Management of desmoid tumours: A large national database of familial adenomatous patients shows a link to colectomy modalities and low efficacy of medical treatments.

BACKGROUND: Desmoid tumours represent a major complication of familial adenomatous polyposis. Our aims were to study the factors associated with the development of desmoid tumours in familial adenomatous polyposis patients, and to describe presentation and management of desmoid tumours. METHODS AND PATIENTS: We reviewed all patients with familial adenomatous polyposis followed at our institution between 1965-2013, with either identified adenomatous polyposis coli gene mutation, or a personal and family history suggesting adenomatous polyposis coli-related polyposis. Response to treatment of desmoid tumours was assessed by Response Evaluation Criteria In Solid Tumor (RECIST) criteria. RESULTS: A total of 180 patients with familial adenomatous polyposis were included with a median follow-up of 19 years since diagnosis. Thirty-one (17%) patients developed 58 desmoid tumours, a median (range) 4.7 (0.8-41.6) years after their diagnosis of familial adenomatous polyposis. The only factor significantly associated with occurrence of desmoid tumours was the type of surgery: 12 (12%) desmoid tumours in 104 patients treated by colectomy, versus 19 (25%) desmoid tumours in 76 patients treated by proctocolectomy, p = 0.027. The localisation of desmoid tumours was: mesenteric (n = 25), abdominal wall (n = 30) or extra-abdominal (n = 3). Nineteen patients underwent 36 surgical procedures for desmoid tumours. Recurrence occurred in 26 (72%) cases and the recurrence-free survival was 2.6 (95% confidence interval (CI), 0.2-5.9) years. Thirteen patients received 27 medical treatments over a median 14 months. Objective response was observed in four (15%) patients and the median progression-free survival was nine (95% CI, 1.1-16.9) months. CONCLUSION: If confirmed, colectomy (versus proctocolectomy) should be performed in adenomatous polyposis coli-related familial adenomatous polyposis patients to avoid desmoid tumours. We show that there is a high prevalence of post-surgical recurrence and the low efficacy of available medical treatments for desmoid tumours.

Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength of recommendations and the quality of evidence. Main Recommendations: 1 ESGE recommends endoscopic en bloc resection for superficial esophageal squamous cell cancers (SCCs), excluding those with obvious submucosal involvement (strong recommendation, moderate quality evidence). Endoscopic mucosal resection (EMR) may be considered in such lesions when they are smaller than 10 mm if en bloc resection can be assured. However, ESGE recommends endoscopic submucosal dissection (ESD) as the first option, mainly to provide an en bloc resection with accurate pathology staging and to avoid missing important histological features (strong recommendation, moderate quality evidence). 2 ESGE recommends endoscopic resection with a curative intent for visible lesions in Barrett's esophagus (strong recommendation, moderate quality evidence). ESD has not been shown to be superior to EMR for excision of mucosal cancer, and for that reason EMR should be preferred. ESD may be considered in selected cases, such as lesions larger than 15 mm, poorly lifting tumors, and lesions at risk for submucosal invasion (strong recommendation, moderate quality evidence). 3 ESGE recommends endoscopic resection for the treatment of gastric superficial neoplastic lesions that possess a very low risk of lymph node metastasis (strong recommendation, high quality evidence). EMR is an acceptable option for lesions smaller than 10 - 15 mm with a very low probability of advanced histology (Paris 0-IIa). However, ESGE recommends ESD as treatment of choice for most gastric superficial neoplastic lesions (strong recommendation, moderate quality evidence). 4 ESGE states that the majority of colonic and rectal superficial lesions can be effectively removed in a curative way by standard polypectomy and/or by EMR (strong recommendation, moderate quality evidence). ESD can be considered for removal of colonic and rectal lesions with high suspicion of limited submucosal invasion that is based on two main criteria of depressed morphology and irregular or nongranular surface pattern, particularly if the lesions are larger than 20 mm; or ESD can be considered for colorectal lesions that otherwise cannot be optimally and radically removed by snare-based techniques (strong recommendation, moderate quality evidence).(AU)

[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.

