Novel controlled attenuation parameter for noninvasive assessment of steatosis using Fibroscan(®): validation in chronic hepatitis C.

A novel controlled attenuation parameter (CAP) has been developed for Fibroscan(®) to assess liver steatosis, simultaneously with liver stiffness measurement (LSM). We assessed CAP diagnostic accuracy in a large cohort of patients with chronic hepatitis C (CHC) virus. A total of 615 patients with CHC, who underwent both Fibroscan(®) and liver biopsy, were analysed. Fibrosis was graded using METAVIR score. Steatosis was categorized by visual assessment as S(0) : steatosis in <10% of hepatocytes, S(1) : 11-33%, S(2) : 34-66% and S(3) : 67-100%. Performances of CAP and liver stiffness were determined using receiver operating characteristic (ROC) curve analysis and cross-validated using the bootstrap method. The Obuchowski measure was used to assess overall accuracy of CAP and to differentiate between steatosis grades. In multivariate analysis, CAP was related to steatosis (P < 10(-15) ) independently of fibrosis stage (which was related to LSM). The areas under ROC curves using CAP to detect steatosis were 0.80 (95% CI, 0.75-0.84) for S ≥ S(1) , 0.86 (0.81-0.92) for S ≥ S(2) and 0.88 (0.73-1) S = S(3) . CAP exhibited a good ability to differentiate steatosis grades (Obuchowski measure = 0.92). Performance of LSM for fibrosis assessment confirmed results from previous studies. CAP is a novel tool to assess the degree of steatosis and both fibrosis and steatosis can be evaluated noninvasively during the same procedure using Fibroscan(®) , in patients with CHC.

HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis.

Liver steatosis is a main histopathological feature of Hepatitis C (HCV) infection because of genotype 3. Steatosis and/or mechanisms underlying steatogenesis can contribute to hepatocarcinogenesis. The aim of this retrospective study was to assess the impact of infection with HCV genotype 3 on hepatocellular carcinoma (HCC) occurrence in patients with ongoing HCV cirrhosis. Three hundred and fifty-three consecutive patients (193 men, mean age 58 ± 13 years), with histologically proven HCV cirrhosis and persistent viral replication prospectively followed and screened for HCC between 1994 and 2007. Log-rank test and Cox model were used to compare the actuarial incidence of HCC between genotype subgroups. The patients infected with a genotype 3 (n = 25) as compared with those infected with other genotypes (n = 328) had a lower prothrombin activity [78 (interquartile range 60-85) vs 84 (71-195) %, P = 0.03] and higher rate of alcohol abuse (48%vs 29%, P = 0.046). During a median follow-up of 5.54 years [2.9-8.6], 11/25 patients (44%) and 87/328 patients (26%) with a genotype 3 and non-3 genotype, respectively, develop a HCC. HCC incidences were significantly different among the genotype subgroups (P = 0.001). The 5-year occurrence rate of HCC was 34% (95% CI, 1.3-6.3) and 17% (95% CI, 5.7-9.2) in genotype 3 and non-3 genotype groups, respectively (P = 0.002). In multivariate analysis, infection with a genotype 3 was independently associated with an increased risk of HCC occurrence [hazard ratio 3.54 (95% CI, 1.84-6.81), P = 0.0002], even after adjustment for prothrombin activity and alcohol abuse [3.58 (1.80-7.13); P = 0.003]. For patients with HCV cirrhosis and ongoing infection, infection with genotype 3 is independently associated with an increased risk of HCC development.

[Extramedullary blastic transformation revealed by a prolonged fever during the course of a 5q- syndrome]. / Fièvre prolongée au cours d'un syndrome 5q- révélant une transformation blastique extramédullaire.

