Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 39
Filter
1.
J Hepatol ; 76(3): 568-576, 2022 03.
Article in English | MEDLINE | ID: mdl-34748893

ABSTRACT

BACKGROUND & AIMS: Ferroportin disease is a rare genetic iron overload disorder which may be underdiagnosed, with recent data suggesting it occurs at a higher prevalence than suspected. Costs and the lack of defined criteria to prompt genetic testing preclude large-scale molecular screening. Hence, we aimed to develop a readily available scoring system to promote and enhance ferroportin disease screening. METHODS: Our derivation cohort included probands tested for ferroportin disease from 2008 to 2016 in our rare disease network. Data were prospectively recorded. Univariate and multivariate logistic regression were used to determine significant criteria, and odds ratios were used to build a weighted score. A cut-off value was defined using a ROC curve with a predefined aim of 90% sensitivity. An independent cohort was used for cross validation. RESULTS: Our derivation cohort included 1,306 patients. Mean age was 55±14 years, ferritin 1,351±1,357 µg/L, and liver iron concentration (LIC) 166±77 µmol/g. Pathogenic variants (n = 32) were identified in 71 patients. In multivariate analysis: female sex, younger age, higher ferritin, higher LIC and the absence of hypertension or diabetes were significantly associated with the diagnosis of ferroportin disease (AUROC in whole derivation cohort 0.83 [0.78-0.88]). The weighted score was based on sex, age, the presence of hypertension or diabetes, ferritin level and LIC. An AUROC of 0.83 (0.77-0.88) was obtained in the derivation cohort without missing values. Using 9.5 as a cut-off, sensitivity was 93.6 (91.7-98.3) %, specificity 49.5 (45.5-53.6) %, positive likelihood ratio 1.8 (1.6-2.0) and negative likelihood ratio 0.17 (0.04-0.37). CONCLUSION: We describe a readily available score with simple criteria and good diagnostic performance that could be used to screen patients for ferroportin disease in routine clinical practice. LAY SUMMARY: Increased iron burden associated with metabolic syndrome is a very common condition. Ferroportin disease is a dominant genetic iron overload disorder whose prevalence is higher than initially thought. They can be difficult to distinguish from each other, but the limited availability of genetic testing and the lack of definitive guidelines prevent adequate screening. We herein describe a simple and definitive clinical score to help clinicians decide whether to perform genetic testing.


Subject(s)
Cation Transport Proteins/analysis , Hemochromatosis/diagnosis , Research Design/standards , Aged , Cation Transport Proteins/blood , Cohort Studies , Female , Hemochromatosis/blood , Humans , Iron/metabolism , Iron Overload/blood , Iron Overload/complications , Logistic Models , Male , Mass Screening/methods , Mass Screening/statistics & numerical data , Middle Aged , ROC Curve , Research Design/statistics & numerical data
2.
Lancet Gastroenterol Hepatol ; 4(6): 454-465, 2019 06.
Article in English | MEDLINE | ID: mdl-30954567

ABSTRACT

BACKGROUND: Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. METHODS: We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m2 doxorubicin-loaded nanoparticles (30 mg/m2 group), 20 mg/m2 doxorubicin-loaded nanoparticles (20 mg/m2 group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01655693. FINDINGS: Between June 15, 2012, and Jan 27, 2017, 541 patients were screened, of whom 144 were excluded and 397 were randomly assigned to one of the groups (133 to the 30 mg/m2 group; 130 to the 20 mg/m2 group; and 134 to the control group). Median follow-up was 22·7 months (IQR 11·2-34·9). After pooling the doxorubicin groups for the efficacy analysis, median overall survival was 9·1 months (95% CI 8·1-10·4) in the pooled doxorubicin-loaded nanoparticles group and 9·0 months (7·1-11·8) in the control group (HR 1·00 [95% CI 0·78-1·28], two-sided p=0·99). 227 (94%) of 242 patients who received doxorubicin-loaded nanoparticles and 100 (75%) of 134 patients in the control group had at least one treatment-emergent adverse event. The most common drug-related grade 3 or 4 treatment-emergent adverse events were neutropenia (25 [10%] of 242 treated with doxorubicin-loaded nanoparticles and eight [6%] of 134 in the control group), asthenia (six [2%] and four [3%]), and thrombocytopenia (three [1%] and ten [7%]). Six (2%) patients treated with doxorubicin-loaded nanoparticles and one (1%) of those in the control group were deemed by investigators to have had a drug-related death. Serious adverse events occurred in 74 (31%) patients who received doxorubicin-loaded nanoparticles and 48 (36%) in the control group. INTERPRETATION: Doxorubicin-loaded nanoparticles did not improve overall survival for patients with hepatocellular carcinoma in whom previous sorafenib treatment had failed. FUNDING: Onxeo.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/mortality , Doxorubicin/administration & dosage , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Aged , Antibiotics, Antineoplastic/adverse effects , Antineoplastic Agents/adverse effects , Asthenia/etiology , Dose-Response Relationship, Drug , Doxorubicin/adverse effects , Female , Humans , Male , Middle Aged , Nanoparticles , Neutropenia/etiology , Sorafenib/adverse effects , Thrombocytopenia/etiology , Treatment Failure
3.
Blood Cells Mol Dis ; 74: 30-33, 2019 02.
Article in English | MEDLINE | ID: mdl-30389309

