Sarah Leblanc

Comparison of 22G reverse-beveled versus standard needle for endoscopic ultrasound-guided sampling of solid pancreatic lesions

Objectives Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using standard needles has a high diagnostic value in the evaluation of solid pancreatic masses. Fenestrated needles have been developed to improve the quality of EUS-guided tissue sampling by providing core biopsies (FNB). Methods Patients with solid pancreatic masses of >2 cm were prospectively included in our study and randomized to receive EUS sampling, using either a standard 22G FNA or a 22G Procore® FNB needle. The main study endpoint was the number of needle passes required to obtain a diagnosis in more than 90% of cases. Results We included 100 patients (male = 63, female = 37; mean age = 68.4 years) in our study. We found that 88% of the lesions were malignant, with a mean size of 32 mm. A sample adequate for diagnosis was obtained in more than 90% of cases after the second needle pass in the FNB group, versus the third needle pass in the FNA group. Slide cellularity and presence of tissue microfragments were significantly higher in the FNB group. Sensitivity for the diagnosis of malignancy was 88.4% versus 97.8% for the EUS-FNA and EUS-FNB group, respectively, while specificity for both techniques was 100%. No complications were recorded. Conclusions Although the accuracy of both needle types for proving malignancy was similar, a lower number of passes was required with the FNB needles to achieve the same contributive sample rate as with the FNA needles. FNB also improved the histopathological quality of specimens, suggesting an overall superiority of FNB sampling.

Iron deficiency: From diagnosis to treatment

Iron deficiency is the most frequent cause of anaemia worldwide. It impairs quality of life, increases asthenia and can lead to clinical worsening of patients. In addition, iron deficiency has a complex mechanism whose pathologic pathway is recently becoming better understood. The discovery of hepcidin has allowed a better clarification of iron metabolism regulation. Furthermore, the ratio of concentration of soluble transferrin receptor to the log of the ferritin level, has been developed as a tool to detect iron deficiency in most situations. The cause of iron deficiency should always be sought because the underlying condition can be serious. This review will summarize the current knowledge regarding diagnostic algorithms for iron deficiency anaemia. The majority of aetiologies occur in the digestive tract, in men and postmenopausal women, and justify morphological examination of the gut. First line investigations are upper gastrointestinal endoscopy and colonoscopy, and when negative, the small bowel should be explored; newer tools such as video capsule endoscopy have also been developed. The treatment of iron deficiency is aetiological if possible and iron supplementation whether in oral or in parenteral form. New parenteral formulations are available and seem to have promising results in terms of efficacy and safety.

Early experience with a novel hemostatic powder used to treat upper GI bleeding related to malignancies or after therapeutic interventions (with videos)

Upper GI bleeding is a common clinical condition associated with considerable morbidity and mortality. Conventional treatment modalities, such as injection and thermal and mechanical therapies used alone or in combination, typically achieve hemostasis in more than 90% of cases. However, treatment of recurrent bleeding (necessary in 10%-30%) introduces additional limitations and adverse events. Epinephrine injection is associated with high rates of recurrent bleeding, and thermal therapies can cause tissue injury. Mechanical methods can be technically challenging and require specialized endoscopic expertise. These conventional modalities also can be challenging during treatment of diffuse, widespread bleeding. Peptic ulcer disease is the most common type of nonvariceal upper GI bleeding. However, bleeding also can occur as a consequence of therapeutic endoscopic interventions and from malignancies. In the latter, bleeding can be induced by tumor necrosis or chemotherapy and is typically diffuse and widespread. Even though conventional treatments can be effective as first-line therapies, hemostasis is often difficult to achieve and maintain

Helpfulness of the combination of acetic acid and FICE in the detection of Barrett's epithelium and Barrett's associated neoplasias

