Endoscopic Follow-Up Between 3 and 7 Years After Sleeve Gastrectomy Reveals Antral Reactive Gastropathy but no Barrett's Esophagus.

BACKGROUND: The main concerns following sleeve gastrectomy (SG) include the risk of gastroesophageal reflux disease (GERD) and its complications, such as Barrett's esophagus (BE). However, there is conflicting data on esophageal conditions, and studies on alterations of gastric mucosa after SG are lacking, despite reported cases of gastric cancer. Our aim was to assess esophageal and gastric lesions after SG. METHODS: From November 2017, an upper gastrointestinal endoscopy (UGE) was proposed at least 3 years after SG to all patients operated on in our institution. Endoscopic results and gastric histological findings were analyzed. BE was defined as endoscopically suspected esophageal metaplasia with histological intestinal metaplasia. RESULTS: Between September 2008 and August 2018, 375 patients underwent SG at our institution, of which 162 (43%) underwent at least one UGE 3 years or more after SG (91% women, mean preoperative age: 43.3±10.3 years). Despite a significant increase in the prevalence of symptomatic GERD, hiatal hernia, and esophagitis after SG (p<0.001 vs. preoperatively), no cases of BE were detected. Gastric dysplasia was not found and the prevalence of gastric atrophy tended to decrease after SG. However, 27% of patients with gastric biopsies developed antral reactive gastropathy. CONCLUSIONS: At a mean follow-up of 54 months after SG, no BE or gastric dysplasia was identified. However, reactive gastric lesions appeared, and their long-term consequences need to be further clarified. Thus, the timing of endoscopic follow-up, starting as early as 3 years after SG should be reevaluated to improve patient adherence with long-term endoscopies.

Daily practices in chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma: METESTOMAC French prospective cohort.

BACKGROUND: Around 50% of gastric cancers are diagnosed at an advanced stage. Several chemotherapy regimens are now internationally validated. Few data are available on the routine daily management of advanced gastric or gastroesophageal junction cancers. We aimed to describe chemotherapy practices, tolerance, and efficacy overall survival (OS) and Progression free survival (PFS) in a prospective French cohort. METHODS: Patients starting palliative chemotherapy were prospectively enrolled in 49 French centres. The primary objective was to report and describe patients' characteristics and treatment strategies. Secondary objectives were OS, PFS, objective response rate, adverse events rate, performance status deterioration during the chemotherapy. RESULTS: A total of 182 patients were included; 179 were analysed. Most patients received platinium-based chemotherapy as the first treatment and FOLFIRI as second; 62.0% of patients received a second line, and 32.4% a third line. More than two thirds of Her2-positive patients were first treated with trastuzumab. The FOLFIRI regimen was the most frequently used second-line therapy. Median OS was 13.3 months, similar whatever the chemotherapy or combinations used in the first line. One- and 2-year OS increased with the number of chemotherapy lines received, from respectively 24.7% and 5.7% (1 line), to 46.9% and 12.4% (2 lines) and 88.1% and 29.9% (3 or more lines) (p < 0.0001). CONCLUSION: Our study showed that treatment strategies in France are based on a succession of doublets, making it possible to offer a second and third line of treatment more often. This treatment strategy must be taken into account for future trials with immunotherapy combinations.

Prognosis and chemosensitivity of non-colorectal alimentary tract cancers with microsatellite instability.

BACKGROUND: Data on outcomes of microsatellite instable and/or mismatch repair deficient (dMMR/MSI) digestive non-colorectal tumors are limited. AIMS: To evaluate overall survival (OS) of patients with dMMR/MSI digestive non-colorectal tumor. METHODS: All consecutive patients with a dMMR/MSI digestive non-colorectal tumor were included in this French retrospective multicenter study. RESULTS: One hundred and sixteen patients were included with a mean age of 63.6 years and 32.6% with a Lynch syndrome. Most tumors were oesophago-gastric (54.3%) or small bowel (32.8%) adenocarcinomas and at a localized stage at diagnosis (86.7%). In patients with localized tumors and R0 resection, median OS was 134.0 ± 64.2 months. Median disease-free survival (DFS) was 100.3 ± 65.7 months. Considering oesophago-gastric tumors, median DFS was improved when chemotherapy was added to surgery (not reached versus 22.8 ± 10.0 months, p = 0.03). In patients with advanced tumors treated by chemotherapy, median OS was 14.2 ± 1.9 months and median progression-free survival was 7.4 ± 1.6 months. CONCLUSION: dMMR/MSI digestive non-colorectal tumors are mostly diagnosed at a non-metastatic stage with a good prognosis. Advanced dMMR/MSI digestive non-colorectal tumors have a poor prognosis with standard chemotherapy.

