[Evaluation of noninvasive diagnostic criteria for hepatocellular carcinoma on pretransplant MRI (2010): correlation between MR imaging features and histological features on liver specimen]. / Évaluation des critères diagnostiques non invasifs du carcinome hépatocellulaire sur IRM pré-greffe hépatique (2010) : corrélations IRM - anatomopathologiques sur explants hépatiques.

PURPOSE: To validate the 2010 diagnostic criteria from the American Association for the Study of Liver Diseases (AASLD) for hepatocellular carcinoma (HCC) on MRI using the surgical liver specimen as a gold standard. PATIENTS AND METHODS: A total of 21 liver transplant recipients were retrospectively included. Each underwent surgery because of HCC between January 2007 and January 2008. Pre-transplant MRI was performed on a 1.5 Tesla MR unit. The T1W and T2W signal and kinetic contrast enhancement were correlated for each lesion with the surgical specimen. Lesion diameters between MRI and specimen were compared (Spearman). A multivariate model was created (R statistics software package) to predict the presence and grade of tumor differentiation (WHO, Edmonson Steiner). RESULTS: A total of 71 nodules were detected at histology, including 54 HCC (mean size: 25.3mm) compared to 68 on MRI. There was moderate agreement (r=0.58, P<0.001) between the maximum lesion diameters measured on MRI and at histology. Wash-out on MRI provided an accuracy of 75 % for the detection of HCC (sensitivity=75 %, specificity=76 %). Adding T2W hyperintensity to the AASLD criteria increased the sensitivity of MRI from 70.3 % to 77.7 % for the diagnosis of HCC and from 67.6 % to 79 % for nodules less than 20mm in diameter, without affecting specificity. On multivariate analysis, wash out as a single variable was significantly associated with a diagnosis of HCC (P<0.01, odds ratio 12.0, CI 95 % [2.6-55.5]). T1W hyperintensity (P=0.04, odds ratio 5.4) and loss of signal on opposed-phase images (P=0.02, odds ratio 9.2) were predictive of good differentiation. CONCLUSION: On MRI, the AASLD criteria or presence of wash out within a liver nodule in patients with underlying chronic hepatocellular disease are suggestive of tumoral transformation. The addition of T2W hyperintensity to the AASLD criteria increases the detection of HCC, especially nodules smaller than 20mm.

Radiation-induced cholangitis with hepatocellular carcinoma.

There are no reports of hepatocellular carcinoma complicating postradiotherapy cholangitis. We report the case of a 45-year-old patient who had undergone upper abdominal radiotherapy for Hodgkin's disease, 21 years before, which was complicated years later by cholangitis with stricture of the common bile duct. Biliodigestive anastomosic surgery was scheduled due to recurrent angiocholitis, and hepatocellular carcinoma was discovered. The patient died from carcinoma some months later.

Chemotherapy has also an effect on primary tumor in colon carcinoma.

BACKGROUND: This study characterizes the histological effect of chemotherapy (CT) on primary colonic tumors. METHODS: Between 2000 and 2006, 38 patients with stage IV colon cancer underwent resection of the primary, after chemotherapy (CT group, n = 16) or without preoperative CT (control group, n = 22). For all primary tumors, histological analysis included: fibrosis, acellular necrosis, acellular mucin pools, lymphoplasmacytic infiltration, and changes at tumor surface. Tumor regression grade (TRG) was determined by the amount of residual tumor cells and was graded from 1 to 5. RESULTS: No patient had complete histological response. Major histological tumor regression (TRG2) was observed in 70% of patients treated by CT and none of the not treated patients (P < 0.0001). Fibrosis, acellular necrosis, and surface changes were significantly increased in the CT group. TRG in the primary was comparable to the TRG in the corresponding liver metastases for 7/9 patients who underwent both colonic and hepatic resection after CT. CONCLUSION: CT induces major histological response in 70% of colon cancers. Response to CT in the primary and the corresponding liver metastases are correlated. These results support a policy of initial CT management for stage IV colon cancer and may warrant future studies of neoadjuvant CT in locally advanced colon carcinomas.