AIM To investigate the mucosal morphology in Barretts oesophagus by chromo and magnifying endoscopy. METHODS A prospective pilot study at a tertiary medical centre was conducted to evaluate the use of acetic acid pulverisation combined with virtual chromoendoscopy using Fujinon intelligent chromoendoscopy (FICE) for semiological characterization of the mucosal morphology in Barretts oesophagus and its neoplastic complications. Upper endoscopy using high definition white light, 2% acid acetic pulverisation and FICE with high definition videoendoscopy were performed in 20 patients including 18 patients who presented with aspects of Barretts oesophagus at endoscopy examination. Two patients used as controls had normal endoscopy and histological results. Prospectively, videos were watched blind from histological results by three trained FICE technique endoscopists. RESULTS The videos of patients with high-grade dysplasia showed an irregular mucosal pattern in 14% using high definition white light endoscopy and in 100% using acid acetic-FICE combined. Videos did not identify irregular vascular patterns using high definition white light endoscopy, while acid acetic-FICE combined visualised one in 86% of cases. CONCLUSION Combined acetic acid and FICE is a promising method for screening high-grade dysplasia and early cancer in Barretts oesophagus.

561 Successive Treatment with Cyclosporine and Infliximab in Severe Ulcerative Colitis (UC)

Introduction: Higher 6-tioguanine nucleotide (6TGN) concentrations have been related to higher probabilities of achieving clinical remission on thiopurinic therapy, but that has been hardly applied to clinical practice. Aims: To establish the utility of systematic determination of 6TGN as a marker or predictor of AZA/mercaptopurine (MP) efficacy in IBD patients. Methods: Prospective, multicenter study. Serum 6TGN and 6-methylmercaptopurine ribonucleotides (6MMPR) levels of patients starting AZA/MP for steroid dependence or resistance were periodically monitored during steroid tapering and, after withdrawal, until a new activity flare (persistence of steroid resistance or dependence), or for 6 months in those showing maintenance of clinical response. Thiopurine methyl-transferase (TPMT) activity above 5 U/ml was required. Results: 153 patients were included, and 140 finished the study. Mean age was 36 years (range 16-77), 50% were males, and 72% had Crohns disease. Mean 6TGN levels (and the ratios 6TGN/6MMPR, 6TGN/TPMT) obtained at basal, 2 weeks, and 1, 2, 4 and 6 months after steroid withdrawal were not significantly different between patients that were or were not in clinical remission at each visit. The area under the ROC curve (AUC) evaluating the accuracy of 6TGN levels for the diagnosis of clinical response for each monitoring point was less than 0.7. No cut-off point with useful sensitivity/specificity values was found, including 230 or 260 pmol/8 x 108 (that are commonly proposed in the literature). The AUC assessing the accuracy of the 6TGN determination at 2 weeks, 1, 2 or 4 months after starting AZA/MP to predict the response by the end of the follow-up was also less than 0.7. Once again, no useful cut-off point was found. Thiopurinic-related toxicity was detected in 9 cases (6.4%): No cases of hepatotoxicity were found, and only 3 cases of myelotoxicity were reported. No differences in 6TGN levels were found in patients suffering AZA-related toxicity. Specifically, 6TGN levels could not be related to the risk of developing myelotoxicity. Conclusions: Systematic quantification of thiopurinic metabolites (6TGN/ 6MMPR) in IBD patients receiving AZA/MP with the aim of predicting or assessing treatment response or safety cannot be recommended.

Feasibility of anti-VEGF agent bevacizumab in patients with Crohn's disease.

