V. Paradis

A Single-Center Surgical Experience of 122 Patients With Single and Multiple Hepatocellular Adenomas

BACKGROUND & AIMS Hepatocellular adenoma (HA) is associated with risk of bleeding and malignancy, justifying resection. Patients with multiple forms of HA are difficult to manage. We evaluated the characteristics and outcome of 122 patients with single and multiple HAs after surgery. METHODS From 1990 to 2004, 122 patients (14 male) underwent surgical resection. Complications (hemorrhage and malignancy) were assessed according to size, number, and histologic subtype (steatotic, telangiectatic, and unclassified), with a mean follow-up period of 70 months. RESULTS Hemorrhagic HA occurred in 21% of cases and malignant HA occurred in 8%. Risk of complications was not related to the number of HAs but was associated with size (>5 cm), especially of telangiectatic and unclassified subtypes. Patients with steatotic HA had a low risk of complications. Malignant HA was more frequent in men (43%); all patients treated by partial resection survived, without recurrent malignancy, after a mean follow-up period of 78 months. After 109 patients with benign HA revealed recurrence or progression of HA in 8% and regression in 9% of cases. No complications were observed in 11 women who became pregnant during the follow-up period. CONCLUSIONS Patients with HAs greater than 5 cm, telangiectatic or unclassified subtypes, and men have an increased risk of complicated disease; resection should be restricted to these patients. The risk of complications was not related to the number of HAs, so patients with multiple HAs do not need liver transplantation.

Changing trends in malignant transformation of hepatocellular adenoma

Objective Hepatocellular adenomas (HCAs) classically develop in women who are taking oral contraceptives and have a risk of malignant transformation into hepatocellular carcinoma (HCC). HCA with malignant transformation is, however, an ill-defined entity thought to be an anecdotic pathway to HCC. The objective of this study was to characterise malignancy occurring within HCA. Design, setting and patients A series of histology proven HCAs managed between 1993 and 2008 in a tertiary hepato-biliary centre (218 patients, 184 women and 34 men) were screened to identify HCA with malignant transformation. Main outcome measures The incidence of HCA with malignant transformation was analysed through the study period and associated conditions were retrieved. They were sub-typed according to their molecular features and the malignant compartment was mapped. Results Areas of HCC within HCA were observed in 23 patients and the risk of malignant transformation was 4% in women and 47% in men. The number of women whose HCA had malignant changes has remained stable during the study period and oral contraception was the only associated condition. The number of men with such transformation has markedly increased since 2000 and the metabolic syndrome has become the most frequent associated condition. Two-thirds of HCAs with malignant transformation were β-catenin activated and one-third displayed cell atypias. Both features were more prevalent in men. The median diameter of HCA with malignancy was 10 cm and only three were 5 cm or less. Conclusion Prevalence of malignancy within HCA is 10 times more frequent in men than in women and management of HCA should primarily be based on gender. Whereas oral contraception is a classical cause of HCA in women but a marginal cause of HCC, the metabolic syndrome appears as an emerging condition associated with malignant transformation of HCA in men, and is the likely predisposing condition for HCC in this setting.

Complete regression of locally advanced hepatocellular carcinoma induced by sorafenib allowing curative resection

We report two cases of locally advanced hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) who complete regression by sorafenib treatment allowed curative resection. Two male adult (59 and 57 years) cirrhotic patients with HCC associated with PVTT including one with lymph node involvement had elevated α‐fetoprotein level (AFP) (867 and 17 000) and were treated with standard sorafenib treatment during 10 and 12 months respectively. Size decrease of the main tumour, disappearance of PVTT and normalization of AFP allowed curative surgical resection. No viable tumour cells were found in the specimen and the two patients are currently alive without recurrence 12 and 16 months after surgery. These first two cases of complete tumour necrosis after sorafenib treatment allow us to reconsider surgical treatment in patients with unresectable HCC responding to this medical treatment.

Quantitative gene expression in Budd-Chiari syndrome: a molecular approach to the pathogenesis of the disease

Background: Budd-Chiari syndrome (BCS) is associated with parenchymal changes leading to major architecture remodelling. In order to gain further insight into the pathogenesis of BCS, we investigated expression of a set of genes involved in the course of chronic liver diseases. Methods: Quantitative expression of 35 selected genes involved in extracellular matrix regulation, growth factors, and angiogenesis was investigated in 13 cases of BCS and compared with 10 normal livers and 13 cirrhosis cases by real time reverse transcription-polymerase chain reaction. Differential gene expression was considered significant for genes showing at least a twofold variation, with p<0.05. Results: Expression of 14 genes was significantly increased in BCS versus normal liver, with the highest increase in superior cervical ganglion 10 (SCG10) gene. BCS cases were classified according to their evolution and morphological pattern as either acute or chronic in six and seven cases, respectively. Unsupervised hierarchical clustering of acute and chronic BCS cases on the basis of similarity in gene expression pattern led to distinction between the two groups. Expression of three genes was significantly different in acute versus chronic BCS (increase in matrix metalloproteinase 7 and SCG10, decrease in thrombospondin-1 for chronic BCS). Seventeen and 10 genes, mainly involved in extracellular matrix and vascular remodelling, were significantly deregulated in acute BCS versus normal liver and cirrhosis, respectively. Conclusion: These results show that BCS cases display a specific gene expression profile that is different from that of normal liver and cirrhosis; the molecular configuration of BCS can be readily distinguished by its evolution and morphological pattern.

