Jérémie Jacques

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

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.

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.

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

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.

Endoscopic haemostasis: An overview of procedures and clinical scenarios

Acute gastrointestinal bleeding is among the most urgent situations in daily gastroenterological practise. Endoscopy plays a key role in the diagnosis and treatment of such cases. Endoscopic haemostasis is probably the most important technical challenge that must be mastered by gastroenterologists. It is essential for both the management of acute gastrointestinal haemorrhage and the prevention of bleeding during high-risk endoscopic procedures. During the last decade, endoscopic haemostasis techniques and tools have grown in parallel with the number of devices available for endotherapy. Haemostatic powders, over-the-scope clips, haemostatic forceps, and other emerging technologies have changed daily practise and complement the standard available armamentarium (injectable, thermal, and mechanical therapy). Although there is a lack of strong evidence-based information on these procedures because of the difficulty in designing statistically powerful trials on this topic, physicians must be aware of all available devices to be able to choose the best haemostatic tool for the most effective procedure. We herein present an overview of procedures and clinical scenarios to optimise the management of gastrointestinal bleeding in daily practise.

Ribavirin: Past, present and future.

Before the advent of direct acting antiviral agents (DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the present era of new potent DAAs, a place is still devoted to the drug. Ribavirin associated with sofosbuvir alone is efficient in the treatment of most cases of G2 infected patients. All options currently available for the last difficult-to-treat cirrhotic G3 patients contain ribavirin. Reducing treatment duration to 12 wk in G1 or G4 cirrhotic compensated patients is feasible thanks to ribavirin. Retreating patients with acquired anti NS5A resistance-associated variants using ribavirin-based strategies could be useful. The addition of ribavirin with DAAs combinations however, leads to more frequent but mild adverse events especially in cirrhotic patients. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized even in difficult-to-treat patients: The optimization of ribavirin dosage according to an early monitoring of blood levels has been suggested to be relevant in double therapy with peginterferon or sofosbuvir but not with very potent combinations of more than two DAAs.

Traction strategy with clips and rubber band allows complete en bloc endoscopic submucosal dissection of laterally spreading tumors invading the appendix

Endoscopic submucosal dissection (ESD) is now the reference method for en bloc resection of large colorectal neoplasia [1]. Nevertheless, appendix invasion is still considered a contraindication to resection because of the risk of perforation and the difficulty in finding the dissection space at the bottom of the appendix. We report on the case of a 72-yearold man referred for resection of a 4 cm granular laterally spreading tumor (LST) of the cecum (▶Fig. 1, ▶Video 1). The lesion had developed on the appendiceal orifice, invading it deeply. As previously demonstrated, we used a traction strategy with two clips and a rubber band [2]. After complete circumferential incision and trimming, we caught the lesion edge with the first clip, which was grasping a rubber band (▶Fig. 2). The second clip was then used to grasp the rubber band and stretch the lesion; the clip was then fixed to the opposite wall of the colon (▶Fig. 3). This traction method is flexible using stretching and relaxing of the rubber band to produce more or less traction, respectively. Greater stretching of the band resulted in strong traction, which allowed the mucosa of the appendix to be dissected and extracted through the appendiceal orifice (▶Fig. 4). Finally, we were able to cut the deep fibrotic fibers that fixed the mucosa at the bottom of the appendix. Pathological examination revealed a granular LST with high grade dysplasia, which was completely removed with free margins. There were no complications either during the procedure or in the postoperative period. The patient was monitored for 48 hours, given the known risk of early and late acute appendicitis of 3% and 5%, respectively [3]. In patients with an intact appendix, there is a high risk of incomplete resection for lesions that reach and enter the appendiceal orifice with invisible margins (Type 3) [4]. Video 1 Endoscopic submucosal dissection procedure with double clip and rubber band traction to allow complete R0 resection of a laterally spreading tumor invading the appendix. ▶ Fig. 1 Granular laterally spreading tumor with regular mucosal and vascular patterns. a White-light imaging; the appendiceal orifice is indicated by the blue arrow. b Far view with narrow-band imaging (NBI). c, d Close-up views with NBI. E-Videos

Double-clip counter-traction using a rubber band is a useful and adaptive tool for colonic endoscopic submucosal dissection

