[Aseptic process validation and stability study of an injectable preparation of fructose (5%)-glycerol (10%) as part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract]. / Validation du procédé aseptique et étude de stabilité d'une préparation injectable de fructose (5 %)-glycérol (10 %) dans le cadre d'un programme hospitalier de recherche clinique portant sur le traitement curatif endoscopique des lésions néoplasiques épithéliales précoces du tube digestif.

INTRODUCTION: As part of a hospital clinical research program on endoscopic curative treatment for early epithelial neoplastic lesions of the gastrointestinal tract, a new hospital sterile and non-pyrogenic preparation of fructose (5%)-glycerol (10%) was realized. Under pharmaceutical legislation, the provision of this hospital preparation involves of aseptic process validation and achieve a stability study. MATERIALS AND METHODS: After the aseptic process validation with Mediafill Test, the preparation was made under aseptic conditions associated with a sterilizing filtration according to the good practices preparation. Prepared flexible bags (100mL of solution) were stored for one year in a climatic chamber (25±2°C). To assess stability, the physicochemical controls (fructose concentration, glycerol concentration, hydroxy-methyl-5 furfural [5-HMF] concentration, sodium concentration, pH measure, osmolality and sub-visible particles count) and microbiological (bioburden, bacterial endotoxin and sterility) were performed at regular intervals for one year. RESULTS: Neither significant decrease of fructose concentration, glycerol concentration and sodium concentration nor pH, 5-HMF, osmolality variations out of specifications were observed for one year. The sub-visible particles count, the bacterial endotoxin and sterility were in accordance with the European pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. DISCUSSION AND CONCLUSION: The hospital preparation was stable over one year at 25±2°C, ensuring safe administration in humans within the framework of this clinical research.

[Early oesophageal cancer: epidemiology diagnosis and management]. / Cancers superficiels de l'oesophage: épidémiologie, diagnostic et traitement.

In Europe, oesophageal cancers are diagnosed at an early stage in less than 10% of the cases. They are superficial tumours whose invasion is limited to the mucosae and the submucosa. Synchronous node invasion is the most important prognosis factor. Oesophagectomy is the benchmark treatment. Nowadays, endoscopic resection is a validated curative therapeutic alternative. Accurate endoscopic evaluation using chemical or virtual colouring as well as an echoendoscopy, followed by an expert pathological review, must be conducted beforehand. It can be realised for good prognosis tumours after evaluation of the synchronous node invasion or its risk. After completion, regular endoscopic follow-ups are compulsory to detect local relapse.

A 3D-printed pedal fixator for connecting different pedal-operated tools reduces the number of mistakes during endoscopic submucosal dissection.

Background and study aims What distinguishes endoscopic submucosal dissection (ESD) from endoscopic mucosal resection is the need for three foot pedals to activate the electrosurgical unit, flushing and knife injection. The lack of connection between the various pedals of different shapes and brands leads to numerous pedals displacements and potential mistakes. The aim of this study was to evaluate an Innovative PEdal FIXator (IPEFIX) to reduce pedal mistakes during ESD. Methods This was a prospective, multicenter, randomized study. Consecutive ESD procedures were randomly assigned to two groups: a control group with the three pedals free and the IPEFIX group in which the three pedals were linked by IPEFIX. The main outcome evaluated was the number of foot mistakes (wrong pedal, foot push beside the pedal). Results A total of 107 ESDs were performed by eight experts in five centers. The median number of mistakes per hour of ESD procedure was 0/h in the IPEFIX group and 1.9/h in the control group ( P <0.001). The mean number of times to look down to control the position of the pedals was 2.2/h the IPEFIX group and 7.7/h in the control group ( P <0.001). Mean replacements of the pedals were 0./h in the IPEFIX group and 1.7/h in the control group ( P <0.001). Similar results were obtained in trainees in simulated ESD on animal models. Conclusions IPEFIX is a simple device to connect different pedals during endoscopic procedures. It helps to reduce the numbers of foot mistakes during ESD and improves operator comfort.

Esophageal cancer - French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, RENAPE, SNFCP, AFEF, SFR).

