Efficacy and safety of a novel submucosal lifting gel used for endoscopic submucosal dissection: a study in a porcine model.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is technically demanding. A viscous gel for submucosal lifting might induce mechanical submucosal dissection facilitating easier and safer ESD. METHODS: In 12 female pigs (median 64 kg), ESDs of simulated lesions were performed at the posterior wall and greater curvature in the gastric body (one ESD per location) with randomly assigned injection fluids: gel or control fluid (0.9% saline with hydroxypropyl methylcellulose 3 mg/ml [7:1] and indigo carmine droplets). Additionally, 10 cc gel was injected into the submucosa at the anterior wall without ESD to assess effects of inappropriate injection. Pigs were euthanized at day 0, 3 or 28. In four additional pigs (euthanized day 3 or 28) 10 cc gel was injected into the muscularis propria (MP) after four endoscopic mucosal resections in the gastric body. RESULTS: Both fluid groups showed equal ESD-procedure times (28 [gel] vs. 26 min [control]) and complications. Gel-ESDs required less accessory interchanges (3.5 vs. 5.5; p = 0.01). Mechanical dissection after circumferential incision was achieved in 25% of gel-ESDs; none in control-ESDs. The severity of inflammation and fibrosis was equal in both fluid groups. Normal architecture and vital mucosa were found after inappropriate submucosal injection. MP-injections resulted in one transmural hematoma (day 3), and intramuscular encapsulation in 25% of the sites (day 28). LIMITATIONS: A pig's stomach differs from the human stomach. CONCLUSIONS: The mechanical dissection properties of the gel may reduce the need for submucosal dissection during ESD. The gel is safe when advertently injected in the submucosa and MP. The porcine model appeared suboptimal to evaluate the true mechanical dissection properties of the gel.

Effects of Lugol staining on stenosis formation induced by radiofrequency ablation of esophageal squamous epithelium: a study in a porcine model.

Preliminary data show higher stricture rates after radiofrequency ablation (RFA) for early esophageal squamous neoplasia compared with Barrett's esophagus. We studied the effects of Lugol stain (LS) directly prior to RFA on stricture formation in squamous epithelium. Of 16 pigs, the distal half of the esophagus was LS, followed by circumferential RFA (single application 12 J/cm(2) ) in the unstained and stained esophagus. Pigs were euthanized at day 0 (n = 4), 3 (n = 4), or 28 (n = 8). Histology was evaluated in four areas: blank-control (no RFA, no LS), blank-RFA (no LS), LS+RFA, and LS-control (no RFA). Stenosis severity in LS+RFA and blank-RFA at 28 days was assessed by the ratio of the mucosal diameter at the RFA area to the diameter 2 cm proximal of this zone. Histology showed submucosal edema in 50% of LS+RFA versus 0% in blank-RFA. Severity and depth of inflammation (day 3) was equal in LS+RFA and blank-RFA. Severity and depth of fibrosis (day 28) appeared more severe in LS+RFA. Consequently, stenosis was present in 100% (LS+RFA) versus 12.5% (blank-RFA). The stenosis-severity ratio was 0.40 (interquartile range 0.29-0.45) in LS+RFA versus 0.73 (interquartile range 0.64-0.78) in blank-RFA (P = 0.012). Limitations of this study were the difference in uptake of LS between pigs and humans, the difference in esophageal anatomy between pigs and humans, and between the proximal and distal esophagus within pigs. In conclusion, in the porcine squamous esophagus, stenosis rate and severity after RFA increased when preceded by LS. LS may be contributing in the altered response of squamous epithelium to RFA as compared with Barrett's esophagus.

Simultaneous use of endoscopic resection and radiofrequency ablation is not safe in an esophageal porcine model.

