmural colic gangrene or colic stricture. Clinical data and laboratory values were compared with color Doppler sonographic findings including colic wall thickness, presence of stratification, and arterial flow in the bowel wall. RESULTS: At univariate analysis, increased age (p = 0.007), leukocyte count (p = 0.030), lactate dehydrogenase level (p = 0.030), blood lactate level (p = 0.041), and absence of vascular flow in the colic wall (p<0.001) were significantly related to complicated ischemic colitis. At multivariate analysis, absence of arterial flow was the only significant predictor of complicated ischemic colitis (p = 0.002), with a sensitivity of 82%, a specificity of 92%, a positive predictive value of 90%, and a negative predictive value of 86%. CONCLUSION: Absence of arterial flow in the wall of the ischemic colon on initial color Doppler sonography is suggestive of an unfavorable outcome and is more closely associated with outcome than early clinical and laboratory findings.

Ornipressin (Por 8): An efficient alternative to counteract hypotension during combined general/epidural anesthesia.

UNLABELLED: We sought to evaluate the efficacy and side effect profile of a small dose of ornipressin, a vasopressin agonist specific for the V1 receptor, administered to reverse the hypotension associated with combined general/epidural anesthesia. A total of 60 patients undergoing intestinal surgery were studied. After the induction of anesthesia, 7-8 mL of bupivacaine 0.5% with 2 microg/kg clonidine and 0.05 microg/kg sufentanil after an infusion of 5 mL of bupivacaine 0.06% with 0.5 microg x kg(-1) x h(-1) clonidine and 0.1 microg/h of sufentanil were administered by an epidural catheter placed at T7-8 vertebral interspace. When 20% reduction of baseline arterial blood pressure developed, patients were randomly assigned to receive, in a double-blinded design, dopamine started at 2 microg x kg(-1) x min(-1), norepinephrine started at 0.04 microg x kg(-1) x min(-1), or ornipressin started at 1 IU/h. Fifteen patients presenting without hypotension were used as control subjects. Beside routine monitoring, S-T segment analysis, arterial lactacidemia, and gastric tonometry were performed. Ornipressin restored arterial blood pressure after 8 +/- 2 vs 7 +/- 3 min in the norepinephrine group and 11 +/- 3 min in the dopamine group (P < 0.05). This effect was achieved with 2 IU/h of ornipressin in most of the patients (11 of 15). Ornipressin did not induce any modification of the S-T segment; however, it significantly increased intracellular gastric PCO(2) (P < 0.05), indicating splanchnic vasoconstriction. IMPLICATIONS: In the population studied, small-dose ornipressin was effective to restore arterial blood pressure without causing major ischemic side effects.

Conservative treatment of postsurgical lymphatic leaks with somatostatin-14.

Successful management of lymphatic leaks by continuous IV administration of somatostatin was first reported by Ulibarri and coworkers in Spain,(1) and more recently by authors from Italy(2) and Switzerland.(3) The present article reports the clinical history of two patients in whom postsurgical lymphatic leak was successfully treated after the administration of either somatostatin-14 alone (case 1) or combined somatostatin-14 and total parenteral nutrition (TPN; case 2). Although further pathophysiologic studies are needed for the elucidation of its mechanisms of action, somatostatin-14 seems to be an intriguing therapy against postsurgical lymphatic leaks that may make potentially risky transthoracic reoperation unnecessary.

Chylous ascites: diagnosis, causes and treatment.

Chylous ascites is a rare form of ascites and generally associated with a poor outcome since it is often secondary to neoplasms. Its true incidence is not well established in the general medico-surgical population. Any source of lymph vessels obstruction or leakage can potentially cause chylous effusions in the peritoneal or retroperitoneal cavities. Any type of cancer and lymph node involvement may be associated with this uncommon type of ascites. Traumatic, and mainly surgical, vessels leakage is the second most common source of chylous effusions. Other even more rare underlying conditions have been described as leading to chyloperitoneum. Large fluid volume losses together with proteins, and lymphocytes can induce additional morbidity in a previously debilitated population or severely ill patients. This includes organ dysfunction related to volume and electrolytes losses, but mainly secondary infections due to impaired immunity by antibodies and lymphocytes depletion. Even if a vast majority of chylous effusions shall heal spontaneously, early and full treatment has to be initiated in order to reduce morbidity and mortality associated with this condition. Adapted oral diet is to be introduced to reduce lymph flow. Low lipid, high medium-chain triglycerides alimentation is the first measure to implement. Total parenteral nutrition is to be reserved to failures of oral diet. In addition, paracentesis is indicated to improve patient comfort, reduce intra-adbominal pressure and secondary renal dysfunction. Somatostatin analogues have been demonstrated to be effective in reducing lymphorragia and may be proposed prior to consider the surgical approach. Direct lymph vessels ligation can be indicated for large lymph vessels leakage demonstrated by radiologic techniques and when medical treatment has failed. Peritoneo-venous shunt becomes a less common technique in refractory chylous effusion because of its high morbidity. Herein, the other causes of chylous effusions are reviewed as the diagnostic procedures. A treatment algorythm is proposed.

Adult liver transplantation: the Université Catholique de Louvain experience.

Liver transplantation remains a formidable surgical and medical procedure. The larger single centre experience confirms that standardization of perioperative care and simplification of the surgical procedure markedly improve results. Further efforts must be made in relation to immunosuppressive therapy in order to minimize late morbidity and mortality.

Adult hepatic retransplantation. UCL experience.