INTRODUCTION: Fever during a myelodysplastic syndrome can be due to infectious complications, systemic disease or acute transformation with clonal evolution. CASE REPORT: A 51-year-old woman, with a 5q- syndrome and neutropenia, presented with a several week fever duration. Infectious work-up was negative and therapy with antibiotics had no influence on the clinical course. Neither bone marrow nor blood blasts were detected, but liver biopsy demonstrated significant blast infiltration compatible with the diagnosis of acute myeloid leukaemia (AML). CONCLUSION: The absence of blasts in blood or bone marrow does not exclude the malignant transformation of a myelodysplastic syndrome to AML. Tissue biopsy may be necessary to confirm the leukaemic progression.

Interleukin-10 inhibits intimal hyperplasia after angioplasty or stent implantation in hypercholesterolemic rabbits.

BACKGROUND: Intimal hyperplasia after stent implantation is the main cause of in-stent restenosis. Activated monocytes play a key role in intimal growth. The anti-inflammatory cytokine interleukin-10 (IL-10) is a potent monocyte deactivator, endogenously produced in the atherosclerotic plaque. We tested the hypothesis that exogenous IL-10 may limit postangioplasty intimal hyperplasia after balloon angioplasty or stenting. METHODS AND RESULTS: Hypercholesterolemic rabbits were treated with recombinant human IL-10 (rhuIL-10) for 3 days after balloon angioplasty or 28 days after stent implantation. High IL-10 serum levels and intense deactivation of circulating monocytic cells, assessed by inhibition of IL-1beta release by lipopolysaccharide-stimulated whole blood, were detected for at least 8 hours after rhuIL-10 intravenous injection (ELISA). Morphometric analyses, performed 28 days after injury, indicated that rhuIL-10 reduced intimal growth by approximately 50% after balloon angioplasty or stenting, resulting in more preserved lumen in stented arteries. Moreover, rhuIL-10 reduced macrophage infiltration by 67% and proliferative activity by 81% in the intima and the media. No toxic effect was detected except minor changes in blood cell count. CONCLUSIONS: The anti-inflammatory cytokine rhuIL-10 reduces postinjury intimal hyperplasia. The potent attenuation of in-stent intimal growth by rhuIL-10 and its favorable toxicity profile suggest that rhuIL-10 may be useful in the prevention of in-stent restenosis.

Regression of primary hepatocarcinoma in cancer-prone transgenic mice by local interferon-gamma delivery is associated with macrophages recruitment and nitric oxide production.

The clinical potential of tumor therapies must be evaluated using animal models closely resembling human cancers. We investigated the impact of locally delivered interferon-gamma (IFN-gamma) on primary hepatocarcinoma spontaneously developed by T-SV40 transgenic mice. A single intratumor injection of adenovirus IFN-gamma was sufficient enough to induce in vivo production of biologically active IFN-gamma, as assessed by STAT1 activation. IFN-gamma secretion led to the regression of primary tumor, principally by apoptosis of tumor hepatocytes. The lack of T-cells infiltrates in the liver upon treatment excluded a role of a specific immune response. In contrast, indirect pathways may include tumoricidal function of macrophages. Indeed, they were massively recruited in the entire liver under IFN-gamma treatment; transmigration through hepatic blood vessels could be observed and co-localization with damaged hepatocytes was obvious. This correlated with nonparenchymal liver cell iNOS expression and high level of NO in hepatic extracts. Moreover, in vitro experiments showed that NO releasing agents induced cell death of freshly isolated tumor hepatocytes, suggesting that NO could be one of the major effector molecules. Altogether, these observations defined an important role of IFN-gamma in controlling tumor development in a model of primary hepatocarcinoma.

Virological and biological characteristics of cervical intraepithelial neoplasia grade I with marked koilocytotic atypia.

