Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

MR1 : ESGE recommends the following standards for Barrett esophagus (BE) surveillance:- a minimum of 1-minute inspection time per cm of BE length during a surveillance endoscopy- photodocumentation of landmarks, the BE segment including one picture per cm of BE length, and the esophagogastric junction in retroflexed position, and any visible lesions- use of the Prague and (for visible lesions) Paris classification- collection of biopsies from all visible abnormalities (if present), followed by random four-quadrant biopsies for every 2-cm BE length.Strong recommendation, weak quality of evidence. MR2: ESGE suggests varying surveillance intervals for different BE lengths. For BE with a maximum extent of ≥ 1 cm and < 3 cm, BE surveillance should be repeated every 5 years. For BE with a maximum extent of ≥ 3 cm and < 10 cm, the interval for endoscopic surveillance should be 3 years. Patients with BE with a maximum extent of ≥ 10 cm should be referred to a BE expert center for surveillance endoscopies. For patients with an irregular Z-line/columnar-lined esophagus of < 1 cm, no routine biopsies or endoscopic surveillance are advised.Weak recommendation, low quality of evidence. MR3: ESGE suggests that, if a patient has reached 75 years of age at the time of the last surveillance endoscopy and/or the patient's life expectancy is less than 5 years, the discontinuation of further surveillance endoscopies can be considered. Weak recommendation, very low quality of evidence. MR4: ESGE recommends offering endoscopic eradication therapy using ablation to patients with BE and low grade dysplasia (LGD) on at least two separate endoscopies, both confirmed by a second experienced pathologist.Strong recommendation, high level of evidence. MR5: ESGE recommends endoscopic ablation treatment for BE with confirmed high grade dysplasia (HGD) without visible lesions, to prevent progression to invasive cancer.Strong recommendation, high level of evidence. MR6: ESGE recommends offering complete eradication of all remaining Barrett epithelium by ablation after endoscopic resection of visible abnormalities containing any degree of dysplasia or esophageal adenocarcinoma (EAC).Strong recommendation, moderate quality of evidence. MR7: ESGE recommends endoscopic resection as curative treatment for T1a Barrett's cancer with well/moderate differentiation and no signs of lymphovascular invasion.Strong recommendation, high level of evidence. MR8: ESGE suggests that low risk submucosal (T1b) EAC (i. e. submucosal invasion depth ≤ 500 µm AND no [lympho]vascular invasion AND no poor tumor differentiation) can be treated by endoscopic resection, provided that adequate follow-up with gastroscopy, endoscopic ultrasound (EUS), and computed tomography (CT)/positrion emission tomography-computed tomography (PET-CT) is performed in expert centers.Weak recommendation, low quality of evidence. MR9: ESGE suggests that submucosal (T1b) esophageal adenocarcinoma with deep submucosal invasion (tumor invasion > 500 µm into the submucosa), and/or (lympho)vascular invasion, and/or a poor tumor differentiation should be considered high risk. Complete staging and consideration of additional treatments (chemotherapy and/or radiotherapy and/or surgery) or strict endoscopic follow-up should be undertaken on an individual basis in a multidisciplinary discussion.Strong recommendation, low quality of evidence. MR10 A: ESGE recommends that the first endoscopic follow-up after successful endoscopic eradication therapy (EET) of BE is performed in an expert center.Strong recommendation, very low quality of evidence. B: ESGE recommends careful inspection of the neo-squamocolumnar junction and neo-squamous epithelium with high definition white-light endoscopy and virtual chromoendoscopy during post-EET surveillance, to detect recurrent dysplasia.Strong recommendation, very low level of evidence. C: ESGE recommends against routine four-quadrant biopsies of neo-squamous epithelium after successful EET of BE.Strong recommendation, low level of evidence. D: ESGE suggests, after successful EET, obtaining four-quadrant random biopsies just distal to a normal-appearing neo-squamocolumnar junction to detect dysplasia in the absence of visible lesions.Weak recommendation, low level of evidence. E: ESGE recommends targeted biopsies are obtained where there is a suspicion of recurrent BE in the tubular esophagus, or where there are visible lesions suspicious for dysplasia.Strong recommendation, very low level of evidence. MR11: After successful EET, ESGE recommends the following surveillance intervals:- For patients with a baseline diagnosis of HGD or EAC:at 1, 2, 3, 4, 5, 7, and 10 years after last treatment, after which surveillance may be stopped.- For patients with a baseline diagnosis of LGD:at 1, 3, and 5 years after last treatment, after which surveillance may be stopped.Strong recommendation, low quality of evidence.

