Socioeconomic status and the effect of prolonged pandemic confinement on anthropometric and glycaemic outcomes in adults with type 2 diabetes mellitus.

AIM: This systematic review and meta-analysis aimed to investigate the impact of COVID19 lockdown on the anthropometric and glycaemic outcomes of adults with type 2 diabetes mellitus (T2DM) and assess whether socioeconomic status (SES) was relevant to these changes. METHODS: A search of three databases was conducted. Meta-analyses using random effects models were undertaken to combine anthropometric and glycaemic measures pre- and post-confinement. Subgroup analyses according to SES were also conducted. RESULTS: This systematic review of 19 articles demonstrated that prolonged pandemic-related confinement is associated with a deterioration in both anthropometric and glycaemic outcomes among adults with T2DM. Furthermore, SES was found to be relevant to these changes. Specifically, BMI (kg/m2) showed an increase in mean difference of 0.72 (95% CI; 0.13, 1.31; p<0.05) between pre and post lockdown cohorts. High income countries displayed a greater increase in BMI compared to their lower middle-income counterparts. Regarding, fasting blood glucose (FBG), a statistically significant difference was observed in the upper middle-income group (mean difference: 5.10; 95% CI: 2.92, 7.27), and high-income group (mean difference: 6.03; 95% CI: 0.04, 12.02). There were no significant changes to weight, waist circumference, or HbA1C over the lockdown period. CONCLUSION: Our findings suggest adults with T2DM may have received less effective care over the lockdown period, particularly in high income countries. Clinics and care providers may need to adopt more intensive contact and treatment plans in the post lockdown period to prevent lasting impacts on disease progression and metabolic sequelae.

Effectiveness of an Oral Gastrografin Regimen for Complete Distal Intestinal Obstruction Syndrome.

Objectives: To assess the effectiveness of oral Gastrografin treatment and outcomes in adult patients with complete distal intestinal obstruction syndrome (cDIOS). Background: DIOS is an important gastrointestinal complication of cystic fibrosis (CF). Conservative treatment options for cDIOS are largely empirical, and the optimal management remains unclear. Surgery should be reserved for patients who have failed nonoperative treatment or have immediate indications for surgery. Methods: A retrospective single-institution cohort study was undertaken of adults with CF who had undergone lung transplantation and were admitted with an episode of cDIOS between 2004 and 2020. The outcomes of treatment in a high-volume CF transplant center with routine oral Gastrografin-based therapy were assessed. Results: Forty-seven episodes of cDIOS were recorded in 29 (23.3%) of 124 patients who had undergone lung transplantation for CF, and mean age at cDIOS was 30.3 years (SD ±11.2). Mean follow-up post cDIOS was 75.6 months (SD ±45.5). Twelve patients had >1 cDIOS episode. One episode occurred during recovery after transplantation, and 5 patients were readmitted within 30 days posttransplant with cDIOS. A history of previous abdominal surgery was associated with the development of cDIOS (P < 0.001). Oral Gastrografin therapy was used in 95.7% of the episodes, at varying doses. Three patients (7.0%) were resistant to oral Gastrografin treatment, requiring laparotomy. There were no deaths due to DIOS. Conclusions: Oral Gastrografin is effective and safe for the treatment of cDIOS, with low treatment failure rates. It should be considered as a first-line treatment option for patients with CF presenting with complete distal intestinal obstruction.

A Method for Increasing the Robustness of Stable Feature Selection for Biomarker Discovery in Molecular Medicine Developed Using Serum Small Extracellular Vesicle Associated miRNAs and the Barrett's Oesophagus Disease Spectrum.

The biomarker development field within molecular medicine remains limited by the methods that are available for building predictive models. We developed an efficient method for conservatively estimating confidence intervals for the cross validation-derived prediction errors of biomarker models. This new method was investigated for its ability to improve the capacity of our previously developed method, StaVarSel, for selecting stable biomarkers. Compared with the standard cross validation method, StaVarSel markedly improved the estimated generalisable predictive capacity of serum miRNA biomarkers for the detection of disease states that are at increased risk of progressing to oesophageal adenocarcinoma. The incorporation of our new method for conservatively estimating confidence intervals into StaVarSel resulted in the selection of less complex models with increased stability and improved or similar predictive capacities. The methods developed in this study have the potential to improve progress from biomarker discovery to biomarker driven translational research.