Efficacy and safety of endoscopic pyloric balloon dilation in patients with refractory gastroparesis.

BACKGROUND AND AIMS: There has been interest in the use of pyloric therapies for the treatment of refractory gastroparesis. However, data on endoscopic pyloric dilation are scarce. We aimed to assess the efficacy and safety of this procedure in refractory gastroparesis. METHODS: We performed a retrospective analysis of 47 patients referred for refractory gastroparesis, confirmed by gastric emptying scintigraphy, and treated with endoscopic pyloric through-the-scope balloon dilation. The primary endpoint was the effectiveness of the procedure, evaluated with the Gastric Cardinal Symptom Index (GCSI) at 2 and 6 months. RESULTS: A clinical response, defined by a 1.0 point decrease in the GCSI score, was observed in 25 patients at 2 months (53%) and in 19 patients at 6 months (40%). The mean GCSI score decreased significantly at 2 and 6 months compared to the preoperative score (3.9 ± 0.87 vs 2.3 ± 1.37 and 3.9 ± 0.87 vs 2.9 ± 1.27, respectively; p < 0.0001). No complication was observed. Nine patients had a delayed relapse at 1 year. A second dilation was performed for eight patients and it was effective in five of them (63%). The mean follow-up time of the patients was 27.0 ± 10.4 months. At 2 years, 15 patients still experienced improvement following this treatment (32%). No predictive factor of clinical response was identified. CONCLUSION: The efficacy of pyloric dilation is 53% at 2 months, with sustained improvement in one third of patients at 2 years. This treatment should be considered as an alternative option to pyloromyotomy.

First-line chemotherapy with raltitrexed in metastatic colorectal cancer: an Association des Gastro-entérologues Oncologues (AGEO) multicentre study.

BACKGROUND: In case of contraindication or intolerance to fluoropyrimidines, raltitrexed is a validated alternative in metastatic colorectal cancer (mCRC), associated or not with oxaliplatin. Little is known about the outcomes of raltitrexed combined with irinotecan or targeted therapies. METHODS: This retrospective multicentre study enroled mCRC patients treated with first-line raltitrexed-based chemotherapy. Treatment-related toxicities were recorded. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. RESULTS: 75 patients were treated with raltitrexed alone, TOMOX, or TOMIRI with or without bevacizumab. Grade 3-4 adverse events were seen in 31% of patients, without significant difference between the different treatment schedules. amongst the 36 patients with a history of fluoropyrimidine-induced cardiac toxicity, none developed cardiovascular events on raltitrexed. Median PFS and OS were 10.6 (95% CI 8.2 - 13.1) and 27.4 months (95% CI 24.1-38.1), respectively. Considering the chemotherapy regimen, TOMOX was significantly associated with better PFS and OS compared to TOMIRI and raltitrexed alone. CONCLUSIONS: In patients with mCRC not eligible for fluoropyrimidines, first-line raltitrexed-based chemotherapy had an acceptable safety profile. PFS and OS were consistent with usual survival data in mCRC, and significantly better in patients treated with TOMOX, independently of associated targeted therapies.

Do Preoperative Esophageal pH Monitoring and High-Resolution Manometry Predict Symptoms of GERD After Sleeve Gastrectomy?