[The endocannabinoid system as a novel target for the treatment of liver fibrosis]. / Le système endocannabinoïde, une nouvelle cible pour le traitement de la fibrose hépatique.

The cannabinoid system comprises specific G protein-coupled receptors (CB1 and CB2), exogenous (marijuana-derived cannabinoids) and endogenous (endocannabinoids) ligands, and a machinery dedicated to endocannabinoid synthesis and degradation. Studies over two decades have extensively documented the crucial role of the cannabinoid system in the regulation of a variety of pathophysiological conditions. However, its role in liver pathology has only been recently unravelled, probably given the low expression of CB1 and CB2 in the normal liver. We have recently demonstrated that CB1 and CB2 receptors display opposite effects in the regulation of liver fibrogenesis during chronic liver injury. Indeed, both receptors are up-regulated in the liver of cirrhotic patients, and expressed in liver fibrogenic cells. Moreover, CB1 receptors are profibrogenic and accordingly, the CB1 antagonist rimonabant reduces fibrosis progression in three experimental models. In keeping with these results, daily cannabis smoking is a risk factor for fibrosis progression in patients with chronic hepatitis C. In contrast, CB2 display antifibrogenic effects, by a mechanism involving reduction of liver fibrogenic cell accumulation. These results may offer new perspectives for the treatment of liver fibrosis, combining CB2 agonist and CB1 antagonist therapy.

[Imaging nodules within cirrhotic liver: how do I do it?]. / Nodules sur foie de cirrhose: quelle imagerie? pourquoi? comment?

Cirrhosis is a chronic liver disease characterized by the presence of diffuse parenchymal necrosis, reactive fibrosis and nodular regeneration. These regenerative nodules may evolve into dysplastic nodules and finally nodules of hepatocellular carcinoma (HCC). Improved survival of cirrhotic patients with HCC depends on eligibility to liver transplantation. The purpose of this paper is to review the imaging features of liver nodules within cirrhotic liver and to propose the imaging strategies when considering the possibility of liver transplantation.

Characteristics of patients with dual infection by hepatitis B and C viruses.

BACKGROUND/AIMS: The purpose of this study was to compare the epidemiological, biochemical, virological and histological characteristics of patients with chronic hepatitis B and C with those of patients suffering from chronic hepatitis C alone. METHODS: Twenty-three patients with chronic hepatitis C, who were anti-HCV positive and HBs antigen positive, were studied and subdivided into two groups according to the presence or absence of HBV DNA replication. They were compared to 69 age- and sex-matched patients with chronic hepatitis who were anti-HCV positive and HBs antigen negative. All patients were HCV RNA positive by PCR, anti-HIV negative and anti-HDV negative. HBV DNA and HCV RNA were detected in serum by means of a branched DNA assay and PCR. The HCV serotypes were determined by the Chiron Riba HCV serotyping SIA technique. The histological characteristics included the Knodell score. RESULTS: Epidemiological, biochemical and virological parameters were not different between the two groups. Only the prevalence of cirrhosis was greater in chronic hepatitis B and C patients than in patients with chronic hepatitis C alone (p = 0.01). Among chronic hepatitis B and C patients, HCV RNA level was significantly lower in HBV DNA positive than in HBV DNA negative patients (p = 0.01). Indeed, histological lesions were more severe in HBV DNA positive than in HBV DNA negative patients, including prevalence of cirrhosis (p = 0.01), Knodell score (p = 0.05) and, among the latter, piecemeal necrosis (p = 0.01) and fibrosis (p = 0.05). The characteristics of patients with dual infection did not differ according to the mode of contamination and duration of HBV disease, except for a shorter duration in patients contaminated by drug abuse than in other patients. CONCLUSIONS: These results suggest that HBV DNA replication inhibits HCV RNA replication in patients with chronic active hepatitis B and C but increases the severity of histological lesions.