How to effectively use and interpret the barium swallow: Current role in esophageal dysphagia.

BACKGROUND: The barium swallow is a commonly performed investigation, though recent decades have seen major advances in other esophageal diagnostic modalities. PURPOSE: The purpose of this review is to clarify the rationale for components of the barium swallow protocol, provide guidance on interpretation of findings, and describe the current role of the barium swallow in the diagnostic paradigm for esophageal dysphagia in relation to other esophageal investigations. The barium swallow protocol, interpretation, and reporting terminology are subjective and non-standardized. Common reporting terminology and an approach to their interpretation are provided. A timed barium swallow (TBS) protocol provides more standardized assessment of esophageal emptying but does not evaluate peristalsis. Barium swallow may have higher sensitivity than endoscopy for detecting subtle strictures. Barium swallow has lower overall accuracy than high-resolution manometry for diagnosing achalasia but can help secure the diagnosis in cases of equivocal manometry. TBS has an established role in objective assessment of therapeutic response in achalasia and helps identify the cause of symptom relapse. Barium swallow has a role in the evaluating manometric esophagogastric junction outflow obstruction, in some cases helping to identify where it represents an achalasia-like syndrome. Barium swallow should be performed in dysphagia following bariatric or anti-reflux surgery, to assess for both structural and functional postsurgical abnormality. Barium swallow remains a useful investigation in esophageal dysphagia, though its role has evolved due to advancements in other diagnostics. Current evidence-based guidance regarding its strengths, weaknesses, and current role are described in this review.

Use of oral contrast for CT scanning and time to diagnosis and treatment of acute appendicitis.

BACKGROUND: The aim of this study was to investigate whether there is a delay in treatment for patients having pre-operative CT imaging with both intravenous and oral contrast (CTIVO) compared to intravenous contrast alone (CTIV). METHODS: A retrospective review of patients who underwent emergency appendicectomy at a single hospital during a two-year period (1/1/2019-31/12/2020) was performed. Demographic details, imaging timing/modality; biochemical markers; American Society of Anaesthesiologists (ASA) physical status classification, anaesthetic induction time; operative report findings; histopathology, peri-operative complications, admission/discharge times were recorded. The Sunshine Appendicitis Grading System (SAGS) score was used for severity of appendicitis. RESULTS: Pre-operative CT was performed in 294 patients; CTIVO: 159 (54%), CTIV: 135 (46%). Both groups were comparable for age, sex, ASA status and inflammatory markers. The median time from CT request to scanning was longer with CTIVO (CTIVO: 170 min, CTIV: 65 min, P < 0.0001). The median time from CT request to induction of anaesthesia was also longer with CTIVO (CTIVO: 780 minutes, CTIV: 406 min, P < 0.0001). A delay to theatre was not significantly associated with severity of appendicitis (SAGS score). The diagnostic accuracy was not reduced in the CTIV group compared to the CTIVO group. CONCLUSION: CTIVO scans significantly delay CT diagnosis and surgical treatment of appendicitis compared to CTIV. Omitting oral contrast does not result in a reduction in diagnostic accuracy for appendicitis.

Reduced number of admissions with acute appendicitis but not severe acute appendicitis at two Sydney hospitals during the first COVID-19 lockdown period.

BACKGROUND: This study investigated whether there was a change in acute appendicitis, appendicectomy admissions or disease severity during the 2020 lockdown period in NSW. METHODS: A retrospective before-and-after study was undertaken of patients admitted to two Sydney hospitals (St. Vincent's and Liverpool Hospitals) who had appendicectomy for presumed acute appendicitis and patients who had confirmed appendicitis but did not undergo surgery. Study periods were the 2020 lockdown period (15 March-15 May 2020), the corresponding period in the previous year, and the 1-month after these periods. Patients were classified as having no, mild or severe appendicitis using operation and histopathological reports. RESULTS: (Thirty-six percent) fewer patients were admitted with acute appendicitis during the lockdown period compared with the previous year with a substantial reduction in normal/mild appendicitis presentations (OR 0.56, 95% CI 0.34-0.93, P = 0.03). There were 46% fewer patients with mild appendicitis during lockdown (56) compared with the previous year (103); numbers of patients with severe appendicitis were very similar (46 vs. 51). There was no increase in number of admissions with severe appendicitis, or in the time from onset of symptoms to admission, in the month following lockdown. CONCLUSION: Compared with the previous year, there were markedly fewer admissions with appendicitis during lockdown, with no evidence of a shift to more cases of severe appendicitis nor delayed presentation in the post-lockdown period. It is plausible that some patients with mild appendicitis may have recovered without hospitalization, supporting the importance of implementing trials on non-surgical management of appendicitis.

