Guillaume Perrod

Cell Sheet Transplantation for Esophageal Stricture Prevention after Endoscopic Submucosal Dissection in a Porcine Model

Background & Aims Extended esophageal endoscopic submucosal dissection (ESD) is highly responsible for esophageal stricture. We conducted a comparative study in a porcine model to evaluate the effectiveness of adipose tissue-derived stromal cell (ADSC) double cell sheet transplantation. Methods Twelve female pigs were treated with 5 cm long hemi-circumferential ESD and randomized in two groups. ADSC group (n = 6) received 4 double cell sheets of allogenic ADSC on a paper support membrane and control group (n = 6) received 4 paper support membranes. ADSC were labelled with PKH-67 fluorophore to allow probe-based confocal laser endomicroscopie (pCLE) monitoring. After 28 days follow-up, animals were sacrificed. At days 3, 14 and 28, endoscopic evaluation with pCLE and esophagography were performed. Results One animal from the control group was excluded (anesthetic complication). Animals from ADSC group showed less frequent alimentary trouble (17% vs 80%; P = 0.08) and higher gain weight on day 28. pCLE demonstrated a compatible cell signal in 4 animals of the ADSC group at day 3. In ADSC group, endoscopy showed that 1 out of 6(17%) animals developed a severe esophageal stricture comparatively to 100% (5/5) in the control group; P = 0.015. Esophagography demonstrated a decreased degree of stricture in the ADSC group on day 14 (44% vs 81%; P = 0.017) and day 28 (46% vs 90%; P = 0.035). Histological analysis showed a decreased fibrosis development in the ADSC group, in terms of surface (9.7 vs 26.1 mm²; P = 0.017) and maximal depth (1.6 vs 3.2 mm; P = 0.052). Conclusion In this model, transplantation of allogenic ADSC organized in double cell sheets after extended esophegeal ESD is strongly associated with a lower esophageal stricture’s rate.

Over-the-scope clip (OTSC) reduces surgery rate in the management of iatrogenic gastrointestinal perforations

Background and study aims Over-the-scope clip (OTSC) has been recently used in management of gastrointestinal perforations, but data on it are still limited. The aim of this study was to compare management of iatrogenic perforations before and after the OTSC was available in our endoscopy unit. Patients and methods We conducted a monocentric retrospective study from June 2007 to June 2015. All iatrogenic gastrointestinal perforations detected during endoscopy were included. Two time periods were compared in terms of surgery and mortality rates: before use of OTSC (June 2007 to June 2011) and after OTSC became available (June 2011 to June 2015). Results During the first period, 24 perforations were recorded. Fifteen (62.5 %) were managed with surgery. The mortality rate was 8 %. During the second period, 16 perforations occurred. In 11 patients (68.7 %), an OTSC was used to close the perforation, with complete sealing of the perforation in 100 % of cases. However, 2 patients with sigmoid perforation had to undergo surgery due to right ureteral obstruction by the clip in 1 case and to presence of a localized peritonitis in the other. The surgery rate during this period was 12.5 % (2 /16), with a statistically significant difference compared to the first period (P = 0.002). There was no mortality in the second period versus 8 % in the first one (P = 0.23). Conclusions OTSC is effective for endoluminal closure of iatrogenic perforations and results in a significant decrease in surgery rate.

ADSC-sheet Transplantation to Prevent Stricture after Extended Esophageal Endoscopic Submucosal Dissection

In past years, the cell-sheet construct has spurred wide interest in regenerative medicine, especially for reconstructive surgery procedures. The development of diversified technologies combining adipose tissue-derived stromal cells (ADSCs) with various biomaterials has led to the construction of numerous types of tissue-engineered substitutes, such as bone, cartilage, and adipose tissues from rodent, porcine, or human ADSCs. Extended esophageal endoscopic submucosal dissection (ESD) is responsible for esophageal stricture formation. Stricture prevention remains challenging, with no efficient treatments available. Previous studies reported the effectiveness of mucosal cell-sheet transplantation in a canine model and in humans. ADSCs are attributed anti-inflammatory properties, local immune modulating effects, neovascularization induction, and differentiation abilities into mesenchymal and non-mesenchymal lineages. This original study describes the endoscopic transplantation of an ADSC tissue-engineered construct to prevent esophageal stricture in a swine model. The ADSC construct was composed of two allogenic ADSC sheets layered upon each other on a paper support membrane. The ADSCs were labeled with the PKH67 fluorophore to allow probe-based confocal laser endomicroscopy (pCLE) monitoring. On the day of transplantation, a 5-cm and hemi-circumferential ESD known to induce esophageal stricture was performed. Animals were immediately endoscopically transplanted with 4 ADSC constructs. The complete adhesion of the ADSC constructs was obtained after 10 min of gentle application. Animals were sacrificed on day 28. All animals were successfully transplanted. Transplantation was confirmed on day 3 with a positive pCLE evaluation. Compared to transplanted animals, control animals developed severe strictures, with major fibrotic tissue development, more frequent alimentary trouble, and reduced weight gain. In our model, the transplantation of allogenic ADSCs, organized in double cell sheets, after extended ESD was successful and strongly associated with a lower esophageal stricture rate.

