Leslie Rinaldi

Association Between Low Trough Levels of Vedolizumab During Induction Therapy for Inflammatory Bowel Diseases and Need for Additional Doses Within 6 Months

BACKGROUND & AIMS: We investigated whether serum trough levels of vedolizumab, a humanized monoclonal antibody against integrin &agr;4&bgr;7, during the induction phase of treatment can determine whether patients will need additional doses (optimization of therapy) within the first 6 months. METHODS: We conducted an observational study of 47 consecutive patients with Crohn’s disease (CD; n = 31) or ulcerative colitis (UC; n = 16) who had not responded to 2 previous treatment regimens with antagonists of tumor necrosis factor and were starting therapy with vedolizumab at 2 hospitals in France, from June 2014 through April 2016. All patients were given a 300‐mg infusion of vedolizumab at the start of the study, Week 2, Week 6, and then every 8 weeks; patients were also given corticosteroids during the first 4–6 weeks. Patients not in remission at Week 6 were given additional doses of vedolizumab at Week 10 and then every 4 weeks (extended therapy or optimization). Remission at Week 6 of treatment was defined as CD activity score below 150 points for patients with CD and a partial Mayo Clinic score of <3 points, without concomitant corticosteroids, for patients with UC. Blood samples were collected each week and serum levels of vedolizumab and antibodies against vedolizumab were measured using an enzyme‐linked immunosorbent assay. Median trough levels of vedolizumab and interquartile ranges were compared using the nonparametric Mann‐Whitney test. The primary objective was to determine whether trough levels of vedolizumab measured during the first 6 weeks of induction therapy associated with the need for extended treatment within the first 6 months. RESULTS: Based on response to therapy at Week 6, extended treatment was required for 30 of the 47 patients (23 patients with CD and 7 patients with UC). At Week 2, trough levels of vedolizumab for patients selected for extended treatment were 23.0 &mgr;g/mL (interquartile range, 14.0–37.0 &mgr;g/mL), compared with 42.5 &mgr;g/mL in patients who did not receive extended treatment (interquartile range, 33.5–50.7; P = .15). At Week 6, trough levels of vedolizumab <18.5 &mgr;g/mL were associated with need for extended therapy (100% positive predictive value, 46.2%; negative predictive value; area under the receiver operating characteristic curve, 0.72) within the first 6 months. Among patients who required extended treatment at Week 10, all of those with trough levels of vedolizumab <19.0 &mgr;g/mL at Week 6 had achieved clinical remission 4 weeks later (secondary responders). CONCLUSIONS: In a prospective study of patients with CD or UC receiving induction therapy with vedolizumab, low trough levels of vedolizumab at Week 6 (<19.0 &mgr;g/mL) are associated with need for additional doses (given at Week 10 and then every 4 weeks). All patients receiving these additional doses achieved a clinical response 4 weeks later.

Laparoscopy could be the best approach to treat colorectal cancer in selected patients aged over 80 years: Outcomes from a multicenter study.

BACKGROUND The efficacy and safety of treating elderly patients with colorectal cancer (CRC) is of concern. This study aimed to compare the short- and long-term outcomes of elective laparoscopic vs. open surgery to treat CRC in very elderly patients. METHODS All patients aged >80 years and who had undergone a colectomy for CRC without metastasis between July 2005 and April 2012 were considered for inclusion. Demographic, clinical, operative, and postoperative data, plus overall and disease-free survival rates, were retrospectively collected and compared between two groups of patients that underwent an open procedure (OP group) or laparoscopy (LG). RESULTS 123 patients were enrolled (55 OPG, 68 LG). Median age was similar between the groups (84 vs. 83 years, respectively; NS). Duration of surgery was significantly lower in OPG (170 vs. 200min; p=0.030). Overall mortality at 3 months was 8.3%: it tended to be greater in the OPG (16.5% vs. 1.5%, NS). Morbidity was significantly greater in the OPG compared to the LG (52.7% vs. 27.5%; p=0.021), resulting in significantly longer hospital stay (12 vs. 8 days, respectively; p<0.001). Pathological findings were similar between the two groups. Cumulative overall survival rates at 3 and 5 years were significantly greater after laparoscopy (85% and 72%) compared to open surgery (58.2% and 48%, respectively; p<0.001). CONCLUSIONS Our study suggests that laparoscopy is safe and could increase overall survival compared to open surgery in elderly patients suffering from CRC. SUMMARY This retrospective study compared the short- and longer-term outcomes of patients aged >80 years and undergoing elective laparoscopic or open surgery for CRC between 2005 and 2012.

Difficult endoscopic diagnosis of a pancreatic plasmacytoma: Case report and review of literature

A 71-year-old man, with history of plasmacytoma in relapse since one year, was hospitalized for a initial presentation of acute pancreatitis and hepatitis. Although there was a heterogeneous infiltration around the pancreas head, the diagnosis of an extramedullary localization of his plasmacytoma was not made until later. This delayed diagnosis was due to the lack of specific radiologic features and the lack of dilatation of biliary ducts at the admission. A diagnosis was made with a simple ultrasound guided paracentesis of the low abundance ascites after a transjugular hepatic biopsy, an endoscopic ultrasound-guided fine needle aspiration of the pancreatic mass, and a failed attempt of biliary drainage through endoscopic retrograde cholangiopancreatography. In order to document the difficulty of this diagnosis, characteristics of 63 patients suffering from this condition and diagnosis were identified and discussed through a systematic literature search.

