Double-clip traction for colonic endoscopic submucosal dissection: a multicenter study of 599 consecutive cases (with video).

BACKGROUND AND AIMS: Colonic endoscopic submucosal dissection (ESD) is particularly challenging and limited to a few expert centers. We recently conducted a pilot study on improvement of colonic ESD with systematic use of a countertraction device (double-clip traction with rubber band [DCT-ESD]). METHODS: A French prospective multicenter study was conducted between March 2017 and September 2019, including all consecutive cases of naive colonic ESD. Since the first case of DCT-ESD in March 2017, all cases of colonic ESD have been performed using the DCT-ESD strategy in the 3 centers involved in the study. RESULTS: Five hundred ninety-nine lesions with a mean size of 53 mm were included in this study, resected by 5 operators in 3 centers. The en bloc, R0, and curative resection rates were 95.7%, 83.5%, and 81.1%, respectively. The adverse event rates were 4.9% for perforation and 4.2% for postprocedure bleeding. Between 2017 and 2019, the rates of R0 and curative resections increased significantly from 74.7% in 2017 to 88.4% in 2019 (P = .003) and from 72.6% in 2017 to 86.3% in 2019 (P = .004), respectively. Procedure duration and speed of resection were 62.4 minutes and 39.4 mm2/minute, respectively. No differences were noted between operators. CONCLUSION: DCT-ESD is a safe and reproducible technique, with results comparable with those of the large Japanese teams with speed of resection twice as high as previously reported studies. The DCT strategy is promising, cheap, and seems to be reproducible. Physicians performing colonic ESD should be aware of this promising tool to improve their results in ESD.

Peroral endoscopic pyloromyotomy is efficacious and safe for refractory gastroparesis: prospective trial with assessment of pyloric function.

BACKGROUND: Gastroparesis is a functional disorder with a variety of symptoms that is characterized by delayed gastric emptying in the absence of mechanical obstruction. A recent series of retrospective studies has demonstrated that peroral endoscopic pyloromyotomy (G-POEM) is a promising endoscopic procedure for treating patients with refractory gastroparesis. The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of G-POEM. METHODS: 20 patients with refractory gastroparesis (10 diabetic and 10 nondiabetic) were prospectively included in the trial. Patients were treated by G-POEM after evaluation of pyloric function using an endoscopic functional luminal imaging probe. Clinical responses were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and quality of life was assessed using the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life scale and the Gastrointestinal Quality of Life Index scores. Gastric emptying was measured using 4-hour scintigraphy before G-POEM and at 3 months. RESULTS: Feasibility of the procedure was 100 %. Compared with baseline values, G-POEM significantly improved symptoms (GCSI: 1.3 vs. 3.5; P < 0.001), quality of life, and gastric emptying (T½: 100 vs. 345 minutes, P < 0.001; %H2: 56.0 % vs. 81.5 %, P < 0.001; %H4: 15.0 % vs. 57.5 %, P = 0.003) at 3 months. The clinical success of G-POEM using the functional imaging probe inflated to 50 mL had specificity of 100 % and sensitivity of 72.2 % (P = 0.04; 95 % confidence interval 0.51 - 0.94; area under the curve 0.72) at a distensibility threshold of 9.2 mm2/mmHg. CONCLUSION: G-POEM was efficacious and safe for treating refractory gastroparesis, especially in patients with low pyloric distensibility.

The "tunnel + clip" strategy standardised and facilitates oesophageal ESD procedures: a prospective, consecutive bi-centric study.

INTRODUCTION: ESD is the treatment of choice for superficial neoplasms of the oesophagus; ESD is oncologically efficient and associated with less morbidity than the surgical alternative. ESD requires a high level of skill, being both technically challenging and time consuming. Therefore, ESD is often reserved for experts. A combination of a tunnel technique with clip-line traction may enable optimisation of oesophageal ESD. PATIENTS AND METHODS: From January 2015 to December 2016, we performed a prospective two-centre case study of consecutive "tunnel + clip" oesophageal ESD. Four young operators (each of whom had performed fewer than 50 ESDs and fewer than five oesophageal ESDs) treated patients requiring ESD using the tunnel + clip method. This involves generation of a classic tunnel beneath the lesion, with constant traction being applied by a clip with a line placed at the oral side of the tunnel. RESULTS: Sixty-two lesions (25 SCCs and 34 ADK/HGDs complicating Barrett's oesophagus) were consecutively resected. The en bloc, R0, and curative resection rates were 100% (62/62), 88.7% (55/62), and 74.2% (46/62), respectively. No perforation was noted. The mean ESD velocity was 24.5 mm2/min for lesions of mean length 59.6 mm. The tunnel + clip approach greatly aided the procedure. No pathological damage caused by clipping was evident. CONCLUSION: Use of the tunnel + clip strategy to treat oesophageal ESD is effective and safe, even when performed by physicians with little prior experience. It is thus possible to standardise ESD of superficial oesophageal neoplasms and increase the velocity of dissection. Our procedure will encourage the use of oesophageal ESD in Western countries.