ABSTRACT

Juvenile hemochromatosis is a rare autosomal recessive disease due to variants in the Hemojuvelin (HJV) gene. Although biological features mimic HFE hemochromatosis, clinical presentation is worst with massive iron overload diagnosed during childhood. Our study describes clinical features and results of genetic testing for a group of patients initially referred for a hepcidino-deficiency syndrome and for whom HJV hemochromatosis was finally diagnosed. 662 patients with iron overload and high serum transferrin saturation were tested, and five genes (HFE, HJV, HAMP, TFR2, SLC40A1) were sequenced. Among our cohort, ten unrelated patients were diagnosed with HJV hemochromatosis. Genetic testing revealed five previously published and five undescribed variants: p.Arg41Pro, p.His180Arg, p.Lys299Glu, p.Cys361Arg and p.Ala384Val. Surprisingly, this study revealed a late age of onset in some patients, contrasting with the commonly accepted definition of "juvenile" hemochromatosis. Five of our patients were 30 years old or older, including two very late discoveries. Biological features and severity of iron overload were similar in younger and older patients. Our study brings new insight on HJV hemochromatosis showing that mild phenotype and late onset are possible. Genetic testing for HJV variants should thus be performed for all patients displaying a non-p.Cys282Tyr homozygous HFE hemochromatosis with hepcidin deficiency phenotype.


Subject(s)
GPI-Linked Proteins , Hemochromatosis/congenital , Hemochromatosis/diagnosis , Adult , Age of Onset , Child , Female , Genetic Variation , Hemochromatosis Protein , Hepcidins/deficiency , Humans , Iron Overload , Male , Transferrin , Young Adult
4.
ESMO Open ; 2(4): e000238, 2017.
Article in English | MEDLINE | ID: mdl-29104762

ABSTRACT

BACKGROUND: Doxorubicin Transdrug (DT), a nanoformulation of doxorubicin, was demonstrated to overcome the chemoresistance of hepatocellular carcinoma (HCC) in preclinical models. Its efficacy and safety were thus investigated in phase I and randomised phase II trials in unresectable HCC. PATIENTS AND METHODS: Phase I was a single dose of DT through the hepatic intra-arterial (HIA) route, dose-escalating 3+3 trial, evaluating five-dose levels from 10 to 40 mg/m2 with maximal tolerated dose (MTD) as primary endpoint. The multicentre phase II trial randomly assigned (2:1 ratio) patients to receive either 30 mg/m2 of DT through HIA route every 4 weeks for up to three courses or best standard of care (BSC). Progression-free survival (PFS) rate at 3 months was the primary endpoint. Overall survival (OS) and disease control rate (DCR) were secondary endpoints. RESULTS: In phase I, haematological and respiratory limited toxicities were reported at 35 and 40 mg/m2, giving MTD at 30 mg/m2. Partial response rate was 10%, and stable disease 70%. Phase II was discontinued due to three severe acute respiratory distress events in the DT group while 17 patients had received 30 mg/m2 DT and 11 BSC. At 3 months, PFS was 64% (95% CI 31 to 89) vs 75% (95% CI 35 to 97), and DCR 35% vs 27% in DT and BSC, respectively (p=NS). Median OS was 32.6 months (95% CI 8.2 to 34.1) in DT group and 15 months (95% CI 8.0 to 18.8) in BSC group (p<0.05). CONCLUSION: DT increased OS in unresectable HCC but induced severe respiratory distress. Efficacy data deserve further investigation using a safer dosing and schedule regimen. TRIAL REGISTRATION NUMBER: EUDRACT 2006-004088-77; Results.