Diagnostic yield of capsule endoscopy in premenopausal and menopausal women with obscure gastrointestinal bleeding

Small bowel bleeding is responsible for 5% of gastrointestinal bleeding and for 30% of iron deficiency anemia (IDA). Depending on melena and/or rectorrhagia association, small bowel bleeding is defined as obscure (with) or occult (without) gastrointestinal bleeding (OGIB). In the general population, first line explorations in OGIB include upper gastrointestinal (GI) endoscopy and complete colonoscopy with a diagnostic yield ranging from 60% to 85% [1]. According to the international consensus statement published in 2005, capsule endoscopy (CE) should be recommended as second line endoscopic exploration for patients with OGIB [2]. CE is a non-invasive technique with a diagnostic yield ranging from 41.9 to 92.3%. This diagnostic yield is comparable to double balloon enteroscopy, and dedicated computed tomography diagnostic yields. In premenopausal women, IDA is the most frequent cause of anemia with a prevalence of 5% in the Western countries [3]. In this population, iron-deficiency etiology is often related to gynecological symptoms and gastrointestinal lesions are diagnosed in less than 20% after endoscopic explorations [4]. Because of the poor diagnostic yield of standard endoscopic exploration in premenopausal women with OGIB, small bowel capsule endoscopy could be of great interest. Herein, we report the result of a multicentric retrospective study evaluating the diagnostic yield of CE in women with OGIB according to their menopausal status. Between January 2009 to January 2014, we conducted a

Duodenal duplication cyst: a rare cause of recurrent pancreatitis

We report the case of a 54-year-old man with a medical history of recurrent pancreatitis who was referred to our department for a novel episode of epigastric pain. A blood test confirmed the diagnosis of acute pancreatitis, and a biliary origin was suspected because of abnormal liver test results and dilatation of the biliary ducts as shown by US. A CT scan confirmed the bile duct dilatation and showed a voluminous cystic lesion of 40 30 mm developed from the duodenal wall (Fig. 1). Upper GI endoscopy identified a submucosal pedunculated lesion likely originating from the papilla area and completely obstructing its lumen. The cystic characteristics of the lesion were confirmed by EUS, but neither the typical

Impact of an optimized colonoscopic screening program for patients with Lynch syndrome: 6-year results of a specialized French network

Background: Despite colonoscopic screening, colorectal cancer (CRC) remains frequent in patients with Lynch syndrome (LS). The objective of this study was to evaluate the impact of an optimized colorectal screening program within a French dedicated network. Methods: All LS patients followed at our institution were consecutively included in the Prédisposition au Cancer Colorectal-Ile de France (PRED-IdF) network. Patients were offered an optimized screening program allowing an adjustment of the interval between colonoscopies, depending on bowel preparation, chromoendoscopy achievement and adenoma detection. Colonoscopies were defined as optimal when all the screening criteria were respected. We compared colonoscopy quality and colonoscopy detection rate before and after PRED-IdF inclusion, including polyp detection rate (PDR), adenoma detection rate (ADR) and cancer detection rate (CDR). Results: Between January 2010 and January 2016, 144 LS patients were consecutively included (male/female = 50/94, mean age = 51 ± 13 years and mutations: MLH1 = 39%, MSH2 = 44%, MSH6 = 15%, PMS2 = 1%). A total of 564 colonoscopies were analyzed, 353 after inclusion and 211 before. After PRED-IdF inclusion, 98/144 (68%) patients had optimal screening colonoscopies versus 33/132 (25%) before (p < 0.0005). The optimal colonoscopy rate was 304/353 (86%) after inclusion versus 87/211 (41%) before, (p < 0.0001). PRED-IdF inclusion was associated with a reduction of CRC occurrence with a CDR of 1/353 (0.3%) after inclusion versus 6/211 (2.8%) before (p = 0.012). ADR and PDR were 99/353 (28%) versus 60/211 (28.8%) (p > 0.05) and 167/353 (48.1%) versus 90/211 (42.2%) (p > 0.05), respectively after and before inclusion. Conclusions: An optimized colonoscopic surveillance program in LS patients seems to improve colonoscopic screening quality and might possibly decrease colorectal interval cancer occurrence. Long-term cohort studies are needed to confirm these results.

