Portal vein embolization before right hepatectomy: prospective clinical trial.

OBJECTIVE: To assess the impact of liver hypertrophy of the future liver remnant volume (FLR) induced by preoperative portal vein embolization (PVE) on the immediate postoperative complications after a standardized major liver resection. SUMMARY BACKGROUND DATA: PVE is usually indicated when FLR is estimated to be too small for major liver resection. However, few data exist regarding the exact quantification of sufficient minimal functional hepatic volume required to avoid postoperative complications in both patients with or without chronic liver disease. METHODS: All consecutive patients in whom an elective right hepatectomy was feasible and who fulfilled the inclusion and exclusion criteria between 1998 and 2000 were assigned to have alternatively either immediate surgery or surgery after PVE. Among 55 patients (25 liver metastases, 2 cholangiocarcinoma, and 28 hepatocellular carcinoma), 28 underwent right hepatectomy after PVE and 27 underwent immediate surgery. Twenty-eight patients had chronic liver disease. FLR and estimated rate of functional future liver remnant (%FFLR) volumes were assessed by computed tomography. RESULTS: The mean increase of FLR and %FFLR 4 to 8 weeks after PVE were respectively 44 +/- 19% and 16 +/- 7% for patients with normal liver and 35 +/- 28% and 9 +/- 3% for those with chronic liver disease. All patients with normal liver and 86% with chronic liver disease experienced hypertrophy after PVE. The postoperative course of patients with normal liver who underwent PVE before right hepatectomy was similar to those with immediate surgery. In contrast, PVE in patients with chronic liver disease significantly decreased the incidence of postoperative complications as well as the intensive care unit stay and total hospital stay after right hepatectomy. CONCLUSIONS: Before elective right hepatectomy, the hypertrophy of FLR induced by PVE had no beneficial effect on the postoperative course in patients with normal liver. In contrast, in patients with chronic liver disease, the hypertrophy of the FLR induced by PVE decreased significantly the rate of postoperative complications.

Subclinical hyperthyroidism and the risk of coronary heart disease and mortality.

BACKGROUND: Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts. METHODS: Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications. RESULTS: Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio[HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR,1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95%CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43).Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% forAF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L(for both, P value for trend, .03). CONCLUSION: Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.

Perry Syndrome

Disease characteristics. Perry syndrome is characterized by parkinsonism, hypoventilation, depression, and weight loss. The mean age at onset is 48 years; the mean disease duration is five years. Parkinsonism and psychiatric changes (depression, apathy, character changes, and withdrawal) tend to occur early; severe weight loss and hypoventilation manifest later. Diagnosis/testing. The diagnosis is based on clinical findings and molecular genetic testing of DCTN1, the only gene known to be associated with Perry syndrome. Management. Treatment of manifestations: Dopaminergic therapy (particularly levodopa/carbidopa) should be considered in all individuals with significant parkinsonism. Although response to levodopa is often poor, some individuals may have long-term benefit. Noninvasive or invasive ventilation support may improve quality of life and prolong life expectancy. Those patients with psychiatric manifestations may benefit from antidepressants and psychiatric care. Weight loss is managed with appropriate dietary changes. Surveillance: routine evaluation of weight and calorie intake, respiratory function (particularly at night or during sleep), strength; and mood. Agents/circumstances to avoid: Central respiratory depressants (e.g., benzodiazepines, alcohol). Genetic counseling. Perry syndrome is inherited in an autosomal dominant manner. The proportion of cases attributed to de novo mutations is unknown. Each child of an individual with Perry syndrome has a 50% chance of inheriting the mutation. No laboratories offering molecular genetic testing for prenatal diagnosis are listed in the GeneTests Laboratory Directory; however, prenatal testing may be available through laboratories offering custom prenatal testing for families in which the disease-causing mutation has been identified.

Enzyme replacement therapy with agalsidase alfa in patients with Fabry's disease: an analysis of registry data.