BACKGROUND: Predictive factors of evolution or appearance of gastroesophageal reflux disease (GERD) after sleeve gastrectomy (SG) have not been identified to date. We aimed to assess the evolution of GERD symptoms 1 year after SG and to determine preoperative predictive factors using high-resolution manometry (HRM) and ambulatory 24-h esophageal pH monitoring (APM). METHODS: We included 160 patients who underwent SG between 2013 and 2017 and performed preoperative APM and HRM. Positive APM was defined according to the Lyon consensus. Symptoms of GERD, proton pump inhibitors (PPI) use, weight loss (WL), and diet were recorded in all patients before and 1 year after surgery. RESULTS: One year after surgery, 58 patients (36.3%) complained of GERD symptoms compared to 52 patients (32.5%) preoperatively (p=0.48). Among patients with preoperative GERD symptoms, only 26/52 patients (50%) still had symptoms, whereas 32/108 (29.6%) asymptomatic patients developed de novo GERD symptoms after surgery. PPI use increased after surgery reaching 36.9% of patients against 15.0% before (p<0.0001). Only preoperative symptoms of GERD were predictive of postoperative symptoms (OR= 2.47 [1.14-5.45]; p=0.023) in multivariate analysis. Preoperative manometric parameters, postoperative diet, and WL were not related to postoperative symptoms. In asymptomatic patients before surgery, silent GERD (positive APM without symptom) was predictive of postoperative GERD symptoms (OR=2.69 [1.00-7.25]; p=0.049). CONCLUSION: Evolution of GERD symptoms after SG reveals improvement for half of the patients and de novo GERD symptoms in one-third of patients. Predictive factors of postoperative symptoms are preoperative symptoms and positive preoperative APM in asymptomatic patients.

Prevalence and prognosis of microsatellite instability in oesogastric adenocarcinoma, NORDICAP 16-01.

BACKGROUND: The prevalence and prognosis association of microsatellite instability (MSI) in oesogastric junction and gastric adenocarcinoma (OGC) have been reported with conflicting results. METHODS: Patients with OGC from 2010 to 2015 were enrolled in this retrospective multicenter study. MSI was determined by genotyping. MLH1 promoter methylation and BRAFV600E mutation were screened in the MSI tumors. RESULTS: Among 315 tumors analyzed, 39 (12.4%) were of the MSI phenotype. Compared to MSS tumors, MSI tumors were more frequent in patients >70 years (17% vs 9%, p=0.048) and in gastric antral primary (20% versus 5% in junction tumor and 12% in fundus tumor. Among 29 MSI tumors analyzed, 28 had a loss of MLH1 protein expression and 27 had MLH1 promotor hypermethylation. None had a BRAF V600E mutation. The 4-year cumulative incidence of recurrence for patients with resected tumor was significantly lower in dMMR tumors versus pMMR tumors (17% versus 47%, p=0.01). For the patients with unresectable tumor the median overall survival was 11 months in MSS group and 14 months in MSI group (p=0.24). CONCLUSION: MSI prevalence in OGC was 12.4%, associated with antral localization and advanced age. Patients with MSI tumors had a lower cumulative incidence of recurrence after surgery. MSI phenotype was mainly associated with loss of MLH1 protein expression, MLH1 promotor hypermethylation and had no BRAFV600E mutation.

Prognostic factors of colorectal cancer patients with brain metastases.

INTRODUCTION: Brain metastases (BMs) from colorectal cancer (CRC) are rare (≈2%) but are increasing with the improvement of CRC prognosis. The main objective of this study was to evaluate the prognostic factors of BM from CRC. MATERIALS AND METHODS: This multicenter retrospective study included all consecutive patients with BM from CRC diagnosed between 2000 and 2017. THEORY/CALCULATION: Prognostic factors of OS were evaluated in univariate (log-rank test) and multivariate analyses (Cox regression model). These prognostic factors could help the management of patients with BM from CRC. RESULTS: A total of 358 patients were included with a median age of 65.5 years. Primary tumors were mostly located in the rectum (42.4%) or left colon (37.2%) and frequently KRAS-mutated (56.9%). The median time from metastatic CRC diagnosis to BM diagnosis was 18.5 ± 2.5 months. BMs were predominantly single (56.9%) and only supratentorial (54.4%). BM resection was performed in 33.0% of the cases and 73.2% of patients had brain radiotherapy alone or after surgery. Median OS was 5.1 ± 0.3 months. In multivariate analysis, age under 65 years, ECOG performance status 0-1, single BM and less than 3 chemotherapy lines before BM diagnosis were associated with better OS. Prognostic scores, i.e. recursive partitioning analysis (RPA), Graded Prognostic Assessment (GPA), Disease Specific-Graded Prognostic Assessment (DS-GPA), Gastro-Intestinal-Graded Prognostic Assessment (GI-GPA) and the nomogram were statistically significantly associated with OS but the most relevant prognosis criteria seemed the ECOG performance status 0-1. CONCLUSIONS: ECOG performance status, number of BM and number of chemotherapy lines are the most relevant factors in the management of patients with BM from CRC.