Hyperintense benign liver lesions on spin-echo T1-weighted MR images: pathologic correlations.

BACKGROUND: To determine the incidence of hyperintensity on T1-weighted spin echo (SE) images in benign liver lesions, value of fat-suppressed magnetic resonance (MR) imaging for the detection of fat within these lesions, and the causes of hyperintensity by correlation to pathologic examinations. METHODS: Five hundred forty-nine patients with 805 benign liver lesions including 585 hemangiomas, 188 focal nodular hyperplasias (FNHs), 14 hepatic adenomas (HAs), 14 focal fatty infiltrations (FFIs), two biliary cystadenomas, and two hemorrhagic cysts were examined by T2-weighted and T1-weighted SE MR imaging. For hyperintense lesions on T1-weighted SE images, fat-suppressed images were obtained by selective presaturation of fat. RESULTS: Thirty-two lesions (four FNHs, 10 HAs, 14 FFIs, two biliary cystadenomas, and two hemorrhagic cysts) appeared hyperintense on T1-weighted SE images; 21 of these became hypointense on the fat-suppressed T1 weighted SE images (one FNH, six HAs, and 14 FFIs) and contained fat at pathological examination. The other 11 lesions remained hyperintense on fat-suppressed T1-weighted SE images and had no fat deposition. Causes of hyperintensity in these cases were sinusoidal dilatation, copper deposition, hemorrhage, and high protein content. CONCLUSION: Among benign liver lesions, hyperintensity on T1-weighted SE images is rare (3.9%). Causes of this hyperintensity are fat deposition, copper accumulation, sinusoidal dilatation, bemorrhage, and high protein content. Fat-suppressed imaging can distinguish fat deposition from other causes of hyperintensity.

Histopathologic impact of GB virus C infection on chronic hepatitis C.

BACKGROUND & AIMS: Dual infection by hepatitis GB virus type C (GBV-C) and hepatitis C virus (HCV) is common. To assess the histopathologic impact of GBV-C infection on liver lesions, liver biopsy specimens of 105 patients chronically infected with HCV, 17 of whom (15%) were also infected with GBV-C, were reviewed. METHODS: Semiquantitative histopathologic assessment of liver lesions was performed using the Knodell's score and the METAVIR grading system. RESULTS: Hepatitis activity was mild, moderate, or severe in 3 (18%), 11 (64%), and 3 (18%) patients, respectively, infected with GBV-C and HCV vs. 26 (29%), 56 (64%), and 6 (7%) patients, respectively, infected with HCV alone (no significant difference). Cirrhosis was present in 4 (24%) coinfected patients vs. 19 (22%) HCV-positive patients (no significant difference). No significant difference in fibrosis, presence of portal lymphoid aggregates, steatosis, and hemosiderosis was observed between the two groups. There was no significant difference in the evaluation of each item of the Knodell's score. CONCLUSIONS: This detailed histopathologic evaluation of GBV-C infection in chronic hepatitis C shows that GBV-C infection does not affect histopathologic severity and characteristics of chronic hepatitis C, thus suggesting a minor role of GBV-C infection in liver disease.

Secondary alveolar proteinosis in cancer patients.

Pulmonary alveolar proteinosis (AP) is a rare cause of progressive respiratory failure in the normal host. It was first described by Rosen and coworkers in 1958 on the morphological basis of the accumulation of a PAS-positive material in the alveolar space. A couple of years later, AP was found to be unexpectedly associated with malignant diseases, especially with acute or chronic myeloid leukemias. These forms were called secondary AP in opposition to the primary forms observed in normal hosts. Probably because of its morphological definition and late diagnosis by means of histology or autopsy material, secondary AP has been considered to be life-threatening for a long time. However, recent observations show that AP can be diagnosed early in the course of the disease, especially through bronchoalveolar lavage, as long as the pathologist is aware of this possibility. Another point is that secondary AP can be reversible, both clinically and morphologically. This article summarizes the clinical features, morphological findings, and the main malignant diseases associated with secondary AP. We also comment on the hypotheses proposed in the literature to explain the association of AP, malignant disease, and immunosuppression. Alveolar macrophage is likely a key factor in the occurrence of secondary AP.