Side-Viewing Duodenoscope versus Forward-Viewing Gastroscope for Endoscopic Retrograde Cholangiopancreatography in Billroth II Gastrectomy Patients.

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Billroth II gastrectomy is still a challenging procedure. The optimal approach, namely the type of endoscope and sphincter management, has yet to be defined. Aim: To compare the efficacy and safety of forward-viewing gastroscope and the side-viewing duodenoscope in ERCP of patients with Billroth II gastrectomy. Methods: We conducted a retrospective, single-center cohort study of consecutive patients with Billroth II gastrectomy submitted to ERCP in an expert center for ERCP between 2005 and 2021. The outcomes assessed were: papilla identification, deep biliary cannulation, and adverse events (AEs). Multivariate analysis was performed to evaluate potential associations and predictors of the main outcomes. Results: We included 83 patients with a median age of 73 (IQR 65-81) years. ERCP was performed using side-viewing duodenoscope in 52 and forward-viewing gastroscope in 31 patients. Patients' characteristics were similar in the two groups. The global rate of papilla identification was 66% (n = 55). The rate of deep cannulation was 58% considering all patients and 87% in the subgroup of patients in which the papilla major was identified. Cannulation was performed with standard methods in 65% of cases and with needle-knife fistulotomy in 35%. AEs occurred in 4 patients. There was no difference between duodenoscope and gastroscope in papilla identification (64% [95% CI: 51-77] vs. 71% [55-87]). Although not statistically significant, duodenoscope had a lower deep cannulation rate when considering all patients (52% [15-39] vs. 68% [7-35]) and a higher AEs rate (8% [1-15] vs. 0% [0-1]). In a multivariate analysis, the use of gastroscope significantly increased the deep cannulation rate (OR = 152.62 [2.5-9,283.6]). Conclusion: This study demonstrates that forward-viewing gastroscope is at least as effective and safe as side-viewing duodenoscope for ERCP in patients with Billroth II gastrectomy. Moreover, our study showed that gastroscope is an independent predictor of successful cannulation.

Introdução: Colangiopancreatografia retrógrada endoscópica (CPRE) em doentes submetidos previamente a gastrectomia com reconstrução Billroth II é ainda um exame desafiante. A melhor abordagem, nomeadamente o tipo de endoscópio e a técnica de canulação biliar, ainda não está definida. Objectivo: Comparar a eficácia e segurança do gastroscópio de visão frontal e do duodenoscópio de visão lateral na CPRE de doentes com gastrectomia com reconstrução Billroth II. Métodos: Conduzimos um estudo de coorte retrospectivo e unicêntrico que incluiu consecutivamente doentes com gastrectomia com reconstrução Billroth II submetidos a CPRE num centro de referência para CPRE entre 2005 e 2021. Os outcomes avaliados foram: identificação da papila, canulação biliar profunda e efeitos adversos (EAs). Regressão logística foi realizada para avaliar possíveis associações e preditores dos outcomes. Resultados: Incluímos 83 doentes com uma idade mediana de 73 (IIQ 65­81) anos. A CPRE foi realizada usando duodenoscópio em 52 doentes e usando o gastroscópio de visão frontal em 31 doentes. As características dos doentes foram semelhantes entre os dois grupos. A taxa global de identificação da papila foi de 66% (n = 55). A taxa de canulação profunda foi de 58% considerando todos os doentes e de 87% considerando apenas o subgrupo de doentes nos quais a papila major foi identificada. A canulação foi realizada usando métodos convencionais em 65% e usando fistulotomia com faca em 35% dos doentes. EAs ocorreram em 4 doentes. Não houve diferenças entre duodenoscópio e gastroscópio relativamente à identificação da papila [64% (95% CI: 51­77) vs 71% (55­87)]. Apesar de estatisticamente não significativo, o uso de duodenoscópio teve uma menor taxa de canulação profunda quando considerados todos os doentes [52% (15­39) vs 68% (7­35)] e uma maior taxa de EAs [8% (1­15) vs 0% (0­1)]. Na regressão logística, o uso de gastroscópio significativamente aumentou a taxa de canulação profunda [OR = 152.62 (2.5­9,283.6)]. Conclusão: Este estudo demonstra que o uso de gastroscópio de visão frontal é pelo menos igualmente eficaz e seguro ao duodenoscópio na CPRE de doentes com gastrectomia com reconstrução Billroth II. Para além disso, o nosso estudo demonstrou que o uso de gastroscópio é um predictor independente para canulação.

