Risk factors of refractory post-endoscopic submucosal dissection esophageal strictures.

INTRODUCTION: our aim was to comparatively assess the treatment outcomes of endoscopic dilatation in Barrett's neoplasia and squamous cell carcinoma (SCC) post-endoscopic submucosal dissection (ESD) strictures, and to determine the risk or factors associated to refractory strictures. METHODS: an observational study. All consecutive patients presenting with a post-ESD stricture in 2007-2016 who underwent dilation therapy were included. Clinical, morphological, and technical features were assessed to determine the risk factors of refractory strictures. RESULTS: of 414 consecutive patients treated by ESD, 83 (mean age: 65 ± 10 years, 76 % men) with 254 dilations (median: 3, range: 1-27) were considered. Barrett's neoplasia and SCC were the indications in 58 (69.9 %) and in 25 (30.1 %) cases, respectively. Clinical success was achieved in 84.3 % with a median of 3 sessions (range: 1-22), with a higher rate in Barrett's neoplasia (89.7 % vs. 72 %, p = 0.042). Circumferential resection in one single procedure (13.2 %) was associated with the need for a higher number of dilation sessions. By multivariate analysis, upper-esophageal location (OR: 11.479 [95 % CI: 2.058-64.043], p = 0.005), recurrent strictures (OR: 17.252 [95 % CI: 2.833-105.069], p = 0.002), and dilation-related complications (OR: 26.420 [95 % CI: 1.736-401.966], p = 0.018) were risk factors of refractory stenosis. CONCLUSION: patients presenting with SCC located in the upper superior esophagus, intra-procedural perforation, and recurrent strictures are at higher risk of developing refractory strictures.

Clinical outcome in patients treated with endoscopic submucosal dissection for superficial Barrett's neoplasia.

BACKGROUND AND STUDY AIMS: The role of endoscopic submucosal dissection (ESD) in Barrett's neoplasia is ill-defined, although it might provide a higher curative resection rate and better histologic assessment than endoscopic mucosal resection (EMR). We aimed to assess efficacy, safety, and long-term results of ESD. PATIENTS AND METHODS: A retrospective analysis was done of 75 consecutive patients with Barrett's esophagus who underwent ESD between January 2007 and February 2014. ESD was performed for visible lesions that were multiple, larger than 15 mm, or poorly lifting, or suspected of submucosal infiltration. The primary end point was the rate of curative resection of carcinoma. RESULTS: Median patient age was 68 years (interquartile range [IQR] 61 - 76), median follow-up was 20 months (IQR 8.5 - 37.5), and median maximum specimen diameter was 52.5 mm (IQR 43 - 71). En bloc resection rate was 90 % (66 /73), and rates of curative resection of carcinoma and high grade dysplasia/carcinoma were 85 % (47 /55) and 64 % (42 /66), respectively. G3 differentiation and invasion to greater than pT1m2 were observed in 25 % (14 /55) and 67 % (37 /55) of patients with adenocarcinoma, respectively. There were 5 early ( < 48 hours) adverse events (2 delayed hemorrhages and 3 perforations), all treated endoscopically. No ESD-specific death occurred. Esophageal strictures developed in 60 % of patients, all treated endoscopically. Additional treatment (median sessions 2 [IQR 2 - 3]) for residual Barrett's esophagus were recommended to 62 % (42 /68). At latest follow-up, complete remission of neoplasia and intestinal metaplasia was found in 92 % (54 /59) and 73 % (43 /59) of patients, respectively. CONCLUSION: ESD appears to be safe and effective, with a high rate of curative resection of carcinoma. ESD should be considered for patients with Barrett's neoplasia at risk of incomplete resection or poor pathologic assessment with conventional EMR.

Is Lugol necessary for endoscopic resection of esophageal squamous cell neoplasia?

Background and study aims Recent evidence suggests that lugol chromoendoscopy (LCE) and narrow-band imaging (NBI) have comparable sensitivity for detection of superficial esophageal squamous cell carcinoma (SCC). However, LCE is time-consuming and associated with side effects. The aim of this study was to compare the effectiveness of NBI and LCE in defining resection margins of esophageal SCC. Patients and methods This was a retrospective observational cohort study of patients with esophageal SCC and dysplasia who underwent en-bloc resection between 1999 and 2017 at the Cliniques universitaires Saint-Luc, Brussels. Two groups were defined: 1) inspection with NBI only; and 2) inspection with LCE (with or without NBI). The primary endpoint was complete lateral resection rate. Multivariate regression was used to adjust for potential confounders. Results A total of 102 patients with 132 lesions were included. Lesions were inspected with LCE in 52 % (n = 68) and with NBI only in 48 % (n = 64). Lesions 0-IIa were more frequent in the NBI group (37 %) and 0-IIb (60 %) in LCE. Lesion location, size, and histology and resection technique (endoscopic submucosal dissection in 122/132 cases, 92 %) were similar between the groups. The rate of complete lateral resection for invasive carcinoma was 90 % in LCE group and 94 % in NBI group ( P  = 0.498) and 65 % and 67 % ( P  = 0.813), respectively, for dysplasia complete lateral resection. These results remained non-significant after adjusting for potential confounders. Conclusions Mucosal inspection and delineation of tumors with lugol chromoendoscopy before endoscopic resection of esophageal squamous cell lesions was not associated with increased complete lateral resection rate when compared to NBI.

