Mirko Olivo

Radiofrequency thermal ablation vs. percutaneous ethanol injection for small hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled trials.

OBJECTIVES:Radiofrequency thermal ablation (RF) and percutaneous ethanol injection (PEI) have been employed in the treatment of small hepatocellular carcinoma (HCC) as curative treatments. The aim of the study was to review the available evidence comparing RF to PEI for small HCC.METHODS:Search strategy: Cochrane, MEDLINE, CANCERLIT, and ENBASE databases were used. Selection criteria: randomized clinical trials evaluating RF vs. PEI. Data were extracted from each randomized controlled trial (RCT). Primary outcomes were overall survival and local recurrence. Meta-analysis software was used and risk differences (RDs) and their 95% confidence intervals and Q-test for heterogeneity were calculated.RESULTS:Five RCTs were identified including 701 patients. The overall survival was significantly higher in patients treated with RF than in those treated with PEI (RD 0.116, 95% CI 0.173/0.060; heterogeneity not present). Local recurrence rate is significantly higher in patients treated with PEI than in those treated with RF. In the RF group the 1, 2, and 3 years cancer-free survival rates were significantly better than in the PEI-treated patients (respectively: RD 0.098—95% CI 0.006/0.189; heterogeneity P=0.57; RD 0.187, 95% CI 0.082/0.293; heterogeneity P=0.98; RD 0.210, 95% CI 0.095/0.325; heterogeneity P = 0.78). A small number of adverse events were reported in the two treatments.CONCLUSIONS:RF ablation is superior to PEI in the treatment of small HCC with respect to overall survival, 1, 2, and 3 years survival rates, 1, 2, and 3 cancer-free survival rates, and tumor response. RF shows a significantly smaller risk of local recurrence.

Efficacy and safety of endoscopic balloon dilation of symptomatic intestinal Crohn's disease strictures.

AIM To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohns disease strictures. METHODS Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohns disease patients with 39 intestinal symptomatic strictures (4 naïve and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were obtained by Kaplan-Meier method. Demographic and disease variables were related to the main outcomes. RESULTS After a mean follow-up of 26.3 months (range, 2-61 months), the long-term global benefit rate was 89% (33/37). The 1-2-3 years cumulative symptom-free rates were respectively: 76%, 55% and 46%. Four patients were operated upon. Technical success predicts a lower rate of surgery. There were no complications related to the endoscopic procedures. CONCLUSIONS Endoscopic balloon dilation of symptomatic Crohns disease strictures may achieve clinical benefit in many patients and is a valid alternative to surgery in the management of the disease. Dilation may be repeated in recurrent intestinal obstructions and appears safe without morbidity.

Transcatheter arterial chemoembolisation for hepatocellular carcinoma in cirrhosis: Survival rate and prognostic factors

BACKGROUND The role of prognostic variables in the treatment of hepatocellular carcinoma (HCC) by transarterial chemoembolisation (TACE) is controversial. AIMS To evaluate the survival of patients with HCC on cirrhosis treated with TACE and to analyse the prognostic factors affecting survival. METHODS From 1996 to 2006, 580 consecutive patients with HCC in cirrhosis were observed. Of these 194 patients underwent TACE. The primary end-point was survival. Independent predictors of survival were identified using the Cox model. RESULTS The cumulative 1-year, 3-year, and 5-year survival rates were 96%, 60%, and 41%, respectively. The multivariate analysis showed significant reduction of survival among patients with serum bilirubin values >2mg/dl compared to patients with values <2mg/dl (Hazard ratio 3.84; CI 95% 1.70-8.66; p-value=0.001). Multivariate analysis performed in the group of patients treated with TACE alone showed that elevated serum bilirubin (Hazard ratio 2.96; CI 95% 1.20-7.3; p-value 0.02) and incomplete tumour response (Hazard ratio 2.88; CI 95% 1.18-7.05; p-value 0.02) are correlated with a worse outcome. CONCLUSIONS TACE was well tolerated and overall survival rate was 41% after 5 years. Complete tumour response and serum bilirubin <2mg/dl were identified as predictors of survival.

CA 19-9 to Rule Out Pancreatic or Biliary Cancer Among Patients with Cholestasis: An Unsuitable Test?

Carbohydrate antigen CA 19-9 was initially proposed as a serologic marker for colorectal cancer [1]. Nowadays its use is not recommended for this purpose [1] and CA 19-9 serum concentration is mostly evaluated in patients with suspected pancreatic or biliary cancer, because of its presumed higher specificity in this setting [2–5]. Unfortunately, CA 19-9 levels have also been reported in other malignancies such as gastric and ovarian cancer and in different benign conditions like cystic fibrosis, hydronephrosis, and Hashimoto thyroiditis [5–7]. Furthermore, elevated CA 19-9 serum concentration can be associated with several conditions producing reduced biliary drainage [8–10], especially in the presence of cholangitis [11]. It is generally be-

Early postoperative recurrence of severe crohn's disease, with colonic involvement and associated human cytomegalovirus infection, treated with oral valganciclovir and adalimumab

