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1.
Cureus ; 15(2): e34702, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36909114

ABSTRACT

Robotic single-site hysterectomy (RSSH) has emerged as a novel surgical approach for the treatment of endometrial cancer and atypical endometrial hyperplasia (AEH). Current research regarding the benefits of RSSH compared to robotic multiport hysterectomy (RMPH) for these indications has been inconclusive. Our team sought to compare surgical outcomes between these two approaches of robotic hysterectomy via systematic review and meta-analysis to ensure optimal surgical practices. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Checklist guided our review. MEDLINE, Clinicaltrials.gov, and Cochrane Library were searched, yielding 59 results. Articles were filtered by title and abstract and then reviewed in full for inclusion and exclusion criteria. Inclusion criteria required that (1) studies compared outcomes for RSSH and RMPH, (2) hysterectomy was indicated for endometrial cancer or hyperplasia with atypia, and (3) studies were available in English. Excluded studies (1) compared single-site and multiport laparoscopic approaches, (2) compared robotic approaches to laparoscopic or abdominal (open) techniques, and (3) employed hysterectomy for benign conditions. Publication bias was assessed using the Egger Regression Correlation analysis. Four studies complied with the selection criteria, comprising 138 patients in the RSSH group and 259 in the RMPH group. Similar outcomes were noted across all measures, including conversion rate (relative risk [RR] = 1.84 and confidence interval [CI] = 0.99-3.43), blood loss (Cohen's d = 1.05 and Z = 18.62), operating time (Cohen's d = 0.29 and Z = 4.38), and length of hospital stay (Cohen's d = 1.06 and Z = 3.86). Publication bias was deemed minimal as indicated by Egger regression values of less than 0.05. These findings suggest that either a surgical approach or AEH with the proper standard of care can provide patients with endometrial cancer.

2.
Cureus ; 14(9): e29070, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36259006

ABSTRACT

Research evaluating optimal repair techniques for the reduction of postpartum dyspareunia following obstetric laceration is severely limited. Prevailing guidelines from the American College of Obstetricians and Gynecologists (ACOG) are reliant on data from just nine clinical trials conducted from 1980 to 2012. While the literature on this topic is still limited today, this review aims to synthesize data from past and present studies to ensure that standing clinical recommendations are supported by current literature. A review was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane Library, and Google Scholar were searched. Included articles (1) compared continuous with interrupted repair techniques for subjects with episiotomies and/or second-degree tears, (2) were available in full length, and (3) reported dyspareunia as an outcome variable. Excluded articles were those (1) inclusive of first-, third-, or fourth-degree tears; (2) comparing suture material rather than technique; and (3) not available in English. A meta-analysis was conducted for both acute dyspareunia (<3 months) and chronic dyspareunia (>3 months) utilizing Meta-Essentials Microsoft Excel (Microsoft Corp., Redmond, WA) workbook. Bias was evaluated via Egger regression and Begg and Mazumdar rank correlation tests. Twelve articles met inclusion and exclusion guidelines, seven for acute dyspareunia and eight for chronic dyspareunia. All publications were randomized controlled trials and were inclusive of a total of 4,081 patients. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random effect model. Analysis revealed no statistically significant difference between continuous and interrupted suture groups for acute dyspareunia (RR: 0.98; 95% CI: 0.89-1.08) or chronic dyspareunia (RR: 0.96; 95% CI: 0.83-1.12). Egger regression test (p-value=0.534) and Begg and Mazumdar rank correlation test (p-value=0.570) indicated minimal publication bias. Compiled data does not indicate a preferential suture technique for the reduction of postpartum dyspareunia. These findings are congruent with the ACOG guidelines; therefore, there is no supporting evidence for ACOG's recommendation of continuous suturing to be overturned.