Botulinum toxin injection for hypercontractile or spastic esophageal motility disorders: may high-resolution manometry help to select cases?

Endoscopic injections of botulinum toxin in the cardia or distal esophagus have been advocated to treat achalasia and spastic esophageal motility disorders. We conducted a retrospective study to evaluate whether manometric diagnosis using the Chicago classification in high-resolution manometry (HRM) would be predictive of the clinical response. Charts of patients with spastic and hypertensive motility disorders diagnosed with HRM and treated with botulinum toxin were retrospectively reviewed at two centers. HRM recordings were systematically reanalyzed, and a patient's phone survey was conducted. Forty-five patients treated between 2008 and 2013 were included. Most patients had achalasia type 3 (22 cases). Other diagnoses were jackhammer esophagus (8 cases), distal esophageal spasm (7 cases), esophagogastric junction outflow obstruction (5 cases), nutcracker esophagus (1 case), and 2 unclassified cases. Botulinum toxin injections were performed into the cardia only in 9 cases, into the wall of the distal esophagus in 19 cases, and in both locations (cardia and distal esophagus) in 17 cases. No complication occurred in 31 cases. Chest pain was noticed for less than 7 days in 13 cases. One death related to mediastinitis occurred 3 weeks after botulinum toxin injection. Efficacy was assessed in 42 patients: 71% were significantly improved 2 months after botulinum toxin, and 57% remained satisfied for more than 6 months. No clear difference was observed in terms of response according to manometric diagnosis; however, type 3 achalasia previously dilated and with normal integrated relaxation pressure (4s-integrated relaxation pressure < 15 mmHg) had the worst outcome: none of these patients responded to the endoscopic injection of botulinum toxin. Endoscopic injections of botulinum toxin may be effective in some patients with spastic or hypercontractile esophageal motility disorders. The manometric Chicago classification diagnosis does not seem to predict the results. Prospective randomized trials are required to identify patients most likely to benefit from esophageal botulinum toxin treatment.

Pancreatic resection in elderly patients: should it be denied?

BACKGROUND: Surgery remains the only potential curative therapy for pancreatic cancer, but compromised physiological reserve and comorbidities may deny pancreatic resection from elderly patients. METHODS: The medical records of all patients who underwent pancreatic resection at our institution (2005-2012) were retrospectively reviewed. Postoperative and long-term outcomes were compared between patients with cutoff age of 70 years. RESULTS: A total of 228 (66 %) and 116 (34 %) patients were <70 and ≥70 years, respectively. Elderly group had worse ASA scores (P < 0.0001) with higher rates of invasive malignant pathologies (75 vs. 67 %, P = 0.14), mainly pancreatic ductal adenocarcinoma (58.6 vs. 44.7 %, P = 0.01). The most common type of resection was pancreaticoduodenectomy (PD) (59 %), followed by distal pancreatectomy (19.8 %). Mean hospital stay was comparable. Elderly patients had less grade ≥IIIb postoperative complications (12 vs. 20.1 %; P = 0.04) and higher postoperative mortality rates (12.9 vs. 3.9 %; P = 0.04). In multivariable Cox proportional hazards model for postoperative mortality, age ≥ 70 years (HR, 3.5; 95 % CI, 1.3-9.3), pancreaticoduodenectomy (HR, 12.6; 95 % CI, 1.6-96), and intraoperative blood loss were significant (P = 0.012; P = 0.015, and P = 0.005, respectively). The overall 5-year survival rates for all patients, for patients aged <70 and ≥70 years were 56, 55, and 41 %, respectively (P = 0.003). CONCLUSIONS: Elderly patients are at higher risk of mortality after pancreatic resection than usually reported case series. Nonetheless, elderly patients can undergo pancreatic resection with acceptable 5-year survival results. Our results contribute for a better, informed decision-making for elderly patients and their family.

Fecal estradiol-17ß and testosterone in prepubertal domestic cats.