The aim of this study was to evaluate virologic and biological significance of marked koilocytotic atypia observed in some cases of grade I cervical intraepithelial neoplasia (CIN I). Thirty-one CIN I cervical biopsy specimens with marked koilocytotic atypia, defined by the presence of meganuclei in the superficial epithelial layers, were compared to 37 CIN I biopsy specimens with usual koilocytes for (1) the human papillomavirus (HPV) type and signal pattern as detected by nonisotopic in situ hybridization (ISH); (2) the proliferation index assessed by Ki 67 immunostaining and (3) the p53 labeling pattern. Interobserver agreement for meganuclei was excellent (k = 0.9). Twenty-five out of 68 biopsies (37%) were positive by ISH for the 6 of 11 HPV probe, 30 (44%) for the 16-18 probe, and 7 (10%) for the 31/33 HPV probe, 6 (9%) were negative for ISH. The presence of meganuclei was strongly related to high and intermediate risk HPV type (P = 0.0001). The sensitivity and specificity of meganuclei for the detection of high or intermediate risk HPV in CINI were 73 and 87%, respectively. Loss of p53 immunostaining in the lower third of the epithelium was also related to the presence of meganuclei (P < .05), but the MIB-1 index and ISH labeling pattern were not. In conclusion, marked koilocytotic atypia in CIN I is a reliable and sensitive marker for infection by high or intermediate-risk HPV, and might be a guide to therapy.

Aortic dissection and cardiovascular syphilis: report of an observation with transesophageal echocardiography and anatomopathologic findings.

We report the case of a man who had thoracic pain and stroke. Transesophageal echocardiography enabled us to diagnose an intramural hematoma and a saccular aneurysm of the thoracic aorta before he died. Autopsy showed lesions compatible with syphilitic aortitis in the aortic wall. Transesophageal echocardiography and anatomopathologic findings are correlated, and the role of syphilis as a causal factor is discussed.

[Looking for large-cell dysplasia in liver needle biopsies how and why?]. / Comment et pourquoi rechercher la dysplasie hépatocytaire à grandes cellules sur ponction-biopsie hépatique?

Liver large cell dysplasia (LCD) is identifiable only at the microscopic level as foci of large hepatocytes with pleomorphic hyperchromatic nuclei and prominent nucleoli. LCD is mainly observed in cirrhotic livers, on surgical specimens, within macroregenerative nodules or low grade dysplastic nodules but also on liver needle biopsies. For needle biopsies, the prevalence of LCD ranges between 15% and 20%. in case of associated hepatocellular carcinoma, the prevalence is around 40%. LCD is more frequent in hepatitis B virus-induced liver cirrhosis than in cirrhosis related to other causes. Two prospective studies showed that LCD is a predictive factor for the occurrence of hepatocellular carcinoma in cirrhotic patients. Nevertheless LCD is probably not a precancerous lesion; dysplastic hepatocytes are biologically senescent polyploid cells unable to carry out normal cell division. Diagnosis of LCD on liver needle biopsy is indicative for the presence of large and numerous foci of LCD within the whole parenchya and allows consequently to select cirrhosis associated with advanced liver cell secescence, i.e. cirrhosis in which multistep genetic alterations of liver cell carcinogenesis could have happened with the greatest probability. Therefore pathologists have to identify and indicate the presence of LCD in the reports of liver needle biopsies

[Laparoscopic surgery. Does smoke transport cells?]. / Chirurgie par laparoscopie. La fumée transporte-t-elle des cellules?

The study was designed to test the hypothesis that whole cells can be carried as an aerosol in the pneumoperitoneum during laparoscopy. Twelve patients undergoing laparoscopic surgery for benign and metastatic disease were included in the study. Throughout the 12 procedures, the smoke and the gas of the pneumoperitoneum was evacuated through 17 filters. Twelve filters and the tubing were washed. The liquid was centrifuged and stained immunocytochemically to identify the cells. Five other filters were also photographed with an electron microscope. On immunocytochemistry, nine of the twelve samples were identified as mesothelial in origin and the electron micrograph show many other cells stuck to the filter which appeared to be blood cells and mesothelial cells. Malignant cells were not conclusively identified, but ethical considerations prevented any intentional coagulation of malignant tissue. The presence of whole identifiable cells in the pneumoperitoneum could partly explain, port site metastasis after laparoscopic surgery for cancer.

[Does laparoscopy reduce the incidence of useless appendectomies?]. / La laparoscopie réduit-elle l'incidence des appendicectomies inutiles?