Diagnosis and management of barrett esophagus: european society of gastrointestinal endoscopy (ESGE) guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It is an update of the previous (2017) Position Statement on the endoscopic management of Barrett esophagus.

Dissolvable Carboxymethylcellulose Microneedles for Noninvasive and Rapid Administration of Diclofenac Sodium.

The aim of this study is to prepare dissolvable biopolymeric microneedle (MN) patches composed solely of sodium carboxymethylcellulose (CMC), a water-soluble cellulose derivative with good film-forming ability, by micromolding technology for the transdermal delivery of diclofenac sodium salt (DCF). The MNs with ≈456 µm in height displayed adequate morphology, thermal stability up to 200 °C, and the required mechanical strength for skin insertion (>0.15 N needle-1 ). Experiments in ex vivo abdominal human skin demonstrate the insertion capability of the CMC_DCF MNs up to 401 µm in depth. The dissolution of the patches in saline buffer results in a maximum cumulative release of 98% of diclofenac after 40 min, and insertion in a skin simulant reveals that all MNs completely dissolve within 10 min. Moreover, the MN patches are noncytotoxic toward human keratinocytes. These results suggest that the MN patches produced with CMC are promising biopolymeric systems for the rapid administration of DCF in a minimally invasive manner.

Risk factors for gastric cancer in patients with Lynch syndrome.

INTRODUCTION: The cumulative lifetime risk of gastric cancer (GC) in patients with Lynch syndrome (LS) is reported to be 8%. There is limited evidence on specific risk factors for GC and no agreement among guidelines on gastric endoscopic surveillance schedule in LS patients. AIMS AND METHODS: We conducted a retrospective cohort study to identify risk factors for gastric precancerous conditions (chronic atrophic gastritis and intestinal metaplasia) and GC in patients with LS and a case-control study to compare the prevalence of these conditions with a control group. RESULTS: We included 385 LS patients (40.5% male, mean age 49.0 years). During a median follow-up period of 48 months (interquartile range, 24-84 months), precancerous conditions were identified in 110 patients (34%) and the prevalence of advanced stages of atrophic gastritis was 3% for OLGA III/IV and 0.6% OLGIM III/IV. Family history of GC was significantly associated with OLGA III/IV ( P = 0.020). Among LS patients, 10 patients (2.6%) were diagnosed with GC (incidence rate of 5/1000 persons-year). Older age and OLGA III/IV were identified as risk factors for GC ( P < 0.001). When compared with controls, patients with LS had significantly higher rates of Hp infection ( P = 0.035) and lower OLGA and OLGIM stages ( P < 0.001 and P = 0.026, respectively). CONCLUSION: In our cohort, the incidence of GC and advanced stages of atrophic gastritis was low. Older age and OLGA III/IV were associated with a higher risk of GC. Identification of risk factors for GC in LS patients can help tailoring endoscopic surveillance.