BACKGROUND: We analysed 5-year treatment with agalsidase alfa enzyme replacement therapy in patients with Fabry's disease who were enrolled in the Fabry Outcome Survey observational database (FOS). METHODS: Baseline and 5-year data were available for up to 181 adults (126 men) in FOS. Serial data for cardiac mass and function, renal function, pain, and quality of life were assessed. Safety and sensitivity analyses were done in patients with baseline and at least one relevant follow-up measurement during the 5 years (n=555 and n=475, respectively). FINDINGS: In patients with baseline cardiac hypertrophy, treatment resulted in a sustained reduction in left ventricular mass (LVM) index after 5 years (from 71.4 [SD 22.5] g/m(2.7) to 64.1 [18.7] g/m(2.7), p=0.0111) and a significant increase in midwall fractional shortening (MFS) from 14.3% (2.3) to 16.0% (3.8) after 3 years (p=0.02). In patients without baseline hypertrophy, LVM index and MFS remained stable. Mean yearly fall in estimated glomerular filtration rate versus baseline after 5 years of enzyme replacement therapy was -3.17 mL/min per 1.73 m(2) for men and -0.89 mL/min per 1.73 m(2) for women. Average pain, measured by Brief Pain Inventory score, improved significantly, from 3.7 (2.3) at baseline to 2.5 (2.4) after 5 years (p=0.0023). Quality of life, measured by deviation scores from normal EuroQol values, improved significantly, from -0.24 (0.3) at baseline to -0.17 (0.3) after 5 years (p=0.0483). Findings were confirmed by sensitivity analysis. No unexpected safety concerns were identified. INTERPRETATION: By comparison with historical natural history data for patients with Fabry's disease who were not treated with enzyme replacement therapy, long-term treatment with agalsidase alfa leads to substantial and sustained clinical benefits. FUNDING: Shire Human Genetic Therapies AB.

Le rein de l'enfant face à la chimiothérapie [The kidney in children under chemotherapy].

Nowadays more and more children survive after an intensive anti-tumoral therapy. The price to pay consists of numerous and relatively frequent long-term sequelae (secondary tumors, neuropsychological deficits, endocrine or cardiac damage). After chemotherapy, we sometimes observe renal side-effects, either tubular (metabolic acidosis, hypokalemia, hypomagnesemia, proteinuria, Fanconi syndrome, rickets) or glomerular (acute or chronic decreased GFR). These renal toxic side-effects are encountered especially after cisplatinum and ifosfamide, less frequently after carboplatin and cyclophosphamide. The pediatrician has to be aware of these toxic nephrologic side-effects, to look out for them and monitor carefully the renal function of all paediatric patients receiving these potentially nephrotoxic chemotherapies.

Dual transplant of marginal kidneys. Case report and review of the literature.

INTRODUCTION: Double transplantation is one possible answer to the shortage of donor organs. While each donor kidney would be unsuitable when considered as a single allograft, use of both kidneys should provide sufficient nephron mass for effective glomerular filtration. CASE REPORT: This is the first Swiss report of a dual adult transplant of marginal kidneys in a 46-year-old man, who was transplanted for the fourth time. Follow-up at 6 months is excellent without acute rejection. CONCLUSION: Recent analysis of dual marginal versus single ideal transplant outcomes, found a comparable 1-yr graft survival in both of the procedures. Long term results are still lacking and guidelines to decide between single, double or no transplantation are emerging.

Magnetic resonance stress tagging in ischemic heart disease.

High-dose dobutamine magnetic resonance stress testing has been shown to be superior to dobutamine stress echocardiography for diagnosis of coronary artery disease (CAD). We determined the feasibility of quantitative myocardial tagging during low- and high-dose dobutamine stress and tested the ability of global systolic and diastolic quantitative parameters to identify patients with significant CAD. Twenty-five patients suspected of having significant CAD were examined with a standard high-dose dobutamine/atropine stress magnetic resonance protocol (1.5-T scanner, Philips). All patients underwent invasive coronary angiography as the standard of reference for the presence (n = 13) or absence (n = 12) of significant CAD. During low-dose dobutamine stress, systolic (circumferential shortening, systolic rotation, and systolic rotation velocity) and diastolic (velocity of circumferential lengthening and diastolic rotation velocity) parameters changed significantly in patients without CAD (all P < 0.05 vs. rest) but not in patients with CAD. Identification of patients without and with CAD during low-dose stress was possible using the diastolic parameter of "time to peak untwist." At high-dose stress, none of the global systolic or diastolic parameters showed the potential to identify the presence of significant CAD. With myocardial tagging, a quantitative analysis of systolic and diastolic function was feasible during low- and high-dose dobutamine stress. In our study, the diastolic parameter of time to peak untwist as assessed during low-dose dobutamine stress was the most promising global parameter for identification of patients with significant CAD. Thus quantitative myocardial tagging may become a tool that reduces the need for high-dose dobutamine stress.