Inflammatory bowel diseases (IBDs) are usually considered chronic conditions, often moving in spurts, which can never be declared cured. Current therapies for IBDs mainly consist of salicylates, corticosteroids, antitumor necrosis factor (TNF) agents, and surgery. Colorectal cancer (CRC) may complicate the natural history of IBDs. Indeed, several studies have suggested that patients with Crohn’s disease (CD) have an increased risk of CRC. Basically, CD patients have an estimated 20 times greater risk than in a control population. Also, patients with a past history of CD represent 2% of patients with CRC. The optimal treatment of advanced CRC includes 5-fluorouracil doublets combined with anti-EGFR or anti-VEGF agents. Bevacizumab, a humanized IgG1 monoclonal antibody to VEGF, exerts clinical activity and improves survival in metastatic CRC patients. However, bleeding occurs in 3.1% of patients receiving bevacizumab, and represents a serious concern for its use in patients with IBD. Furthermore, we have previously reported exacerbation of hemorrhagic rectocolitis in patients receiving sunitinib and sorafenib, two oral multikinase inhibitors targeting the VEGF pathway. Hence, the safety of bevacizumab in IBD patients is uncertain, and few data are available in the literature. We report on two patients with IBD who received bevacizumab-based chemotherapy for metastatic CRC. The first patient is a 47-year-old man with a 2-year history of CD controlled with oral corticosteroids and 5-aminosalicylate, with two exacerbations per year. During a screening colonoscopy the patient was diagnosed with a right colon carcinoma and pancolitis in September 2008. He was treated by subtotal colectomy followed by 12 cycles of FOLFOX adjuvant chemotherapy until April 2009. Six months later a peritoneal recurrence was diagnosed. The patient received first-line chemotherapy combining 5-FU, irinotecan, and bevacizumab (5 mg/kg every 2 weeks), allowing complete tumor response. For a total of 14 cycles of bevacizumab he did not experience any acute CD outbreak. At the time of this report the patient is still alive without evidence of disease. The second patient is a 57-yearold woman with a 14-year history of CD with pancolitis who underwent colectomy. Four years later she was diagnosed with rectal carcinoma. She subsequently underwent curative surgical resection with ileostomy. Three years later she developed peritoneal recurrence and was subsequently started on capecitabine, oxaliplatin, and bevacizumab as part of a phase III clinical trial. She received two cycles of this regimen and developed severe (grade 4) diarrhea, without bleeding or inflammatory syndrome. The grade 4 digestive toxicity was considered as being triggered by capecitabine, and possibly worsened by ileostomy. Therefore, the patient was excluded from the study and chemotherapy was changed to 5-FU plus oxaliplatin. The patient experienced disease progression after 4 cycles and she died of disease 20 months later. Importantly, no acute CD outbreak was observed while the patient was under bevacizumab. In our experience, bevacizumab did not worsen CD in metastatic CRC patients. In contrast, we observed exacerbation of IBD-related symptoms in patients receiving the multikinase inhibitors sunitinib and sorafenib. Importantly, these tyrosine kinase inhibitors target not only the VEGF signaling pathway, but also the PDGF receptors. The PDGF signaling pathway was shown to be critically involved in the pathophysiology of IBDs, suggesting that the deleterious effects of sorafenib and sunitinib might be related to PDGFR inhibition and not VEGFR inhibition. Our safety data with bevacizumab, an anti-VEGF agent, are consistent with this hypothesis. Further clinical reports are required to determine whether bevacizumab can be safely used in cancer patients with IBDs.

Pancreatoscopy-guided intracorporeal laser lithotripsy for difficult pancreatic duct stones: a case series with prospective follow-up (with video)

Pancreatic stones develop in patients with chronic pancreatitis, with as many as 90% of alcoholic chronic pancreatitis patients bearing ductal stones during long-term follow-up. 1 Main pancreatic duct calculi can lead to an outflow obstruction with increased parenchymal pressure, upstream dilation (ie, toward the tail of the pancreas), and ischemia. Untreated stones can also trigger bouts of acute pancreatitis sometimes associated with life-threatening adverse events. Pain is the predominant symptom in most patients with obstructive chronic pancreatitis, often alleviated only by narcotics and inducing anorexia, malabsorption, and weight loss. It is only with main pancreatic duct decompression from impacted stones that such adverse events can be avoided. 2,3 Small stones can be extracted by using various endoscopic techniques during ERCP, such as pancreatic sphincterotomy with balloon or basket sweeping, pancreatic duct stricture dilation, or stent placement. Larger and impacted stones typically require lithotripsy or surgery. Endoscopic lithotripsy options include (1) mechanical lithotripsy, for which data are scarce but suggest that this procedure may carry an increased risk of adverse events when compared with lithotripsy for biliary stones 2 ; (2) extracorporeal shock wave lithotripsy (ESWL), which overcomes the problem of size by fragmenting calculi and reducing the stone burden, thus facilitating endoscopic duct clearance 3 ; (3) contact lithotripsy by using pancreatoscopy with a mother-baby endoscope system. 4 Directcontact lithotripsy of biliopancreatic stones can be achieved by means of electrohydraulic lithotripsy (EHL) or pulseddye laser, both of which must be done under direct vision. Scant clinical outcome data are available regarding the application of these methods for pancreatic duct stone fragmentation. 5 Our aim was to evaluate the endoscopic treatment at our center by intracorporeal laser lithotripsy (ILL) with a single-operator mini-endoscope (SpyGlass; Boston Scientific, Natick, Mass) during ERCP, for its performance, feasibility, and safety in the treatment of difficult main pancreatic duct stones.

