Claudio Avellini

Portal vein thrombosis in hepatocellular carcinoma: age and sex distribution in an autopsy study

Abstract The purpose of this work was to investigate the prevalence, associated features and effect on survival of portal vein thrombosis (PVT) complicating hepatocellular carcinoma (HCC). The autopsy data of a series of 72 consecutive patients (57 male, 15 female) with HCC were reviewed. PVT was found in 32/72 patients (44%), and tended to be more common in female patients (10/15 versus 22/57, P = 0.052). Stratifying the data according to gender, it appeared that the mean age of patients with PVT compared to those without was greater in woman (71.9 ± 5.9 versus 63.2 ± 6.9 years, P = 0.024) and younger in men (58.8 ± 8.9 versus 66.0 ± 9.9 years, P = 0.007). When PVT was present, it was more likely that a definite diagnosis of HCC had been obtained before autopsy (P = 0.0001) and that death had been caused by bleeding complications (P = 0.007). Median survival times were similar, irrespective of the presence of PVT. During the natural history of HCC, PVT occurs in a substantial proportion of patients. Hormonal factors may have a permissive role in thrombus formation or neoplastic vascular invasion. Although in the presence of PVT a diagnosis of HCC is rarely missed and bleeding complications are likely to occur, patient survival does not seem to be significantly affected.

Low-Dose Maintenance Therapy With Infliximab Prevents Postsurgical Recurrence of Crohn's Disease

BACKGROUND & AIMS Infliximab might prevent postsurgical recurrence of Crohns disease. However, it is unclear whether long-term therapy is necessary and whether alternative strategies could be applied to minimize potential side effects and reduce the costs of treatment. METHODS We performed a prospective cohort study in 12 consecutive patients, treated immediately after surgery with maintenance infliximab (5 mg/kg), who did not have clinical or endoscopic evidence of disease recurrence after 24 months; they were followed up for an additional year. Infliximab treatment was then discontinued; patients with disease recurrence, based on endoscopy (Rutgeerts score, >or=2), were given lower doses of infliximab (starting with 1 mg/kg) to re-establish mucosal integrity. Surrogate markers of disease activity (fecal calprotectin [FC], C-reactive protein, and erythrocyte sedimentation rate) were assessed after each infliximab dose. RESULTS None of the patients had clinical or endoscopic recurrence of Crohns disease 3 years after surgery. However, discontinuation of infliximab caused endoscopic recurrence after 4 months in 10 of 12 patients (83%). All 10 patients then were treated again with infliximab, which, at a dose of 3 mg/kg every 8 weeks, restored and maintained mucosal integrity for 1 year. Among the surrogate markers, FC levels correlated with endoscopic scores (Wald test, P < .0001). CONCLUSIONS Long-term maintenance therapy with infliximab is required to maintain mucosal integrity in patients after surgery for Crohns disease. However, a dose of 3 mg/kg (a 40% reduction from the standard dose) was sufficient to avoid disease recurrence, determined by endoscopy, in all patients at 1 year. FC levels correlate with mucosal status at different infliximab doses.

A case-control study of cancers of the gastric cardia in Italy

In a case-control study of gastric cancer (GC) in high-risk and low-risk areas in Italy, 923 GCs were reviewed by one pathologist and classified according to anatomic site. There were 68 (7.4%) cancers occurring in the gastric cardia. Compared to other GCs, cardia cancer tended to occur more often in males (sex ratio 2.8 vs 1.7) and as intestinal or unclassified histologic types. Nutritional factors for cardia tumours resembled those of other GCs, showing inverse associations with the consumption of raw vegetables, citrus and other fresh fruit, and ascorbic acid, and positive associations with the intake of traditional soups and meat, protein and cholesterol, and preference for salty foods. Cigarette smoking and wine consumption were unrelated to cardia cancer risk, and there was only a weak association with total alcohol intake. Cardia tumours showed a greater familial occurrence of GC than did other sites, with a 7-fold increase in risk for those reporting two first-degree relatives with GC. The authors discuss these findings in view of the rising incidence of adenocarcinomas of the cardia and lower oesophagus that has been reported in some western countries.