Radiofrequency ablation (RFA) is safe and effective for eradication of Barrett's esophagus after endoscopic resection (ER) of neoplasia. Widespread ER, however, is likely to induce stenosis, hampering subsequent circumferential RFA. A 'single step' procedure with ER and circumferential RFA in the same session may avoid this problem. Two variants are possible: circumferential RFA of Barrett's esophagus including the lesion followed by ER of the ablated lesion ('RFA→ER'), or ER of the lesion directly followed by circumferential RFA of remaining Barrett's esophagus including the resection wound ('ER→RFA'). First aim was to evaluate perforation risk of 'ER→RFA' using increasing RFA energies. Second aim was to compare stenosis rate after 'ER→RFA' versus 'RFA→ER'. In Experiment 1, 24 areas in six pigs underwent widespread ER directly followed by circumferential RFA with increasing energies (2 x 10, 2 x 12-6 x 12 J/cm(2)) in the esophagus. In Experiment 2, eight pigs each had four treatment areas randomized: 'ER→RFA', RFA alone, ER alone, and 'RFA→ER'. No acute perforations occurred when ablating ER wounds. Two delayed perforations occurred: one in experiment 1, another in experiment n2 at the 'ER→RFA' area. The remaining seven pigs in experiment 2 showed stenosis in all 'ER→RFA' and 'RFA→ER' areas versus 5/7 RFA alone areas, and 0/7 ER alone areas. In conclusion, the 'single step' variant 'ER→RFA' is not safe in this porcine model and seems therefore not ethical to evaluate in humans at this stage. Given the high rate of stenosis after 'RFA→ER' and RFA alone, one might question the validity of the porcine model for this type of experiments.

Predictive factors for initial treatment response after circumferential radiofrequency ablation for Barrett's esophagus with early neoplasia: a prospective multicenter study.

BACKGROUND AND STUDY AIMS: Radiofrequency ablation (RFA) is safe and effective for the eradication of neoplastic Barrett's esophagus; however, occasionally there is minimal regression after initial circumferential balloon-based RFA (c-RFA). This study aimed to identify predictive factors for a poor response 3 months after c-RFA, and to relate the percentage regression at 3 months to the final treatment outcome. METHODS: We included consecutive patients from 14 centers who underwent c-RFA for high grade dysplasia at worst. Patient and treatment characteristics were registered prospectively. "Poor initial response" was defined as < 50 % regression of the Barrett's esophagus 3 months after c-RFA, graded by two expert endoscopists using endoscopic images. Predictors of initial response were identified through logistic regression analysis. RESULTS: There were 278 patients included (median Barrett's segment C4M6). In poor initial responders (n = 36; 13 %), complete response for neoplasia (CR-neoplasia) was ultimately achieved in 86 % (vs. 98 % in good responders; P < 0.01) and complete response for intestinal metaplasia (CR-IM) in 66 % (vs. 95 %; P < 0.01). Poor responders required 13 months treatment (vs. 7 months; P < 0.01) for a median of four RFA sessions (vs. three; P < 0.01). We identified four independent baseline predictors of poor response: active reflux esophagitis (odds ratio [OR] 37.4; 95 % confidence interval [CI] 3.2 - 433.2); endoscopic resection scar regeneration with Barrett's epithelium (OR 4.7; 95 %CI 1.1 - 20.0); esophageal narrowing pre-RFA (OR 3.9; 95 %CI 1.0 - 15.1); and years of neoplasia pre-RFA (OR 1.2; 95 %CI 1.0 - 1.4). CONCLUSIONS: Patients with a poor initial response to c-RFA have a lower ultimate success rate for CR-neoplasia/CR-IM, require more treatment sessions, and a longer treatment period. A poor initial response to c-RFA occurs more frequently in patients who regenerate their endoscopic resection scar with Barrett's epithelium, and those with ongoing reflux esophagitis, neoplasia in Barrett's esophagus for a longer time, or a narrow esophagus.

Foundry sands as low-cost adsorbent material for Cr (VI) removal.

The potential of foundry sands, industrial waste from the iron foundry industry, was evaluated for the removal of Cr (VI) using discontinuous assays. Chemical foundry sands are composed of fine silica sand, furanic resins as binder, chemical catalyst and residual iron particles. The influence ofpH, agitation rate and metal concentration on the removal process was investigated. Kinetic and equilibrium tests were conducted to determine Cr (VI) removal from aqueous solutions at a temperature range of 25-55 degrees C. Cr (VI) removal of 40-100% for a range of pH 6-1.6 was obtained. This removal was attributed to the presence of a large number of protonated silanol and aluminol groups. Cr (VI) adsorption in foundry sands follows a pseudo-second-order kinetic reaction (Ho model, r2 > 0.999) reaching kinetic constants of 0.341, 0.551, 0.775 and 0.920 g/mg h at 25, 35, 45 and 55 degrees C, respectively. The adsorption data were fitted to the Langmuir adsorption isotherm model (r > 0.99) obtaining adsorption capacities (q(max)) of 1.99, 2.40, 2.50, and 3.14 mg Cr (VI)/g sand at 25, 35, 45 and 55 degrees C, respectively. Calculated Gibbs free energy change (deltaG0), adsorption energy (E) and activation energy (E(a)) values indicate that a physisorption mechanism governs Cr (VI) adsorption process in foundry sands.