HybridKnife high-pressure glycerol jet injection for endoscopic submucosal dissection increases procedural ease and speed: a randomised study in pigs and a human case series.

BACKGROUND AND AIMS: Good use of the submucosal space is key during endoscopic submucosal dissection (ESD). High-pressure injection of a long-lasting viscous solution using the HybridKnife water-jet system has been demonstrated to be feasible. We compared jet injection of glycerol and normal saline during pig gastric ESD and assessed its feasibility and efficiency during human ESD. MATERIALS AND METHODS: A blinded randomised controlled study of ESD with the HybridKnife injecting either a glycerol mixture or normal saline and a prospective human case series were performed. Twenty gastric pig dissections (10/group) and 38 human ESDs along the gastrointestinal tract were performed. Dissection speed, specimen size, procedure duration, rates of en bloc and R0 resection, and rates of bleeding and perforation were prospectively recorded. An evaluation of operator comfort and perceived safety (dissection score) was performed using a visual analogue scale with zero being the worst score and ten the best. RESULTS: Dissection was significantly more rapid (1.38-fold) with glycerol injection than with normal saline injection (28.94 vs. 20.91 mm(2)/min; p = 0.037). The dissection score was significantly higher in the glycerol group than in the normal saline group (7.3 vs. 4.7; p = 0.0064). No differences were observed in the rates of en bloc resection, bleeding, or perforation. The 38 human cases along the gastrointestinal tract revealed good results (en bloc resection rate = 100 %, R0 resection rate = 90 %) without any complications. CONCLUSION: High-pressure jet injection of glycerol with the HybridKnife for ESD increased the speed and operator comfort of the procedure compared with the use of normal saline, and the procedure was safe and efficient for human ESD. The advantages of using a combination of the HybridKnife system and a viscous glycerol solution will help to spread the use of the ESD technique, particularly in non-Asian countries.

Impact of chromoscopy on adenoma detection in patients with Lynch syndrome: a prospective, multicenter, blinded, tandem colonoscopy study.

OBJECTIVES: In Lynch syndrome, flat and diminutive adenomas are particularly prone to malignant transformation, but they can be missed by standard colonoscopy. It is not known whether chromocolonoscopy is able to detect more adenomas than standard colonoscopy in patients with Lynch syndrome. METHODS: We conducted a prospective, multicenter, randomized trial to compare standard colonoscopy with standard colonoscopy followed by pancolonic chromoscopy with indigo carmine in patients with a proven germline mutation in a mismatch-repair gene related to Lynch syndrome and who were undergoing screening or surveillance colonoscopy. Standard colonoscopy was used first to detect visible lesions. Colonoscopy with chromoscopy was then performed by a second gastroenterologist (blinded to the findings of the first colonoscopy) to detect additional lesions. The primary end point was the number of patients in whom at least one adenoma was detected. RESULTS: A total of 78 eligible patients (median age, 45 years) were enrolled at 10 centers from July 2008 to August 2009. Significantly more patients with at least one adenoma were identified by chromocolonoscopy (32/78 (41%)) than by standard colonoscopy (18/78 (23%); P<0.001). The percentage of patients in whom at least one additional adenoma was detected during the chromoscopy was 31% (24/78). Overall, chromocolonoscopy plus colonoscopy detected a total of 55 adenomas in 32 patients (mean number of adenomas detected per patient: 0.7 vs. standard colonoscopy alone: 0.3; P<0.001). CONCLUSION: The results support the proposition that chromocolonoscopy may significantly improve the detection rate of colorectal adenomas in patients undergoing screening or surveillance colonoscopy for Lynch syndrome.

eGFR decrease during antiviral C therapy with first generation protease inhibitors: a clinical significance?