Deep Eutectic Solvent Formulations and Alginate-Based Hydrogels as a New Partnership for the Transdermal Administration of Anti-Inflammatory Drugs.

The transdermal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is a valuable and safer alternative to their oral intake. However, most of these drugs display low water solubility, which makes their incorporation into hydrophilic biopolymeric drug-delivery systems difficult. To overcome this drawback, aqueous solutions of bio-based deep eutectic solvents (DES) were investigated to enhance the solubility of ibuprofen, a widely used NSAID, leading to an increase in its solubility of up to 7917-fold when compared to its water solubility. These DES solutions were shown to be non-toxic to macrophages with cell viabilities of 97.4% (at ibuprofen concentrations of 0.25 mM), while preserving the anti-inflammatory action of the drug. Their incorporation into alginate-based hydrogels resulted in materials with a regular structure and higher flexibility. These hydrogels present a sustained release of the drug, which is able, when containing the DES aqueous solution comprising ibuprofen, to deliver 93.5% of the drug after 8 h in PBS. Furthermore, these hydrogels were able to improve the drug permeation across human skin by 8.5-fold in comparison with the hydrogel counterpart containing only ibuprofen. This work highlights the possibility to remarkably improve the transdermal administration of NSAIDs by combining new drug formulations based on DES and biopolymeric drug delivery systems.

Targeting cannabinoid receptor 2 (CB2) limits collagen production-An in vitro study in a primary culture of human fibroblasts.

Previous studies showed that cannabinoid 2 (CB2) receptor is involved in skin inflammation, fibrogenesis and re-epithelialization in mice, indicating that this receptor may be implicated in wound healing. Thus, topical use of cannabinoids may have a role in local fibrotic and wound healing diseases such as scars or keloids. We investigate the effect of the CB2 selective receptor agonist (6aR,10aR)-3-(1,1-Dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran (JWH133) and the CB2 selective receptor antagonist (6-Iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl)(4-methoxyphenyl)-methanone (AM630), on primary cultures of human fibroblasts. Primary cultures of adult human fibroblasts were obtained from abdominal human skin samples. Fibroblasts pretreated with JWH133 and/or AM630 were stimulated with TGF-ß (10 ng/ml). Fibroblast activation into myofibroblasts was quantified by the expression of alpha-smooth muscle actin (α-SMA) using Immunocytochemistry and Western Blot assays. Collagen content was quantified with the Sirius red staining assay. Upon human fibroblasts stimulation with TGF-ß, a significant increase on α-SMA and CB2 receptor expression was observed. In these cells, JWH133 decreased α-SMA expression and collagen content. However, this effect was not observed in resting human fibroblasts. AM630 decreased α-SMA expression and collagen content in both resting and activated fibroblasts. This effect was time- and concentration-dependent with an IC50 value of 11 µM. The CB2 receptor appears to be involved in fibroblast repair during skin wound healing in humans, as TGF-ß increases CB2 receptor expression and JWH133 produces an anti-fibrotic effect in human fibroblasts. AM630 also showed an anti-fibrotic effect hypothesizing that other cannabinoid receptors, such as TRPV, may be involved in this response.

Gender differences in Barrett's esophagus and progression of disease: a systematic review and meta-analysis.