MRI scoring system including dynamic motility evaluation in assessing the activity of Crohn's disease of the terminal ileum

RATIONALE AND OBJECTIVES We sought to investigate the value of a MRI scoring system including dynamic motility evaluation in the assessment of small bowel Crohns disease activity. MATERIALS AND METHODS From March 2005 to December 2006, 52 patients with suspected Crohns disease onset or relapse underwent MRI on a 1.5-T magnet. Bowel distention was achieved orally assuming a mean of 1.6 L of a polyethyleneglycol (PEG) preparation. Per-patient assessment of disease activity was based on a scoring system including evaluation of morphology and motility of the small bowel and perivisceral structures (true-FISP, cine-true-FISP, and HASTE T2W sequences) and dynamic assessment of parietal contrast enhancement (FLASH T1W sequence). Patients were included in three categories, using endoscopic biopsy as the standard reference: no activity/quiescent disease, mild activity, or moderate-to-severe activity. Patients without terminal ileum involvement were excluded from data analysis. RESULTS MRI allowed a detailed and panoramic evaluation of the small bowel in all subjects examined. MRI properly assessed 14 of 16 (87.5%) cases of no activity/quiescent disease, 12 of 14 (85.7%) cases of mild activity, and 15 of 15 (100%) cases of severe activity. Overall, activity score led to a per-patient misdiagnosis of disease activity in a nonsignificant proportion of subjects (4 of 45; 8.8%) (P > .05), determining two false-positive and two false-negative results of mild disease activity. Sensitivity, specificity, PPV, NPV, and overall accuracy in assessing disease activity were 93.1%, 87.5%, 93.1%, 87.5%, and 91.1%, respectively. CONCLUSION Accurate assessment of Crohns disease activity is achieved by using an activity score providing an overall interpretation of MRI findings.

Pegylated versus standard interferon-α in antiviral regimens for post-transplant recurrent hepatitis C: Comparison of tolerability and efficacy

Background: In the treatment of hepatitis C virus (HCV) infection, regimens including pegylated interferon‐α are superior to those including standard interferon; the present retrospective study was performed to verify whether the same is applicable to biopsy‐proven recurrent hepatitis C (genotype 1b) after liver transplantation (OLT).

Subcellular localization of APE1/Ref-1 in human hepatocellular carcinoma : Possible prognostic significance

APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular response to oxidative stress. Cytoplasmic localization has been observed in several tumors and correlates with a poor prognosis. Because no data are available on liver tumors, we investigated APE1/Ref-1 subcellular localization and its correlation with survival in 47 consecutive patients undergoing hepatocellular carcinoma (HCC) resection. APE1/Ref-1 expression was determined by immunohistochemistry in HCC and surrounding liver cirrhosis (SLC) and compared with normal liver tissue. Survival probability was evaluated using Kaplan-Meier curves (log-rank test) and Cox regression. Cytoplasmic expression of APE1/Ref-1 was significantly higher in HCC than in SLC (P = 0.00001); normal liver showed only nuclear reactivity. Patients with poorly differentiated HCC showed a cytoplasmic expression three times higher than those with well-differentiated HCC (P = 0.03). Cytoplasmic localization was associated with a median survival time shorter than those with negative cytoplasmic reactivity (0.44 compared with 1.64 years, P = 0.003), and multivariable analysis confirmed that cytoplasmic APE1/Ref-1 localization is a predictor of survival. Cytoplasmic expression of APE1/Ref-1 is increased in HCC and is associated with a lower degree of differentiation and a shorter survival time, pointing to the use of the cytoplasmic localization of APE1/Ref-1 as a prognostic marker for HCC.

