Marcello Covino

Effect of different probiotic preparations on anti-helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study

OBJECTIVES:Several studies show that probiotics may prevent side effects during therapy against Helicobacter pylori (H. pylori). Other reports indicate competitive interaction between some probiotics and H. pylori. We compared efficacy of two different probiotics and one probiotic combination with placebo for preventing anti-H. pylori therapy-related side effects and for improving the eradication rate.METHODS:A total of 85 H. pylori positive, asymptomatic patients were randomized in four groups to receive probiotic or placebo both during and for 7 days after a 1-wk triple therapy scheme (rabeprazole 20 mg b.i.d., clarithromycin 500 mg b.i.d., and tinidazole 500 mg b.i.d.). Group I (n = 21) received Lactobacillus GG; group II (n = 22), Saccharomyces boulardii; group III (n = 21), a combination of Lactobacillus spp. and biphidobacteria; and group IV (n = 21), placebo. Subjects filled in weekly symptom questionnaires for 4 wk. Blinded investigators collected and analyzed data. H. pylori status was rechecked after 5–7 wk.RESULTS:Side effects occurred mainly during the eradication week. None of them caused therapy discontinuation. In all probiotic-supplemented groups, there was a significantly lower incidence of diarrhea and taste disturbance during the eradication week with respect to the placebo group. Overall assessment of tolerability was significantly better in the actively treated patients than in the placebo group. No differences in the incidence of side effects between the probiotic groups were observed. The H. pylori eradication rate was almost identical between the probiotic and placebo groups.CONCLUSIONS:All the probiotics used were superior to placebo for side effect prevention, but were not associated with better compliance with antibiotic therapy. The effect of probiotic supplementation on side effects during anti-H. pylori regimens seemed to be independent of the probiotic species used.

Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre.

Background: Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring systems) in a large series of cirrhotic patients with HCC undergoing non-surgical treatment in terms of their ability to classify patients into different risk groups Methods: We retrospectively studied 268 Italian patients with HCC. A total of 146 patients were treated with ablation, 132 with percutaneous ethanol injection, and 14 with radiofrequency ablation; 103 underwent transcatheter arterial chemoembolisation and 19 had supportive care alone. Factors determining survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, CLIP, and BCLC scores evaluated before treatment were applied. Results: Median survival was 25.7 months. In a multivariate analysis, portal vein thrombosis, α fetoprotein, total bilirubin, and tumour size were significant predictors of survival. Okuda, CLIP, and BCLC scores were all able to predict survival (p<0.001). They identified two, four, and six risk groups, respectively, with a median survival ranging from 27 to 19 months for Okuda, 30 to 5 months for CLIP, and 43 to 7 months for BCLC. Conclusions: Both CLIP and BCLC scores were more effective than the Okuda score in stratifying patients into different risk groups with early-intermediate HCC. However, the BCLC scoring system gave a better prediction of prognosis in patients with disease diagnosis at a very early stage.

Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted to liver transplantation: Assessment of efficacy at explant analysis and of safety for tumor recurrence

Aims of this retrospective study were to analyze the efficacy and safety of percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) in cirrhotic patients with hepatocellular carcinoma (HCC) submitted to orthotopic liver transplantation (OLT). We studied 40 patients undergoing OLT in whom 46 HCC nodules had been treated with PEI (13 nodules), RFA (30 nodules), or PEI+RFA (3 nodules). Child‐Turcotte‐Pugh class was A in 18 cases, B in 18, and C in 4. The mean waiting time for OLT was 9.5 months. The effectiveness of ablation techniques was evaluated by histological examination of the explanted livers. Complete necrosis was found in 19 nodules (41.3%), partial or absent necrosis in 27 nodules (58.7%). Among the 30 nodules treated by RFA, 14 were completely necrotic (46.7%) and 16 demonstrated partial necrosis (53.3%). Considering the 13 neoplasms undergoing PEI, 3 nodules showed complete necrosis (23.1%), 6 partial necrosis (46.1%), and 4 absent necrosis (30.8%). The rate of complete necrosis was 53.1% for nodules smaller than 3 cm and 14.3% for larger lesions (P = 0.033) but increased to 61.9% when considering only the lesions smaller than 3 cm treated by RFA. During the follow up, HCC recurred in 3 patients treated by PEI. No cases of HCC recurrence at the abdominal wall level were recorded. Percutaneous ablation procedures are effective treatments in cirrhotic patients with HCC submitted to OLT and are not associated to an increased risk of tumor recurrence. RFA provides complete necrosis in most nodules smaller than 3 cm, and appears to be the best treatment option in these cases. (Liver Transpl 2005;11:1117–1126.)

Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer

Mismatch repair genes MSH2 and MLH1 are considered to be the two major genes that are responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Germline heterozygous inactivating mutations of MSH2 and MLH1 have been identified previously in a substantial fraction of individuals who are predisposed genetically to colorectal carcinoma (CRC) and other tumors of the HNPCC spectrum. With the aim of determining the relevance of these two genes in the Italian population, we submitted to mutational analysis a set of 17 HNPCC families, all of which fulfilled the “Amsterdam criteria.” A combination of different techniques, including reverse transcription‐polymerase chain reaction (RT‐PCR) of long fragments and single‐strand conformation polymorphism (SSCP) on cDNA and genomic DNA, allowed the identification of ten molecular variants, seven of which are predicted to inactivate mismatch repair function. The mutated predisposing gene was MSH2 in two families and MLH1 in five other families. All of the mutations were characterized by DNA sequencing and appeared to involve different molecular mechanisms, such as short in‐frame and out‐of‐frame deletions, splicing errors, and nonsense mutations. This study also demonstrates that, in the Italian population, a considerable fraction of HNPCC families (at least 41%) is linked to MSH2 and MLH1 mutations. Genes Chromosom. Cancer 18:8–18, 1997.

Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after percutaneous ethanol injection therapy

The objective of this study was to identify clinical, biochemical, ultrasound, and/or pathologic parameters capable of predicting survival in a cohort of patients with well compensated cirrhosis and small hepatocellular carcinoma (HCC) who were treated with percutaneous ethanol injection (PEI).

-Increased carotid intima-media thickness in patients with inflammatory bowel disease

Background : Patients with inflammatory bowel disease have an increased risk of thrombotic complications; moreover, mesenteric microvascular thrombosis has been hypothesized as a contributing factor in the pathogenesis of inflammatory bowel disease.

Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas

BACKGROUND Alterations in epithelial proliferation and apoptosis in colonic mucosa are associated with an increased risk of colon cancer. It is unclear if these alterations represent a generalised “field defect”. AIMS To analyse segmental patterns of cell proliferation and apoptosis in the colon of subjects with a high and no apparent risk of colon cancer. METHODS Pancolonoscopy was performed in 15 patients with resected adenomas (⩾1.5 cm) and in nine subjects without an apparent risk of colorectal cancer. Mucosal biopsies were taken from the right colon, left colon, and sigmoid rectum. Crypt cell proliferation and apoptosis were evaluated, respectively, with bromodeoxyuridine immunohistochemistry and terminal deoxyuridine nucleotidyl nick end labelling of DNA strand breaks. Results are expressed as total labelling index (TLI) and labelling index (LI) for each of the five compartments in which colonic crypts were divided (fourth and fifth compartments were evaluated together) for cell proliferation and as apoptotic index (AI) for apoptosis assessment. RESULTS No significant segmental variations in proliferation were found in either group. Compared with controls, adenoma patients had higher TLIs for the right (p>0.05), left (p<0.005), and sigmoid rectum (p<0.05) segments, and higher left colon LIs for crypt compartments (compartment 1, p<0.01; compartment 2, p<0.005; compartment 3, p<0.001; compartments 4–5, p<0.01). Control AIs were similar in all segments but in the adenoma patients left colon and sigmoid rectum AIs were lower than their right colon indexes (p<0.05, p<0.05) and corresponding values for controls (p<0.01, p<0.05). CONCLUSIONS The colonic mucosa of patients with past adenomas presents diffuse hyperproliferation and, distally, abnormally distributed proliferating cells and markedly reduced apoptosis. These changes represent a significant risk for malignancies and could account for the high prevalence of left colon tumours.

Pancreatoduodenectomy for Tumors of Vater’s Ampulla: Report on 94 Consecutive Patients