Optimal timing of simethicone administration prior to upper endoscopy: A multicenter, single-blind, randomized controlled trial.

Background and study aims Simethicone is useful as premedication for upper endoscopy because of its antifoaming effects. We aimed to evaluate the effect of timing of simethicone administration on mucosal visibility. Patients and methods In this multicenter, randomized, endoscopist-blinded study, patients scheduled for upper endoscopy were randomized to receive 40 mg simethicone at the following time points prior to the procedure: 20 to 30 minutes (early group), 0 to 10 minutes (late group) or 20 mg simethicone at both time points (split-dose group). Images were taken from nine predefined locations in the esophagus, stomach, and duodenum before endoscopic flushing. Each image was scored on mucosal visibility by three independent endoscopists on a 4-point scale (lower scores indicating better visibility), with adequate mucosal visibility defined as a score ≤ 2. Primary outcome was the percentage of patients with adequate total mucosal visibility (TMV), reached if all median subscores for each location were ≤ 2. Results A total of 386 patients were included (early group: 132; late group: 128; split-dose group: 126). Percentages of adequate TMV were 55%, 42%, and 61% in the early, late, and split-dose group, respectively ( P < 0.01). Adequate TMV was significantly higher in the split-dose group compared to the late group ( P < 0.01), but not compared to the early group ( P = 0.29). Differences between groups were largest in the stomach, where percentages of adequate mucosal visibility were higher in the early (68% vs 53%, P = 0.03) and split-dose group (69% vs 53%, P = 0.02) compared to the late group. Conclusions Mucosal visibility can be optimized with early simethicone administration, either as a single administration or in a split-dose regimen.

A deep learning system for detection of early Barrett's neoplasia: a model development and validation study.

BACKGROUND: Computer-aided detection (CADe) systems could assist endoscopists in detecting early neoplasia in Barrett's oesophagus, which could be difficult to detect in endoscopic images. The aim of this study was to develop, test, and benchmark a CADe system for early neoplasia in Barrett's oesophagus. METHODS: The CADe system was first pretrained with ImageNet followed by domain-specific pretraining with GastroNet. We trained the CADe system on a dataset of 14 046 images (2506 patients) of confirmed Barrett's oesophagus neoplasia and non-dysplastic Barrett's oesophagus from 15 centres. Neoplasia was delineated by 14 Barrett's oesophagus experts for all datasets. We tested the performance of the CADe system on two independent test sets. The all-comers test set comprised 327 (73 patients) non-dysplastic Barrett's oesophagus images, 82 (46 patients) neoplastic images, 180 (66 of the same patients) non-dysplastic Barrett's oesophagus videos, and 71 (45 of the same patients) neoplastic videos. The benchmarking test set comprised 100 (50 patients) neoplastic images, 300 (125 patients) non-dysplastic images, 47 (47 of the same patients) neoplastic videos, and 141 (82 of the same patients) non-dysplastic videos, and was enriched with subtle neoplasia cases. The benchmarking test set was evaluated by 112 endoscopists from six countries (first without CADe and, after 6 weeks, with CADe) and by 28 external international Barrett's oesophagus experts. The primary outcome was the sensitivity of Barrett's neoplasia detection by general endoscopists without CADe assistance versus with CADe assistance on the benchmarking test set. We compared sensitivity using a mixed-effects logistic regression model with conditional odds ratios (ORs; likelihood profile 95% CIs). FINDINGS: Sensitivity for neoplasia detection among endoscopists increased from 74% to 88% with CADe assistance (OR 2·04; 95% CI 1·73-2·42; p<0·0001 for images and from 67% to 79% [2·35; 1·90-2·94; p<0·0001] for video) without compromising specificity (from 89% to 90% [1·07; 0·96-1·19; p=0·20] for images and from 96% to 94% [0·94; 0·79-1·11; ] for video; p=0·46). In the all-comers test set, CADe detected neoplastic lesions in 95% (88-98) of images and 97% (90-99) of videos. In the benchmarking test set, the CADe system was superior to endoscopists in detecting neoplasia (90% vs 74% [OR 3·75; 95% CI 1·93-8·05; p=0·0002] for images and 91% vs 67% [11·68; 3·85-47·53; p<0·0001] for video) and non-inferior to Barrett's oesophagus experts (90% vs 87% [OR 1·74; 95% CI 0·83-3·65] for images and 91% vs 86% [2·94; 0·99-11·40] for video). INTERPRETATION: CADe outperformed endoscopists in detecting Barrett's oesophagus neoplasia and, when used as an assistive tool, it improved their detection rate. CADe detected virtually all neoplasia in a test set of consecutive cases. FUNDING: Olympus.