MILD SIALOADENITIS : A COMMON FINDING IN PATIENTS WITH HEPATITIS C VIRUS INFECTION

BACKGROUND Sjögrens syndrome (SS) is an autoimmune disease of presumed viral origin; sialoadenitis has been reported to occur in hepatitis C virus (HCV) infection. METHODS Lip biopsy specimens were graded in 32 consecutive patients with either HCV-related chronic liver disease or SS. RESULTS Seventeen of 22 HCV-positive patients had sialoadenitis, although generally mild (15 of 17, grades I-II). Severe inflammation (grades III-IV) was observed in 8 of 10 patients with SS (chi-square = 12.6; P < 0.0005). Moreover, HCV-positive patients with sialoadenitis differed from patients with SS in female sex prevalence (6 of 17 versus 10 of 10; chi-square = 10.9; P = 0.0001) and presence of serum antinuclear autoantibodies (0 of 17 versus 9 of 10; chi-square = 23.0; P < 0.0001). Five of 13 HCV-positive patients and 7 of 8 patients with SS were HLA-DR3-positive (chi-square = 4.9; P < 0.05). CONCLUSIONS Sialoadenitis of HCV-related liver disease is common but differs from SS with regard to predisposing genetic factors, expression of autoimmune markers, and histopathologic severity.

Role of AST to platelet ratio index in the detection of liver fibrosis in patients with recurrent hepatitis C after liver transplantation

Background and Aim:  Per protocol annual liver biopsy represents the gold standard in the assessment of graft fibrosis progression due to recurrent hepatitis C after liver transplantation. Non‐invasive liver fibrosis tests have been proposed as surrogate markers of liver fibrosis in hepatitis C virus (HCV)‐positive immune‐competent patients. No data are available in the literature on the usefulness of non‐invasive liver fibrosis tests in liver transplanted patients with recurrent HCV infection.

Prevention of postoperative recurrence of Crohn's disease by infliximab

The prevention of the recurrence of Crohns disease after surgery remains difficult. The monoclonal antibody anti-TNF-alpha, infliximab, is very effective in inducing and maintaining the remission of uncomplicated, active Crohns disease. We present here the case of a 23-year-old white woman who underwent resection for a sigmoid stricture caused by Crohns disease. Surgery removed the involved colon, and pathology confirmed the stricture to be fibrotic. Two weeks after the operation she was given infliximab at the dose of 5 mg/kg body weight and followed in time. Since then, she has been disease free for approximately 4 years after surgery on clinical, radiological and endoscopic/histological grounds (Crohns Disease Activity Index < or = 110 on all occasions). Up to now, she has had no increase in inflammatory indices, no anaemia and no abnormal blood tests. In contrast, all of five control patients operated in the same period with colonic or ileocolonic resection for symptomatic strictures and treated with mesalamine or no medication developed endoscopic or clinical recurrence (abdominal pain or diarrhoea) by year 3. This is the first case, to our knowledge, in which infliximab has been successfully used to prevent the postsurgical recurrence of Crohns disease, an event so far considered to be inescapable. We believe that, with this aim in mind, clinical trials with this drug are warranted.

Portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient

Hepatocytes transplantation is viewed as a possible alternative or as a bridge therapy to liver transplantation for patients affected by acute or chronic liver disorders. Very few data regarding complications of hepatocytes transplantation is available from the literature. Herein we report for the first time a case of portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient. A patient affected by acute graft dysfunction, not eligible for retransplantation, underwent intraportal infusion of 2 billion viable cryopreserved ABO identical human allogenic hepatocytes over a period of 5 h. Hepatocytes were transplanted at a concentration of 14 million/ml for a total infused volume of 280 ml. Doppler portal vein ultrasound and intraportal pressure were monitored during cell infusion. The procedure was complicated, 8 h after termination, by the development of portal vein thrombosis with liver failure and death of the patient. Autopsy showed occlusive thrombosis of the intrahepatic portal vein branches; cells or large aggregates of epithelial elements (polyclonal CEA positive), suggestive for transplanted hepatocytes, were co‐localized inside the thrombus.