To the Editor: In the natural course of Crohn’s disease (CD), postoperative recurrence and opportunistic infections such as human cytomegalovirus (HCMV) infection are two conditions that may lead to a more disabling behavior, despite intensive first-line treatments. Early recognition of these conditions may help to manage severe CD by choosing adequate treatments to avoid more severe disease complications. We describe an early postoperative recurrence of severe CD, with colonic involvement and superimposed HCMV infection, treated with oral valganciclovir and adalimumab subcutaneously. A 52-year-old female patient, affected by a recently diagnosed ileocolonic steroid-dependent CD, was admitted to our department with a history of nonbloody diarrhea and severe weight loss, without abdominal pain or other symptoms of possible intestinal obstruction. Six months previously she underwent a bowel resection with ileocolonic anastomosis for an intestinal subocclusion due to a stenosis of the ileocecal valve, complicated by pelvic abscess. On physical examination the patient presented signs of severe malnutrition (body mass index [BMI] 12), without any abdominal tenderness or fever, with a blood pressure of 100/50 mmHg and pulse rate of 80 beats/min. Her Crohn’s Disease Activity Index (CDAI) score on admission was 297. Laboratory tests showed neutrophilic leukocytosis, erythrocite sedimentation rate (ESR) of 45 mm/hr, C-reactive protein (CRP) of 7 mg/L (n.v. 0.5 mg/L), and severe hypoalbuminemia (1.7 g/dL). X-ray of the abdomen showed no signs of megacolon. Therapy with systemic corticosteroid was started. An elementary diet to correct malnutrition was also tried; however, it was not tolerated by the patient (worsening of the diarrhea), so a total parenteral nutrition was started. Stool cultures, parasitologic tests, pp65-antigenemia on peripheral leukocytes to check HCMV in serum were performed. Abdominal ultrasound showed thickening of the preanastomotic ileum and diffuse edema of descending colon walls. X-ray enteroclysis showed an irregular and marked mucosal relief into duodenum and proximal jejunum, which appeared with a nodular aspect and a ‘‘jejunalization’’ of the remaining ileal loops. Colonoscopy, with multiple biopsies, was also performed, showing a severe CD with multiple ulcerations around the ileocolonic anastomosis and in the whole colon. Histology showed typical features of active CD, while hematoxylin and eosin staining and immunohistochemistry were markedly positive for CMV detection. Stool cultures and parasitologic tests were negative, while the pp65-antigenemia showed a positivity of 72 fluorescent nuclei/2 10 leukocytes. Antiviral therapy with oral valganciclovir (450 mg twice daily) was started for systemic infection due to HCMV and prolonged for 21 days, concomitant to steroid tapering and resumption of oral alimentation, with a good clinical response and viral undetectability 15 days after the first pp65-antigenemia. The presence of marked disease activity with severe colonic involvement led us to an aggressive therapeutic approach, starting biologic therapy with adalimumab, at the induction dosage of 160 mg followed by 80 mg 2 weeks later, after performing the recommended screening. After the second injection the patient was in clinical remission (CDAI score <150) and with improved nutritional status (BMI 14), so adalimumab was maintained at a dose of 40 mg every other week. Six months later remission was maintained and nutrition status further improved. Laboratory tests, including ESR and CRP, were normal. Since 2007, adalimumab has been endorsed for the treatment of moderateto-severe luminal CD. However, starting a biologic therapy means paying attention to serious adverse events such as opportunistic infections, such as HCMV, whose role in inflammatory bowel disease is still unclear. Its pharmacological treatment is mandatory when it causes a systemic infection or a symptomatic end-organ disease. It is not clear which is the correct approach when HCMV is detected only in the colon, such as detection of colitis, thus antiviral therapy should be initiated. Our patient was affected with severe colonic CD, needing an early and aggressive therapeutic approach, but adalimumab was only started after treating the HCMVwith oral valganciclovir. In the scientific literature a case of Crohn’s colitis complicated by HCMV infection, in which oral valganciclovir was used as switching therapy after intravenous ganciclovir has been described. We report a case of severe Crohn’s colitis complicated by HCMV infection, in which oral valganciclovir therapy allowed us to start biologic therapy with quick, long, and safe efficacy.

W1113 Efficacy and Safety of Endoscopic Balloon Dilation of Symptomatic Intestinal Crohn's Disease Strictures

Aim: To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohn’s disease strictures. Methods: Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohn’s disease patients with 39 intestinal symptomatic strictures (4 naive and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were obtained by Kaplan–Meier method. Demographic and disease variables were related to the main outcomes. Results: After a mean follow-up of 26.3 months (range, 2–61 months), the long-term global benefit rate was 89% (33/37). The 1–2–3 years cumulative symptom-free rates were respectively: 76%, 55% and 46%. Four patients were operated upon. Technical success predicts a lower rate of surgery. There were no complications related to the endoscopic procedures. Conclusions: Endoscopic balloon dilation of symptomatic Crohn’s disease strictures may achieve clinical benefit in many patients and is a valid alternative to surgery in the management of the disease. Dilation may be repeated in recurrent intestinal obstructions and appears safe without morbidity.