The aim of this retrospective study is to evaluate the impact of laparoscopic appendicectomy on the incidence of histologically normal appendices. Between 1987 and 1997, 1220 consecutives patients--with an average age of 23.5 years (17-73) and including 841 women (69%)--underwent appendicectomy due to the presence of at least one of the following 3 criteria: right iliac fossa guarding, fever greater than 38 degrees C and hyperleucocytosis greater than 10,000. Patients were divided into two group.: First group with 930 patients were operated by laparotomy and the other group of 355 patients underwent laparoscopic exploration with appendicectomy when macroscopic abnormalities were observed (290 cases). In all cases, the appendices were examined under blind conditions and classified as normal or pathological, and were subsequently classified according to the nature and the severity of the lesions. In group I (laparotomy), the incidence of histologically normal appendices was 25.1%. In group II (laparoscopic), this incidence was only 8.2%. The difference was significant (p = 0.015). In 65 cases (18.3%), a macroscopically normal appendix was left in place: in 55 cases the symptoms were due to another identified cause, however, in 10 cases no cause was found. This study suggests that laparoscopy significantly reduces the number of histologically normal appendices because an other cause is identified more easily provided macroscopically normal appendices are not removed with a small proportion (5-10%) cases of early appendicitis with only mucosal involvement. In the absence of other causes for the symptoms, a three-day course of antibiotics can be tried in order to treat possible mucosal lesions. This approach reduces costs without having any adverse consequences on outcome.

[Can we recognize the pathological character of the appendix during laparoscopy? Prospective study: 81 cases]. / Peut-on reconnaître le caractère pathologique de l'appendice en laparoscopie? Etude prospective : 81 cas.

In a prospective study of 81 patients, the appendix was photographed during a laparoscopy performed for pain in the right iliac fossa. An appendicectomy was performed in 65 patients, for the remaining 16, another cause for the pain was found and the appendix was left in place. The evaluation of the photographed appendix was formed afterwards by a group of 10 surgeons and compared with the histopathological results. In 20 cases (30%) the appendix was normal. In 7 (10%) minimal mucosal inflammation was found and in 38 (60%) acute appendicitis. All the surgeons correctly recognised acute appendicitis. The accuracy of recognition of a normal appendix was 70% overall, and the maximum risk of leaving an early form of appendicitis to evolve was 14%. We propose not removing an appendix judged to be normal during laparoscopy if no other cause for the pain is found. A short course of antibiotics would cover the low risk of allowing a very early appendicitis to develop.

[Laparoscopic resection of gastric conjunctive tumor. Apropos of 2 cases]. / Résection laparoscopique de tumeurs conjonctives de l'estomac. 2 cas.

We report two cases of benign gastric tumours which were resected laparoscopically. The lesions were diagnosed pre-operatively by upper endoscopy and endoscopic ultrasound. Excisions were complete with satisfactory resection margins. The post-operative courses were uncomplicated: the length of hospital stay for both patients was 6 days. This technique would appear to be a promising alternative to laparotomy for selected cases.

GH administration rescues fatty liver regeneration impairment by restoring GH/EGFR pathway deficiency.

GH pathway has been shown to play a major role in liver regeneration through the control of epidermal growth factor receptor (EGFR) activation. This pathway is down-regulated in nonalcoholic fatty liver disease. Because regeneration is known to be impaired in fatty livers, we wondered whether a deregulation of the GH/EGFR pathway could explain this deficiency. Hepatic EGFR expression and triglyceride levels were quantified in liver biopsies of 32 obese patients with different degrees of steatosis. We showed a significant inverse correlation between liver EGFR expression and the level of hepatic steatosis. GH/EGFR down-regulation was also demonstrated in 2 steatosis mouse models, a genetic (ob/ob) and a methionine and choline-deficient diet mouse model, in correlation with liver regeneration defect. ob/ob mice exhibited a more severe liver regeneration defect after partial hepatectomy (PH) than methionine and choline-deficient diet-fed mice, a difference that could be explained by a decrease in signal transducer and activator of transcription 3 phosphorylation 32 hours after PH. Having checked that GH deficiency accounted for the GH signaling pathway down-regulation in the liver of ob/ob mice, we showed that GH administration in these mice led to a partial rescue in hepatocyte proliferation after PH associated with a concomitant restoration of liver EGFR expression and signal transducer and activator of trnascription 3 activation. In conclusion, we propose that the GH/EGFR pathway down-regulation is a general mechanism responsible for liver regeneration deficiency associated with steatosis, which could be partially rescued by GH administration.

