Molecular detection of Helicobacter pylori and clarithromycin resistance in gastric biopsies: a prospective evaluation of RIDA®GENE Helicobacter pylori assay.

Background: Empirical treatment of Helicobacter pylori (HP) depends on the local prevalence of clarithromycin resistance but data are lacking and culturing of HP is time-consuming. We evaluated RIDA®GENE Helicobacter pylori assay (r-biopharm), a quantitative PCR assay for detecting HP and clarithromycin resistance mutations in gastric biopsies.Material/methods: Gastric biopsies were obtained from each of 436 consecutive patients referred for gastroscopic investigation and results of qPCR were compared to culture and immunohistochemical staining (IHCS).Results: Of 436 samples, 47 were positive for HP by PCR (11%), 42 by culture (9.7%) and 44 by IHCS (10%). Compared to culture, sensitivity and specificity of the qPCR were 100% and 99%, respectively, and 96% and 99% compared to IHCS. The sensitivity and specificity for clarithromycin resistance detection were 92% and 97%, respectively.Conclusions: RIDA®GENE Helicobacter pylori assay reliably and rapidly detects HP and its resistance to clarithromycin in human gastric biopsies.

The McCAVE Trial: Vanucizumab plus mFOLFOX-6 Versus Bevacizumab plus mFOLFOX-6 in Patients with Previously Untreated Metastatic Colorectal Carcinoma (mCRC).

BACKGROUND: Bevacizumab, a VEGF-A inhibitor, in combination with chemotherapy, has proven to increase progression-free survival (PFS) and overall survival in multiple lines of therapy of metastatic colorectal cancer (mCRC). The angiogenic factor angiopoetin-2 (Ang-2) is associated with poor prognosis in many cancers, including mCRC. Preclinical models demonstrate improved activity when inhibiting both VEGF-A and Ang-2, suggesting that the dual VEGF-A and Ang-2 blocker vanucizumab (RO5520985 or RG-7221) may improve clinical outcomes. This phase II trial evaluated the efficacy of vanucizumab plus modified (m)FOLFOX-6 (folinic acid (leucovorin), fluorouracil (5-FU) and oxaliplatin) versus bevacizumab/mFOLFOX-6 for first-line mCRC. PATIENTS AND METHODS: All patients received mFOLFOX-6 and were randomized 1:1 to also receive vanucizumab 2,000 mg or bevacizumab 5 mg/kg every other week. Oxaliplatin was given for eight cycles; other agents were continued until disease progression or unacceptable toxicity for a maximum of 24 months. The primary endpoint was investigator-assessed PFS. RESULTS: One hundred eighty-nine patients were randomized (vanucizumab, n = 94; bevacizumab, n = 95). The number of PFS events was comparable (vanucizumab, n = 39; bevacizumab, n = 43). The hazard ratio was 1.00 (95% confidence interval, 0.64-1.58; p = .98) in a stratified analysis based on number of metastatic sites and region. Objective response rate was 52.1% and 57.9% in the vanucizumab and bevacizumab arm, respectively. Baseline plasma Ang-2 levels were prognostic in both arms but not predictive for treatment effects on PFS of vanucizumab. The incidence of adverse events of grade ≥3 was similar between treatment arms (83.9% vs. 82.1%); gastrointestinal perforations (10.8% vs. 8.4%) exceeded previously reported rates in this setting. Hypertension and peripheral edema were more frequent in the vanucizumab arm. CONCLUSION: Vanucizumab/mFOLFOX-6 did not improve PFS and was associated with increased rates of antiangiogenic toxicity compared with bevacizumab/mFOLFOX-6. Our results suggest that Ang-2 is not a relevant therapeutic target in first-line mCRC. IMPLICATIONS FOR PRACTICE: This randomized phase II study demonstrates that additional angiopoietin-2 (Ang-2) inhibition does not result in superior benefit over anti-VEGF-A blockade alone when each added to standard chemotherapy. Moreover, the performed pharmacokinetic and pharmacodynamic analysis revealed that vanucizumab was bioavailable and affected its intended target, thereby strongly suggesting that Ang-2 is not a relevant therapeutic target in the clinical setting of treatment-naïve metastatic colorectal cancer. As a result, the further clinical development of the dual VEGF-A and Ang-2 inhibitor vanucizumab was discontinued.

Lanreotide in the prevention and management of high-output ileostomy after colorectal cancer surgery.

Objective: Patients with stage III and high-risk stage II colorectal cancer (CRC) are advised to initiate adjuvant treatment as soon as feasible and certainly before 8 to 12 weeks after resection of the tumor. A protective ileostomy is often constructed during surgery to protect a primary anastomosis "at risk", especially in rectal cancer surgery. However, up to 17% of patients with a stoma suffer from high output, a major complication that can prevent adjuvant treatment implementation or completion. To avoid delay or cancellation of adjuvant therapy after CRC resection, effective strategies must be implemented to successfully treat and/or prevent high-output stoma (HOS). Methods: We report two clinical case reports clearly demonstrating the impact and management of HOS in this setting. A review of the available literature and ongoing clinical studies is provided. Results: The clinical cases describe patients with advanced stage CRC and focus on the different strategies for HOS management, presenting their outcome and how each strategy affects the implementation of adjuvant treatment. The patient population with the highest risk of developing HOS is described, along with the rationale for using somatostatin analogs, such as lanreotide, to treat and prevent high output. Conclusion: In patients with CRC and protective ileostomies after primary resection, HOS could be treated with somatostatin analogs in combination with dietary recommendations and Saint Mark's solution. The role of this therapeutic approach as a preventive strategy in patients at high risk of developing HOS, deserves further exploration in a prospective randomized clinical trial.

