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Biomedical subjects

E Giostra

Publications and source records attributed to E Giostra.

At least 19 recordsLinked to original sources

Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery.

BACKGROUND: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome. PATIENTS AND METHODS: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG. RESULTS: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR. CONCLUSION: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcome.

Adult↗

[Management of patients after liver transplantation].

The success of liver transplantation essentially depends on the prevention and treatment of long term complications, which may be due to surgery, opportunistic infections, organ rejection and relapse of the initial liver disease. The side effects of immunosuppressive drugs--arterial hypertension, glucose intolerance and diabetes, dyslipidemia and obesity, renal failure, osteoporosis, malignancy, and anaemia--should be regularly screened and treated without delay. Surgical procedures in transplanted patients are safe and rarely followed by complications. Although pregnancy in this setting is considered at risk, because of prematurity and low birth weight, overall outcomes are favourable. The yearly influenza vaccination is strongly recommended. The survival and the quality of life of liver transplant patients also depend on a good communication between the general practitioner and the transplantation centre.

Follow-Up Studies↗

In vivo microscopic examination of the esophagus for the detection of cancer before liver transplantation in patients with alcoholic cirrhosis.

Esophageal squamous-cell carcinoma is relatively common in alcohol and tobacco abusers, and it can develop rapidly after liver transplantation. We report the early detection of an esophageal squamous-cell carcinoma in a patient with alcoholic cirrhosis, diagnosed during the pre-enlistment work-up that he was undergoing before liver transplantation. This lesion had not been detected at standard endoscopy, but was well characterized using in vivo staining and microscopic examination with an "endocytoscopy" system.

Carcinoma, Squamous Cell↗

Hepatopulmonary syndrome increases the postoperative mortality rate following liver transplantation: a prospective study in 90 patients.

Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of patients with end-stage liver diseases. HPS is diagnosed by hypoxemia and pulmonary vascular dilatation and is an independent risk factor of mortality. Orthotopic liver transplantation (OLT) is the only factor that modifies the natural course of HPS. Once patients with HPS have been transplanted, their long-term survival rate is similar to transplanted patients without HPS. Consequently, HPS is an indication of OLT whatever the severity of hypoxemia. However, besides the favorable long-term survival of HPS patients with OLT, a high postoperative mortality (mostly within 6 months) has been suggested. The aim of our study was to analyze the incidence of HPS and postoperative outcome after OLT in 90 consecutive patients. All patients were prospectively included and had blood gas analysis to detect HPS. Patients with hypoxemia had contrast echocardiography to confirm HPS. Nine patients had HPS with a 50 </= PaO(2)</= 70 mmHg. Among them 3 (33%) died while the mortality rate was 9.2% in the group without HPS (7 over 76 patients). In the HPS patients who survived, the syndrome completely recovered within 6 months. In conclusion, our study shows a high postoperative mortality rate following OLT even though the preoperative PaO(2) was >50 mmHg in all HPS patients transplanted.

Adult↗

[New aspect in the treatment of chronic hepatis B].

The pegylated interferon is now the first choice of treatment for patients without a counter-indication. The association of this treatment with lamivudine does not increase the effectiveness. For patients non-responders to the PEG-IFN or presenting counter-indications, the long-term administration of lamivudine is limited by the frequent appearance of mutations, so that escape from the treatment requires the use of other antivirals. Adefovir is currently the treatment of choice in the event of resistance to lamivudine. Its effectiveness is confirmed by many studies and the risk of emergence of resistance is very low. Entecavir is a selective inhibitor of polymerase HBV and shows a better efficacy than lamivudine. It is well tolerated and is associated only with a weak risk of resistance, even after a prolonged treatment.

Antiviral Agents↗

[Wilson's disease: Clinical presentations].

