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.

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.

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.

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.

High proficiency of colonic endoscopic submucosal dissection in Europe thanks to countertraction strategy using a double clip and rubber band.

Background and study aims ESD in the colon is more challenging technically than in other locations. Here, we report the first comparative case series of colon ESD using a systematic countertraction strategy using two clips and a rubber band. Patients and methods Retrospective comparative study of classic versus countertraction colon ESD performed in colon ESD cases collected prospectively at Lyon Edouard Herriot Hospital and Limoges University Hospital from January 2016 until December 2017. Results The study included 192 cases (control = 76, countertraction = 116). Countertraction using the double clip and rubber band technique versus the control group resulted in a significant decrease in the procedure time (94.7 vs . 117 min; P  = 0.004) and significant increases in procedure speed (28.2 vs . 16.7 mm 2 /min; P  < 0.0001), en bloc resection rate (95.7 % vs . 76.3 %, P  < 0.0001), and R0 resection rate (78.5 % vs . 64.5 %, P  = 0.04). At an individual operator point of view, results varied between operators but the double clip countertraction strategy significantly increased the en bloc resection rate, R0 resection rate, and speed of dissection for each of the 4 operators. Conclusion Systematic countertraction using a double clip and rubber band facilitates colon ESD. This strategy should become the standard for colon ESD.

What is the cost of endoscopic submucosal dissection (ESD)? A medico-economic study.

Introduction: Endoscopic submucosal dissection (ESD) is the gold-standard treatment for superficial lesions of the digestive tract. No medico-economic study has been conducted in Europe. Material and methods: A monocentric study was conducted including all patients undergoing ESD between January 2015 and December 2017. The global cost of hospital stays was measured by microcosting, and revenue was based on the diagnosis-related group (DRG) system. The primary objective was to assess the cost/revenue balance. A medico-economic comparison with surgery was performed as a secondary outcome. Results: A total of 193 patients were prospectively included. The cost per procedure was €3463.79, subtracted from a €2726.84 revenue, with a deficit of -€736.96 per stay. Presence of comorbidities/complications increasing DRG value was the only predictive factor for a positive budgetary balance in a multivariate analysis (odds ratio 49.21, 95% confidence interval 11.3-214.25, p < 0.0001). In comparison with surgery, ESD was associated with shorter length of stay (11 vs 2 days; p < 0.0001) and lower morbidity (28% vs 14%; p = 0.061), lower cost (€8960 vs €1770; p < 0.0001). Conclusion: The ESD cost/revenue balance is negative in 80% of cases. Given the benefits of ESD in terms of patient morbidity and financial savings compared with surgery, the implementation of a specific ESD reimbursement is warranted.

Outcomes and Future Directions of Per-Oral Endoscopic Pyloromyotomy: A View from France.

Gastroparesis is a challenging functional gastroenterological disorder, the complex pathophysiology of which hampers development of therapeutic modalities. Per-oral pyloromyotomy (POP) is a promising endoscopic therapy with a short-term clinical success rate of greater than 80%. Interest in POP is increasing, particularly in France, a country in which there is considerable expertise in submucosal endoscopy and functional disorders. Long-term follow-up and pyloric function evaluation are needed to assess the efficacy of POP in gastroparetic patients.

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.

Efficacy and safety of pasireotide-LAR for the treatment of refractory bleeding due to gastrointestinal angiodysplasias: results of the ANGIOPAS multicenter phase II noncomparative prospective double-blinded randomized study.