Long-term follow-up after endoscopic resection for superficial esophageal squamous cell carcinoma: a multicenter Western study

BACKGROUND  Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are the first-line treatments for superficial esophageal squamous cell carcinoma (SCC). This study aimed to compare long-term clinical outcome and oncological clearance between EMR and ESD for the treatment of superficial esophageal SCC. METHODS  We conducted a retrospective multicenter study in five French tertiary care hospitals. Patients treated by EMR or ESD for histologically proven superficial esophageal SCC were included consecutively. RESULTS  Resection was performed for 148 tumors (80 EMR, 68 ESD) in 132 patients. The curative resection rate was 21.3 % in the EMR group and 73.5 % in the ESD group (P < 0.001). The recurrence rate was 23.7 % in the EMR group and 2.9 % in the ESD group (P = 0.002). The 5-year recurrence-free survival rate was 73.4 % in the EMR group and 95.2 % in the ESD group (P = 0.002). Independent factors for cancer recurrence were resection by EMR (hazard ratio [HR] 16.89, P = 0.01), tumor infiltration depth ≥ m3 (HR 3.28, P = 0.02), no complementary treatment by chemoradiotherapy (HR 7.04, P = 0.04), and no curative resection (HR 11.75, P = 0.01). Risk of metastasis strongly increased in patients with tumor infiltration depth ≥ m3, and without complementary chemoradiotherapy (P = 0.02). CONCLUSION  Endoscopic resection of superficial esophageal SCC was safe and efficient. Because it was associated with an increased recurrence-free survival rate, ESD should be preferred over EMR. For tumors with infiltration depths ≥ m3, chemoradiotherapy reduced the risk of nodal or distal metastasis.

Thermoresponsive Gel Embedded with Adipose Stem-Cell-Derived Extracellular Vesicles Promotes Esophageal Fistula Healing in a Thermo-Actuated Delivery Strategy

Extracellular vesicles (EVs) are increasingly envisioned as the next generation of biological pro-regenerative nanotherapeutic agents, as has already been demonstrated for heart, kidney, liver, and brain tissues; lung injury repair; and skin regeneration. Herein, we explore another potential EV therapeutic application, fistula healing, together with a local minimally invasive delivery strategy. Allogenic extracellular vesicles (EVs) from adipose tissue-derived stromal cells (ASCs) are administered in a porcine fistula model through a thermoresponsive Pluronic F-127 (PF-127) gel, injected locally at 4 °C and gelling at body temperature to retain EVs in the entire fistula tract. Complete fistula healing is reported to be 100% for the gel plus EVs group, 67% for the gel group, and 0% for the control, supporting the therapeutic use of Pluronic F-127 gel alone or combined with EVs. However, only the combination of gel and EVs results in a statistically significant (i) reduction of fibrosis, (ii) decline of inflammatory response, (iii) decrease in the density of myofibroblasts, and (iv) increase of angiogenesis. Overall, we demonstrate that ASC-EV delivery into a PF-127 gel represents a successful local minimally invasive strategy to induce a therapeutic effect in a swine fistula model. Our study presents prospects for EV administration strategies and for the management of post-operative fistulas.

Efficacy of double-balloon enteroscopy for small-bowel polypectomy: clinical and economic evaluation

Background: We evaluated first the feasibility of endoscopic small-bowel polypectomy and second, the economic aspects, by comparing the cost of endoscopic and surgical polyp resection. Methods: A prospective, observational, multicenter study included 494 patients with positive capsule endoscopy (CE) before double-balloon enteroscopy (DBE). We selected only CE with at least one polyp. The retrospective economic evaluation compared patients treated by DBE or surgery for small-bowel polypectomy. Hospital readmission because of repeat polyp resection or complication-related interventions was noted. The 1-year cost was estimated from the viewpoint of the healthcare system and included procedures, hospital admissions and follow up. Results: CE indicated one or more polyps in 62 (12.5%) patients (32 males, 49 ± 5 years), all of whom underwent a successful DBE exploration. The DBE polyp diagnostic yield was 58%. There were no major complications. A total of 26 (42%) patients in the DBE group and 19 (39%) in the control group required hospital readmission. All readmissions in the DBE group were for repeat procedures to remove all polyps, and in the control group, for surgical complications. The total cost of the initial hospitalization (€4014 ± 2239 DBE versus €11,620 ± 7183 surgery, p < 0.0001) and the 1-year total cost (€8438 ± 9227 DBE versus €13,402 ± 7919 surgery, p < 0.0001) were lower in the DBE group. Conclusions: Endoscopic polypectomy was efficient and safe. The total cost at 1 year was less for endoscopy than surgery. DBE should be proposed as the first-line treatment for small-bowel polyp resection.

Esophageal intramural pseudodiverticulosis, a rare cause of stenosis

A 53-year-old man with a medical history of tobacco and alcohol abuse, was referred to our department for dysphagia and weight loss in the past three months. The upper GI endoscopy showed honeycombed aspect with multiple small diverticular orifices in the esophageal wall and several esophageal strictures ranging from 35 to 25 cm from the dental arches (Fig. 1). The esophageal biopsies showed aspecific