BACKGROUND & AIMS: Renal toxicity of first generation protease inhibitors (PIs) was not a safety signal in phase III clinical trials, but was recently reported in recent studies. It appeared important to determine the clinical significance of these findings. METHODS: We retrospectively analysed 101 HCV patients receiving triple therapy with telaprevir (n = 36) or boceprevir (n = 26) or double therapy (n = 39) with peginterferon and ribavirin and having a close monitoring of eGFR (MDRD formula) during and after treatment. EGFR decline over time was assessed by a linear mixed-effects model (LMEM) with search for possible explanatory covariates. RESULTS: Patients treated with telaprevir presented a significant decrease of eGFR with the same kinetics: initial decrease at W (week) 4, nadir at W8 (mean decrease 17.0 ± 18.9 ml/min/1.73 m(2)) and return to baseline at W16. The W8 eGFR was correlated with the D0 eGFR (R(2) = 0.49). The LMEM showed that interindividual variability in the slope of eGFR vs time between D0 and W8 was non-significant and eGFR nadir could be predicted from eGFR obtained at D0. In multivariate analysis, eGFR intercept (i.e. baseline value) was associated with older age and male sex. CONCLUSION: The eGFR significantly varied in telaprevir group only. Our model showed that eGFR nadir mainly depended on initial eGFR. As telaprevir has been shown to inhibit mostly the drug transporter OCT2 which interacts with creatinine transport, the early decrease of eGFR observed could be a benign phenomenon. However, as unpredictable true renal toxicity may occur during therapy, we recommend a thorough follow-up of eGFR.

HCV-associated B-cell non-Hodgkin lymphomas and new direct antiviral agents.

BACKGROUND & AIMS: Hepatitis C virus-related B-cell proliferation is a model of virus-driven autoimmune/neoplastic disorder leading to mixed cryoglobulinaemia and/or B-cell non-Hodgkin lymphoma. These lymphomas are often marginal zone lymphomas or diffuse large B-cell lymphomas. Peginterferon/Ribavirin therapy has proved its crucial role in the cure of these non-Hodgkin lymphomas, but data are lacking concerning new direct anti-viral agents. METHODS: We report five cases of Hepatitis C virus-associated B-cell non-Hodgkin lymphoma treated with direct anti-viral agents: two marginal zone lymphomas received direct anti-viral agents alone (one with a leukaemic phase only, one with splenic and deep lymph nodes localizations); one renal marginal zone lymphoma with renal insufficiency received direct anti-viral agents and four rituximab infusions simultaneously; two diffuse large B-cell lymphomas were treated with direct ant-viral agents following chemotherapy. RESULTS: Sustained virological response was obtained in all patients, and complete remission of NHL was noted 6 months after cessation of any treatment except for one patient with a persistent small leukaemic phase. CONCLUSION: Direct anti-viral agents might be proposed as a first-line treatment in marginal zone lymphomas in the case of no life-threatening complications with the precaution of a long-term follow-up. In the setting of diffuse large B-cell lymphomas, well-tolerated direct anti-viral agents could potentially be introduced very early not only to prevent relapse of these lymphomas but also to limit the liver toxicity of chemotherapy and rituximab by preventing outbreaks of viral load. New observations and trials should support these assumptions.

High-pressure injection of glycerol with HybridKnife for ESD is feasible and increases the ease and speed of the procedure: an in vivo study in pigs and first use in human.

BACKGROUND AND AIMS: The HybridKnife water-jet system (ERBE, Tubingen, Germany) has been shown to increase dissection speed and decreased the risk of perforation during endoscopic submucosal dissection (ESD). Glycerol mixture is a viscous, long-lasting solution preferentially used by Japanese ESD experts. The combination of the HybridKnife system with a glycerol solution has not been evaluated to date. MATERIALS AND METHODS: A prospective non-randomised comparative study of ESD with HybridKnife injecting of either a glycerol mixture or normal saline was performed. Twenty dissections (ten per group) were performed on four anaesthetised domestic mini-pigs. Dissection speed (mm(2)/min), size of the specimen (mm(2)), duration (min), en bloc resection rate, and bleeding and perforation rates were prospectively recorded. An evaluation of operator comfort and perception of safety (dissection score) was performed using a visual analogue scale with 0 being the worst score and 10 the best. RESULTS: High-pressure injection of the glycerol mixture and dissection with the HybridKnife was feasible without complications. Dissection was significantly more rapid (1.67-fold) with glycerol injection than normal saline injection (27.44 vs. 16.44 mm(2)/min; p < 0.001). The dissection score was significantly higher in the glycerol group than in the normal saline group (5.9 vs. 2.9; p < 0.001). No differences were observed in the rates of en bloc resection, bleeding and perforation. Seven first human cases were also easy without need of preliminary incision and technical complication. CONCLUSION: High-pressure jet injection of glycerol with HybridKnife for ESD is feasible and increases the speed and safety of the procedure compared with use of normal saline.

The COlorectal NEoplasia Endoscopic Classification to Choose the Treatment classification for identification of large laterally spreading lesions lacking submucosal carcinomas: A prospective study of 663 lesions.