Combined excision and ablation of ampullary tumors with biliary or pancreatic intraductal extension is effective even in malignant neoplasms.

Background: The feasibility and outcome of endoscopic resection in ampullary tumors with intraductal growth remains unclear. Objective: To assess the safety, feasibility and outcomes of these patients treated by thermal ablation. Methods: Retrospective observational study. All consecutive patients who underwent an endoscopic snare papillectomy with a 6-month minimum follow-up were included. Ablation was performed with cystotomes and soft/forced coagulation. Successful endoscopic treatment was defined as no adenomatous residual tissue or recurrence observed at follow-up. Results: Of 86 patients presenting with an ampullary tumor, 73 (58 ± 14 years old, 49% men, 34% familial adenomatous polyposis) (median tumor size: 20 mm, range: 8-80) were included. En bloc and curative resection rates were achieved in 46.6% and 83.6%, respectively.Intraductal ingrowth was seen in 18 (24.7%) patients and histologically confirmed in 12 (16.4%). Intraductal ablation achieved a 100% success rate, with a 20-month median follow-up. Most of these patients had malignant forms (n = 8, 66.7%), with a higher adenocarcinoma rate (33.3% versus 3.3%, p = 0.001) compared to extraductal tumors.Overall, there was a 20.5% complication rate with no significant differences between both groups (p = 0.676). Conclusions: Intraductal ablation achieves a high therapeutic success rate in ampullary tumors with ≤20 mm ductal extension, even in malignant forms or biliary and pancreatic involvement. The technique is feasible, cheap and safe and may avoid major surgery.

Comparative analysis of ESD versus EMR in a large European series of non-ampullary superficial duodenal tumors.

BACKGROUND AND STUDY AIMS: The choice of endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) in non-ampullary superficial duodenal tumors (NASDTs) is challenging and the benefits of ESD remain unclear. The aim was to comparatively analyze the feasibility, outcomes and safety of these techniques in these lesions. PATIENTS AND METHODS: This is an observational and retrospective study. All consecutive patients presenting with NASDTs who underwent EMR or ESD between 2005 and 2017 were included. The following main outcomes were comparatively evaluated: en-bloc and complete (R0) resection rates, and local recurrence. Secondary outcomes were perforation and delayed bleeding. RESULTS: One hundred sixty-six tumors in 150 patients (age: 66 years, range: 31 - 83, 42.7 % males) were resected by ESD (n = 37) or EMR (n = 129) and included. The median procedure time (81 vs. 50 min, P  = 0.007) and tumor size (25 vs. 20 mm, P  = 0.01) were higher in the ESD group. The global malignancy rate was 50.3 %. There were no differences in en-bloc resection (29.7 % vs. 44.2 %, P  = 0.115), complete resection (19.4 % vs. 35.5 %, P  = 0.069), and local recurrence (14.7 % vs. 16.7 %, P  = 0.788) rates. Tumor size was associated with recurrence (28 vs. 20 mm, P  = 0.008), with a median follow-up of 6.5 months. Focal recurrence (n = 22, 13.3 %) was treated endoscopically in 86.4 %. En-bloc resection in the ESD group was comparable in large ( ≥ 20 mm) and small lesions (27.6 % vs. 37.5 %, P  = 0.587), while this outcome decreased significantly in large lesions resected by EMR (17.4 % vs. 75 %, P  < 0.001). Nine perforations were confirmed in 6 lesions (16.2 %) resected by ESD and 3 (2.3 %) by EMR ( P  = 0.001). Endoscopic therapy was successful in all but 1 patient (88.9 %) presenting with a delayed perforation. CONCLUSIONS: ESD may be an alternative to EMR and surgery in selected NASDTs, such as large duodenal tumors where EMR achieves low en-bloc resection rates and the local recurrence may be higher. However, this technique may have a higher risk of perforations.