Association of clinically significant weight loss with number of patient visits and months of attendance at an Australian multidisciplinary weight management clinic.

Despite the obesity epidemic, there are relatively few multidisciplinary obesity services in Australia, and only limited data on the effectiveness of these services. The aim of this study was to evaluate the effectiveness of a university hospital-based weight management clinic-the 'Healthy Weight Clinic' in supporting patients to achieve clinically significant weight loss (≥5% reduction in body weight), weight maintenance, and changes in body composition. A retrospective review was conducted to determine weight and associated health outcomes in patients who attended an initial consultation in the first 2 years of the clinic-between March 2017 and March 2019. Follow up was at least 1 year for all patients. Patients who underwent bariatric surgery were excluded. Of 213 total patients, 172 patients attended more than one follow-up consultation for lifestyle modification. Mean weight change and percentage total weight change at last follow-up was -6.2 kg (SD 7.4) and - 6.0% (SD 6.9), respectively. For every additional clinic follow-up, there was 21.4% increased odds of achieving clinically significant weight loss, and for every additional month of follow-up, there was 10.1% increased odds of achieving clinically significant weight loss. Twenty percent of patients (34/172) maintained ≥5% of initial body weight loss for at least 1 year. Body composition measurements were also favourable, with significant changes in percentage skeletal muscle mass of +0.8% (SD 1.5) and in percentage fat mass by -1.4% (SD 3.2). Regular support in a structured holistic multidisciplinary obesity service enables patients to achieve clinically meaningful weight loss and improved skeletal muscle mass to body fat ratio, and maintain this loss for at least 1 year. Improved weight loss was associated with more patient visits and longer duration of attendance at the clinic.

Clinical pathways and outcomes of patients with Barrett's esophagus in tertiary care settings: a prospective longitudinal cohort study in Australia, 2008-2016.

BACKGROUND: Clinical services for Barrett's esophagus have been rising worldwide including Australia, but little is known of the long-term outcomes of such patients. Retrospective studies using data at baseline are prone to both selection and misclassification bias. We investigated the clinical characteristics and outcomes of Barrett's esophagus patients in a prospective cohort. METHODS: We recruited patients diagnosed with Barrett's esophagus in tertiary settings across Australia between 2008 and 2016. We compared baseline and follow-up epidemiological and clinical data between Barrett's patients with and without dysplasia. We calculated age-adjusted incidence rates and estimated minimally and fully adjusted hazard ratios (HR) to identify those clinical factors related to disease progression. RESULTS: The cohort comprised 268 patients with Barrett's esophagus (median follow-up 5 years). At recruitment, 224 (84%) had no dysplasia, 44 (16%) had low-grade or indefinite dysplasia (LGD/IND). The age-adjusted incidence of esophageal adenocarcinoma (EAC) was 0.5% per year in LGD/IND compared with 0.1% per year in those with no dysplasia. Risk of progression to high-grade dysplasia/EAC was associated with prior LGD/IND (fully adjusted HR 6.55, 95% confidence interval [CI] 1.96-21.8) but not long-segment disease (HR 1.03, 95%CI 0.29-3.58). CONCLUSIONS: These prospective data suggest presence of dysplasia is a stronger predictor of progression to cancer than segment length in patients with Barrett's esophagus.

Development and validation of a targeted gene sequencing panel for application to disparate cancers.

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour's molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy.

Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes.

Adipocytes support key metabolic and endocrine functions of adipose tissue. Lipid is stored in two major classes of depots, namely visceral adipose (VA) and subcutaneous adipose (SA) depots. Increased visceral adiposity is associated with adverse health outcomes, whereas the impact of SA tissue is relatively metabolically benign. The precise molecular features associated with the functional differences between the adipose depots are still not well understood. Here, we characterised transcriptomes and methylomes of isolated adipocytes from matched SA and VA tissues of individuals with normal BMI to identify epigenetic differences and their contribution to cell type and depot-specific function. We found that DNA methylomes were notably distinct between different adipocyte depots and were associated with differential gene expression within pathways fundamental to adipocyte function. Most striking differential methylation was found at transcription factor and developmental genes. Our findings highlight the importance of developmental origins in the function of different fat depots.