INTRODUCTION: Retransplantation is a rescue operation in orthotopic liver transplantation. Its appropriateness has been questioned on medical, economical and also on ethical grounds. MATERIAL AND METHODS: During the period february 1984-december 1997, 54 (14.5%) of 372 adult patients were retransplanted; three (0.8%) of them had two retransplantations. Indications were graft dysfunction [(primary non function (8x) and early dysfunction (14x in 13 patients)], immunological failure [acute (9x in 8 patients) and chronic (9x) rejection], technical failure [(hepatic artery thrombosis (5x in four patients), allograft decapsulation (1x), ischaemic biliary tract lesions (6x)] and recurrent viral allograft disease [HBV (4x) and HCV (1x)]. RESULTS: Five year actuarial patient survival after retransplantation was 70.8%, which was identical to this of non retransplanted patients (72%). Early (< 3 mo) mortality was significantly lower in elective procedures (9.1%--2/22 pat. vs 34.4%--11/32 pat. in urgent procedures--p < 0.05). Mortality was highest in the graft dysfunction (23.8%, 5/21 pat.) and immunological failure (41%, 7/17 pat.) groups. Five of six patients retransplanted for rejection, whilst being on renal support, and two of three patients retransplanted urgently twice died of infectious complications. All patients retransplanted because of recurrent allograft disease were long-term (> 3 mo) survivors. Both HBV-infected patients died of allograft reinfection 7 months later; the two HBV-Delta infected patients were, free of infection, 44 and 6 months after retransplantation under HBV-immunoprophylaxis. Length of hospitalisation after primary transplantation and retransplantation were identical (median of 16 days--range 11 to 40 vs 14 days (range 7 to 110). Economical study during the period 1990-1995 showed that costs of the first hospitalization of primary transplantation and of retransplantation could be equalized during the period 1994-1995 as a consequence of the more frequent use of elective retransplantation (median 1.3 million BF, range 720,988 to 8,887,145 vs 1.1 million BF, range 943,685 to 1,940,409). CONCLUSIONS: Hepatic retransplantation is a successful safety net for many liver transplant patients. Every effort should be made to do this intervention electively under minimal immunosuppression. In case of immunological graft failure and hepatic artery thrombosis retransplantation must be done early in order to avoid infectious complications; the same holds for ischaemic biliary tract lesions which cannot be cured by interventional radiology. Retransplantation for recurrent benign disease should be restricted to those diseases which can be effectively treated by (neo- and) adjuvant antiviral therapy.

Adult liver transplantation: UCL experience.

OBJECTIVE: To evaluate the impact of standardized operative and peri-operative care on the outcome of liver transplantation in a single center series of 395 adult patients. METHOD AND MATERIAL: Between February 1984 and December 31, 1998, 451 orthotopic liver transplantations were performed in 395 adult patients (> or = 15 years) at the University Hospitals St-Luc in Brussels. Morbidity and mortality of the periods 1984-1990 (Gr I--174 pat.) and 1991-1998 were compared (Gr II--221 pat.). During the second period anti-infectious chemotherapy and perioperative care were standardized and surgical technique changed from classical orthotopic liver transplantation with recipients' vena cava resection (and use of veno-venous bypass) towards liver implantation with preservation of the vena cava (without use of bypass). Immunosuppression was cyclosporine based from 1984 up to 1996 and tacrolimus based during the years 1997 and 1998. Immunosuppression was alleviated during the second period due to change from quadruple to triple and even double therapy and due to the introduction of low steroid dosing and of steroid withdrawal, once stable graft function was obtained. Indications for liver grafting were chronic liver disease (284 pat--71.9%), hepatobiliary tumor (52 pat--13.2%), acute liver failure (40 pat--10.1%) and metabolic disease (19 pat--4.8%). Regrafting was necessary because of graft dysfunction (21 pat), technical failure (12 pat), immunological failure (18 pat) and recurrent viral allograft disease (5 pat); three of these patients were regrafted at another institution. Follow-up was complete for all patients with a minimum of 9 months. RESULTS: Actuarial 1, 5 and 10 years survival rates for the whole group were 77.9%, 65.7% and 58.3%. These survival rates were respectively 77.3%, 69.7%, 62.5% and 73.2%, 59.6% 51.4% for benign chronic liver disease and acute liver failure; those for malignant liver disease were 80.6%, 44.3% and 36.7%. Early (< 3 months) and late (> 3 months) posttransplant mortalities were. 14.4% (57 pat) and 21.2% (84 pat). Early mortality lowered from 20% in Gr I to 9.4% in Gr II (p < 0.02); this was due to a significant reduction during the second period of bacterial (99/174 pat.--56.9% vs 82/221 pat.--37.1%), fungal (14 pat.--8% vs 7 pat.--3.2%) and viral (87 pat.--50% vs 49 pat.--22.2%) infections (p < 0.05) as well as of perioperative bleeding (92 pat.--52.9% vs 39 pat.--17.6%--p < 0.001). Late mortality remained almost identical throughout the two periods as lethal outcome was mainly caused by recurrent allograft diseases, cardiovascular and tumor problems. Morbidity in these series was important considering that almost, half of the patients had a technical complication, mostly related to bleeding (131 pat--33.2%) and biliary problems (66 pat--16.7%). Retransplantation index was 1.1 (54 pat.--14%). Early retransplantation mortality was 24%; it lowered, although not yet significantly, during the second period (8/25 pat.--32% vs. 5/29 pat.--17.2%). CONCLUSION: Despite a marked improvement of results, liver transplantation remains a major medical and surgical undertaking. Standardization of operative and perioperative care, less haemorraghic surgery and less aggressive immunosuppression are the keys for further improvement.