Evaluation of prognostic factors of adenocarcinoma of Vater’s ampulla is still a matter of debate. The aim of this study was to evaluate retrospectively factors that influence early and long-term outcomes in a 20-year single-institution experience on ampullary carcinoma. A total of 94 consecutive patients with ampullary carcinoma or adenoma with severe dysplasia were managed from 1981 to 2002. Among them, 64 underwent pancreatoduodenectomy, and the remaining 30 submitted to surgical (n = 5) or endoscopic (n = 25) palliative treatment. Demographic, clinical, and pathologic data were collected, and a comparison was made between patients who did or did not undergo resection. Standard statistical analyses were carried out in an attempt to establish a correlation between clinical variables, intraoperative and pathologic factors, and survival in patients with resection. A total of 85 (90.4%) patients had potentially resectable lesions due to the extent of the tumor, but only 64 (68%) underwent curative resection. The surgical morbidity rate was 34.3%. Postoperative mortality was 9.3%, with no deaths among the 38 more recently treated patients. Median survivals were 9 and 54 months for nonresected and resected patients, respectively. The overall 5-year survival was 64.4% for patients undergoing pancreatoduodenectomy. Survival was found to be significantly affected by resection, tumor size, tumor grade, and tumor infiltration. Patients with negative lymph nodes show a trend toward longer survival. In a multivariate analysis, only the depth of tumor infiltration influenced patient survival.Pancreatoduodenectomy is the treatment of choice for ampullary carcinoma and adenomas with high-grade dysplasia, with a good chance of long-term survival. Surgical resection remains the most important factor influencing outcome.

Contrast‐enhanced power Doppler of the intestinal wall in the evaluation of patients with Crohn disease

Background: Crohn disease (CD) manifests with highly variable signs and symptoms, and assessment of the status of the disease in the single patient can be difficult. This study was conducted to evaluate the efficacy of power colour Doppler ultrasonography, with and without echo‐enhancement, in distinguishing active from quiescent CD. Methods: Resistance Index (RI) of the superior mesenteric artery (SMA), bowel thickness of the affected loops and the presence of colour signals at power Doppler analysis prior to and after ultrasonography contrast agent injection (Levovist®) were evaluated in 48 patients with CD. Results: In our series, 26/48 patients had active and 22/48 had quiescent CD. A CDAI score ≥150 and a pathological (>5 mg/dL) C reactive protein were significantly correlated with active disease (P < 0.001 and P = 0.004, respectively). Intestinal wall thickness showed no significant correlation with disease status (7.5 ± 1.3 mm in active disease versus 6.8 ± 1.3 mm in quiescent disease; P = 0.11). Vascular signals in the affected loops were revealed in 11/22 patients (50%) with active disease and in 5/26 (20%) with quiescent disease (P = 0.052). After Levovist injection, colour signals were found in 22/22 with active and in 8/26 with quiescent CD (P < 0.001). SMA RI was significantly lower in active CD patients (0.81 ± 0.01 versus 0.83 ± 0.02; P = 0.001). Conclusions: Our data suggest that in patients with CD a finding of a SMA RI ≤ 0.81, or the presence of a colour signal in the wall of the affected loops, at power Doppler sonography, is indicative of active disease. Utilization of echo‐enhancer media can greatly improve the diagnostic sensitivity of intestinal wall power Doppler scan. A finding of intestinal wall thickening is not associated with active disease in our series.

Impact of Emergency Surgery in the Outcome of Rectal and Left Colon Carcinoma

The negative results in terms of morbidity, mortality and survival among emergency treated patients affected by colorectal cancer are well known. The specific contribution of emergency surgery to adverse outcome is not clear because of the presence in all series of other possible determinants of a poor prognosis. We used a case-control study design to compare a group of 50 patients operated on for cancer of the rectum and left colon presented as emergencies in our department during the last 14 years, and an equal number of patients who underwent elective procedures during the same period. All records of these patients were reviewed and matched for age, stage, tumor location, and medical comorbidities (coronaropathy, diabetes mellitus, cerebral vascular deficiency, chronic obstructive pulmonary disease). Outcome measures included length of hospital stay, morbidity, mortality, and actuarial 5-year survival. Univariate and multivariate analysis of factors potentially influencing survival was performed on the entire population of 100 patients. Age, tumor location, stage of disease, and medical comorbidities were well matched by intent of the study design. Overall surgical morbidity (44% versus 12% P = 0.0004), length of hospital stay (16, 64 versus 10, 97 days P = 0.0026) and postoperative mortality (4% versus 0% P = 0.4949) resulted higher in the emergency group. Actuarial overall 5-year survival was not different between the two groups. The only variables independently predictive of survival in multivariate analysis were age and rectal location of the tumor. Postoperative surgical mortality and long-term survival appear not to be influenced by emergency presentation of colorectal cancer; the negative impact of the emergency procedures is confined to the immediate postoperative period and is probably connected to the acute medical pathology often presented by patients in emergency situations. Dealing with this kind of patient’s accurate preoperative assessment and solution of acute medical pathologies before surgical treatment are mandatory.