5.
Scand J Gastroenterol ; 51(11): 1380-5, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27595309

ABSTRACT

INTRODUCTION: There is still uncertainty regarding the efficacy and optimal modalities of extracorporeal shock wave lithotripsy (ESWL) in the treatment of chronic pancreatitis. The aims of the present study were to assess the safety and the efficacy of ESWL, either alone or followed by therapeutic endoscopic retrograde cholangiopancreatography (adjuvant ERCP) and to determine predictive factors of efficacy, in a real-life setting. PATIENTS AND METHODS: This study included all consecutive patients who underwent an ESWL in a single University Hospital between 2001 and 2012. The indication for ESWL was obstructive stone(s) of the main pancreatic duct resulting in either painful chronic pancreatitis or recurrent acute pancreatitis. Success was defined by resolution of pain, no analgesic treatment, no acute pancreatitis and no surgical treatment for chronic pancreatitis 6 months after the ESWL. RESULTS: One hundred and forty-six patients were studied; 6/146 (4%) had a complication of ESWL. Among the 132 patients in whom follow-up was completed, 91 (69%) had an adjuvant ERCP. After 6 months of follow-up, 100/132 (76%) patients achieved success. In multivariate analysis, the single significant predictive factor of the success of the ESWL treatment was chronic pain (p = 0.03). Patients who had chronic pain and needed opioid treatment had less chance of success than patients without chronic pain (OR 95%CI 0.31 [0.07-1.14]). We found no difference in the success rates between patients who underwent adjuvant ERCP and those who had ESWL only (p = 0.93). CONCLUSION: This study shows that the ESWL is a safe and effective treatment for patients with chronic pancreatitis and obstructive stones within the main pancreatic duct. Systematic association with therapeutic ERCP appears to provide no additional benefit and is therefore not recommended.


Subject(s)
Calculi/therapy , Cholangiopancreatography, Endoscopic Retrograde , Lithotripsy , Pancreatitis, Chronic/therapy , Abdominal Pain/etiology , Adult , Female , France , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Pancreatic Ducts/physiopathology , Postoperative Complications/epidemiology , Quality of Life , Retrospective Studies , Treatment Outcome
6.
Ann Surg ; 264(1): 155-63, 2016 07.
Article in English | MEDLINE | ID: mdl-26649581

ABSTRACT

BACKGROUND DATA: In compensated cirrhotics with early hepatocellular carcinoma (HCC-cirr), upfront liver resection (LR) and salvage liver transplantation (SLT) in case of recurrence may have outcomes comparable to primary LT (PLT). OBJECTIVE: An intention-to-treat (ITT) analysis comparing PLT and SLT strategies. METHODS: Of 130 HCC-cirr patients who underwent upfront LR (group LR), 90 (69%) recurred, 31 could undergo SLT (group SLT). During the same period, 366 patients were listed for LT (group LLT); 26 dropped-out (7.1%), 340 finally underwent PLT (group PLT). We compared survival between groups LR and LLT, LR and PLT, and PLT and SLT. RESULTS: Feasibility of SLT strategy was 34% (31/90). In an ITT analysis, group LLT had better 5-yr/10-yr overall survival (OS) compared with group LR (68%/58% vs. 58%/35%; P = 0.008). Similarly, 5-yr/10-yr OS and disease-free survival (DFS) were better in group PLT versus group LR (OS 73%/63% vs. 58%/35%, P = 0.0007; DFS 69%/61% vs. 27%/21%, P < 0.0001). Upfront resection and microvascular tumor invasion were poor prognostic factors for both OS and DFS, presence of satellite tumor nodules additionally predicted worse DFS. Group SLT had similar postoperative and long-term outcomes compared with group PLT (starting from time of LT) (OS 54%/54% vs. 73%/63%, P = 0.35; DFS 48%/48% vs. 69%/61%, P = 0.18, respectively). CONCLUSIONS: In initially transplantable HCC-cirr patients, ITT survival was better in group PLT compared with group LR. SLT was feasible in only a third of patients who recurred after LR. Post SLT, short and long-term outcomes were comparable with PLT. Better patient selection for the "resection first" approach and early detection of recurrence may improve outcomes of the SLT strategy.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Liver Transplantation , Neoplasm Recurrence, Local/surgery , Salvage Therapy , Aged , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/therapy , Feasibility Studies , Female , Humans , Liver Cirrhosis/complications , Liver Neoplasms/etiology , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Liver Transplantation/mortality , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/therapy , Prognosis , Reoperation , Retrospective Studies , Salvage Therapy/methods , Survival Analysis , Treatment Outcome
7.
Hepatology ; 62(1): 179-87, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25914217