The colon is the most technically challenging location for endoscopic submucosal dissection (ESD) of large, superficial, precancerous and cancerous lesions [1]. Appropriate exposure of the submucosal space can be very difficult, even when performed by experts, owing to the thinness of the submucosal space in this location and because the gravitational assistance is not constant. Moreover, the presence of colonic loops, bowel and respiratory movements, and position modifications resulting from insufflation increase the difficulty of performing ESD in this location. Various strategies have been proposed to overcome these challenges, including pocket ESD [2] and the clip-with-line technique [3]. We recently reported the double-clip counter-traction method using a rubber band for large adenomas involving the appendix [4]. Here, we report a new strategy, which involves double-clip counter-traction using a rubber band and adjustment of the countertraction during the procedure. As shown in ▶Fig. 1 and ▶Video1, after hemicircumferential mucosal incision of a large sigmoid adenoma, the first clip was attached to the anal side of the lesion, grasping both the specimen and the rubber band. A second clip was then placed on the bowel wall in front of the lesion on the cecum side of the colonic wall to allow exposure of the submucosal space. Rapid and safe dissection was performed using this counter-traction method. However, the submucosal space narrowed progressively as the counter-traction effect subsided due to the specimen turning in on itself (▶Fig. 1 c). The clip that was attached to the colonic wall was therefore removed using a 10-mm polypectomy snare with gentle traction. A new clip, grasping the rubber band, was then placed on the colonic wall in front of the lesion on the anal side of the colonic wall, 5 cm distal to the specimen, to create traction in a tent-like fashion (▶Fig. 1d). Traction allowed rapid and safe completion of the dissection of this 7-cm adenoma with low grade dysplasia in less than 2 hours. E-Videos

A combination of pocket, double-clip countertraction, and isolated HybridKnife as a quick and safe strategy for colonic endoscopic submucosal dissection

The colon is considered to be one of the most technically challenging locations for endoscopic submucosal dissection (ESD) when superficial neoplastic lesions are being treated [1]. The difficulties include: the colonic loops, intestinal motility, the folded anatomy, problems caused by inconstant gravity, and constant modification of the operative fieldof-view attributable to insufflation. Good exposure of the submucosal layer is key for safe and efficient ESD; this can be particularly challenging in the colon where it is difficult to maintain a tangential position close to the muscle layer. Many tips and tricks have been reported to facilitate colonic ESD, including: ▪ the use of gravity; ▪ creation of a pocket [2]; ▪ tunnel dissection; ▪ clip [3] or double-clip countertraction (ring-thread countertraction [4]); ▪ the use of a waterjet injection knife [5]. Although individual physicians will prefer certain tips or tricks with which they are familiar, little information is available on combinations of these technical approaches. As case numbers are increasing worldwide, and as colorectal cancer screening programs are becoming more common and effective, further technical improvements are imperative. Here, we report on our treatment strategy for colonic ESD and seek to facilitate the resection of large superficial colonic lesions.

Anchoring the snare tip by means of a small incision facilitates en bloc endoscopic mucosal resection and increases the specimen size

Endoscopic mucosal resection (EMR) allows curative resection of superficial colorectal neoplasms up to 2 cm in diameter. En bloc resection is generally not possible for larger lesions and for some smaller very flat lesions because of the difficulty in capturing them appropriately [1]. Piecemeal EMR is possible for larger colonic lesions, but carries a high risk (~20%) of recurrence [2]. Hybrid procedures, involving use of an endoscopic submucosal dissection (ESD) device to make mucosal incisions around the lesion, have been proposed for the colon, to increase the lesion size for which en bloc snare resection is possible, and to achieve snare resection in all cases of very flat lesions. However, in the colon, ESD is particularly technically challenging [3], and mucosal incision can be quite time-consuming and risky in nonexpert hands in this location because of the folded anatomy and the bowel movement. Moreover the ESD devices are expensive, with no specific reimbursement in most European countries. We here propose a new, simple, and reproducible maneuver to facilitate colonic mucosal resection. In the case of large (2–3-cm) colonic polyps (▶Fig. 1, ▶Video1) or very flat lesions (▶Fig. 2, ▶Video2), after submucosal injection, we have made a small (0.2-mm) incision at the distal part of the lesion, using the tip of the snare with an endocut current. This incision allows anchoring of the snare tip and thereby opening of the snare in a circular shape. This method holds the snare in place and avoids slippage during the resection. Moreover, the circular opening allows a larger resection. We currently use this trick for borderline lesions (approximately 2 cm) or very flat lesions in the colon, and no complications due to the small incision have been observed. This method is useful in cases of difficult or very flat lesions, or large colonic polyps, for increasing the en bloc resection rate, allowing higher quality pathological analysis, and decreasing the risk of residual or recurrent disease. E-Videos

Deep endoscopic submucosal dissection of a refractory tracheoesophageal fistula using clip-and-line traction: a successful closure

Chronic tracheoesophageal fistula is a rare disease presenting a therapeutic challenge. Unlike the case with most digestive fistulas, drainage with a pigtail stent [1] is not possible. We present here the case of a 47-yearold man referred for a chronic 2-mm tracheoesophageal fistula (23 cm from mouth) of unknown cause. His past history revealed several pulmonary infections since childhood. Several endoscopic treatments were attempted with clip closure and then hot biopsy forceps abrasion of the surrounding mucosa, but complete closure was not obtained. We therefore proposed endoscopic submucosal dissection (ESD) of the surrounding mucosa, namely a 1-cm mucosal patch (▶Fig. 1 and ▶Fig. 2, ▶Video1) centered on the fistula, as previously described [2]. The patient underwent tracheal intubation with balloon placement just under the fistula. To allow deep dissection of the fistula tract we added a clip-and-line traction (▶Fig. 3) [3] to pull the fistula Trachea a b c Fistula