Radiofrequency ablation and endoscopic resection in a single session for Barrett's esophagus containing early neoplasia: a feasibility study.

BACKGROUND AND STUDY AIM: Endoscopic resection with radiofrequency ablation (RFA) 6 weeks later safely and effectively eradicates Barrett's esophagus with high grade dysplasia (HGD) and early cancer. After widespread endoscopic resection, related scarring may hamper balloon-based circumferential RFA (c-RFA). However c-RFA immediately followed by endoscopic resection in the same session might avoid the impact of scarring and reduce laceration and stenosis risk. We aimed to assess the feasibility of such an approach. PATIENTS AND METHODS: Patients with Barrett's esophagus ≥ 3 cm and ≥ 1 visible lesion (HGD/early cancer) were included. Visible lesions were marked with cautery, and c-RFA (12 J/cm2) was delivered using two applications and a cleaning step, followed by resection of the delineated area. Outcome measures were surface regression of Barrett's esophagus at 3 months, need for subsequent c-RFA, complications, and quality of resection specimens. RESULTS: 24 patients (20 men, 4 women; mean age 68 years, standard deviation [SD] 12; Barrett's esophagus median length C6M8) underwent single-session c-RFA + endoscopic resection, providing a median of 4 (interquartile range [IQR] 2 - 6) resection specimens (early cancer 18 patients; HGD 6). Complications included 1 perforation, 4 bleedings, and 5 stenoses; all were managed endoscopically. Specimens allowed assessment of neoplasia depth, differentiation, and lymphatic/vascular invasion. Median Barrett's esophagus surface regression at 3 months was 95 %. No patient required a second c-RFA procedure and 40 % required repeat endoscopic resection for visible lesions. Complete response for neoplasia was achieved in 100 % and complete response for intestinal metaplasia (CR-IM) in 95 %. CONCLUSIONS: c-RFA followed by endoscopic resection in the same session is feasible, but technically demanding and associated with a substantial rate of complications and repeat endoscopic resection. This approach should be reserved for selected cases in expert centers, with endoscopic resection and RFA 6 - 8 weeks later remaining the standard combined approach.

Learning to perform endoscopic resection of esophageal neoplasia is associated with significant complications even within a structured training program.

BACKGROUND AND STUDY AIMS: Endoscopic resection is the cornerstone of endoscopic treatment of esophageal high grade dysplasia or early cancer. Endoscopic resection is, however, a technically demanding procedure, which requires training and expertise. The aim of the current study was to prospectively evaluate efficacy and safety of the first 120 endoscopic resection procedures of early esophageal neoplasia performed by six endoscopists (20 endoscopic resections each) who were participating in an endoscopic resection training program. PATIENTS AND METHODS: The program consisted of four tri-monthly 1-day courses with lectures, live-demonstrations, hands-on training on anesthetized pigs, and one-on-one hands-on training days. Gastroenterologists from centers with multidisciplinary expertise in upper gastrointestinal oncology participated, together with an endoscopy nurse and a pathologist. Outcome measures were complete endoscopic removal of the target area and acute complications. RESULTS: A total of 120 consecutive esophageal endoscopic resection procedures (85 ER-cap, 35 multiband mucosectomy [MBM]) were performed by six endoscopists: 109 in Barrett's esophagus, 11 for squamous neoplasia; 85 piecemeal endoscopic resections (median 3 specimens, interquartile range 2 - 4 specimens). Complete endoscopic removal was achieved in 111 /120 cases (92.5 %). Six perforations occurred (5.0 %): five were effectively treated endoscopically (clips, covered stent), and one patient underwent esophagectomy. There were 11 acute mild bleedings (9.2 %), which were managed endoscopically. Perforations occurred in ER-cap procedures performed by four participants (7.1 % ER-cap vs. 0 % MBM; P = 0.18), and in 1.7 % of the first 10 endoscopic resections and 8.3 % of the second 10 endoscopic resections per endoscopist (P = 0.26). CONCLUSION: In this intense, structured training program, the first 120 esophageal endoscopic resections performed by six participants were associated with a 5.0 % perforation rate. Although perforations were adequately managed, performing 20 endoscopic resections may not be sufficient to reach the peak of the learning curve in endoscopic resection.