ABSTRACT

UNLABELLED: Liver transplantation (LT) is the best curative treatment for early hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the current shortage of organs causes prolonged waiting times and poorer intention-to-treat (ITT) survival (i.e., after listing) owing to tumor progression and dropout. Portal hypertension (PH) is a recognized risk factor of HCC development in patients with cirrhosis and its recurrence after resection. The aim of this study was to evaluate the potential impact of PHT on the results of LT on an ITT basis. Patients with cirrhosis listed for LT for HCC were included and their outcomes after listing were compared according to the presence or absence of PH defined as presence of esophageal varices or ascites or low platelet count and splenomegaly. Among 243 consecutively listed patients, 70% were affected by PH, which was associated with a significantly higher risk of tumor progression (38% vs. 22%; P = 0.017) and a higher risk of dropout (22% vs. 8%; P = 0.01). Transarterial chemoembolization (TACE) was similarly applied to the two groups (60% vs. 67%; P = 0.325). An absence of TACE was the only other independent risk factor of dropout owing to tumor progression. Under an ITT analysis, PH reduced overall survival (OS), but there was no difference in OS and time to recurrence post-LT. The only pathological feature that could potentially explain this observation was the lower complete response to TACE in the PHT group (12% vs. 36%; P = 0.001). CONCLUSION: PH should be regarded as a major risk factor of dropout owing to tumor progression and should be taken into consideration when managing patients with HCC who are waiting for LT.


Subject(s)
Carcinoma, Hepatocellular/complications , Hypertension, Portal/complications , Liver Neoplasms/complications , Liver Transplantation/mortality , Neoplasm Recurrence, Local/epidemiology , Adolescent , Adult , Aged , Carcinoma, Hepatocellular/surgery , Case-Control Studies , Female , France/epidemiology , Humans , Liver Neoplasms/surgery , Male , Middle Aged , Waiting Lists , Young Adult
8.
Ann Surg ; 256(6): 883-91, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23108125

ABSTRACT

BACKGROUND: Resection and liver transplantation (LT) are the only curative options for hepatocellular carcinoma in cirrhotic patients (HCC-cirr). OBJECTIVE: We tried to define the best primary intention-to-treat strategy in patients undergoing either resection or LT for early single HCC-cirr (≤5 cm). METHODS: From 1990 to 2010, 198 patients with early HCC-cirr underwent either resection (group R, n = 97) or LT (group T, n = 101) as the primary procedure. Our policy was to prioritize Childs A patients with peripheral lesions for resection rather than LT. Patient and tumor characteristics, and outcomes (recurrence-free survival [RFS] and overall survival [OS]), were studied. RESULTS: A longer diagnosis-to-surgery interval, more Child Pugh B/C patients, and more tumor nodules (on histopathological examination) were found in group T patients. The postoperative mortality (4.1% vs 3.0%, P = 0.72) and rate of major complications (19.1% vs 24.7%, P = 0.35) were similar in groups R and T, respectively, whereas tumor recurrence was higher in group R (62% vs 10% in group T, P < 0.0001). The 5-year OS (75% vs 52%, P = 0.0008) and RFS (72% vs 20%, P < 0.0001) were better in group T; similarly, more patients were disease free at last follow-up (27% vs 62%, P < 0.0001). Resection as the surgical procedure, tumor diameter 3 cm or more on histology, and microvascular tumor invasion were poor prognostic factors for OS and RFS. Including dropout patients from LT list in the analysis, the outcomes in group T were still better (70% and 61% vs 51% and 36% at 5 and 10 years, P = 0.01). CONCLUSIONS: On an intention-to-treat basis, LT is associated with the best survival outcomes in patients with early HCC-cirr. Resection may achieve comparable OS in patients with single HCC-cirr of size smaller than 3 cm; however, the RFS still remains lower than that in patients of group T. This study could serve as a guide for HCC-cirr patients who are candidates for either resection or LT.