Wilson's disease is a rare genetic condition, transmitted on a recessive autosomal mode, which involves a disturbance of copper metabolism. Its prevalence is 1: 30000. It is treatable but may be lethal if not managed early and treated adequately. It is caused by the loss of function of an adenosine triphosphatase (ATP 7B), which is due to a mutation in the ATP 7B gene on chromosome 13. This leads to a decrease or absence of copper transport to the bile and its accumulation within certain organs, particularly the liver and the brain. In this article we present two cases of Wilson's disease in two young male patients. We also briefly review the pathophysiology of the illness, discuss the latest guidelines for diagnosis and treatment and outline the recent genetic discoveries.

Adult↗

Steatosis affects chronic hepatitis C progression in a genotype specific way.

BACKGROUND AND AIMS: Liver steatosis is frequent in chronic hepatitis C, particularly in patients infected with hepatitis C virus (HCV) genotype 3. The aim of this study was to determine the relationship between steatosis and fibrosis in chronic hepatitis C as a function of viral genotype. METHODS: A multivariable logistic regression analysis was carried out in 755 chronic hepatitis C patients (mean body mass index (BMI) 24.11 kg/m(2); 178 with genotype 3), consecutively admitted to three referral hospitals. Liver histology showed steatosis in 315 and fibrosis in 605 patients, of whom 187 had cirrhosis (78 compensated and 109 decompensated). RESULTS: Steatosis was independently associated with fibrosis (p<0.001), genotype 3 (p<0.001), BMI (p<0.001), ongoing alcohol abuse (p<0.001), and age (p = 0.001). Fibrosis was associated with the Metavir activity score (p<0.001), age (p<0.001), steatosis (p = 0.001), past alcohol abuse for >5 years (p = 0.015), and BMI (p = 0.034). When regression analysis was repeated on patients divided according to viral genotype (that is, 3 v non-3) to identify type specific risk factors, steatosis was associated with ongoing alcohol abuse (p<0.001) and age (p = 0.01) only in non-3 genotype infected patients and with Metavir activity (p = 0.044) only in genotype 3 infected patients. Similarly, fibrosis was associated with steatosis only in genotype 3 infected individuals (p = 0.018), and with past alcohol abuse (p = 0.003) and (marginally) diabetes (p = 0.078) only in non-3 genotype infected patients. CONCLUSIONS: Steatosis influences chronic hepatitis C progression in a genotype specific way. Patients infected with genotype 3 and histologically confirmed steatosis should not be deferred from effective antiviral therapy.

Adult↗

Adult-to-adult living-donor liver transplantation. A summary of current status and an outline of the program in Geneva.

Living donor liver transplantation is a relatively new procedure in which the right side of the liver is harvested in a healthy donor and transplanted into a recipient. After the first case in 1994, over 3000 cases have been done worldwide. This review summarizes the reasons why the procedure is needed, describes its main technical aspects, highlights the boundaries in which it can be done safely, summarizes the current experience worldwide and describes the main points of the program in our unit. We argue that living-donor transplantation is a viable alternative to a long time on the waiting list for several patients, and it can be performed safely and successfully provided that all precautions are undertaken to minimize the risks in the donor and to increase the chances of a good outcome in the recipients. If these prerequisites are met, and within the framework of a structured multidisciplinary program, we believe that living-donor liver transplantation should be funded by health insurances as a recognized therapeutic option.

Adult↗

Medical problems occurring during the long-term follow-up after liver transplantation.

Liver transplantation is a standardized therapy for end-stage liver disease. With current immunosuppressive protocols and patient care, ten-year patient survival rate has reached 60%. Several medical complications may develop during this period, including renal dysfunction, hypertension, diabetes mellitus, hyperlipidemia, and metabolic bone disease. The aim of this article is to analyze long-term results of several clinical trials reporting common medical dysfunctions after liver transplantation and to discuss their management.

Cause of Death↗

Rapid changes in alcoholic hepatitis histology under steroids: correlation with soluble intercellular adhesion molecule-1 in hepatic venous blood.