ESD versus EMR in non-ampullary superficial duodenal tumors: a systematic review and meta-analysis.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has been developed as an option for treatment of esophageal, gastric and colorectal lesions. However, there is no consensus on the role of ESD in duodenal tumors. METHODS: This systematic review and meta-analysis compared ESD and endoscopic mucosal resection (EMR) in sporadic non-ampullary superficial duodenal tumors (NASDTs), including local experience. We conducted a search in PubMed, Scopus and the Cochrane library up to August 2017 to identify studies that compared both techniques reporting at least one main outcome (en-bloc/complete resection, local recurrence). Pooled outcomes were calculated under fixed and random-effect models. Subgroup analyses were conducted. RESULTS: A total of 753 patients presenting with 784 NASDTs (242 ESD, 542 EMR) in 14 studies were included. Tumor size (MD: 5.88, [CI95 %: 2.15, 9.62], P  = 0.002, I 2  = 79 %) and procedure time (MD: 65.65, [CI95 %: 40.39, 90.92], P  < 0.00001, I 2  = 88 %) were greater in the ESD group. En-bloc resection rate was significantly higher in Asian studies (OR: 2.16 [CI95 %: 1.15, 4.08], P  = 0.02, I 2 : 46 %). ESD provided a higher complete resection rate (OR: 1.63 [I95 %: 1.06, 2.50], P  = 0.03, I 2 : 59 %), but there was no risk difference in the risk of local recurrence (RD: - 0.03 [CI95 %: - 0.07, 0.01], P  = 0.15, I 2 : 0 %) or delayed bleeding. ESD was associated with an increased number of intraoperative perforations [RD: 0.12 (CI95 %: 0.04, 0.20), P  = 0.002, I 2 : 56 %] and emergency surgery for delayed perforations. The inclusion of eligible studies was limited to retrospective series with inequalities in comparative groups. CONCLUSIONS: Duodenal ESD for NASDTs may achieve higher en-bloc and complete resections at the expense of a greater perforation rate compared to EMR. The impact on local recurrence remains uncertain.

Phenotypic analysis of a family of transcriptional regulators, the zinc cluster proteins, in the human fungal pathogen Candida glabrata.

Candida glabrata is the second most important human fungal pathogen. Despite its formal name, C. glabrata is in fact more closely related to the nonpathogenic budding yeast Saccharomyces cerevisiae. However, less is known about the biology of this pathogen. Zinc cluster proteins form a large family of transcriptional regulators involved in the regulation of numerous processes such as the control of the metabolism of sugars, amino acids, fatty acids, as well as drug resistance. The C. glabrata genome encodes 41 known or putative zinc cluster proteins, and the majority of them are uncharacterized. We have generated a panel of strains carrying individual deletions of zinc cluster genes. Using a novel approach relying on tetracycline for conditional expression in C. glabrata at the translational level, we show that only two zinc cluster genes are essential. We have performed phenotypic analysis of nonessential zinc cluster genes. Our results show that two deletion strains are thermosensitive whereas two strains are sensitive to caffeine, an inhibitor of the target of rapamycin pathway. Increased salt tolerance has been observed for eight deletion strains, whereas one strain showed reduced tolerance to salt. We have also identified a number of strains with increased susceptibility to the antifungal drugs fluconazole and ketoconazole. Interestingly, one deletion strain showed decreased susceptibility to the antifungal micafungin. In summary, we have assigned phenotypes to more than half of the zinc cluster genes in C. glabrata. Our study provides a resource that will be useful to better understand the biological role of these transcription factors.

Reflections as near-peer facilitators of an inquiry project for undergraduate anatomy: Successes and challenges from a term of trial-and-error.

Near-peer facilitators (senior students serving as facilitators to their more junior peers) bring a unique student-based perspective to teaching. With fewer years of teaching experience however, students who become involved in a facilitator role typically develop related skills quickly through a process of trial-and-error within the classroom. The aim of this paper is to report on the authors' own experiences and reflections as student near-peer facilitators for an inquiry-based project in an undergraduate anatomy course. Three areas of the facilitator experience are explored: (1) offering adequate guidance as facilitators of inquiry, (2) motivating students to engage in the inquiry process, and (3) fostering creativity in learning. A practical framework for providing guidance to students is discussed which offers facilitators a scaffold for asking questions and assisting students through the inquiry process. Considerations for stimulating intrinsic motivations toward inquiry learning are made, paying attention to ways in which facilitators might influence feelings of motivation towards learning. Also, the role of creativity in inquiry learning is explored by highlighting the actions facilitators can take to foster a creative learning environment. Finally, recommendations are made for the development of formalized training programs that aid near-peer facilitators in the acquisition of facilitation skills before entering into a process of trial-and-error within the classroom.