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Liver Transplantation , Carcinoma, Hepatocellular/complications , Early Medical Intervention , Female , Humans , Intention to Treat Analysis , Liver Cirrhosis/complications , Liver Neoplasms/complications , Male , Middle Aged , Prognosis
9.
J Hepatol ; 57(6): 1374-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22885386

ABSTRACT

Hepatitis E is currently diagnosed after all other causes of hepatitis have been excluded. Moreover, HEV testing is not performed to prevent blood transmission in developed countries. We report here on the case of a patient with acute hepatitis while receiving potentially hepatotoxic medications for autoimmune disorders, with low-level autoimmune markers and negative "standard" viral markers; it was finally determined that he was suffering from transfusion-transmitted hepatitis E.


Subject(s)
Autoimmune Diseases/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Hepatitis E/etiology , Transfusion Reaction , Aged , Aged, 80 and over , Female , Hepatitis E/transmission , Humans , Male , Middle Aged
10.
Presse Med ; 40(6): 567-80, 2011 Jun.
Article in French | MEDLINE | ID: mdl-21397448

ABSTRACT

No treatment is recommended for silent gallstones. The diagnosis of acute cholecystitis is based on clinical and biological signs and on abdominal sonography. Early laparoscopic cholecystectomy is the treatment of choice, except in case of severe (grade III) cholecystitis where a percutaneous cholecystostomy associated with antibiotic therapy is recommended. The diagnostic accuracy of abdominal sonography for the diagnosis of common bile duct stones is poor. A second-line MR cholangiopancreatography or an endoscopic sonography is often needed to confirm the diagnosis. The treatment of acute cholangitis is based on both antibiotic therapy and biliary drainage. Results of the treatment of common bile duct stone with either laparoscopic surgery or with the combined endoscopic sphincterotomy plus laparoscopic cholecystectomy are comparable when performed by well-trained practitionners. The choice of the method should be based on the locally available treatment.


Subject(s)
Gallstones , Anti-Bacterial Agents/therapeutic use , Biomarkers , Cholangiopancreatography, Endoscopic Retrograde , Cholangiopancreatography, Magnetic Resonance , Cholangitis/complications , Cholangitis/diagnosis , Cholangitis/drug therapy , Cholangitis/surgery , Cholecystectomy/methods , Cholecystectomy, Laparoscopic , Cholecystitis/complications , Cholecystitis/diagnosis , Cholecystitis/drug therapy , Choledocholithiasis/diagnosis , Choledocholithiasis/diagnostic imaging , Choledocholithiasis/surgery , Cholesterol/metabolism , Combined Modality Therapy , Drainage , Female , Gallstones/complications , Gallstones/diagnosis , Gallstones/drug therapy , Gallstones/epidemiology , Gallstones/genetics , Gallstones/physiopathology , Gallstones/surgery , Humans , Meta-Analysis as Topic , Pigments, Biological/metabolism , Predictive Value of Tests , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/diagnostic imaging , Prevalence , Risk Factors , Sphincterotomy, Endoscopic , Ultrasonography
11.
Gastrointest Endosc ; 72(4): 728-35, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20883850