Heat-Zone Effect after Surface Application of Dissecting Sealer on the “In Situ Margin” after Tumorectomy for Liver Tumors

BACKGROUND Resection remains the gold standard in the treatment of liver tumors. But radiofrequency ablation allows destruction of small liver tumors. The aim of this study was to evaluate the effect of surface application of a saline-linked dissecting sealer (TL) on the tumor bed that might contain residual microscopic tumor cells after resection (in situ margin). STUDY DESIGN Five hepatitis-infected woodchucks bearing primary liver tumors were used. Tumors > 1 cm in diameter were removed by tumorectomy. Alternately, the in situ margins were treated or not by TL. All samples were frozen and stained with hematoxylin and eosin and nicotine adenine dinucleotide (cell viability test). The median tumor diameter was 22 mm (range 10 to 53 mm). Among 84 in situ retrieved samples, 50 were from TL-treated tumors and 34 were from untreated controls. RESULTS The mean (+/-SD) heat-zone area was 12.6+/-2.8 mm in TL-treated tumors and 0.6+/-0.7 mm in controls (p < 0.001). Hematoxylin and eosin and nicotine adenine dinucleotide analyses showed 70% to 98% of cell destruction inside the heat-zone area in the TL-treated samples. There were macroscopic residual tumor cells (R2 resection) in 53 samples, with a median length of tumoral tissue inside the in situ margin of 3.5 mm. Among them, the heat-zone area was considerably longer in TL-treated versus untreated controls (13.3+/-2.6 mm versus 0.7+/-0.9 mm, p < 0.001). In samples with no residual tumor cells or microscopic residual tumor cells (R0/R1; n=31), the length of the tumoral margin was similar between TL-treated and untreated controls (0.7+/-0.2 mm and 0.9+/-0.2 mm, respectively, p=NS). Compared with controls, no viable cell was visible (up to 5 mm of depth) in the in situ margins in the TL-treated samples (p < 0.05). CONCLUSIONS These results support the hypothesis that surface application of the TL device on the in situ margins after tumorectomy could induce a substantial heat-zone area ranging from 10 to 13 mm, inside which, on a regressive heat gradient, up to 98% of cells could be destroyed. These observations could help to reduce marginal recurrence, especially in patients requiring multiple tumorectomies or complex liver resections for malignancy.

Intracystic concentrations of tumour markers for the diagnosis of cystic liver lesions

Imaging occasionally fails to differentiate hepatic simple cysts from malignant or premalignant mucinous cystic lesions such as biliary cystadenomas. Hepatic simple cysts can be treated conservatively, whereas malignant or premalignant cysts require complete resection. This study assessed the ability of intracystic tumour marker concentrations to differentiate these disease entities.

Detection of liver micrometastases from colorectal origin by perfusion CT in a rat model

BACKGROUND Some patients with colorectal carcinoma have liver metastases (LMs) which cannot be detected by conventional imaging. This study aimed to assess whether hepatic perfusion changes induced by micrometastases can be detected by perfusion computed tomography (CT). METHODS LMs were produced in rats by injecting carcinoma cells into the portal vein. Perfusion CT was performed at microscopic (day 10), interval (day 17), and macroscopic stage (day 34). Perfusion parameters were computed using a dual-input one-compartmental model. RESULTS Micro and macro LMs presented a mean diameter of 0.5 and 2.6 mm, respectively. Compared to controls, LMs at interval (1.1 mm) and macroscopic stage induced significant perfusion changes: a decrease of 42% (P=0.004) and 41% (P=0.029) in hepatic transit time and an increase of 292% (P=0.073) and 240% (P=0.001) in portal delay, respectively. CONCLUSIONS LMs with a mean diameter between 1.1 and 2.6 mm induced significant hepatic perfusion changes, detected by CT. Such detection may help to select patients and propose chemotherapy at the time of primary tumor resection.

Cystic fibrosis liver disease in adults: Limits of noninvasive tests of fibrosis

pital stay was, however, longer than the time taken to recover from overt HE, because there were other complications of cirrhosis, such as gastrointestinal bleeding and septicemia, which also required treatment. In the LOLA arm, rapid improvement of HE translated into a rapid mobilization and improvement in general condition and a shorter hospital stay. Lactulose syrup has been used in all the patients in both groups, because it is a part of the standard care of treatment of HE. Lactulose syrup was used in the dose of 30-120 mL in 3 divided doses through a nasogastric tube/orally to produce two to three semiformed stools and/or lactulose retention enemas (300 mL of lactulose 1 700 mL of water) twice-daily. In patients with constipation, higher dosage of oral lactulose (120 mL TID) along with lactulose enemas were given. There was no significant difference in the mean lactulose dose in each group. The incidence of diarrhea was 2 (2.0%) in the LOLA arm and 5 (5.2%) in the placebo arm. The authors of this letter also stated that the use of LOLA in grade 3-4 HE did not reduce the time to resolution or hospital stay in this group, limiting its potential use in such patients until the availability of further evidence. However, the results of subgroup analysis based on baseline grade of HE have to be interpreted cautiously, given that the type 1 error rate of observing a false-negative result is increased because of multiple testing.