Acute-phase response in pigs undergoing laparoscopic, transgastric or transcolonic notes peritoneoscopy with us or eus exploration.

BACKGROUND: Laparoscopic surgery is associated with reduced surgical trauma, therefore with acute-phase response of lower magnitude as compared with open surgery. We hypothesized that NOTES might induce reduced immune response as compared with laparoscopy. OBJECTIVE: To compare acute-phase reactants in a controlled trial of laparoscopic peritoneoscopy and ultrasonography versus transgastric or transcolonic NOTES peritoneoscopy and intraperitoneal endoscopic US. METHODS: Eighteen pigs were divided in 3 groups: laparoscopy, transgastric and transcolonic NOTES. Serum levels of IL-6 and TNF-α were determined preoperatively and at day 2. Serum levels of haptoglobin and IL-6 mRNA levels from isolated white blood cells were measured by RT-PCR at days 0, 1, 2 and 7. Necropsy was performed at sacrifice, with peritoneal fluid microbiological analysis, macroscopic and microscopic examinations on gastrotomy/colotomy or abdominal wall closure sites, liver and parietal peritoneum biopsy sites and any area suggestive of infection. RESULTS: The groups were similar with regards to peritoneoscopy completeness, ultrasonographic examination and biopsies. The duration of NOTES procedures was significantly longer than laparoscopic procedures. Minor complications were observed in most animals by macroscopic and microscopic examination, but NOTES procedures were associated with severe complications in 3 pigs (fistula, abscess, mortality). No significant differences in acute-phase reactants levels were found between groups. CONCLUSIONS: No significant difference in the acute-phase reactants could be demonstrated between surgical and NOTES procedures. NOTES was however associated with more severe septic complications. Optimal closure remains a challenge and better devices are needed to avoid them.

Acute upper gastrointestinal bleeding in cirrhosis: changes and advances over the past two decades.

BACKGROUND AND AIMS: Few studies have compared two or more cohorts of cirrhotic patients admitted for upper gastrointestinal bleeding (UGIB) several decades apart. Our aim was to compare epidemiological, clinical, therapeutic and prognostic characteristics of UGIB (whatever the source) in two cohorts of cirrhotic patients admitted to the emergency room of the same general hospital 2 decades apart. METHODS: One-hundred cases of UGIB in cirrhotic patients consecutively admitted between 1984 and 1990 (cohort A) were compared with 100 similar cases admitted between 2004 and 2009 (cohort B). RESULTS: The sex ratio (M/F: 2/1), mean age (approximately 55Y) and the proportion of patients with alcoholic cirrhosis (approximately 80%) did not change. Mean Child-Pugh score and the proportion of patients in Child-Pugh stage C increased from 7.6 and 19% in cohort A to 8.8 and 35% in cohort B (p < 0.001). Therapeutic intervention was performed during initial endoscopy in 13 cases from cohort A and 50 from cohort B (p < 0.001), respectively. The number of transfused patients (85 in cohort A, 58 in cohort B) and the number of red blood cell units administered on the first day (median: 4 in cohort A, 2 in cohort B) were significantly decreased in cohort B (p < 0.001). The rate of rebleeding (45 in cohort A, 11 in cohort B), the need for rescue surgery (8 in cohort A, 0 in cohort B) and the in-hospital mortality (24 in cohort A, 9 in cohort B) significantly decreased in the more recent cohort (p < 0.005). CONCLUSION: This study demonstrated that several characteristics of cirrhotic patients admitted with UGIB have changed over the past 2 decades. Above all, outcome has improved despite an increase in the severity of cirrhosis.

Excited-state structural dynamics of 5-fluorouracil.

5-Fluorouracil is an analogue of thymine and uracil, nucleobases found in DNA and RNA, respectively. The photochemistry of thymine is significant; UV-induced photoproducts of thymine in DNA lead to skin cancer and other diseases. In previous work, we have suggested that the differences in the excited-state structural dynamics of thymine and uracil arise from the methyl group in thymine acting as a mass barrier, localizing the vibrations at the photochemical active site. To further test this hypothesis, we have measured the resonance Raman spectra of 5-fluorouracil at wavelengths throughout its 267 nm absorption band. The spectra of 5-fluorouracil and thymine are very similar. Self-consistent analysis of the resulting resonance Raman excitation profiles and absorption spectrum using a time-dependent wave packet formalism suggests that, at most, 81% of the reorganization energy upon excitation is directed along photochemically relevant modes. This compares well with what was found for thymine, supporting the mass barrier hypothesis.