It is known that Barrett's esophagus (BE) and esophageal adenocarcinoma occur more commonly in men. What is unknown are the prevalence of BE and rates of neoplastic progression in women. Our aim was to determine the prevalence of Barrett's and its progression to esophageal cancer in women through systematic review and meta-analysis. A comprehensive search was conducted using PubMed, Scopus, and Google Scholar. Studies were included that reported prevalence rates of BE or progression rates to neoplastic disease stratified by gender. Barrett's was defined by updated criteria as salmon-colored mucosa ≥1 cm proximal to the gastroesophageal junction. Pooled rates and odds ratios (ORs) at 95% confidence interval (CI) of the prevalence of BE and its progression to neoplastic disease were calculated. Ten studies with 19,337 patients (50.6% women) reported on prevalence and six studies with 5137 patients (24.3% women) reported on neoplastic progression of disease between genders. The rate of BE in women was 1.29% ([95% CI: 0.76-2.19], I2 = 91%) compared to men at 4.66% ([95% CI: 3.31-6.53], I2 = 89%); OR: 0.33 ([95% CI: 0.27-0.42], I2 = 0%). The rate of annual progression of Barrett's to high-grade dysplasia or adenocarcinoma was 0.62% ([95% CI: 0.22-1.75]) in women compared to 1.54% ([95% CI: 0.83-2.81], I2 = 96%) in men; OR: 0.44 ([95% CI: 0.30-0.65], I2 = 22%). This study demonstrates a 70% lower rate of prevalence and a 60% lower rate of neoplastic progression of Barrett's in women. Future BE guidelines should tailor screening and surveillance practices by gender.

Prevalence of Barrett's esophagus in a Southern European country: a multicenter study.

BACKGROUND: Identification of Barrett's esophagus (BE) with the treatment of dysplasia is essential to prevent esophageal adenocarcinoma (EAC). Moreover, determination of BE prevalence is important to define subsequent management strategies. However, precise estimates on BE prevalence from several European countries are lacking. We aimed to determine BE prevalence in a Southern European country. METHODS: A cross-sectional, multicenter study from November 2019 to February 2020 was performed defining BE as a columnar extent in the distal esophagus greater than or equal to 1 cm with intestinal metaplasia. RESULTS: A total of 1550 individuals, 51% male with a mean age of 62 (SD = 15) years undergoing upper endoscopy were included. The overall BE prevalence was 1.29% (95% confidence interval: 0.73-1.85); significantly higher in men [2.05% (1.06-3.04)] vs. women [0.53% (0.01-1.04)]. Of the 20 BE patients, eight were newly diagnosed and 12 were under surveillance. The median extent was C3 (min 0; max 16) M4.5 (min 2; max 16). One patient each had EAC (0.06%) and high-grade dysplasia (0.06%) at the time of endoscopy. There was no difference in prevalence between geographical regions, centers, use of sedation or experience of endoscopists. Considering all reports, 93% used standardized terminology, 23% accurate photodocumentation and 69% photodocumented the esophagogastric junction (EGJ). Furthermore, 80% used Prague classification, 55% Seattle protocol, 60% distance to the squamocolumnar junction, 75% to the EGJ and 40% to the hiatal pinch. When considering only reports with EGJ photodocumentation or Prague classification, the prevalence was 1.78% (0.91-2.64) or 1.03% (0.53-1.53). CONCLUSION: We report for the first time BE prevalence in Southern Europe and report a low overall prevalence in an unselected population. Future studies need to determine progression rates and how to improve quality metrics.

AM251, a cannabinoid receptor 1 antagonist, prevents human fibroblasts differentiation and collagen deposition induced by TGF-ß - An in vitro study.

Previous studies showed that cannabinoid 1 receptor (CB1) is linked with skin fibrosis and scar tissue formation in mice. Therefore, the topical use of cannabinoids may have a role in the prevention or treatment of local fibrotic and wound healing diseases as hypertrophic scars or keloids. In this study, we asked whether CB1 activation or inactivation would change fibroblast differentiation into myofibroblast and collagen deposition in skin human fibroblast. Primary cultures of adult human fibroblasts were obtained from abdominal human skin. Cells were stimulated with transforming growth factor-beta (TGF-ß, 10ng/ml) and treated with a CB1 selective agonist (arachidonyl-2-chloroethylamide, ACEA 1 µM) and an antagonist (AM251 1, 5 and 10 µM). Alpha-smooth muscle actin (α-SMA) was quantified using Immunocytochemistry and Western Blot. Collagen was quantified with Sirius Red staining assay. Significance was assessed by One-way ANOVA. P < 0.05 was considered significant. TGF-ß significantly increases α-SMA expression. ACEA 1 µM significantly increases collagen deposition but does not change α-SMA expression. AM251 10 µM added in the absence and the presence of ACEA reduces α-SMA expression and collagen content in TGF-ß treated cells. AM251 shows a concentration-dependent effect over collagen deposition with a pIC50 of 5.5 (4.6-6.4). TGF-ß significantly increases CB1 receptor expression. CB1 inactivation with AM251 prevents fibroblasts differentiation and collagen deposition, induced by TGF-ß in human fibroblasts. The outcome supports that CB1 is a molecular target for wound healing disorders and in vivo and pre-clinical studies should be implemented to clarify this premise.