Complex structural rearrangements are present in high-grade dysplastic Barrett's oesophagus samples.

BACKGROUND: Oesophageal adenocarcinoma (EAC) incidence is increasing and has a poor survival rate. Barrett's oesophagus (BE) is a precursor condition that is associated with EAC and often occurs in conjunction with chronic gastro-oesophageal reflux, however many individuals diagnosed with BE never progress to cancer. An understanding of the genomic features of BE and EAC may help with the early identification of at-risk individuals. METHODS: In this study, we assessed the genomic features of 16 BE samples using whole-genome sequencing. These included non-dysplastic samples collected at two time-points from two BE patients who had not progressed to EAC over several years. Seven other non-dysplastic samples and five dysplastic BE samples with high-grade dysplasia were also examined. We compared the genome profiles of these 16 BE samples with 22 EAC samples. RESULTS: We observed that samples from the two non-progressor individuals had low numbers of somatic single nucleotide variants, indels and structural variation events compared to dysplastic and the remaining non-dysplastic BE. EAC had the highest level of somatic genomic variations. Mutational signature 17, which is common in EAC, was also present in non-dysplastic and dysplastic BE, but was not present in the non-progressors. Many dysplastic samples had mutations in genes previously reported in EAC, whereas only mutations in CDKN2A or in the fragile site genes appeared common in non-dysplastic samples. Rearrangement signatures were used to identify a signature associated with localised complex events such as chromothripsis and breakage fusion-bridge that are characteristic of EACs. Two dysplastic BE samples had a high contribution of this signature and contained evidence of localised rearrangements. Two other dysplastic samples also had regions of localised structural rearrangements. There was no evidence for complex events in non-dysplastic samples. CONCLUSIONS: The presence of complex localised rearrangements in dysplastic samples indicates a need for further investigations into the role such events play in the progression from BE to EAC.

Evaluation of Serum Glycoprotein Biomarker Candidates for Detection of Esophageal Adenocarcinoma and Surveillance of Barrett's Esophagus.

Esophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett's esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance of BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker candidate panel for BE surveillance. Serum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and the United States (1 clinic) using previously established lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS) tier 3 assay. The area under receiver operating characteristic curve (AUROC) was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multi-marker panel for BE surveillance. Complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarkers in lectin pull-down samples for EAC across both cohorts. A panel of 10 serum glycoprotein biomarker candidates discriminated BE patients not requiring intervention (BE± low grade dysplasia) from those requiring intervention (BE with high grade dysplasia (BE-HGD) or EAC) with an AUROC value of 0.93. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that have progressed toward EAC, levels of serum C9 were significantly (p < 0.05) increased with disease progression in EPHA (erythroagglutinin from Phaseolus vulgaris) and NPL (Narcissus pseudonarcissus lectin) pull-down samples. The results confirm alteration of complement pathway glycoproteins during BE-EAC pathogenesis. Further prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted, prior to development of a first-line BE surveillance blood test.

Safety and Effectiveness of an Endoscopically Placed Duodenal-Jejunal Bypass Device (EndoBarrier®): Outcomes in 114 Patients.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopically placed device designed to achieve weight loss and improve glycemic control in obese patients. Previous studies report promising results but typically included small patient numbers and short follow-up. This study aims to determine the safety and effectiveness of the device. METHODS: Study design: A series of all patients treated by the DJBL at our institutions. OUTCOME MEASUREMENTS: Weight loss, biochemical measures, complications. RESULTS: Between July 2012 and March 2015, 114 consecutive patients were treated for a mean 51.1 weeks (standard deviation (SD) 19.9 weeks). Mean total body weight change from baseline was 12.0 kg (SD 8.5 kg, p < 0.001). Mean percent total body weight loss (%TWL) was 10.5% (SD 7.3%). Mean HbA1c was not significantly improved, but of 10 patients on insulin, 4 ceased insulin and 4 reduced insulin dosages. There was a significant decrease in hemoglobin and total cholesterol and a significant increase in serum alkaline phosphatase. Seventy-four percent of patients experienced at least one adverse event, some of them serious including 6 device obstructions, 5 gastrointestinal hemorrhages, 2 liver abscesses, and 1 acute pancreatitis. Seventy-four percent of patients experienced weight gain after removal with a mean 4.5 ± 6.1 kg (p < 0.0001) within the first 6 months after explantation. CONCLUSIONS: The DJBL provides significant but highly variable weight loss. Glycemic control was variable. Most insulin-requiring T2DM patients ceased or reduced insulin. Most patients experience an adverse event and most regain significant weight after device removal. Major adverse events can occur, including the potentially life-threatening complications of hepatic abscess and gastrointestinal hemorrhage.