The aim of this article was to describe the time course of prepubertal sexual steroids in domestic cats. Fourteen newborn kittens were followed up until puberty (physical, behavioral, and hormonal changes). Fecal testosterone [T; males] and E estradiol 17-ß [E2; females] concentrations were analyzed by repeated measures ANOVA and two consecutive time windows (TWs) were used to compare changes in both male (postnatal weeks 1-4 vs. 5-14) and females (postnatal weeks 1-5 vs. 6-13). Puberty was achieved 14.3 ± 0.3 and 13.3 ± 0.4 weeks after birth in male and female cats, respectively. In both genders, during TW-1 fecal steroids concentrations were similar (males) or even higher (females) to that previously described for mature cats. Fecal T (P < 0.01) and E2 (P < 0.01) varied throughout the weeks. Differences were found when hormonal concentrations of TW-1 were compared with those of TW-2 both for male (61.4 ± 7.9 vs. 16.9 ± 2.2 ng/g; P < 0.01) and female (78.2 ± 12.5 vs. 11.2 ± 4.0 ng/g; P < 0.01) cats. It is concluded that in domestic cats there is a sexual steroid surge during the first 4 and 5 postnatal weeks in male and female animals, respectively.

Management of bile duct leaks.

The cause of bile duct leaks can be either iatrogenic or more rarely, traumatic. The most common cause is related to laparoscopic cholecystectomy. While surgical repair has been the standard for many years, management in these often morbid and complex situations must currently be multidisciplinary incorporating the talents of interventional radiologists and endoscopists. Based on the literature and in particular the recent recommendations of the European Society of Gastrointestinal Endoscopy (ESGE), this review aims to update the management strategy. The incidence of these complications decreases with surgeon experience attesting to the value of training to prevent these injuries. Bile duct injuries must be categorized and their mapping detailed by magnetic resonance cholangiography MRCP or endoscopic cholangiography (ERCP) when endoscopic therapy is considered. Endoscopic management should be preferred in the absence of complete circumferential interruption of the common bile duct. The ESGE recommends insertion of a plastic stent for 4 to 8 weeks without routine sphincterotomy. For complete circumferential injuries, hepaticojejunostomy is usually necessary. In conclusion, adequate training of surgeons is essential for prevention since the incidence of bile duct injury decreases with experience. Faced with a bile duct injury, a multidisciplinary team approach, involving radiologists, endoscopists and surgeons improves patient outcome.

Fully covered self-expanding metal stents for benign colonic strictures.

BACKGROUND AND STUDY AIMS: Uncovered self-expanding metal stents offer effective relief for colonic obstruction. The aim of this study was to determine the effectiveness of fully covered self-expanding metal stents (FCSEMSs) in the treatment of benign colonic strictures. PATIENTS AND METHODS: All patients presenting with a symptomatic benign colonic stricture (occlusion or subocclusion) during a 6-year study period were treated with FCSEMSs. The stents were placed and removed 4 - 6 weeks later at one of 10 endoscopy centers. The efficacy of the stent (clinical and radiological signs of colonic decompression within 48 hours), technical success, stent retrieval, safety, and recurrence of symptoms were evaluated during follow-up. Univariate and multivariate analyses were performed to identify variables associated with clinical success, stent migration, and symptom recurrence. RESULTS: The study included 43 patients (24 men, 19 women; mean age 67.6 ± 10.4) with occlusive (n = 18) or subocclusive symptoms (n = 25) due to anastomotic (n = 40), post-ischemic (n = 2), or post-radiation (n = 1) strictures. Insertion was successful in all patients. Clinical success was obtained in 35 patients (81 %). Migration was observed in 27 patients (63 %). The median duration of stenting was 21 days (95 %CI 17.8 - 35.4 days). Multivariate analysis showed that stents more than 20 mm wide migrated significantly less often. Recurrence of obstructive symptoms was observed in 23 patients (53 %), irrespective of migration. No predictive factors for recurrence or clinical efficacy were found. CONCLUSIONS: FCSEMSs for treatment of symptomatic benign colonic strictures are safe and effective, despite a high rate of spontaneous migration.