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.

Long term exposure to antiangiogenic therapy, bevacizumab, induces osteonecrosis.

PURPOSE: Bevacizumab, a monoclonal VEGF-A antibody, has been identified as an aetiology of osteonecrosis of the femoral head. Long exposure to anti VEGF therapy induced chronic hypoperfusion of normal tissues. Osteonecrosis is a musculo-skeletal disease secondary to cellular death of bone component mainly induced by corticosteroids, alcohol use, or connective tissue disorders. METHODS: The medical records of patients with metastatic colorectal carcinoma receiving Bevacizumab between January 2006 and November 2013 were retrospectively reviewed and we had looked for osteonecrosis. Every disorder of musculoskeletal mobility were examined by orthopaedist and evaluated by imaging. RESULTS: We report on osteonecrosis of humeral and femoral head in patient with metastatic colon adenocarcinoma receiving a long-term exposure to anti angiogenic based treatment (>6 months), lack of other factors predisposing to osteonecrosis. These observations, according to literature, suggests that long exposure to anti VEGF-A, Bevacizumab, promote bone hypoperfusion and may induced osteonecrosis either on the femoral head or the humeral head with an incidence of 4 out of 1000 patients. CONCLUSIONS: With an incidence of 4 out of 1000 patients osteonecrosis is a rare side effect of anti-angiogenic agent. With the increasing utilisation and duration of exposure of anti-VEGF therapy some rare side effect due to chronic ischemia may appear. The clinician should be aware about uncommon symptoms.

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.

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.

A local structured training program with live pigs allows performing ESD along the gastrointestinal tract with results close to those of Japanese experts.

BACKGROUND AND AIMS: The high specific skill needed by ESD limit its widespread use in Europe and animal training is recommended in Europe to improve the results of ESD that are far from Japanese at present. We create a local training program using live pigs as models, along with our human cases, to provide continuous exposure to the technique. METHODS: Between February 2013 and December 2015, two young operators performed 55 pig gastric ESDs in parallel with 62 human cases for large superficial cancerous lesions. The number and training dates of pig cases were adapted to those of the human cases to achieve continuous exposure to ESD cases. RESULTS: The en bloc, R0, and curative resection rates were 100%, 85.5% (53/62), and 77.5% (48/62), respectively with no recurrence observed during the one year follow up. There was no statistically significant difference in terms of the R0 or curative resection rates among ESDs performed during 2013-2015 (R0: 80% vs. 86.6% vs. 86.4%; Curative: 80% vs. 86.6% vs. 73%). CONCLUSION: A local structured training program using live pig models was used to train endoscopists for ESD in humans with high safety and efficiency, similar to results published by Japanese experts.

Personalized adapted physical activity before liver transplantation: acceptability and results.

BACKGROUND: Altered aerobic capacity and muscular strength among patients suffering from cirrhosis are poor prognosis factors of the overall survival after liver transplantation (LT). A program of adapted physical activity (APA) is recommended in patients awaiting solid organ transplantation. However, there is no standard program in LT, and therefore none is applied. METHODS: Prospective pilot study to evaluate the acceptability of a 12-week personalized APA and its impact on aerobic capacity, muscle strength, and quality of life before LT. RESULTS: Thirteen patients (six men, seven women) were included. Five patients interrupted the program: two for personal convenience, two were transplanted before the end of the program, and one for deterioration of the general condition. Eight patients (mean age, 51 ± 12 years; mean Child Pugh, 7 ± 3; and mean model for end-stage liver disease score, 13 ± 6) completed the program. The mean VO2 peak values increased from 21.5 ± 5.9 mL/kg per min at baseline to 23.2 ± 5.9 mL/kg per min after 12 weeks of training (P<0.008). The maximum power (P=0.02), the 6-min walk distance (P<0.02), the strength testing of knee extensor muscles (P=0.008), and the ventilatory threshold power (P=0.02) were also significantly increased. Quality of life scale showed a global trend to improvement. No adverse event was observed. CONCLUSION: A personalized and standardized APA is acceptable, effective and safe in patients awaiting LT. It positively influences the index of fitness and quality of life. Its promising impact on the posttransplantation period, duration of hospitalization, and 6-month survival needs to be prospectively evaluated in a large randomized study.