MicroRNA profile in neosquamous esophageal mucosa following ablation of Barrett's esophagus.

AIM: To investigate the microRNA expression profile in esophageal neosquamous epithelium from patients who had undergone ablation of Barrett's esophagus. METHODS: High throughput screening using TaqMan® Array Human MicroRNA quantitative PCR was used to determine expression levels of 754 microRNAs in distal esophageal mucosa (1 cm above the gastro-esophageal junction) from 16 patients who had undergone ablation of non-dysplastic Barrett's esophagus using argon plasma coagulation vs pretreatment mucosa, post-treatment proximal normal non-treated esophageal mucosa, and esophageal mucosal biopsies from 10 controls without Barrett's esophagus. Biopsies of squamous mucosa were also taken from 5 cm above the pre-ablation squamo-columnar junction. Predicted mRNA target pathway analysis was used to investigate the functional involvement of differentially expressed microRNAs. RESULTS: Forty-four microRNAs were differentially expressed between control squamous mucosa vs post-ablation neosquamous mucosa. Nineteen microRNAs were differentially expressed between post-ablation neosquamous and post-ablation squamous mucosa obtained from the more proximal non-treated esophageal segment. Twelve microRNAs were differentially expressed in both neosquamous vs matched proximal squamous mucosa and neosquamous vs squamous mucosa from healthy patients. Nine microRNAs (miR-424-5p, miR-127-3p, miR-98-5p, miR-187-3p, miR-495-3p, miR-34c-5p, miR-223-5p, miR-539-5p, miR-376a-3p, miR-409-3p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These microRNAs were also more highly expressed in Barrett's esophagus mucosa than matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these microRNAs may be involved in the regulation of cell survival signalling pathways. Three microRNAs (miR-187-3p, miR-135b-5p and miR-31-5p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These miRNAs were expressed at similar levels in pre-ablation Barrett's esophagus mucosa, matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these microRNAs may be involved in regulating the expression of proteins that contribute to barrier function. CONCLUSION: Neosquamous mucosa arising after ablation of Barrett's esophagus expresses microRNAs that may contribute to decreased barrier function and microRNAs that may be involved in the regulation of survival signaling pathways.

Oesophageal Adenocarcinoma: A Patient and Physician's Perspective.

This article is co-authored by a patient with oesophageal adenocarcinoma and his physician, who performed oesophagectomy. The patient relates his pre-operative preparation and post-operative experience. The physician comments on the alarming increase in the incidence of this cancer, risk factors, and treatment. As illustrated by the patient's report, the physician also discusses the importance of maintaining adequate nutrition, cardiorespiratory fitness, and a positive psychological attitude.

Novel Aberrations Uncovered in Barrett's Esophagus and Esophageal Adenocarcinoma Using Whole Transcriptome Sequencing.

Esophageal adenocarcinoma (EAC) has one of the fastest increases in incidence of any cancer, along with poor five-year survival rates. Barrett's esophagus (BE) is the main risk factor for EAC; however, the mechanisms driving EAC development remain poorly understood. Here, transcriptomic profiling was performed using RNA-sequencing (RNA-seq) on premalignant and malignant Barrett's tissues to better understand this disease. Machine-learning and network analysis methods were applied to discover novel driver genes for EAC development. Identified gene expression signatures for the distinction of EAC from BE were validated in separate datasets. An extensive analysis of the noncoding RNA (ncRNA) landscape was performed to determine the involvement of novel transcriptomic elements in Barrett's disease and EAC. Finally, transcriptomic mutational investigation of genes that are recurrently mutated in EAC was performed. Through these approaches, novel driver genes were discovered for EAC, which involved key cell cycle and DNA repair genes, such as BRCA1 and PRKDC. A novel 4-gene signature (CTSL, COL17A1, KLF4, and E2F3) was identified, externally validated, and shown to provide excellent distinction of EAC from BE. Furthermore, expression changes were observed in 685 long noncoding RNAs (lncRNA) and a systematic dysregulation of repeat elements across different stages of Barrett's disease, with wide-ranging downregulation of Alu elements in EAC. Mutational investigation revealed distinct pathways activated between EAC tissues with or without TP53 mutations compared with Barrett's disease. In summary, transcriptome sequencing revealed altered expression of numerous novel elements, processes, and networks in EAC and premalignant BE.Implications: This study identified opportunities to improve early detection and treatment of patients with BE and esophageal adenocarcinoma. Mol Cancer Res; 15(11); 1558-69. ©2017 AACR.