Radiofrequency ablation for the endoscopic eradication of esophageal squamous high grade intraepithelial neoplasia and mucosal squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: Radiofrequency ablation (RFA) with or without prior endoscopic resection safely and effectively removes early neoplasia in Barrett's esophagus. We speculated that this approach might also be suited for early squamous neoplasia of the esophagus. The aim of the study was to assess our initial experiences with RFA for high grade intraepithelial neoplasia (HGIN) and esophageal squamous cell cancer (ESCC) limited to the mucosa. PATIENTS AND METHODS: This was a prospective case series study in two tertiary centers. Patients with at least one unstained lesion (USL) of the esophagus using Lugol's chromoendoscopy and squamous HGIN/ESCC upon biopsy were included. In the case of nonflat USLs, endoscopic resection was performed for staging and to render the mucosa flat. After endoscopic resection and subsequent circumferential RFA, chromoendoscopy was repeated every 3 months with focal RFA of residual USLs. Follow-up chromoendoscopy was repeated at 6 months and annually thereafter. The main outcome measure was complete histological response for any squamous intraepithelial neoplasia or ESCC. RESULTS: A total of 13 patients (10 HGIN, three ESCC) were included. Following endoscopic resection in nine patients, the median extent of USLs was 4 cm and 50 % of circumference. All 13 patients achieved a complete response after a median of 2 RFA sessions (IQR 1 - 3 sessions). RFA-related complications included two mucosal lacerations (at the endoscopic resection scar) and one intramural hematoma, none requiring therapy. Endoscopic resection-/RFA-related complications were three stenoses. Dilation resulted in perforation in one patient (managed with a covered stent). There were no recurrences (median follow-up 17 months [IQR 11 - 22 months]). CONCLUSIONS: This study suggests that RFA with or without prior endoscopic resection for esophageal squamous HGIN and mucosal ESCC is feasible and effective.

Observer agreement in the assessment of narrowband imaging system surface patterns in Barrett's esophagus: a multicenter study.

BACKGROUND AND STUDY AIMS: The clinical utility of narrow-band imaging (NBI) for Barrett's esophagus is limited by the multiplicity of classification schemes. We evaluated the interobserver agreement and accuracy of a new consensus-driven simplified binary classification of NBI surface patterns.

Safety and efficacy of multiband mucosectomy in 1060 resections in Barrett's esophagus.

INTRODUCTION: Multiband mucosectomy (MBM) is a relatively new technique for endoscopic resection in Barrett's esophagus. This ligate-cut technique uses a modified variceal band ligator allowing for six consecutive resections without prior submucosal lifting. The aim was to evaluate the safety of MBM and its efficacy for complete endoscopic removal of delineated target areas in Barrett's esophagus. METHODS: Prospective registration of all MBM procedures in Barrett's esophagus was carried out between November 2004 and October 2009 in two hospitals. Prior to MBM, the target area was delineated with coagulation markings, followed by endoscopic resection until the delineated area was completely resected. Primary end points were acute (during procedure) plus early complications (<30 days) and the rate of complete endoscopic resection of the delineated target area. RESULTS: A total of 243 MBM procedures, with 1060 resections, were performed in 170 patients. MBM was performed for focal lesions (n=113), for Barrett's esophagus removal as part of a (stepwise) radical endoscopic resection protocol (n=117), and as escape treatment after radiofrequency ablation (n=13). The only acute complication was bleeding (in 3%, endoscopically managed); no perforations occurred despite absence of submucosal lifting. Early complications consisted of delayed bleeding (in 2%, endoscopically managed) and stenosis, which occurred in 48% of patients treated in a (stepwise) radical resection protocol; patients treated for focal lesions or in escape treatment showed no stenosis. Complete endoscopic resection was achieved in 91% of the focal lesions, in 86% of cases treated under the (stepwise) radical endoscopic resection protocol, and 100% for escape treatment after radiofrequency ablation. CONCLUSION: MBM is a safe and effective technique for the removal of delineated target areas in Barrett's esophagus.