Experience in Management of Burn Injury During Pregnancy in a Burn Unit.

Burns injuries during pregnancy are rarely reported in developed countries, but an increasing in mortality and morbidity has been observed. The authors describe their experience in the treatment of pregnant women in a burn unit. A 12-year retrospective study of burns in pregnant women hospitalized was conducted. Since 2008, two pregnant women were admitted in their unit. Patient 1, a 32-year-old pregnant woman on second trimester (27s6d), suffered a second-degree burn injury, 16% total body surface area (TBSA), caused by fire. She was admitted in their burn unit and submitted to medical treatment, wound dressing, and surgical treatment. Cerium nitrate and silver sulfadiazine were used in burn lesions and the patient was submitted to debridement and skin graft surgery. No uneventful events occurred with the fetus. Patient 2 was a 32-year-old pregnant woman on second trimester (26s), HVC positive, admitted with a second-degree flash burn, 8% TBSA. She was submitted to endotracheal intubation before arriving to the hospital due to risk of airway burn. Dexamethasone was administered for fetus lung maturation. No uneventful events were observed. The incidence of thermal injury in pregnancy in Portugal is low. Active medical treatment together with conservative wound care should be the standard in each trimester of pregnancy. Although there is limited safety information on cerium nitrate or silver sulfadiazine during pregnancy, those were used with no adverse effects on one of their patients. Obstetrical management should be individualized.

Systematic review of the published guidelines on Barrett's esophagus: should we stress the consensus or the differences?

Multiple guidelines on Barrett's esophagus (BE) have being published in order to standardize and improve clinical practice. However, studies have shown poor adherence to them. Our aim was to synthetize, compare, and assess the quality of recommendations from recently published guidelines, stressing similarities and differences. We conducted a search in Pubmed and Scopus. When different guidelines from the same society were identified, the most recent one was considered. We used the GRADE system to assess the quality of evidence. We included 24 guidelines and position/consensus statements from the European Society of Gastrointestinal Endoscopy, British Society of Gastroenterology, American Society for Gastrointestinal Endoscopy, American Gastroenterological Association, American College of Gastroenterology, Australian guidelines, and Asia-Pacific consensus. All guidelines defend that BE should be diagnosed when there is an extension of columnar epithelium into the distal esophagus. However, there is still some controversy regarding length and histology criteria for BE diagnosis. All guidelines recommend expert pathologist review for dysplasia diagnosis. All guidelines recommend surveillance for non-dysplastic BE, and some recommend surveillance for indefinite dysplasia. While the majority of guidelines recommend ablation therapy for low-grade dysplasia without visible lesion, others recommend ablation therapy or endoscopic surveillance. However, controversy exists regarding surveillance intervals and biopsy protocols. All guidelines recommend endoscopic resection followed by ablation therapy for neoplastic visible lesion. Several guidelines use the GRADE system, but the majority of recommendations are based on low and moderate quality of evidence. Although there is considerable consensus among guidelines, there are some discrepancies resulting from low-quality evidence. The lack of high-quality evidence for the majority of recommendations highlights the importance of continued well-conducted research in this field.

A new role for anandamide: defective link between the systemic and skin endocannabinoid systems in hypertrophic human wound healing.