Changes in gene expression of neo-squamous mucosa after endoscopic treatment for dysplastic Barrett's esophagus and intramucosal adenocarcinoma.

BACKGROUND: Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). OBJECTIVE: The purpose of this study was to investigate the molecular effects of endotherapy. METHODS: mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. RESULTS: Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. CONCLUSION: Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more "normal" profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.

The prognostic value of TP53 mutations in oesophageal adenocarcinoma: a systematic review and meta-analysis.

OBJECTIVE: To clarify the prognostic role of tumour protein 53 (TP53) mutations in patients with oesophageal adenocarcinoma (OAC) as there is a need for biomarkers that assist in guiding management for patients with OAC. DESIGN: A systematic review was conducted using MEDLINE, Embase, PubMed and Current Contents Connect to identify studies published between January 1990 and February 2015 of oesophageal cancer populations (with OAC diagnoses >50% of cases) that measured tumoural TP53 status and reported hazard ratios (HR), or adequate data for estimation of HR for survival for TP53-defined subgroups. Risk of bias for HR estimates was assessed using prespecified criteria for the appraisal of relevant domains as defined by the Cochrane Prognosis Methods Group including adherence to Grading of Recommendations, Assessment, Development and Evaluation and REporting recommendations for tumor MARKer prognostic studies guidelines, as well as assay method used (direct TP53 mutation assessment vs immunohistochemistry) and adjustment for standard prognostic factors. A pooled HR and 95% CI were calculated using a random-effects model. RESULTS: Sixteen eligible studies (11 with OAC only and 5 mixed histology cohorts) including 888 patients were identified. TP53 mutations were associated with reduced survival (HR 1.48, 95% CI 1.16 to 1.90, I2=33%). A greater prognostic effect was observed in a sensitivity analysis of those studies that reported survival for OAC-only cohorts and were assessed at low risk of bias (HR 2.11, 95% CI 1.35 to 3.31, I2=0%). CONCLUSIONS: Patients with OAC and TP53 gene mutations have reduced overall survival compared with patients without these mutations, and this effect is independent of tumour stage.

Effect of Laparoscopic Sleeve Gastrectomy on Fasting Gastrointestinal, Pancreatic, and Adipose-Derived Hormones and on Non-Esterified Fatty Acids.

BACKGROUND: Alterations in gastrointestinal, pancreatic, and adipose hormone levels may have a greater role in weight loss than initially appreciated. The laparoscopic sleeve gastrectomy (LSG) operation is now the most frequently performed bariatric operation in many countries, but there are relatively few data regarding its molecular effects. We sought to characterize the effect of LSG on fasting plasma levels of selected hormones and on non-esterified fatty acids (NEFA), and to compare these to levels in non-obese control individuals. MATERIALS AND METHODS: The levels of nine plasma hormones were measured using a multiplex bead-based assay at baseline and at 3 months after operation in 11 obese patients undergoing LSG. NEFA levels were also measured. The levels were compared to those for 22 age- and sex-matched non-obese individuals. RESULTS: At baseline, obese patients showed significantly higher expression of C-peptide, insulin, and leptin and significantly lower ghrelin, glucose-dependent insulinotropic peptide (GIP), and resistin compared to non-obese controls (p < 0.05). LSG resulted in a reduction in BMI from 42.5 ± 6.47 kg/m2 at operation to 35.2 ± 5.14 kg/m2 at 3 months (42 % mean excess weight loss, p < 0.001). LSG led to a significant decrease in ghrelin, glucagon-like peptide-1 (GLP-1), glucagon, leptin, plasminogen activator inhibitor-1 (PAI-1), and NEFA. CONCLUSION: LSG induces marked early changes in the fasting levels of factors thought to be important regulators of obesity and metabolic health. These changes differ somewhat from the findings for operations with a malabsorptive component, suggesting that subtle differences exist in the mechanisms of weight loss between LSG and other bariatric operations.