BACKGROUND: Gastrointestinal angiodysplasias (GIADs) could be responsible for recurrent bleeding and severe anemia. Somatostatin analogs could reduce transfusion requirements in these patients but no randomized controlled study is available. The main objective of the ANGIOPAS phase II double-blinded randomized, noncomparative study was to assess the effectiveness of pasireotide-LAR in reducing transfusion requirements in patients with refractory GIADs bleeding. METHODS: A total of 22 patients with transfusion requirements ⩾6 units of packed red blood cells (pRBCs) during the 6 months prior to inclusion were randomized to receive pasireotide-LAR 60 mg (n = 10) or placebo (n = 12) every 28 days for 6 months. Patients were then followed for an additional 6 months after stopping treatment. RESULTS: The pasireotide-LAR and placebo groups were equivalent for age, sex, comorbidities and transfusion requirement during the reference period (median 13 and 9.5 pRBCs). A 50 and 83% success rate (success defined as a decrease of at least 30% of transfused pRBCs) was observed in the pasireotide-LAR arm in the Intent to Treat (ITT) and per protocol (PP) analysis respectively. The need for transfusion during the intervention period was 3 pRBC units in the pasireotide-LAR group (range 0-26) and 11.5 pRBC units in the placebo group (range 0-23). Overall, three cases with glycemic control impairment were observed in the pasireotide-LAR group including one de novo diabetes. CONCLUSION: This double-blinded noncomparative randomized phase II study suggests, for the first time, the effectiveness of pasireotide-LAR 60 mg every 28 days to decrease the transfusion requirement in patients with recurrent bleeding due to GIADs.

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.

Anti-hepatitis C virus drugs and kidney.

Hepatitis C virus (HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease (CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in end-stage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents (DAAs) while avoiding peginterferon and ribavirin. The first results were convincing. To aid in the correct use of these drugs in patients with renal insufficiency, their pharmacokinetic properties and potential renal toxicity must be known. The renal toxicity of these new drugs was not a safety signal in clinical trials, and the drugs are generally efficient in these frail populations. These drugs are usually well tolerated, but recent cohort studies have demonstrated that these new regimens may be associated with renal side effects, especially when using sofosbuvir combinations. HCV, renal diseases and comorbidities are intimately linked. The close monitoring of renal function is required, particularly for at-risk patients (transplanted, HIV-coinfected, CKD, hypertensive or diabetic patients). New DAA regimens, which will soon be approved, will probably change the landscape.

Influence of Donor and Recipient CYP3A4, CYP3A5, and ABCB1 Genotypes on Clinical Outcomes and Nephrotoxicity in Liver Transplant Recipients.

BACKGROUND: This study investigated the influence of the CYP3A4*22, CYP3A5*3, and ABCB1 exons 12, 21, and 26 polymorphisms in donors and recipients on clinical outcomes and renal function in 170 liver transplant patients on cyclosporin A (CsA) or tacrolimus (Tac). METHODS: Allelic discrimination assays were used for genotyping. Multivariate time-dependent Cox proportional hazard models, multiple linear regression using the generalized estimating equation and linear mixed-effect models were used for statistical analysis. RESULTS: Expression of CYP3A5 by either or both the donor and the recipient was significantly associated with lower Tac, but not CsA, dose-normalized trough levels. In the whole population, graft loss was only significantly associated with longer exposure to high calcineurin inhibitor (CNI) concentrations (hazard ratio, 6.93; 95% confidence interval, 2.13-22.55), P = 0.00129), whereas in the Tac subgroup, the risk of graft loss was significantly higher in recipient CYP3A5*1 expressers (hazard ratio, 3.39; 95% confidence interval, 1.52-7.58; P = 0.0028). Renal function was significantly associated with: (1) baseline modification of diet in renal disease (ß = 0.51 ± 0.05; P < 0.0001); (2) duration of patient follow-up (per visit, ß = -0.98 ± 0.22; P < 0.0001); and (3) CNI exposure (per quantile increase, ß = -2.42 ± 0.59; P < 0.0001). No genetic factor was associated with patient survival, acute rejection, liver function test results, recurrence of viral or other initial liver disease, or renal function. CONCLUSIONS: This study confirms the effect of CYP3A5*3 on tacrolimus dose requirement in liver transplantation and shows unexpected associations between the type of, and exposure to, CNI and either chronic rejection or graft loss. None of the genetic polymorphisms studied had a noticeable impact on renal function degradation at 10 years.