Surgery for biliary obstruction by tumour thrombus in primary liver cancer.

Five patients with primary liver cancer presented with obstructive jaundice due to extension of tumour thrombus into the biliary ducts. Three patients had hepatocellular carcinoma, two of whom had alcoholic cirrhosis, and the other two had a peripheral cholangiocarcinoma. Preoperative diagnosis of biliary thrombus was best achieved by ultrasonography and computed tomography which showed peripheral hepatic tumour with dilated bile ducts containing dense material. All patients underwent liver resection associated with biliary exploration, clearance and T-tube drainage. Major hepatectomy was required in four cases. There were no postoperative deaths; one patient developed a subphrenic collection of bile which was drained percutaneously. All patients survived more than a year; median survival was 29 months. There are two long-term survivors without recurrence at 29 and 80 months. Patients with primary liver cancer and jaundice due to migrated tumour fragments in the common bile duct may benefit from surgical resection which can result in long-term resolution of symptoms and occasional cure.

Serial quantitative determination of hepatitis C virus RNA levels after liver transplantation. A useful test for diagnosis of hepatitis C virus reinfection.

After liver transplantation for hepatitis C virus (HCV)-related cirrhosis, recurrent viral infection is almost constant, resulting in acute graft dysfunction in 30-75% of cases. Acute graft dysfunction in the post-transplant period may also be the result of various causes (such as rejection, CMV infection, sepsis, or technical problems). Therefore, the role of HCV reinfection is often difficult to document. The aim of this study was to assess the diagnostic value of serial HCV RNA quantitation in this setting. Fourteen patients transplanted with follow-up greater than 6 months were studied. HCV RNA was quantitated before and serially after transplantation, using branched DNA technology. In cases of acute graft dysfunction, usual investigations and additional HCV RNA quantitation were conducted. There were 15 episodes of acute graft dysfunction in 12 patients. Six episodes had a hepatitic biochemical pattern, and 5 of them were associated with a concomitant HCV RNA peak. Nine episodes had a mixed, hepatitic, and cholestatic biochemical pattern, and 5 of them were associated with a concomitant peak of HCV RNA. Overall, 10 of 15 (66%) episodes of acute graft dysfunction were associated with HCV RNA peak, which strongly suggests that HCV was the etiologic factor. In 9 of these 10 episodes, no other cause of dysfunction was found, and one had associated CMV disease. In 5 cases, no peak of HCV RNA was observed and the causes of dysfunction were CMV (in 2 cases) and rejection, granulomatosis, and unknown (in 1 case each). Serial quantitations of HCV RNA levels after liver transplantation for cirrhosis C provide a useful tool in the diagnosis of HCV reinfection of the graft.

Multimodal adjuvant treatment and liver transplantation for advanced hepatocellular carcinoma. A pilot study.