Diagnosis of Iron Deficiency in Inflammatory Bowel Disease by Transferrin Receptor-Ferritin Index.

Iron deficiency is common in patients with inflammatory bowel disease (IBD), but can be difficult to diagnose in the presence of inflammation because ferritin is an acute phase reactant. The transferrin receptor-ferritin index (TfR-F) has a high sensitivity and specificity for iron deficiency diagnosis in chronic diseases. The diagnostic efficacy of TfR-F is little known in patients with IBD. The aim of the study was to assess the added value of TfR-F to iron deficiency diagnosis in a prospective cohort of patients with IBD.Consecutive IBD patients were prospectively enrolled. Patients were excluded in case of blood transfusion, iron supplementation, or lack of consent. IBD activity was assessed on markers of inflammation (C-reactive protein, endoscopy, fecal calprotectin). Hemoglobin, ferritin, vitamin B9 and B12, Lactate dehydrogenase, haptoglobin, and soluble transferrin receptor (sTfR) were assayed. TfR-F was calculated as the ratio sTfR/log ferritin. Iron deficiency was defined by ferritin <30 ng/mL or TfR-F >2 in the presence of inflammation.One-hundred fifty patients with median age 38 years (16-78) and Crohn disease (n = 105), ulcerative colitis (n = 43), or unclassified colitis (n = 2) were included. Active disease was identified in 45.3%. Anemia was diagnosed in 28%. Thirty-six patients (24%) had ferritin <30 ng/mL. Thirty-two patients (21.3%) had ferritin levels from 30 to 100 ng/ml and inflammation: 2 had vitamin B12 deficiency excluding TfR-F analysis, 13 of 30 (43.3%) had TfR-F >2. Overall, iron deficiency was diagnosed in 32.7% of the patients.TfR-F in addition to ferritin <30 ng/mL criterion increased by 36% diagnosis rates of iron deficiency. TfR-F appeared as a useful biomarker that could help physicians to diagnose true iron deficiency in patients with active IBD.

[Gastric signet ring cell adenocarcinoma: A distinct entity]. / Adénocarcinome gastrique à cellules indépendantes : une entité à part.

Gastric signet ring cell carcinoma (GSRC) is a distinct entity. Their incidence is increasing. The pathologist plays a central role in the identification of this entity. Diagnosis is based on an adenocarcinoma containing a majority of signet ring cells (above 50 %). The prognosis of GSRC is the same as gastric adenocarcinoma while GSRC appeared more aggressive. Signet ring cells present a low sensitivity to chemotherapy. This review aimed to discuss the histological, the prognostic and the therapeutic aspect of this entity.

Gastric emptying evaluation by ultrasound prior colonoscopy: an easy tool following bowel preparation.

AIM: To investigate the gastric emptying after bowel preparation to allow general anaesthesia. METHODS: A prospective, non-comparative, and non-randomized trial was performed and registered on Eudra CT database (2011-002953-80) and on www.trial.gov (NCT01398098). All patients had a validated indication for colonoscopy and a preparation using sodium phosphate (NaP) tablets. The day of the procedure, patients took 4 tablets with 250 mL of water every 15 min, three times. The gastric volume was estimated every 15 min from computed antral surfaces and weight according to the formula of Perlas et al (Anesthesiology, 2009). Colonoscopy was performed within the 6 h following the last intake. RESULTS: Thirty patients were prospectively included in the study from November 2011 to May 2012. The maximum volume of the antrum was 212 mL, achieved 15 min after the last intake. 24%, 67% and 92% of subjects had an antral volume below 20 mL at 60, 120 and 150 min, respectively. 81% of patients had a Boston score equal to 2 or 3 in each colonic segment. No adverse events leading to treatment discontinuation were reported. CONCLUSION: Gastric volume evaluation appeared to be a simple and reliable method for the assessment of gastric emptying. Data allow considering the NaP tablets bowel preparation in the morning of the procedure and confirming that gastric emptying is achieved after two hours, allowing general anaesthesia.