Effect of Endocuff-assisted colonoscopy on adenoma detection rate: meta-analysis of randomized controlled trials

BACKGROUND Yield of Endocuff-assisted colonoscopy (EAC) compared with standard colonoscopy is conflicting in terms of adenoma detection rate (ADR). A meta-analysis of randomized controlled trials (RCTs) appears necessary. METHODS PubMed and Google Scholar were searched in December 2017. Abstracts from Digestive Disease Week and United European Gastroenterology Week meetings were also searched to 2017. All RCTs comparing EAC with standard colonoscopy were included. Analysis was conducted by using the Mantel-Haenszel models. Heterogeneity was quantified using the I2 test. RESULTS Of the 265 articles reviewed, 12 RCTs were included, with a total of 8376 patients (EAC group 4225; standard colonoscopy group 4151). In the meta-analysis, ADR was significantly increased in the EAC group vs. the standard colonoscopy group (41.3 % vs. 34.2 %; risk ratio [RR] = 1.20, 95 % confidence interval [CI] 1.06 to 1.36; P = 0.003; I2 = 79 %), especially for operators with low-to-moderate ADRs (< 35 %): RR = 1.51, 95 %CI 1.35 to 1.69; P < 0.001; I2 = 43 %). In contrast, this benefit was not reached for operators with high ADRs (> 45 %): RR = 1.01, 95 %CI 0.93 to 1.09; P = 0.87; I2 = 0.0 %). The mean number of adenomas per patient tended to be higher with EAC (mean difference = 0.11 adenomas/patient, 95 %CI - 0.17 to 0.38). Similar results were shown for polyp detection rates (61.6 % vs. 51.4 %; RR = 1.20, 95 %CI 1.06 to 1.36; P = 0.004). Use of the Endocuff did not impact the cecal intubation rate (95.1 % vs. 95.7 %; P = 0.08), or the procedure time compared with standard colonoscopy. Adverse events related to Endocuff were rare and exclusively mild mucosal erosion (4.0 %; 95 %CI 2.0 % to 8.0 %). CONCLUSION With moderate-quality evidence, this study showed an improvement in ADR with EAC without major adverse events, especially for operators with low-to-moderate ADRs.

The level of epidermal growth factor receptors expression is correlated with the advancement of colorectal adenoma: validation of a surface biomarker

Introduction Data about the expression of Epidermal Growth Factor Receptors (EGFRs) in colorectal adenomas remain scarce. Results 101 patients were enrolled including 53 controls. All adenomas (n = 38) and CRC (n = 5) were EGFR positive. Hyperplastic polyps (HP) (n = 8) and control colons (n = 53) were EGFR negative in half of cases (p < 0.0001). A well significant gradient of increased EGFR expression was observed between adjacent mucosa, hyperplastic lesions, low grade dysplasia (LGD) (n = 30), high grade dysplasia (HGD) adenomas (n = 9) and cancers (p < 0.0001). EGFR overexpression was reported in 100% of cancers, 77.8% of HGD, and 10% of LGD adenomas. By multivariate analysis in adenomas, associated factors with EGFR overexpression were HGD and tubulo-villous feature. Materials and Methods All patients undergoing colonoscopy in the university center of Saint-Etienne were eligible to the study from December 2015 to March 2016. In patients with colorectal neoplasia (lesions group), biopsies were performed on the lesion before its resection, and on the adjacent and distal colon mucosa. In control group, biopsies were performed in the right and left side colon. The EGFR expression was assessed by immunohistochemical scores (Goldstein grade, intensity of staining, composite score), using a primary mouse monoclonal antibody (EGFR, clone 113, Novocastra). Outcomes were compared using Kruskal-Wallis and/or Mann-Whitney-U tests, appropriately. The associated clinical, endoscopic and histological factors with EGFR overexpression (composite score ≥ 6) were assessed for adenomas by logistic regression. Conclusions EGFR are early involved in colorectal carcinogenesis, and their expression is strongly correlated to the neoplasia stage, leading to validate EGFR as an interesting surface biomarker of adenomas.

Metals distribution in colorectal biopsies: New insight on the elemental fingerprint of tumour tissue

BACKGROUND Some studies have linked colorectal cancer to metal exposure. AIMS Our objective was to evaluate the element distribution in colorectal adenocarcinoma biopsies, adjacent non-tumour tissues, and healthy controls. METHODS The study is a case-control study which compared the element distribution in colon biopsies from two groups of patients: with colorectal cancer (2 types of samples: colorectal cancer biopsies and adjacent non-tumour tissues) and healthy controls. Fifteen metal concentrations (Aluminium, Boron, Cadmium, Chromium, Copper, Iron, Magnesium, Manganese, Nickel, Lead, Selenium, Silicon, Titanium, Vanadium, and Zinc) were quantified by using inductively coupled plasma atomic emission spectrometry. RESULTS 104 patients were included: 76 in the colorectal cancer group, 28 in the healthy control group. Among the 15 elements analyzed, only boron, chromium, zinc, silicon and magnesium were found at clearly detectable concentrations. Colorectal tumour biopsies had significantly higher concentrations of magnesium as compared to adjacent non-tumour or healthy tissues. Zinc concentration followed the same trend but differences were not statistically significant. In addition, concentration of silicon was higher in colorectal cancer tissue than in healthy non-cancer tissue, while chromium was mostly found in adjacent non-tumour tissue. CONCLUSION Magnesium, chromium, zinc and silicon were found in noteworthy concentrations in colorectal tumour. Their potential role in colorectal carcinogenesis should be explored.

Management of an Esojejunal Intrathoracic Leak Using an Endoscopic Vacuum-assisted Closure Technique

Management of intrathoracic anastomotic leaks remains an important clinical challenge. We describe a case about a patient with intrathoracic esophageal anastomotic leaks after oesogastrectomy. Ndoscopic Vacuum-assisted closure technique today is an effective alternative in the treatment of anastomotic leaks after upper gastrointestinal tract surgery.