BACKGROUND: Orthotopic liver transplantation has been used in a large number of patients with primary liver cancer because it increases the possibilities of resection of large tumors. Despite isolated cases of prolonged survival, however, the results of liver transplantation for advanced tumors have been universally disappointing because of high rates of tumor recurrence. In an attempt to reduce the recurrence rate, a pilot study testing a multimodal adjuvant treatment in patients undergoing liver replacement for hepatocellular carcinoma was undertaken. METHODS: The treatment consisted of preoperative hepatic arterial chemoembolization (iodized oil, doxorubicin, and gelatin sponge) and radiotherapy (5 Gy in one fraction immediately before surgery), and postoperative systemic chemotherapy with mitoxantrone. Nine patients entered this study. The tumor was solitary in two cases (5 cm and 8 cm) and multifocal in seven cases (2-9 nodules, 3-9 cm). The postoperative TNM stages were II in one case, III in one case, and IVA in seven cases. RESULTS: Chemoembolization and radiotherapy were performed in seven cases each (five patients had both treatments). All patients underwent liver transplantation with conventional immunosuppression. One patient died of heart failure 4 days after surgery. The remaining eight patients received 4 to 10 courses of chemotherapy (mean 9). The main toxicity of chemotherapy was leucopenia. Two patients died of recurrence: one at 7 months and one at 11 months. Six patients are alive, five of them without evidence of disease, with a mean follow-up of 30 months (range 16-45) after liver transplantation. The 3-year actuarial survival is 64%. CONCLUSIONS: These results show that an aggressive adjuvant therapy can be used in association with liver transplantation in the treatment of advanced hepatocellular carcinoma without increased mortality and suggest that such a protocol could be effective in preventing tumor recurrence.

Expression of tumor necrosis factor-alpha gene in alveolar macrophages from patients with the adult respiratory distress syndrome.

The adult respiratory distress syndrome (ARDS) is a complex syndrome in which pathogenesis is multifactorial. TNF-alpha, known to be pivotal in tissue damage, has been shown to have high levels in blood and alveolar fluid in ARDS. The identification of the cells responsible for this production in the alveolar milieu has not yet been reported. In order to evaluate the TNF-alpha gene expression in ARDS we have analyzed by in situ hybridization, using RNA probes, alveolar macrophages (AM) obtained by BAL from seven patients with ARDS, eight patients with miscellaneous respiratory diseases, and three control patients. In freshly collected AM from patients with ARDS, 66 +/- 14.5% cells expressed the TNF-alpha gene without in vitro stimulation. This TNF-alpha expression does not result from the BAL procedure itself since only a few unstimulated control AM contained TNF-alpha mRNA transcripts. TNF-alpha expression in AM is not restricted to patients with ARDS since it has also been observed in miscellaneous respiratory diseases; however, this expression is a constant feature in ARDS. These results demonstrated the major role of AM in the intra-alveolar production of TNF-alpha, and they point out the necessity in ARDS for a specific intra-alveolar therapy.

Pulmonary alveolar proteinosis associated with Pneumocystis carinii. Ultrastructural identification in bronchoalveolar lavage in AIDS and immunocompromised non-AIDS patients.

Pneumocystis carinii (PC) has been recognized as frequently responsible for most opportunistic pulmonary infections occurring in immunocompromised AIDS and non-AIDS patients. Moreover, these patients can be considered at risk for secondary pulmonary alveolar proteinosis. Therefore, we have investigated the occurrence of associated secondary alveolar proteinosis and PC pneumonitis in AIDS and non-AIDS immunocompromised patients. In a series of 26 bronchoalveolar lavages (BAL) in patients with PC pneumonitis (19 AIDS and seven non-AIDS patients), we observed on light microscopy, in addition to the honeycombed material, areas of an extracellular material that had a different pattern which was suggestive of that described in alveolar proteinosis. A systematic ultrastructural study of these 26 BAL fluid samples demonstrated in each of them an accumulation of phospholipid surfactantlike extracellular material mixed or not with the PC cysts. In nine cases, the observation of lipoproteinaceous material on light microscopy and abundant phospholipid material with myelinlike and myelin tubular laminated structures on electron microscopy was highly suggestive of an associated pulmonary alveolar proteinosis (PAP). Such an accumulation of extracellular material was not observed in the 11 BAL fluid samples collected in immunocompromised patients (seven AIDS and four non-AIDS patients) without PC pneumonitis. These findings demonstrated a particular frequency of associated PAP with PC pneumonitis. These results raise important questions concerning (1) the consequence of such an alveolar accumulation of lipoproteinaceous material on the clinical status and prognosis of the pneumonitis, and (2) the mechanisms responsible for this accumulation.