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

BACKGROUND: Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting. MATERIALS AND METHODS: This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR). RESULTS: A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007). CONCLUSION: Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF. IMPLICATIONS FOR PRACTICE: For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.

Inhibitory Effect of Ursodeoxycholic Acid on Clostridium difficile Germination Is Insufficient to Prevent Colitis: A Study in Hamsters and Humans.

Introduction: Bile acids (BA) influence germination and growth of Clostridium difficile. Ursodeoxycholic acid (UDCA), a BA minor in human, used for cholestatic liver diseases, inhibits germination and growth of C. difficile in vitro, but was never tested in vivo with an infectious challenge versus control. We hypothesized that UDCA could prevent CDI. We evaluated the effects of UDCA on C. difficile in vitro and in hamsters, with pharmacokinetics study and with an infectious challenge. Then, we studied CDI incidence in UDCA-treated patients. Methods: We evaluated germination and growth of C. difficile, with 0.01, 0.05, and 0.1% UDCA. We analyzed fecal BA of hamsters receiving antibiotics and UDCA (50 mg/kg/day), antibiotics, or UDCA alone. Then, we challenged with spores of C. difficile at D6 hamsters treated with UDCA (50 mg/kg/day) from D1 to D13, versus control. In human, we analyzed the database of a cohort on CDI in acute flares of inflammatory bowel disease (IBD). As PSC-IBD patients were under UDCA treatment, we compared PSC-IBD patients to IBD patients without PSC. Results: In vitro, UDCA inhibited germination and growth of C. difficile at 0.05 and 0.1%, competing with 0.1% TCA (with 0.1%: 0.05% ± 0.05% colony forming unit versus 100% ± 0%, P < 0.0001). In hamsters, UDCA reached high levels only when administered with antibiotics (43.5% UDCA at D5). Without antibiotics, UDCA was in small amount in feces (max. 4.28%), probably because of UDCA transformation into LCA by gut microbiota. During infectious challenge, mortality was similar in animals treated or not with UDCA (62.5%, n = 5/8, P = 0.78). UDCA percentage was high, similar and with the same kinetics in dead and surviving hamsters. However, dead hamsters had a higher ratio of primary over secondary BA compared to surviving hamsters. 9% (n = 41/404) of IBD patients without PSC had a CDI, versus 25% (n = 4/12) of PSC-IBD patients treated with UDCA. Conclusion: We confirmed the inhibitory effect of UDCA on growth and germination of C. difficile in vitro, with 0.05 or 0.1% UDCA. However, in our hamster model, UDCA was inefficient to prevent CDI, despite high levels of UDCA in feces. Patients with PSC-IBD treated with UDCA did not have less CDI than IBD patients.

Invasive pit pattern, macronodule and depression are predictive factors of submucosal invasion in colorectal laterally spreading tumours from a Western population.

BACKGROUND: Laterally spreading tumours are separated in subclasses: granular, homogenous or nodular mixed; and non-granular, flat or pseudodepressed. For every subtype, a proper risk of submucosal invasive cancer has been described in Asian series. OBJECTIVE: The aim of the study was to determine the rate of cancer and submucosal invasive cancer in a Western series of endoscopic-resected laterally spreading tumours and their endoscopic predictive factors. METHODS: A total of 374 laterally spreading tumours ≥20 mm were resected by endoscopy in our single centre between 2012-2016. We analysed endoscopic and pathological data from our prospective database, determining the rates of cancer and submucosal invasive cancer according to the subtype of laterally spreading tumour. RESULTS: The rates of submucosal invasive cancer for granular homogenous, granular nodular mixed, non-granular flat, non-granular pseudodepressed laterally spreading tumours were 4.9%, 15.9%, 3.0% and 19.4%, respectively. Endoscopic mucosal resection was used in 58.0% and endoscopic submucosal dissection in 42.0%. Endoscopic submucosal dissection was associated with a higher rate of en-bloc resection (87.3% vs 26.3%; p < 0.0001), and a lower risk of recurrence (7.6% vs 15.2%; p = 0.026). Adverse event rates were not statistically different (9.5% vs 6.4%, p = 0.26). Predictive endoscopic factors of submucosal invasive cancer were: invasive pit pattern (hazard ratio = 33 (8.81-143.3)), non-granular pseudodepressed laterally spreading tumours (hazard ratio = 11.9 (0.89-146.2)), and granular nodular mixed laterally spreading tumours (hazard ratio = 3.42 (0.99-13.0)). CONCLUSIONS: The risk of submucosal invasive cancer varies according to the laterally spreading tumour subtype. Three factors were associated with submucosal invasion and should justify an endoscopic submucosal dissection: non-granular pseudodepressed laterally spreading tumours, granular nodular mixed laterally spreading tumours subtypes and invasive pit pattern.