The expansion of endoscopic submucosal dissection in France: A prospective nationwide survey

Introduction Early reports of endoscopic submucosal dissection (ESD) in Europe suggested high complication rates and disappointing outcomes compared to publications from Japan. Since 2008, we have been conducting a nationwide survey to monitor the outcomes and complications of ESD over time. Material and methods All consecutive ESD cases from 14 centers in France were prospectively included in the database. Demographic, procedural, outcome and follow-up data were recorded. The results obtained over three years were compared to previously published data covering the 2008–2010 period. Results Between November 2010 and June 2013, 319 ESD cases performed in 314 patients (62% male, mean (±SD) age 65.4 ± 12) were analyzed and compared to 188 ESD cases in 188 patients (61% male, mean (±SD) age 64.6 ± 13) performed between January 2008 and October 2010. The mean (±SD) lesion size was 39 ± 12 mm in 2010–2013 vs 32.1 ± 21 for 2008–2010 (p = 0.004). En bloc resection improved from 77.1% to 91.7% (p < 0.0001) while R0 en bloc resection remained stable from 72.9% to 71.9% (p = 0.8) over time. Complication rate dropped from 29.2% between 2008 and 2010 to 14.1% between 2010 and 2013 (p < 0.0001), with bleeding decreasing from 11.2% to 4.7% (p = 0.01) and perforations from 18.1% to 8.1% (p = 0.002) over time. No procedure-related mortality was recorded. Conclusions In this multicenter study, ESD achieved high rates of en bloc resection with a significant trend toward better outcomes over time. Improvements in lesion delineation and characterization are still needed to increase R0 resection rates.

Endoscopic submucosal dissection for early Barrett's neoplasia.

Introduction The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett’s esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett’s neoplasia. Methods All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett’s esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors. Results Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett’s segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%. Conclusion In this early experience, ESD yielded a moderate curative resection rate in Barrett’s neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett’s neoplasia.

A self-assembling matrix-forming gel can be easily and safely applied to prevent delayed bleeding after endoscopic resections

Background: Endoscopic resections have low morbidity and mortality. Delayed bleeding has been reported in approximately 1 – 15 % of cases, increasing with antiplatelet/anticoagulant therapy or portal hypertension. A self-assembling peptide (SAP) forming a gel could protect the mucosal defect during early healing. This retrospective trial aimed to assess the safety and efficacy of SAP in preventing delayed bleeding after endoscopic resections. Methods: Consecutive patients with endoscopic resections were enrolled in two tertiary referral centers. Patients with a high risk of bleeding (antiplatelet agents, anticoagulation drugs with heparin bridge therapy, and cirrhosis with portal hypertension) were also included. The SAP gel was applied immediately after resection to cover the whole ulcer bed. Results: In total, 56 patients were included with 65 lesions (esophagus [n = 8], stomach [n = 22], duodenum [n = 10], ampullary [n = 3], colon [n = 7], and rectum [n = 15]) in two centers. Among those 65 lesions, 29 were resected in high risk situations (9 uninterrupted aspirin therapy, 6 heparin bridge therapies, 5 cirrhosis and portal hypertension, 1 both cirrhosis and heparin bridge, 3 both cirrhosis and uninterrupted aspirin, 3 large duodenal lesions > 2 cm, and 2 early introduction of clopidogrel at day 1). The resection technique was endoscopic submucosal dissection (ESD) in 40 cases, en bloc endoscopic mucosal resection (EMR) in 16, piecemeal EMR in 6, and ampullectomy in 3. The mean lesion size was 37.9 mm (SD: 2.2 mm) with a mean area of 6.3 cm2 (SD: 3.5 cm2). No difficulty was noted during application. Four delayed overt bleedings occurred (6.2 %) (3 hematochezia, 1 hematemesis) requiring endoscopic hemostasis. The mean hemoglobin drop off was 0.6 g/dL (– 0.6 to 3.1 g/dL). No adverse events occurred. Conclusion: The use of this novel extracellular matrix scaffold may help to reduce post-endoscopic resection bleedings including in high risk situations. Its use is easy and safe but further comparative studies are warranted to completely evaluate its effectiveness.