BACKGROUND/AIMS: In alcoholic hepatitis (AH), enhanced expression of intercellular adhesion molecule-1 (ICAM-1) correlates to neutrophil infiltration and histology. In severe AH under steroids, the evolution of the hepatocyte membranous ICAM-1 expression and its soluble form (sICAM-1) is not known. METHODS: Twenty-six consecutive patients with biopsy-proven severe AH had liver tissue studies for hepatocyte membranous ICAM-1 expression by immunostaining. Lobular neutrophils (mean per high power field) were counted after chloracetate esterase staining. Histological damage was assessed semiquantitatively. Circulating levels of sICAM-1 and TNFalpha in peripheral and hepatic vein were measured using immunoassays. After 8 days on steroids, 19 patients had repeat biopsy. RESULTS: At baseline, hepatocyte membranous ICAM-1 correlated both to histology (r=0.55, P<0.01) and to lobular neutrophils (r=0.56, P<0.01). On steroids, sICAM-1 in hepatic vein and TNFalpha in both vascular beds decreased. Hepatocyte membranous ICAM-1 and hepatocellular damage decreased, but lobular neutrophils increased. Changes in sICAM-1 in hepatic vein correlated to histological changes (r=0.68, P<0.01). CONCLUSIONS: In severe AH under steroids, the short term histological improvement was associated with a decrease in circulating TNFalpha, a decrease in ICAM-1 expression, and correlated to hepatic vein sICAM-1 changes.

Adult↗

Liver steatosis in chronic hepatitis C: a morphological sign suggesting infection with HCV genotype 3.

AIMS: To identify factors associated with liver steatosis in chronic hepatitis C. METHODS AND RESULTS: Occurrence and severity of liver steatosis in 254 chronic hepatitis C patients were compared with presence of alcohol abuse, body mass index (BMI) >26, history of intravenous drug addiction and hepatitis C virus (HCV) genotype. Steatosis was found in 109 (43%) patients. The occurrence of steatosis was significantly associated with ongoing alcohol abuse (P=0.03) or HCV genotype 3 (P= 0.003), but not with BMI >26. A moderate to severe steatosis was present in 60% of patients infected with HCV genotype 3, irrespective of the presence of alcohol abuse, BMI >26 or history of intravenous drug addiction. Using a multivariable stepwise logistic regression analysis, infection with genotype 3 had an odds ratio (OR) of 10 (95% confidence interval (CI)=4.56-22) for a liver steatosis, whereas the presence of a cirrhosis at histology had an OR=0.256 (95% CI=0.07-0.92). CONCLUSIONS: A moderate to severe degree of steatosis of the liver is a morphological sign suggestive of infection with HCV genotype 3, independent of other risk factors of a fatty liver, but it may disappear at late stages of the disease.

Adult↗

Validation of color Doppler EUS for azygos blood flow measurement in patients with cirrhosis: application to the acute hemodynamic effects of somatostatin, octreotide, or placebo.

BACKGROUND: Color Doppler EUS (CD-EUS) allows minimally invasive measurement of azygos blood flow (AzBF) in portal hypertension, but further validation of the method is needed. Because a limited number of patients has been studied, the acute hemodynamic effects of somatostatin and octreotide on AzBF and gastric mucosal perfusion are poorly defined in portal hypertension. METHODS: A double-blind hemodynamic study was designed to assess rapid changes in AzBF over a 60-minute period after intravenous administration of somatostatin, octreotide, and placebo in 30 stable patients with biopsy-proven cirrhosis. AzBF was measured by using both CD-EUS and the invasive thermal dilution technique in the first 10 patients (phase 1). Then, with CD-EUS alone, the hemodynamic study was extended to a further 20 patients (phase 2). In addition, gastric mucosal perfusion changes were assessed by using laser Doppler flowmetry at endoscopy. RESULTS: In phase 1, the 2 methods for AzBF measurement showed significant correlations both for baseline values (r = 0.685) and for AzBF changes over 60 minutes after drug administration (r = 0.733). In phase 2, a reduction was observed in AzBF 10 minutes after octreotide or somatostatin administration (-47% and -23%, p < 0.0001 vs. placebo, p = 0.058 vs. placebo, respectively). After 60 minutes of somatostatin infusion, AzBF increased 27% over placebo values (p < 0.04). Gastric mucosal perfusion was transiently reduced 5 minutes after octreotide or somatostatin (-21% and -32%, respectively, p < 0.02 vs. placebo). CONCLUSIONS: This is the first study to validate CD-EUS AzBF measurement with reference to the invasive thermodilution technique in cirrhosis. It confirmed the transient effects of somatostatin and octreotide on both AzBF and gastric mucosal perfusion. In addition, a significant rebound phenomenon after 60 minutes of continuous intravenous somatostatin infusion was observed.

