Research from JAMA Surgery — Bile Duct Injury During Laparoscopic Cholecystectomy — Results of an Italian National Survey on 56 591 Cholecystectomies

SUMMARY: Background : Antibiotic‐associated diarrhoea can be attributed in part to imbalances in intestinal microflora. Therefore, probiotic preparations are used to prevent this diarrhoea. However, although several trials have been conducted, no conclusive evidence has been found of the efficacy of different preparations, e.g. Lactobacillus spp. and Saccharomyces spp.Aim : To conduct a meta‐analysis of the data in the literature on the efficacy of probiotics in the prevention of antibiotic‐associated diarrhoea.Methods : A literature search was performed of electronic databases, Abstract Books and single paper references. Data were also obtained from the authors. Only placebo‐controlled studies were included in the search. The Mantel–Haenszel test was used to estimate the relative risk for single studies and an overall combined relative risk, each study being submitted to the Mantel–Haenszel test for homogeneity.Results : Twenty‐two studies matched the inclusion criteria. Only seven studies (881 patients) were homogeneous. The combined relative risk was 0.3966 (95% confidence interval, 0.27–0.57).Conclusions : The results suggest a strong benefit of probiotic administration on antibiotic‐associated diarrhoea, but further data are needed. The evidence for beneficial effects is still not definitive. Published studies are flawed by the lack of a placebo design and by peculiar population features.

B-cell chronic lymphocytic leukemia (B-CLL) follows heterogeneous clinical courses, and several biological parameters need to be added to the current clinical staging systems to predict which patients will experience an indolent or an aggressive outcome. This study analyzed CD38 expression by flow cytometry and soluble APO1/Fas (sAPO1/Fas), Bcl-2 (sBcl-2), and CD23 (sCD23) proteins by immunoenzymatic methods to evaluate their effect on the clinical course of 168 unselected B-CLL patients. Intermediate/high risk modified Rai stages were characterized by a higher CD38⁺ B-cell number (P = .0002) and higher sCD23 levels (P < .0001). Moreover, CD38⁺ B-cell percentages were significantly and directly associated both with β₂-microglobulin and sCD23 concentrations (P < .0001 and P = .002, respectively). Both a higher tumor burden (lymphadenopathy/splenomegaly) and a lymphocyte doubling time less than 12 months were significantly associated with higher CD38⁺ percentages (P < .0001 and P = .0001, respectively). With regard to clinical outcome, progression-free survival was significantly longer (75% versus 37% at 5 years; P = .00006) in patients with lower CD38⁺ B-cell percentages. Furthermore, the risk of partial or no response to fludarabine increased with increasing CD38 expression (P = .003), and a shorter overall survival (50% versus 92% at 8 years; P < .00001) characterized patients with more than 30% CD38⁺ B-cell number. The predictive value of CD38 expression was maintained among the patients within the Rai intermediate risk group and was confirmed in multivariate analysis. Thus, the percentage of CD38⁺ B cells appears to be an accurate predictor of clinical outcome and therefore could be used to indicate when more novel chemotherapeutic approaches are needed.

In laboratory studies electromotive mitomycin C (MMC) demonstrated markedly increased transport rates compared with passive transport. We performed a prospective study in patients with high risk superficial bladder cancer to assess the efficacy of intravesical electromotive vs passive MMC using bacillus Calmette-Guerin (BCG) as a comparative treatment. Following transurethral resection and multiple biopsies 108 patients with multifocal Tis, including 98 with T1 tumors, were randomized into 3 equal groups of 36 each who underwent 40 mg electromotive MMC instillation with 20 mA electric current for 30 minutes, 40 mg passive MMC with a dwell time of 60 minutes or 81 mg BCG with a dwell time of 120 minutes. Patients were scheduled for an initial 6 weekly treatments, a further 6 weekly treatments for nonresponders and a followup 10 monthly treatments for responders. Primary end points were the complete response rate at 3 and 6 months. MMC pharmacokinetics were assessed. The complete response for electromotive vs passive MMC at 3 and 6 months was 53% versus 28% (p = 0.036) and 58% versus 31% (p = 0.012). For BCG the responses were 56% and 64%. Median time to recurrence was 35 vs 19.5 months (p = 0.013) and for BCG it was 26 months. Peak plasma MMC was significantly higher following electromotive MMC than after MMC (43 vs 8 ng/ml), consistent with bladder content absorption. Intravesical electromotive administration increases bladder uptake of MMC, resulting in an improved response rate in cases of high risk superficial bladder cancer.