Estimation of the post-mortem interval of human skeletal remains using Raman spectroscopy and chemometrics.

An important demand exists in the field of forensic analysis to objectively determine the post-mortem interval (PMI) when human skeletal remains are discovered. It is widely known that bones undergo different chemical and physical processes after death, mainly due to their interaction with the environment in which they are found, although it is not known exactly what these processes consist of. Multiple techniques have been used so far to follow up these and other post-mortem changes and thus establish the time elapsed since the individual's death, but they present important drawbacks in terms of reliability and accuracy. The aim of this research was to propose an analytical methodology capable of determining the PMI by using non-destructive Raman spectroscopy measurements of human skeletal remains. The recorded Raman spectra provided valuable and potentially useful information from which a multivariate study was performed by means of orthogonal partial least squares regression (OPLSR) in order to correlate the PMI with the detected spectral modifications. A collection of 53 real human skeletal remains with known PMI (15 years ≤ PMI ≤ 87 years) was analysed and used for building and validating the OPLS model. The PMI of 10 out of 14 validation samples could be determined with an accuracy error of less than 30%, demonstrating the adequate predictive performance of the OPLS model even in spite of the large inter-individual variability it handled. This opens up the possibility of applying the OPLS model in combination with non-destructive techniques to the determination of the PMI of human skeletal remains that have been buried in conditions similar or equal to those of cemetery niches and in a geographic location with a Mediterranean climate, which is an important achievement for forensic medicine and anthropology.

Endoscopic Resection Without Subsequent Ablation Therapy for Early Barrett's Neoplasia: Endoscopic Findings and Long-Term Mortality.

INTRODUCTION: After endoscopic resection (ER) of neoplasia in Barrett's esophagus (BE), it is recommended to ablate the remaining BE to minimize the risk for metachronous disease. However, we report long-term outcomes for a nationwide cohort of all patients who did not undergo ablation of the remaining BE after ER for early BE neoplasia, due to clinical reasons or performance status. METHODS: Endoscopic therapy for BE neoplasia in the Netherlands is centralized in 8 expert centers with specifically trained endoscopists and pathologists. Uniformity is ensured by a joint protocol and regular group meetings. We report all patients who underwent ER for a neoplastic lesion between 2008 and 2018, without further ablation therapy. Outcomes include progression during endoscopic FU and all-cause mortality. RESULTS: Ninety-four patients were included with mean age 74 (± 10) years. ER was performed for low-grade dysplasia (LGD) (10%), high-grade dysplasia (HGD) (25%), or low-risk esophageal adenocarcinoma (EAC) (65%). No additional ablation was performed for several reasons; in 73 patients (78%), the main argument was expected limited life expectancy. Median C2M5 BE persisted after ER, and during median 21 months (IQR 11-51) with 4 endoscopies per patient, no patient progressed to advanced cancer. Seventeen patients (18%) developed HGD/EAC: all were curatively treated endoscopically. In total, 29/73 patients (40%) with expected limited life expectancy died due to unrelated causes during FU, none of EAC. CONCLUSION: In selected patients, ER monotherapy with endoscopic surveillance of the residual BE is a valid alternative to eradication therapy with ablation.

Risk of lymph node metastasis associated with deeper invasion by early adenocarcinoma of the esophagus and cardia: study based on endoscopic resection specimens.

BACKGROUND: Most risk estimations for lymph node metastasis in adenocarcinoma of the esophagus and cardia (AEC) with invasion into the muscularis mucosae (m3) or submucosa are based on surgical series. This study aimed to correlate the lymph node metastasis rate with m3 and submucosal infiltration depth of AEC in endoscopic resection specimens. METHODS: Patients undergoing endoscopic resection for AEC between January 2000 and March 2008 at two centers were included if the endoscopic resection specimen showed m3 or submucosal cancer. Infiltration into the muscularis mucosae was defined as m3. Submucosal invasion was classified as sm1 (≤ 500 µm) or sm2/3 (> 500 µm). Exclusion criteria were chemotherapy or radiotherapy and nonradical endoscopic resection. RESULTS: 82 patients included 57 with m3, 12 with sm1, and 13 with sm2/3 cancers. Of the tumors, 13 were poorly differentiated and five showed lymphovascular invasion. After initial endoscopic resection, seven patients underwent surgery and 75 endoscopic therapy. No lymph node metastases were found in 158 lymph nodes of the esophagectomy specimens and none of the endoscopically treated patients were diagnosed with lymph node metastasis during a median follow-up of 26 months (interquartile range [IQR] 14 - 41). CONCLUSION: This study suggests that lymph node metastasis risk for m3 and submucosal AEC may be lower than has been assumed on the basis of surgical series, and that current guidelines are valid regarding suitability of m3 AECs for endoscopic therapy. It may also suggest that selected patients with submucosal cancers are also eligible for endoscopic management. Confirmation of these results is needed in larger series with longer follow-up.