Integrating geriatric assessment in the first line chemotherapy treatment in older patients with metastatic colorectal cancer: Results of a prospective observational cohort study (AVAPLUS).

OBJECTIVES: This study aims to investigate the use of chemotherapy with or without bevacizumab in older patients with metastatic colorectal cancer (mCRC) in current daily practice and to identify predictive parameters for treatment-related outcomes. PATIENTS AND METHODS: This is a Belgian multi-centre, observational cohort study. Patients≥70years old with mCRC considered suitable for first-line chemotherapy were eligible for inclusion. At baseline geriatric screening and assessment was performed. Treatment choice was at the discretion of the investigator. Treatment duration, Progression Free Survival (PFS) and safety were recorded. RESULTS: Between August 2011 and July 2013, 252 patients with mCRC were included of which 50.8% were treated with bevacizumab. Median treatment duration was 5.5months and median PFS was 8.9months. Approximately 50% of patients experienced severe adverse events, most frequently diarrhea. In multivariate analysis, baseline Eastern Cooperative Oncology Group (ECOG)-performance status (PS) was predictive for treatment duration (p=0.0047), PFS (p<0.0001) and severe toxicity and baseline nutritional status for PFS (p=0.0007). In patients with a good ECOG-PS, nutritional status was predictive for PFS. CONCLUSIONS: In current daily practice in Belgium, half of older patients with colorectal cancer treated with chemotherapy also receive bevacizumab. Nearly half of older patients presented with severe toxicity during treatment. Baseline nutritional status is a predictive marker for PFS. Patients with a baseline ECOG-PS≥2 have shorter PFS and higher risk of severe toxicity and should therefore be treated with caution.

Comparison of six different calprotectin assays for the assessment of inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: Faecal calprotectin is a valuable noninvasive marker for inflammatory bowel disease (IBD). The aim of our study was to determine the correlation between six different calprotectin assays and compare their performance for diagnosis and follow up of IBD. METHODS: Thirty-one patients with suspected IBD and 31 patients in follow up were included. We determined calprotectin by means of three rapid immmunochromatographic tests, two enzyme-linked immunosorbent assays, and one automated fluoroimmunoassay. Results were correlated with endoscopic and histological findings. RESULTS: Although all methods correlated significantly, slopes and intercepts differed extensively, with up to 5-fold quantitative differences between assays. Sensitivity and specificity for diagnosis of IBD were 82-83 and 84-89%, respectively. For follow up, sensitivity in detecting mild ulcerative colitis was 71-100%. In moderate-to-severe ulcerative colitis, sensitivity was 100% for all assays. Specificity was 67-86% in both subgroups. In Crohn's disease, only moderate-to-severe disease could be differentiated from remission, with sensitivity 83-86% and specificity 75% for all tests. CONCLUSIONS: All calprotectin assays showed comparable clinical performance for diagnosis of IBD. For follow up, performance was acceptable, except for mild Crohn's disease. Because of the large quantitative differences, further efforts are needed to standardize calprotectin assays.

Endoscopic trimming of metallic stents with the use of argon plasma.

BACKGROUND: The endoscopic placement of metallic stents for palliation of malignant obstruction of the GI or biliary tract is an established practice and as such is often applied. Use of these stents, however, has its problems. Stent migration may cause obstruction of the bowel lumen. Migration of a biliary stent into the contralateral duodenal wall may cause difficulty in gaining access to the biliary tract, as will the placement of a duodenal stent across the ampulla. OBJECTIVE: We report on 6 patients in whom trimming of the metallic nitinol stent was performed. DESIGN: Single-center, retrospective case series. SETTING: Secondary referral center. PATIENTS: Of 6 patients included, 2 patients each had an uncovered duodenal stent, 2 had an uncovered biliary stent each, 1 had an uncovered colorectal stent, and 1 had a covered gastroduodenal stent. INTERVENTIONS: Under direct endoscopic vision, an argon plasma beam was used to cut self-expandable metallic stents, as appropriate. MAIN OUTCOME MEASUREMENT: The main objective was relief of the obstruction to the bowel lumen or bile duct, facilitating successful passage of an endoscope or biliary canulation, respectively. RESULTS: In all 5 patients with uncovered metallic stents, we were able to re-establish access to the obstructed bowel lumen or the biliary tree, as indicated. An attempt to tailor the length of a covered metallic gastroduodenal stent failed. No complications were observed and no hemorrhage or perforation occurred. LIMITATIONS: The study was limited by retrospective design and small sample size. CONCLUSIONS: The endoscopic cutting and tailoring of an uncovered metallic prosthesis, by means of an argon plasma beam, is feasible, effective, and safe. Trimming of covered stents is not advocated.

Cytomegalovirus colitis in an apparently immunecompetent host after biliopancreatic diversion for obesity.

CMV colitis in an immunocompetent host is a rare occurrence. We report a case of CMV colitis after biliopancreatic diversion surgery. The diagnosis of primary CMV infection with CMV colitis was based on histological examination of tissues biopsies obtained at colonoscopy, serology positive for CMV-IgM and CMV-IgG antibodies and a good response to systemic gancyclovir treatment. Malnutrition and colonic mucosal damage, both consequences of biliopancreatic diversion surgery, were thought to be predisposing factors. To our knowledge this is the first report in the English language literature of an association between CMV colitis and status following biliopancreatic diversion surgery.