INTRODUCTION: This document is a summary of the French intergroup guidelines regarding the management of esophageal cancer (EC) published in July 2022, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of several French medical and surgical societies involved in the management of EC. Recommendations were graded in three categories (A, B and C), according to the level of evidence found in the literature until April 2022. RESULTS: EC diagnosis and staging evaluation are mainly based on patient's general condition assessment, endoscopy plus biopsies, TAP CT-scan and 18F FDG-PET. Surgery alone is recommended for early-stage EC, while locally advanced disease (N+ and/or T3-4) is treated with perioperative chemotherapy (FLOT) or preoperative chemoradiation (CROSS regimen) followed by immunotherapy for adenocarcinoma. Preoperative chemoradiation (CROSS regimen) followed by immunotherapy or definitive chemoradiation with the possibility of organ preservation are the two options for squamous cell carcinoma. Salvage surgery is recommended for incomplete response or recurrence after definitive chemoradiation and should be performed in an expert center. Treatment for metastatic disease is based on systemic therapy including chemotherapy, immunotherapy or combined targeted therapy according to biomarkers testing such as HER2 status, MMR status and PD-L1 expression. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice and are subject to ongoing optimization. Each individual case should be discussed by a multidisciplinary team.

Macroscopic and histologic regression of duodenal polyposis with FOLFOX4 chemotherapy for an ileal pouch adenocarcinoma in a patient with familial adenomatous polyposis.

Severe (stage IV) duodenal polyposis is difficult to manage in patients with familial adenomatous polyposis (FAP), with no effective medical treatment, complex endoscopic treatment modalities, and a high morbidity and mortality from pancreaticoduodenectomy. We present the case of a 44-year-old woman with FAP, stage IV duodenal polyposis, and with an ileal pouch adenocarcinoma that required surgery and adjuvant chemotherapy. Her duodenal polyposis regressed to stage II after four sessions of FOLFOX4 adjuvant chemotherapy, which avoided the need for aggressive endoscopic therapy or pancreatoduodenectomy in this patient.

A new partially covered nitinol stent for palliative treatment of malignant bile duct obstruction: a multicenter single-arm prospective study.

BACKGROUND AND STUDY AIMS: Covered self-expanding metal stents (SEMSs) have proven effective for managing malignant bile duct strictures and may reduce risk of tumor ingrowth. A new nitinol partially covered biliary SEMS was prospectively evaluated. PATIENTS AND METHODS: 70 patients with inoperable extrahepatic biliary obstructions were enrolled in a prospective multicenter trial, and followed up to 6 months or death, whichever came first. Primary endpoint was adequate palliation defined as absence of recurrent biliary obstruction from partly covered SEMS placement to end of follow-up. RESULTS: Mean age of the patients was 69 years and 52 % were men. Pancreatic carcinoma was present in 68 %. One stent was placed in 67 patients, two patients received two, and in one patient a guide wire could not traverse the stricture. In 55 % of patients the SEMS was inserted de novo and in 45 % for exchange with a plastic stent. Technical success was 97 %. At 6 months, 62 % of patients were free of obstructive symptoms; compared with baseline the mean number of symptoms per patient was significantly reduced (3.1 at baseline, 0.6 at 6 months; P < 0.0001) and total bilirubin levels dropped by 73 %. There were four cases of recurrent biliary obstruction, due to stent migration (2), tumor overgrowth (1), and sludge formation (1). Device-related complications included cholecystitis (3), right upper quadrant pain (1), and moderate pancreatitis (1). No tumor ingrowth was reported. CONCLUSIONS: This new partially covered nitinol SEMS is easily inserted, and safe and effective in the palliation of biliary obstruction secondary to malignant bile duct strictures.