Postmortem findings in bone cement implantation syndrome-related deaths.

Several mechanisms have been postulated as potentially involved in life-threatening complications during cemented surgery. In this study, we evaluated the role of anaphylaxis and pulmonary fat embolism in the pathophysiology of bone cement implantation syndrome in a series of fatal cases that underwent medicolegal investigations. Postmortem findings in these cases were compared with those obtained from individuals who died after other injuries and/or interventions and in which activated mast cells and pulmonary fat embolism were involved in the pathogenesis of death. Fifty subjects were selected including 6 individuals who had undergone cemented total hip arthroplasty and died intraoperatively, 32 subjects who died shortly after being involved in traffic accidents, 8 individuals who died shortly after the injection of contrast material, and 4 subjects who had undergone orthopedic surgery and died postoperatively. Massive pulmonary fat embolism was determined to be the cause of death in all the 6 subjects who died intraoperatively as well as the main cause of death in traffic-road victims with rapid respiratory function deterioration. Mast cell activation was identified exclusively in the group of subjects who died shortly after contrast material administration. Massive pulmonary fat embolism appears to be the most important factor responsible for severe cardiorespiratory function deterioration during cemented arthroplasty. Cardiac comorbidities can also significantly influence the severity of intraoperative complications, thus corroborating the hypothesis of a multifactorial model in the pathogenesis of bone cement implantation syndrome.

Magnetic resonance cholangiography features of biliary abnormalities due to cavernous transformation of the portal vein.

BACKGROUND: The aim of this retrospective and monocentric study was to describe the magnetic resonance cholangiography (MRC) features of biliary abnormalities related to extrahepatic obstruction of the portal vein (EHOPV). METHODS: From September 2001 to May 2003, MRC was performed in 10 consecutive patients who had a portal thrombosis. RESULTS: Biliary ductal pathology was demonstrated via MRC in nine patients. It consisted of stenoses, ductal narrowing or irregularities involving the common bile duct for three patients with extrahepatic portal vein thrombosis discovered a mean of 1.5 years ago, or involving both right and left intrahepatic bile ducts and common bile duct for six patients with extrahepatic portal vein thrombosis discovered a mean of 16.2 years ago. Dilation of intrahepatic bile ducts was seen for seven patients, four of them having cholestasis. For three patients with symptomatic cholestasis, direct cholangiography (DC) was performed and showed the same findings as MRC which nevertheless overestimated the degree of bile duct stenosis. CONCLUSIONS: MRC seems to constitute an accurate tool to investigate noninvasively patients with portal biliopathy.

Hepatic Manifestations of Wilson Disease - CHUV Experience 2005-2010

Background and aim: Wilson disease (WD) is an inherited disorder ofhepatic copper excretion leading to toxic accumulation of copper in theliver as well as the brain, cornea, and other organs. The defect is due tomutations of the copper-transporting ATPase ATP7B. Here, we describethe adult cases of hepatic WD diagnosed at the CHUV between 2005and 2010.Methods: Clinical manifestions, results of diagnostic tests, and follow-upof adult patients with hepatic WD were recorded systematically.Results: Seven new adult cases of hepatic WD were diagnosed in ourcenter between 2005 and 2010. Three were women and 4 men, with amedian a ge at d iagnosis o f 24 (range, 1 8-56) years. Three patientspresented with acute liver failure (ALF), three with persistently elevatedliver function tests, and one with a dvanced cirrhosis. None hadneurological manifestations. Only one patient, presenting with ALF, had aKayser-Fleischer corneal ring. Median ceruloplasmin levels at diagnosiswere 0.13 (range, <0.03-0.30) g/l, median 24 h urinary copper excretion6.3 (range, 0.4-62.0) μmol/24 h, and median hepatic copperconcentration 591 (range, 284-1049) μg/g. At least one mutation in theATP7B g ene was i dentified in a ll patients. Allelic frequency of t hecommon H1069Q mutation was 14%. Two patients presenting with ALFand the one with advanced cirrhosis underwent successful l ivertransplantation. One patient with ALF recovered under chelator therapy.D-penicillamine was used as first-line chelator treatment, with a switch totrientine due to adverse effects in 2 out of 4 patients u nder l ong-termtreatment.Conclusions: The clinical presentation of WD and the performance ofdiagnostic tests are variable. A high index of suspicion i n clinicallycompatible situations i s key, with a combination of tests allowing thediagnosis of WD.