Addition of an antiangiogenic therapy, bevacizumab, to gemcitabine plus oxaliplatin improves survival in advanced biliary tract cancers.

Background The prognosis of patients with metastatic carcinoma of the biliary tract (mBTC) is poor and a systemic therapy with gemcitabine and platinum-based is the gold standard. The addition of bevacizumab to the chemotherapy might increase patients' survival. Our aim was to assess and compare the efficacy of GEMOX (gemcitabine and oxaliplatin regimen) plus bevacizumab to GEMOX alone in mBTC. Methods Patients with mBTC who received the GEMOX-bevacizumab (n = 32; Group A) or GEMOX (n = 25; Group B) regimen as first-line treatment were compared. Treatment was repeated every two weeks until disease progression or unacceptable adverse effects occurred. The primary evaluation criterion was the progression-free survival (PFS). Results A quarter of patients (8/32) from Group A and a fifth of patients (13/25) from Group B had an objective response. The median PFS was 6.48 months and 3.72 months in Group A and B, respectively (p = 0.049). The median OS was 11.31 months and 10.34 months in Group A and B, respectively. Grade 3/4 sepsis was identified in 9.4% and 12% in Group A and B, respectively, (p = 0.64). Conclusion In mBTC, the addition of bevacizumab to GEMOX increased the progression-free survival and was associated with manageable toxicity. These data pave the way for further evaluation of antiangiogenic agents in mBTC.

Immune Checkpoint Inhibitor-Induced Colitis: Diagnosis and Management.

Immune checkpoint inhibitors are monoclonal antibodies indicated for an increasing number of malignant diseases. These agents can cause specific side effects, which need to be anticipated while clear patterns of management need to be established. Immune checkpoint inhibitor-mediated gastrointestinal side effects, including diarrhea and colitis, occur in up to 30% of patients. Severe colitis can lead to severe dehydration or intestinal perforation. Endoscopic lesions and histopathological features of immune checkpoint inhibitor-induced colitis are similar to an inflammatory bowel disease (IBD) flare. Patients with immune checkpoint inhibitor-induced diarrhea and colitis are treated with corticosteroids. Infliximab can be used in cases of corticosteroid failure. Rectosigmoïdoscopy or colonoscopy should be performed when severe immune checkpoint inhibitor-induced colitis is suspected, but endoscopic investigations should not delay treatment. Specific patient education as well as co-operation between oncologists and gastroenterologists is essential.

[Mid gut neuroendocrine tumors: News on medical treatment]. / Tumeurs neuroendocrines de l'intestin grêle : actualités sur le traitement médical.

CONTEXT: Mid gut neuroendocrine tumors (NET) are rare tumors whose incidence is increasing. Curative surgery remains the gold standard for the treatment of NETs of the small intestine. Surgery should be considered as soon as possible even if a metastatic stage is diagnosed. The management of unresectable well-differentiated metastatic NETs of the small intestine recently changed with the publication of trials demonstrating the benefit of targeted therapies and metabolic radiotherapy, leading to a change of practices and update of French and international recommendations. OBJECTIVE: The objective of this review is to present the recent data consisting of three phase III studies, which modify the management of well-differentiated metastatic midgut NETs and make an inventory of the available treatment options. DOCUMENTARY SOURCES: The documentary sources used were gathered through the PubMed website using keyword searching (neurendocrine tumor, mid gut, treatment). We also referred to recommendations of the European Society of neuroendocrine tumors (ENETS) trials presented at ESMO Congress 2015 (European Society for Medical Oncology). STUDY SELECTION: We excluded studies of exclusive extra-digestive NETs, poorly differentiated NETs, surgical treatments and phase I studies. RESULTS: We discussed three randomized phase III trials: CLARINET, RADIANT and NETTER studies. These studies demonstrated the efficacy of respectively somatostatin analogues, mTOR inhibitors and metabolic radiotherapy. CONCLUSION: This review highlights the validation by randomized studies of an mTOR inhibitor and metabolic radiotherapy in metastatic non-pancreatic digestive NETs unresectable well-differentiated grade of G1/2 in progression under somatostatin analogues.