ABSTRACT

BACKGROUND: The optimal endoscopic approach to the drainage of malignant hilar strictures remains controversial, especially with regard to the extent of desirable drainage and unilateral or bilateral stenting. OBJECTIVE: To identify useful criteria for predicting successful endoscopic drainage. DESIGN AND SETTING: Retrospective 2-center study in the greater Paris area in France. PATIENTS: A total of 107 patients who had undergone endoscopic stenting for hilar tumors Bismuth type II, III, or IV and a set of contemporaneous cross-sectional imaging data available. INTERVENTIONS: The relative volumetry of the 3 main hepatic sectors (left, right anterior, and right posterior) was assessed on CT scans. The liver volume drained was estimated and classified into 1 of 3 classes: less than 30%, 30% to 50%, and more than 50% of the total liver volume. MAIN OUTCOME MEASUREMENTS: The primary outcome was effective drainage, defined as a decrease in the bilirubin level of more than 50% at 30 days after drainage. Secondary outcomes were early cholangitis rate and survival. RESULTS: The main factor associated with drainage effectiveness was a liver volume drained of more than 50% (odds ratio 4.5, P = .001), especially in Bismuth III strictures. Intubating an atrophic sector (<30%) was useless and increased the risk of cholangitis (odds ratio 3.04, P = .01). A drainage > 50% was associated with a longer median survival (119 vs 59 days, P = .005). LIMITATIONS: Heterogeneous population and volume assessment methodology to improve in further prospective studies. CONCLUSION: Draining more than 50% of the liver volume, which frequently requires bilateral stent placement, seems to be an important predictor of drainage effectiveness in malignant, especially Bismuth III, hilar strictures. A pre-ERCP assessment of hepatic volume distribution on cross-sectional imaging may optimize endoscopic procedures.


Subject(s)
Cholestasis/surgery , Digestive System Neoplasms/complications , Drainage/methods , Liver/pathology , Stents , Aged , Atrophy , Bile Duct Neoplasms/complications , Bile Ducts, Intrahepatic , Bilirubin/blood , Cholangiocarcinoma , Cholangiopancreatography, Endoscopic Retrograde , Cholangitis/epidemiology , Cholangitis/surgery , Cholestasis/mortality , Digestive System Neoplasms/pathology , Endoscopy, Digestive System , Female , Gallbladder Neoplasms/complications , Humans , Kaplan-Meier Estimate , Liver/diagnostic imaging , Liver Neoplasms/complications , Liver Neoplasms/secondary , Male , Middle Aged , Multivariate Analysis , Organ Size , Prosthesis Design , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
12.
World J Gastroenterol ; 15(3): 328-33, 2009 Jan 21.
Article in English | MEDLINE | ID: mdl-19140232

ABSTRACT

AIM: To study predictive factors of thyroid dysfunction associated with interferon-alpha (IFNalpha) therapy in chronic hepatitis C (CHC) and to describe its long-term evolution in a large population without previous thyroid dysfunction. METHODS: We performed a follow-up of thyroid function and detection of thyroid antibodies in 301 patients treated for CHC with IFNalpha from 1999 to 2004. RESULTS: Thyroid disorder developed in 30/301 (10%) patients with a mean delay of 6 +/- 3.75 mo: 13 patients had hyperthyroidism, 11 had hypothyroidism, and 6 had biphasic evolution. During a mean follow-up of 41.59 +/- 15.39 mo, 9 patients with hyperthyroidism, 3 with hypothyroidism, and 4 with biphasic evolution normalized thyroid function in 7.88 +/- 5.46 mo. Recovery rate of dysthyroidism was not modified by treatment discontinuation, but was better for patients with negative thyroid antibodies before antiviral treatment (P = 0.02). Women had significantly more dysthyroidism (P = 0.05). Positive thyroid peroxidase and thyroglobulin antibodies were more frequent before antiviral treatment in patients who developed dysthyroidism (P < 0.0003 and P = 0.0003, respectively). In a multivariate model, low fibrosis was found to be a predictive factor of dysthyroidism (P = 0.039). CONCLUSION: In this monocentric population of CHC, dysthyroidism, especially hyperthyroidism, developed in 10% of patients. Low fibrosis was found to be a predictive factor of dysthyroidism. Thyroid disorder recovered in 16/30 patients (53%) and recovery was better in the non-autoimmune form.


Subject(s)
Antiviral Agents , Hepatitis C/drug therapy , Interferon-alpha , Thyroid Diseases/chemically induced , Adult , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Autoantibodies/immunology , Female , Fibrosis/pathology , Follow-Up Studies , Hepatitis C/diagnosis , Humans , Interferon-alpha/adverse effects , Interferon-alpha/therapeutic use , Male , Middle Aged , Thyroid Diseases/classification , Thyroid Diseases/pathology
13.
J Occup Environ Med ; 50(2): 212-20, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18301178