Q fever and Mediterranean spotted fever associated with hemophagocytic syndrome: case study and literature review.

BACKGROUND: Hemophagocytosis during Q fever (QF) and Mediterranean spotted fever (MSF) is rare and only a few cases have been reported. We aimed to investigate the characteristics, outcome, and treatment of QF/MSF-associated hemophagocytosis. METHODS: We retrospectively reviewed all patients with a diagnosis of QF or MSF and suspected hemophagocytic syndrome (HS), according to Henter's criteria, between 2002 and 2011, and compared the latter to patients without HS or with lymphoma-associated HS. RESULTS: Seventeen patients with HS (median age 42 years, range 5-68 years; five females (29%)) with QF (n=8) and MSF (n=9) were included in this study. When comparing patients with QF- and MSF-associated HS with patients without HS (n=11), HS-associated signs (splenomegaly, ferritinemia, hypertriglyceridemia, and cytopenia) were significantly more frequent in patients with histological HS (p<0.05), along with a greater number of Henter's criteria. Despite the presence of HS-associated signs, treatment was similar in these two subgroups, including the time to recovery and the outcome. When compared to lymphoma-associated HS (n=10), the outcome in QF/MSF-associated HS was significantly different, with mortality in 70% of lymphoma patients versus none in QF- and MSF-associated HS (p<0.05). CONCLUSION: Hemophagocytosis is a rare occurrence during the course of QF and MSF. The presence of profound cytopenia is quite unusual in QF and MSF and should bring to mind the presence of associated HS. Nevertheless, hemophagocytic syndrome is associated with a good outcome in this condition.

Systematic cavity shaving: modifications of breast cancer management and long-term local recurrence, a multicentre study.

BACKGROUND: The status of the surgical margins of lumpectomy is one of the most important determinants of local recurrence in breast cancer. Systematically practicing cavity margin resection is debated but may avoid surgical re-excision and allow the diagnosis of multifocality. METHODS: This multicentric retrospective study included 294 patients who underwent conservative management of breast cancer with 2-4 systematic cavity shavings. Clinico-biological characteristics of the patients were collected in order to establish whether surgical management was modified by systematic cavity shaving. Local recurrence rate with a long-term follow up of minimum 4 years was evaluated. RESULTS: Cavity shaving avoided the need for re-excision in 25% of cases and helped in the diagnosis of multifocality in 8% of cases. Resection volume was not associated with usefulness of the cavity shaving. No predictive factor of positive cavity shaving was found. The rate of local recurrence was 3.7% and appeared in a median time of 3 years and 8 month. Only one quarter of the patients with local recurrence had initially positive lumpectomy margins but negative cavity shaving. DISCUSSION: Systematic cavity shaving can change surgical management of conservative treatment. No specific target population for useful cavity shaving was found, such that we recommend utilising it systematically.

[Realizing systematic cavity margins in conservative breast cancer surgery]. / Intérêt de la réalisation de recoupes systématiques dans la chirurgie conservatrice du cancer du sein.

The quality of surgical margins in lumpectomy are strong criteria to define risk of locoregional recurrence when conservative treatment is undertaken. Intraoperatively, the limits of adequate resection are sometimes difficult to define. This is why some teams propose the realization of systematic cavity margins during the excision of lumpectomy during the same operation. We expose the potential benefits of this type of practice using data from the literature.