Endoscopic submucosal dissection in a European setting. A multi-institutional report of a technique in development.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a technique for "en bloc" resection of superficial tumors of the gastrointestinal tract. In France, experience with this technique is still limited. We wanted to assess the development of ESD in France, with special attention to short term outcomes. PATIENTS AND METHODS: Members of the Société Française d'Endoscopie Digestive (SFED) who declared performing ESD reported their cases prospectively on a voluntary basis. Demographic, clinical, and technical data, and the results of immediate complications were collected. Case reports were completed prospectively by each investigator before pooled analysis. RESULTS: A total of 188 consecutive case reports were collected from 16 centers. The median case mix per center was 6 patients (range 1-43). The lesion sites treated by ESD were the stomach (n = 75), esophagus (n = 27), duodenum (n = 1), cecum (n = 2), right colon (n = 3), transverse colon (n = 5), sigmoid (n = 3), and rectum (n = 72). The median size of the lesions was 26 mm (range 2-150 mm). En bloc resection was achieved in 77.1% of cases, with complete R0 resection in 72.9%. Histopathology results showed high grade dysplasia or superficial cancer in 71.2%. The median duration of ESD was 105 minutes (range 20-450 minutes). The short term morbidity was 29.2% including 34 cases of perforation (18.1%), and 21 hemorrhages (11.2%) during the 24 hours following ESD, 89% of which were managed conservatively or endoscopically. CONCLUSION: In this early experience, the feasibility of ESD appeared to be good but R0 resection and complication rates did not match those reported by Japanese authors and must be improved by an extended practice.

Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study.

BACKGROUND AND STUDY AIMS: Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques. This prospective study aimed to evaluate the accuracy of a new procedure, imaging the microcirculation pattern of the pancreas by contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) with a new Olympus prototype echo endoscope. PATIENTS AND METHODS: 35 patients presenting with solid pancreatic lesions were prospectively enrolled. All patients had conventional B mode and power Doppler EUS. After an intravenous bolus injection of 2.4 ml of a second-generation ultrasound contrast agent (SonoVue) CEH-EUS was then performed with a new Olympus prototype echo endoscope (xGF-UCT 180). The microvascular pattern was compared with the final diagnosis based on the pathological examination of specimens from surgery or EUS-guided fine-needle aspiration (EUS-FNA) or on follow-up for at least 12 months. RESULTS: The final diagnoses were: 18 adenocarcinomas, 9 neuroendocrine tumors, 7 chronic pancreatitis, and 1 stromal tumor. Power Doppler failed to display microcirculation, whereas harmonic imaging demonstrated it in all cases. Out of 18 lesions with a hypointense signal on CEH-EUS, 16 were adenocarcinomas. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of hypointensity for diagnosing pancreatic adenocarcinoma were 89 %, 88 %, 88 %, 89 %, and 88.5 %, compared with corresponding values of 72 %, 100 %, 77 %, 100 %, and 86 % for EUS-FNA. Of five adenocarcinomas with false-negative results at EUS-FNA, four had a hypointense echo signal at CEH-EUS. CONCLUSIONS: CEH-EUS with the new Olympus prototype device successfully visualizes the microvascular pattern in pancreatic solid lesions, and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

Endoscopic resection of sporadic duodenal adenomas: an efficient technique with a substantial risk of delayed bleeding.

INTRODUCTION: Data on endoscopic resection of sporadic duodenal adenoma (SDA) are sparse; we present our results concerning safety and efficacy in a retrospective analysis of saline-assisted endoscopic resection of SDA. PATIENTS AND METHODS: The cases of all patients who underwent endoscopic resection for SDA between May 1998 and May 2006 were analyzed. Endoscopic resection was carried out using standard injection and cut methods. In some patients hemoclips and argon plasma coagulation were used, either for prophylaxis or for the treatment of procedure-related bleeding. RESULTS: Thirty-six patients with a total of 37 lesions (mean size 19 mm, range 4 - 50 mm) were analyzed. Lesions larger than 20 mm were more frequently resected piecemeal ( P = 0.022). Intraprocedural bleeding occurred in 14 % of cases, without any significant association with lesion size or the resection technique. One fatal perforation occurred. Macroscopically complete resection was achieved in 97 % of cases, as confirmed by at least one negative control endoscopy with biopsies after a mean follow-up of 15 months. Although clipping and argon plasma coagulation were not applied in any systematic way, it was noticeable that in the 20 cases in which they were used for hemostasis or prevention, no delayed bleeding was observed after the procedures. In contrast, bleeding occurred in 22 % of the 23 procedures performed without these additional techniques. CONCLUSION: Endoscopic resection is an efficient and acceptably safe technique for treating SDA. Further studies need to assess whether systematic bleeding prophylaxis will reduce the incidence of delayed hemorrhage after endoscopic resection.