ABSTRACT

OBJECTIVE: The principal objective of this work was to evaluate the association between the risk of hepatocellular carcinoma (HCC) and various occupations. METHODS: This case-control study, conducted during 2000 to 2003 in four French hospitals, included 125 men younger than 75 years with incident HCC and 142 men as control subjects. RESULTS: An association with HCC was observed for machinery fitters and machine assemblers (odds ratio [OR] = 4.4 [1.0-19.0], eight exposed cases and three exposed controls). A higher percentage of cases than controls were metal machinists (OR = 2.2 [0.8-5.8], 14 exposed cases and 10 exposed controls), although the difference was not statistically significant. These associations were strongest for subjects with duration of employment greater than 20 years. CONCLUSIONS: Our findings suggest an association between metal machining jobs and hepatocellular carcinoma, although we cannot rule out the possibility that it was observed by chance.


Subject(s)
Carcinoma, Hepatocellular/epidemiology , Liver Neoplasms/epidemiology , Occupational Diseases/epidemiology , Occupational Exposure/adverse effects , Occupations/classification , Adult , Aged , Carcinoma, Hepatocellular/blood , Case-Control Studies , France/epidemiology , Humans , Interviews as Topic , Liver Neoplasms/blood , Male , Middle Aged , Risk Factors , Time Factors
14.
Eur J Gastroenterol Hepatol ; 20(2): 127-30, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18188033

ABSTRACT

OBJECTIVE: To evaluate the biliary penetration of ciprofloxacin and cefotaxime in patients with obstructed bile ducts and to determine simple predictive markers of effective biliary concentrations of these drugs. METHODS: Sixty-two patients treated with endoscopic biliary drainage were prospectively included in a nonrandomized way and received intravenous ciprofloxacin (200 mg twice daily) or cefotaxime (1 g three times a day) for more than 24 h before exploration. Blood and bile samples were collected at the time of drainage. Ciprofloxacin and cefotaxime concentrations were measured using high-performance liquid chromatography. Biliary penetration was assessed by the bile-to-plasma ratio of the concentrations of both antibiotics. RESULTS: Biliary penetration ranged from 0.06 to 42.7 for ciprofloxacin and from 0.01 to 1.14 for cefotaxime. The ratio was more than one in only 10 patients (35%) and three patients (9%) in ciprofloxacin and cefotaxime groups, respectively. Biliary concentration of the drug was more than 10 times the minimal inhibitory concentration in only 10 patients (35%) and in 12 patients (35%) in ciprofloxacin and cefotaxime groups, respectively. Serum bilirubin, alkaline phosphatase or gamma-glutamyl-transpeptidase were not good predictive markers of the biliary diffusion of the antibiotics. CONCLUSION: In patients with obstructed bile ducts, the biliary penetration of ciprofloxacin is poor and reaches effective biliary concentrations in a minority of patients. Cefotaxime biliary penetration is even poorer. No liver test can predict accurately the biliary penetration of the drugs.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefotaxime/pharmacokinetics , Cholangitis/drug therapy , Cholestasis/metabolism , Ciprofloxacin/pharmacokinetics , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Bile/metabolism , Bilirubin/blood , Cefotaxime/therapeutic use , Cholangiopancreatography, Endoscopic Retrograde , Cholangitis/etiology , Cholangitis/metabolism , Cholestasis/etiology , Cholestasis/surgery , Chromatography, High Pressure Liquid/methods , Ciprofloxacin/therapeutic use , Female , Humans , Male , Middle Aged , Prospective Studies
15.
Ann Diagn Pathol ; 11(6): 460-3, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18022134

ABSTRACT

We report the case of a 41-year-old man presenting with multiple calcifying fibrous tumor (CFT) revealed by ischemic colitis. Peritoneal nodular lesions involved omental, mesenteric, mesorectal, and mesocolic serosal surfaces. Histologically, nodules were composed of dense bundles of collagen, calcifications, and lymphoplasmacytic infiltrate. These findings were diagnostic of CFTs, a rare and often asymptomatic benign fibrous process. Multiple peritoneal CFTs are very uncommon and usually occur in women. Calcifying fibrous tumors are usually cured by surgical excision. The differential diagnosis and histogenesis of this entity are discussed.