Olmesartan-induced enteropathy associated with cutaneous lesions.

Olmesartan is an angiotensin II receptor antagonist which may cause severe sprue-like enteropathy with duodenal villous atrophy. Skin lesions may be associated as reported for the first time in our case. Clinicians should be informed of this side effect and its reversibility after suspension of the drug.

Does endoscopic mucosal resection for large colorectal polyps allow ambulatory management?

BACKGROUND: Endoscopic mucosal resection (EMR) is an efficacious endoscopic therapy for large adenoma or confined neoplasia. The most frequent complication is delayed hemorrhage, and hemoclips appear to be an effective therapeutic option. The aim of this study was to determine if large EMR could allow ambulatory management. METHODS: Colorectal polyps ≥20 mm in size treated by EMR in one endoscopy unit were prospectively included. The period from September 2007 to September 2008 was considered as the reference period (period 1). From September 2008 on, patients were hospitalized in an ambulatory unit. Periods from September 2008 to September 2009 (period 2), from September 2009 to September 2010 (period 3), and from September 2010 to September 2011 (period 4) were compared to the reference period. Patients receiving anticoagulation drugs were excluded from the study. RESULTS: A total of 138 patients were treated by 139 EMRs for large colorectal polyps. EMRs were completed by at least one clip per centimeter in 10.7 %, 30.2 % (p = NS), 50 % (p = 0.015), and 76 % (p = 0.001). Ambulatory EMRs were performed in 21 %, 52.4 % (p = 0.008), 67.6 % (p = 0.02), and 88.2 % (p = 0.004) of cases during periods 1, 2, 3, and 4. The complication rate was stable during the four periods. No patients with more than one hemoclip per EMR centimeter experienced delayed bleeding. CONCLUSIONS: The low complication rate during the four periods allows us to consider ambulatory EMR for large colorectal lesions ≥20 mm in diameter as an option. One hemoclip per centimeter may help prevent delayed hemorrhage in patients without anticoagulation drugs.

A rare hematological adverse event induced by bevacizumab: severe thrombocytopenia.

BACKGROUND: Bevacizumab, a monoclonal antibody to vascular endothelial growth factor-A, is approved for the treatment of various malignancies, and its hematological toxicities are considered infrequent. METHODS: A colorectal cancer patient receiving chemotherapy (5-fluorouracil and oxaliplatin) plus bevacizumab developed acute, severe thrombocytopenia. We postulated that this thrombocytopenia could be directly triggered by bevacizumab. RESULTS: A man with stage IV colorectal cancer and synchronous liver metastasis had received 10 cycles of FOLFOX plus bevacizumab (5 mg/kg) without significant hematological toxicity. Due to thrombocytopenia, oxaliplatin was withdrawn after cycle 11. On cycle 12, shortly after bevacizumab infusion and before 5-fluorouracil infusion, the patient developed fever, lower limbs purpura, grade 1 proctorrhagia, and epistaxis. Platelets had decreased from 105,000/mm(3) to 3000/mm(3) within 1 hour after bevacizumab infusion. Flow cytometry identified platelet-associated immunoglobulins. Despite 2 apheresis-derived platelet transfusions, oral corticotherapy, and gamma globulin infusions, thrombocytopenia persisted, but was finally successfully treated with a peptibody thrombopoietin mimetic, which was introduced 28 days after the last bevacizumab infusion. CONCLUSIONS: Clinicians should keep in mind that bevacizumab can induce acute and potentially severe immune-mediated thrombocytopenia.