Aged↗

Wilson's disease with severe hepatic insufficiency: beneficial effects of early administration of D-penicillamine.

BACKGROUND: Wilson's disease, heralded by severe hepatic insufficiency, is a rare disorder for which emergency liver transplantation is considered to be the only effective therapy. AIMS: To report the features of Wilson's disease with severe hepatic insufficiency in a series of 17 patients and, during the second period of the study, to assess the efficacy of a policy consisting of early administration of D-penicillamine. PATIENTS: Seventeen consecutive patients with Wilson's disease were studied. During the first period of the study (up to 1979), none of the patients received D-penicillamine. During the second period (after 1979), all patients without encephalopathy at admission received D-penicillamine. RESULTS: The four patients observed during the first period who did not have encephalopathy at admission and did not receive D-penicillamine progressed to encephalopathy and died. Among the 13 consecutive patients observed during the second period, two patients with encephalopathy at admission did not receive D-penicillamine and were transplanted. The 11 remaining patients all received D-penicillamine. Ten of these patients survived without the need for transplantation and returned to compensated liver disease without liver insufficiency. In one patient, liver insufficiency progressed and transplantation had to be performed. CONCLUSIONS: In most patients with Wilson's disease heralded by severe hepatic insufficiency and without encephalopathy at admission, early administration of D-penicillamine was associated with survival without transplantation. These results suggest the importance of early diagnosis of this form of Wilson's disease before the onset of encephalopathy, and favour early administration of D-penicillamine which could avoid the need for transplantation in most cases.

Acute Kidney Injury↗

[Start of an adult living donor liver transplantation program in Switzerland].

The shortage of cadaver organs has prompted transplant centres to seek new sources of grafts. While living-donor left lobe transplantation (segments II and III) is an established procedure for children, living donor right liver transplantation (segments V, VI, VII, VIII), which can provide adequate liver mass for an average-sized adult patient, is technically more demanding and potentially associated with higher risks for the donor. In view of the permanent shortage of organs in Switzerland, we started an adult living donor liver transplantation programme in 1999 with the approval of the Clinical Ethics Committee of Geneva University Hospitals. Donor evaluation was performed only after the recipient had been officially registered for transplantation in the national waiting list. Preoperative evaluation consisted of a preliminary information phase with blood tests and Doppler ultrasonography, a second phase with radiological non invasive investigations (CT scan with volume measurements, magnetic resonance cholangiography) and a third phase including liver biopsy and angiography. A formal psychiatric evaluation was performed in all cases and detailed consent was required. Eight potential donors were investigated, 5 were not retained because of too small right liver or steatosis, and 3 were accepted (wife, son, sister). Living-donor hepatectomy was performed without interrupting the vascular blood flow. The liver graft was perfused ex-situ with University of Wisconsin solution. The grafts were anastomosed to the preserved vena cava of the recipient and the portal and arterial anastomoses were performed without interposition grafts, with short cold ischaemic times in the 3 cases. The graft-to-recipient weight ratio ranged from 1.04 to 1.12%. The grafts worked immediately; the post-operative course in the 3 recipients was unremarkable and no rejection episode occurred. Significant complications were observed in one donor (percutaneously drained bilioma and spontaneously resolved popliteal sensory palsy). Living-donor right liver transplantation is a potentially valuable solution to the increasing shortage of donor organs. The procedure can be performed safely provided stringent criteria for donor selection, for donor-recipient coupling (> 1% graft to body weight ratio) and for centre selection (experience in liver surgery, reduced and split liver transplantation) are applied.

Adenosine↗