Young man with asthma and infertility.

Asthma and male infertility are common diseases that can occur in the same patient. In some cases they could have patho-physiological changes common to both diseases. Our patient was seen as a result of having an irritating cough with wheezing, mainly at night, for more than a month. Asthma was diagnosed, and he responded favourably to the treatment given. Upon being informed that he had been examined for infertility for 5 years, alpha-1 antitrypsin (AAT) levels were requested. These confirmed that he had a phenotype SZ AAT deficiency. These findings, together with some evidence published recently, suggested that there is a need to rule out AAT deficiency in males with asthma and infertility.

OPLS multivariate regression of FTIR-ATR spectra of acrylic paints for age estimation in contemporary artworks.

In recent years the interest and demand for artworks has been increasing as they are an interesting commercial investment due to their growing value in the market. This explains the increasing number of counterfeits dealing with artworks that has led to the development of new methodologies for their characterization. The material characterization of these types of works can provide relevant information for both authentication and conservation/restoration. Thus, in this study multivariate chemometric methods were applied to FTIR-ATR spectroscopic data for artwork dating purposes. To that end, ageing prediction models were developed for Liquitex® and Hyplar® brands. Paint samples containing the green synthetic organic pigment (PG7), were exposed to artificial ageing and analysed with FTIR-ATR and Py-GC/MS for characterization and monitorization of the main components (binding medium, pigment and additives). Although the OPLS ageing models were mainly characterized by the modifications suffered by both the binder and the surfactants, a universal model could not be developed due to differences in the modification trends of the different brands. The applicability of the OPLS modelling for artwork dating purposes was tested in artworks provided by internationally recognized contemporary Basque artists. For Liquitex® a significant correlation (p < 0.05) between natural and accelerated ageing could be established, in which approximately 50 h of accelerated ageing under the applied conditions were equivalent to one natural year. This correlation might have possible applications in the dating of artworks for up to at least 22 years. Thus, the study demonstrates that FTIR-ATR combined with chemometrics is a potential method for artwork dating and a valuable source of information about the chemical processes involved in paint ageing, which can be of great help in the conservation and restoration steps.

Afferent and efferent connections of the mesencephalic reticular formation in goldfish.

The physiology of the mesencephalic reticular formation (MRF) in goldfish suggests its contribution to eye and body movements, but the afferent and efferent connections underlying such movements have not been determined. Therefore, we injected the bidirectional tracer biotinylated dextran amine into functionally identified MRF sites. We found retrogradely labelled neurons and anterogradely labelled boutons within nuclei of the following brain regions: (1) the telencephalon: a weak and reciprocal connectivity was confined to the central zone of area dorsalis and ventral nucleus of area ventralis; (2) the diencephalon: reciprocal connections were abundant in the ventral and dorsal thalamic nuclei; the central pretectal nucleus was also reciprocally wired with the MRF, but only boutons were present in the superficial pretectal nucleus; the preoptic and suprachiasmatic nuclei showed abundant neurons and boutons; the MRF was reciprocally connected with the preglomerular complex and the anterior tuberal nucleus; (3) the mesencephalon: neurons and boutons were abundant within deep tectal layers; reciprocal connections were also present within the torus semicircularis and the contralateral MRF; neurons were abundant within the nucleus isthmi; and (4) the rhombencephalon: the superior and middle parts of the reticular formation received strong projections from the MRF, while the projection to the inferior area was weaker; sparse neurons were present throughout the reticular formation; a reciprocal connectivity was observed with the sensory trigeminal nucleus; the medial and magnocellular nuclei of the octaval column projected to the MRF. These results support the participation of the MRF in the orienting response. The MRF could also be involved in other motor tasks triggered by visual, auditory, vestibular, or somatosensory signals.