Dilatation pyélocalicielle chez le nouveau-né: attitude pratique pour le pédiatre [Antenatally detected hydronephrosis: practical approach for the pediatrician]

Approximately 1% of the fetuses present some dilatation of their urinary tract in utero. More than 50% of these antenatally detected hydronephrosis will disappear spontaneously after birth. The other 50% comprises ureteropelvic junction obstruction, vesico-ureteral reflux and primary megaureters. Postnatal radiological evaluation (renal ultrasonography and VCUG) is performed in every infant with a significantly dilated renal pelvis (> 8 mm between 20 and 30 weeks or > 10 mm after 30 weeks in utero). Renal nuclear scan should be done in every child with significant/worsening post-natal hydronephrosis. Antibioprophylaxis will be started from birth to prevent urinary tract infection. Medical or surgical approach will be chosen in the light of the uroradiological exam results and the clinical progress.

Interprétation de la volémie dans l'insuffisance rénale aiguë [Interpretation of volemia in acute kidney injury].

Assessment of volume status is often challenging in daily clinical practice. One of the clinician's tasks is to prevent or to treat organ systems failures that arise from a mismatch between the transport of oxygen and metabolic needs. Renal failure is a frequently encountered in-hospital diagnosis that is known to alter significantly the prognosis. In patients with acute renal failure in particular, the consequences of an inadequate volume management further increase morbidity and mortality.

Chronic subjective dizziness

CONCLUSION: Chronic subjective dizziness (CSD) is frequent and affects twice as many women as men. Anxiety is a strong predisposing factor. The pathophysiologic concept of this disorder assumes that balance function and emotion share common neurologic pathways, which might explain that the balance disorder can provoke fear and vice versa, giving rise to a problem in perception of space and motion. In anxious patients this can turn into a space and motion phobia, with avoidance behaviour. OBJECTIVE: CSD is a diagnosis based on the hypothesis of an interaction between the vestibular system and the psychiatric sphere. Patients complain of chronic imbalance, worsened by visual motion stimulation, and frequently suffer from anxiety. Vestibular examination reveals no anomalies. We evaluated the incidence and characteristics of CSD in patients referred to our neuro-otology centre (tertiary hospital outpatient clinic). SUBJECTS AND METHODS: This was a retrospective study of 1552 consecutive patients presenting with vertigo. CSD was diagnosed in 164 patients (female:male=111:53). RESULTS: CSD represents 10.6% of the dizzy patients in our clinic. Psychiatric disorder, mainly anxiety, was found in 79.3% of the cases. Other frequently associated factors were fear of heights and former vestibular lesion (healed). In all, 79.0% of the patients with CSD had poor balance performance on dynamic posturography testing.

Measurement of glomerular filtration rate in obese patients: pitfalls and potential consequences on drug therapy.

Epidemiological studies have shown that obesity is associated with chronic kidney disease and end stage renal disease. These studies have used creatinine derived equations to estimate glomerular filtration rate (GFR) and have indexed GFR to body surface area (BSA). However, the use of equations using creatinine as a surrogate marker of glomerular filtration and the indexation of GFR for BSA can be questioned in the obese population. First, these equations lack precision when they are compared to gold standard GFR measurements such as inulin clearances; secondly, the indexation of GFR for 1.73 m(2) of BSA leads to a systematic underestimation of GFR compared to absolute GFR in obese patients who have BSA that usually exceed 1.73 m(2). Obesity is also associated with pathophysiological changes that can affect the pharmacokinetics of drugs. The effect of obesity on both renal function and drug pharmacokinetics raises the issue of correct drug dosage in obese individuals. This may be particularly relevant for drugs known to have a narrow therapeutic range or excreted by the kidney.