Subject(s)
Calcinosis/pathology , Colitis, Ischemic/complications , Neoplasms, Fibrous Tissue/pathology , Peritoneal Neoplasms/complications , Peritoneal Neoplasms/pathology , Adult , Colitis, Ischemic/pathology , Humans , Male , Neoplasms, Fibrous Tissue/complications
16.
Liver Int ; 27(10): 1389-93, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18036102

ABSTRACT

UNLABELLED: AIMS/BACKGROUNDS: Large spontaneous portal-systemic shunts can occasionally be the cause of chronic and disabling encephalopathy in cirrhotic patients. Shunt embolization has been proposed, however the clinical relevance of this technique remains uncertain. METHODS/RESULTS: We report our results in seven patients treated by shunt embolization. Although the procedure was achieved and technically successful in all patients, the clinical results were poor as long-term improvement was obtained in only one patient. Three patients died within 3 months after the procedure from cirrhoses' end stage complications. CONCLUSION: We believe that optimal management of these patients with chronic spontaneous encephalopathy is liver transplantation.


Subject(s)
Embolization, Therapeutic , Hepatic Encephalopathy/therapy , Liver Cirrhosis, Alcoholic/therapy , Aged , Angiography , Chronic Disease , Hepatic Encephalopathy/diagnostic imaging , Hepatitis C, Chronic/diagnostic imaging , Hepatitis C, Chronic/therapy , Humans , Liver Cirrhosis, Alcoholic/diagnostic imaging , Liver Transplantation , Middle Aged , Portal System/diagnostic imaging , Retrospective Studies , Survival Rate , Treatment Outcome
17.
Gastroenterol Clin Biol ; 31(8-9 Pt 1): 670-1, 2007.
Article in French | MEDLINE | ID: mdl-17925766

ABSTRACT

We report the case of a 17 year old man who presented with several episodes of acute pancreatitis due to a duodenal duplication. This was successfully treated by an incision by sphincterotome during interventional duodenoscopy. The patient is symptom free without recurrence 20 months after endoscopic treatment.


Subject(s)
Duodenoscopy , Duodenum/abnormalities , Duodenum/surgery , Pancreatitis/etiology , Acute Disease , Adolescent , Humans , Male
18.
Presse Med ; 36(4 Pt 2): 687-93, 2007 Apr.
Article in French | MEDLINE | ID: mdl-17329066

ABSTRACT

All cases of diarrhea involve increased fecal excretion of water. Understanding the mechanisms of infectious diarrhea requires review of the physiology of water and electrolyte absorption. Every day, 8 to 9 liters of fluid flow into the intestine, most of it reabsorbed in the small bowel. There are 2 main types of infectious diarrhea: secretory noninvasive diarrhea, such as cholera, due to impairment of water absorption mechanisms in the small bowel and inducing watery stools and dehydration; and enteroinvasive diarrhea, due to alteration of the colonic mucosa, inducing dysentery. Most cases of infectious diarrhea are acute. Some pathogens, mainly parasites, can induce chronic diarrhea. A HIV serology is then warranted. Some patients develop chronic irritable bowel syndrome after acute gastroenteritis.


Subject(s)
Diarrhea/physiopathology , Tropical Climate , Dehydration/microbiology , Dehydration/parasitology , Dehydration/physiopathology , Diarrhea/microbiology , Diarrhea/parasitology , Dysentery/microbiology , Dysentery/parasitology , Dysentery/physiopathology , Humans
19.
Gastroenterol Clin Biol ; 30(11): 1301-4, 2006 Nov.
Article in French | MEDLINE | ID: mdl-17185972

ABSTRACT

We report the case of a 67-year-old man presenting with an isolated 3 cm mass of the pancreatic tail revealed by weight loss. Distal pancreatectomy and splenectomy were performed. Microscopically, the tumor filled the main pancreatic duct, extending into the smaller ducts and was associated with a minor adenocarcinomatous invasive component. The intraductal tumor showed a cribriform pattern, atypical cells without mucus and a MUC1+, MUC2-, MUC5AC- phenotype, all characteristics of intraductal tubular carcinoma, a new entity described by Japanese authors. The differential diagnosis and its relationship with intraductal papillary-mucinous tumors are discussed.


Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Pancreatic Neoplasms/pathology , Aged , Carcinoma, Pancreatic Ductal/surgery , Diagnosis, Differential , Humans , Immunohistochemistry/methods , Male , Pancreatectomy/methods , Pancreatic Neoplasms/surgery
SELECTION OF CITATIONS
SEARCH DETAIL
...