The use of cannabinoids to treat fibrotic skin diseases is an emergent issue. Therefore, we aimed to evaluate systemic and skin endocannabinoid responses in the wound-healing process in humans. A prospective study was performed in 50 patients who underwent body-contouring surgery. Anandamide (N-arachidonoylethanolamine, AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were quantified using LC-MS/MS. Ten (20%) patients developed hypertrophic (HT) scars. No significant changes were observed between the normal (N) scar and HT scar groups in terms of plasma and skin endocannabinoids. Nevertheless, a positive correlation between plasma and skin AEA concentrations was found in the N group (r = 0.38, p = 0.015), which was absent in the HT group. Moreover, the AEA concentration was significantly lower in HT scar tissue than in normal scar tissue (0.77 ± 0.12 ng/g vs 1.15 ± 0.15 ng/g, p < 0.001). Interestingly, in all patients, the surgical intervention produced a time-dependent effect with a U shape for AEA, PEA and OEA plasma concentrations. In contrast, 2-AG plasma concentrations increased 5 days after surgery and were reduced and stabilized 3 months later. These results suggest crosstalk between systemic and local skin endocannabinoid systems during human wound healing. AEA appears to be the most likely candidate for this link, which is deficient in patients with HT scars.

The global prevalence of Barrett's esophagus: A systematic review of the published literature.

BACKGROUND: Determining the prevalence of Barrett's esophagus is important for defining screening strategies. We aimed to synthesize the available data, determine Barrett's esophagus prevalence, and assess variability. METHODS: Three databases were searched. Subgroup, sensitivity, and meta-regression analyses were conducted and pooled prevalence was computed. RESULTS: Of 3510 studies, 103 were included. In the general population, we estimated a prevalence for endoscopic suspicion of Barrett's esophagus of (a) any length with histologic confirmation of intestinal metaplasia as 0.96% (95% confidence interval: 0.85-1.07), (b) ≥1 cm of length with histologic confirmation of intestinal metaplasia as 0.96% (95% confidence interval: 0.75-1.18) and (c) for any length with histologic confirmation of columnar metaplasia as 3.89% (95% confidence interval: 2.25-5.54) . By excluding studies with high-risk of bias, the prevalence decreased to: (a) 0.70% (95% confidence interval: 0.61-0.79) and (b) 0.82% (95% confidence interval: 0.63-1.01). In gastroesophageal reflux disease patients, we estimated the prevalence with afore-mentioned criteria to be: (a) 7.21% (95% confidence interval: 5.61-8.81) (b) 6.72% (95% confidence interval: 3.61-9.83) and (c) 7.80% (95% confidence interval: 4.26-11.34). The Barrett's esophagus prevalence was significantly influenced by time period, region, Barrett's esophagus definition, Seattle protocol, and study design. There was a significant gradient East-West and North-South. There were minimal to no data available for several countries. Moreover, there was significant heterogeneity between studies. CONCLUSION: There is a need to reassess the true prevalence of Barrett's esophagus using the current guidelines in most regions. Having knowledge about the precise Barrett's esophagus prevalence, diverse attitudes from educational to screening programs could be taken.

Pullulan microneedle patches for the efficient transdermal administration of insulin envisioning diabetes treatment.

The present study reports the fabrication of dissolvable microneedle (MN) patches using pullulan (PL), a water-soluble polysaccharide with excellent film-forming ability, for the transdermal administration of insulin, envisioning the non-invasive treatment of diabetes. PL MNs patches were successfully prepared by micromoulding and revealed good thermal stability (Tdmax = 294 °C) and mechanical properties (>0.15 N needle-1), penetrating skin up to 381 µm depth, as revealed by in vitro skin tests. After application into human abdominal skin in vitro, the MNs dissolved within 2 h releasing up to 87% of insulin. When stored at 4, 20 and 40 °C for 4 weeks, insulin was able to retain its secondary structure, as shown by circular dichroism spectropolarimetry. The prepared PL MNs were non-cytotoxic towards human keratinocytes, being suitable for skin application. These findings suggest that PL MNs have potential to deliver insulin transdermally, thus avoiding its subcutaneous administration.