INTRODUCTION: Optical diagnosis is necessary when selecting the resection modality for large superficial colorectal lesions. The COlorectal NEoplasia Endoscopic Classification to Choose the Treatment (CONECCT) encompasses overt (irregular pit or vascular pattern) and covert (macroscopic features) signs of carcinoma in an all-in-one classification using validated criteria. The CONECCT IIC subtype corresponds to adenomas with a high risk of superficial carcinoma that should be resected en bloc with free margins. METHODS: This prospective multicentre study investigated the diagnostic accuracy of the CONECCT classification for predicting submucosal invasion in colorectal lesions >20 mm. Optical diagnosis before en bloc resection by endoscopic submucosal dissection (ESD) was compared with the final histological diagnosis. Diagnostic accuracy for the CONECCT IIC subtype was compared with literature-validated features of concern considered to be risk factors for submucosal invasion (non-granular large spreading tumour [NG LST], macronodule >1 cm, SANO IIIA area, and Paris 0-IIC area). RESULTS: Six hundred 63 lesions removed by ESD were assessed. The en bloc, R0, and curative resection rates were respectively 96%, 85%, and 81%. The CONECCT classification had a sensitivity (Se) of 100%, specificity (Sp) of 26.2%, positive predictive value of 11.6%, and negative predictive value (NPV) of 100% for predicting at least submucosal adenocarcinoma. The sensitivity of CONECCT IIC (100%) to predict submucosal cancer was superior to all other criteria evaluated. COlorectal NEoplasia Endoscopic Classification to Choose the Treatment IIC lesions constituted 11.5% of all submucosal carcinomas. CONCLUSION: The CONECCT classification, which combines covert and overt signs of carcinoma, identifies with very perfect sensitivity (Se 100%, NPV 100%) the 30% of low-risk adenomas in large laterally spreading lesions treatable by piecemeal endoscopic mucosal resection or ESD according to expertise without undertreatment. However, the low specificity of CONECCT leads to a large number of potentially not indicated ESDs for suspected high-risk lesions.

Effect of implementing a regional referral network on surgical referral rate of benign polyps found during a colorectal cancer screening program: A population-based study.

INTRODUCTION: Surgical management is too often performed as the first-line treatment for large, benign colorectal polyps. We report the management of benign lesions detected by organised colorectal cancer (CRC) screening. METHODS: Population-based study in 2012, 2016, and 2017, analyzing the evolution of surgical management of benign polyps of≥2cm diameter discovered in the context of organised CRC screening after the implementation of a regional referral network for the management of superficial colorectal lesions. RESULTS: A total of 1571 patients underwent colonoscopy following a positive test during the study period, among which 981 colonoscopies yielded at least one lesion. The adenoma detection rate was lower in 2012 (Guaiac test) than in 2016 and 2017 (fecal immunochemical test) (40% vs. 60% vs. 57%, P<0.0001). The surgery rate for benign lesions decreased from 14.6% in 2012 to 7.7% in 2016 and 5% in 2017 (P=0.017). The risk factors for surgery for benign lesions were year 2012 (odds ratio [OR]=3.35, P=0.022), high-grade dysplasia (OR=2.49, P=0.04), in situ carcinoma (OR=5, P=0.003), size≥20mm (OR=17.39, P<0.0001), and private sector (OR=6.6, P=0.0002). The morbidity rate of surgery for benign polyp≥2cm was 20.4% at 1month and its cost was sixfold higher than that of endoscopy. CONCLUSION: The establishment of a regional referral network for the management of large colorectal polyps reduces the rate of surgical management of such lesions.

Video clips compared with high-definition still images for characterization of colorectal neoplastic lesions: a randomized comparative prospective study.

Background and study aims Accurate real-time characterization of colorectal neoplastic lesions (CNLs) during colonoscopy is important for deciding appropriate treatment. No studies have evaluated whether still images or video clips are better for characterization. We compared histological predictions and size estimations of CNLs between two groups of gastroenterologists: one viewing still images and the other viewing video clips. Materials and methods Participants were shown 20 CNLs as either 3-5 still images or a video clip. Three endoscopy experts obtained the images using high-definition white light and virtual chromoendoscopy without magnification. Stratified randomization was performed according to experience. For each lesion, participants assessed the size and histological subtype according to the CONECCT classification (hyperplastic polyp [IH], sessile serrated lesion [IS], adenoma [IIA], high-risk adenoma or superficial adenocarcinoma [IIC], or deeply invasive adenocarcinoma [III]). The correct histological status and size were defined by the pathology reports or combined criteria between histology and expert opinion for high-risk adenoma or superficial adenocarcinoma (CONECCT IIC). Results 332 participants were randomized and 233 performed the characterization. Participants comprised 118 residents, 75 gastroenterologists, and 40 endoscopy experts; 47.6 % were shown still images and 52.4 % viewed video clips. There was no statistically significant difference between the two groups in histological prediction, our primary end point. However, the lesion size was better assessed using still images than video clips ( P  = 0.03). Conclusions Video clips did not improve the histological prediction of CNLs compared with still images. Size was better assessed using still images.