3.
Eur J Gastroenterol Hepatol ; 33(6): 852-858, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33136721

ABSTRACT

BACKGROUND: Endoscopic full-thickness resection (eFTR) of the colon using the full-thickness resection device (FTRD) is a novel method for removing lesions involving, or tethered to, deeper layers of the colonic wall. The UK FTRD Registry collected data from multiple centres performing this procedure. We describe the technical feasibility, safety and early outcomes of this technique in the UK. METHODS: Data were collected and analysed on 68 patients who underwent eFTR at 11 UK centres from April 2015 to June 2019. Outcome measures were technical success, procedural time, specimen size, R0 resection, endoscopic clearance, and adverse events. Reported technical difficulties were collated. RESULTS: Indications for eFTR included non-lifting polyps (29 cases), T1 tumour resection (13), subepithelial tumour (9), and polyps at the appendix base or diverticulum (17). Target lesion resection was achieved in 60/68 (88.2%). Median specimen size was 21.7 mm (10-35 mm). Histologically confirmed R0 resection was achieved in 43/56 (76.8%) with full-thickness resection in 52/56 (92.9%). Technical difficulties occurred in 17/68 (25%) and complications in 3/68 (5.9%) patients. CONCLUSION: eFTR is a useful technique with a high success rate in treating lesions not previously amenable to endoscopic therapy. Whilst technical difficulties may arise, complication rates are low and outcomes are acceptable, making eFTR a viable alternative to surgery for some specific lesions.


Subject(s)
Adenoma , Rectum , Colon , Humans , Registries , Retrospective Studies , Treatment Outcome , United Kingdom/epidemiology
5.
Gut ; 67(6): 1000-1023, 2018 06.
Article in English | MEDLINE | ID: mdl-29478034

ABSTRACT

These are updated guidelines which supersede the original version published in 2004. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG. The original guidelines have undergone extensive revision by the 16 members of the Guideline Development Group with representation from individuals across all relevant disciplines, including the Heartburn Cancer UK charity, a nursing representative and a patient representative. The methodological rigour and transparency of the guideline development processes were appraised using the revised Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.Dilatation of the oesophagus is a relatively high-risk intervention, and is required by an increasing range of disease states. Moreover, there is scarcity of evidence in the literature to guide clinicians on how to safely perform this procedure. These guidelines deal specifically with the dilatation procedure using balloon or bougie devices as a primary treatment strategy for non-malignant narrowing of the oesophagus. The use of stents is outside the remit of this paper; however, for cases of dilatation failure, alternative techniques-including stents-will be listed. The guideline is divided into the following subheadings: (1) patient preparation; (2) the dilatation procedure; (3) aftercare and (4) disease-specific considerations. A systematic literature search was performed. The Grading of Recommendations Assessment, Develop-ment and Evaluation (GRADE) tool was used to evaluate the quality of evidence and decide on the strength of recommendations made.


Subject(s)
Dilatation/methods , Endoscopy/methods , Esophageal Stenosis/surgery , Esophagus/surgery , Dilatation/adverse effects , Esophagus/pathology , Humans , United Kingdom
6.
Indian J Pharmacol ; 49(2): 161-167, 2017.
Article in English | MEDLINE | ID: mdl-28706329

ABSTRACT

OBJECTIVES: The objective of this study is to evaluate the beneficial effect of karanjin for the treatment of experimental colitis. METHODS: Colitis was induced in the Balb/c mice by rectal administration of 2% solution of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in 50% methanol. Karanjin (>98% pure) was administered in two different concentrations 100 and 200 mg/kg and sulfasalazine (100 mg/kg) as reference for 7 consecutive days to colitic mice. On the 8 day, mice were euthanized and degree of inflammation was assessed by macroscopic, microscopic, histology and biochemical estimation of myeloperoxidase (MPO), nitric oxide (NO), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) level were measured. RESULTS: Karanjin significantly and dose dependently ameliorate the macroscopic damage, histological changes such as cellular infiltration, tissue necrosis, mucosal and submucosal damage as compared to the TNBS control group. Karanjin reduces the activity of MPO, depressed MDA, and NO level and helps in restoring the level of CAT, SOD, and GSH to normal when compared to the TNBS colitis group. CONCLUSION: Result of the present study indicates that karanjin has the potential to cure colitis induced by intracolonic administration of TNBS.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Benzopyrans/therapeutic use , Colitis/drug therapy , Animals , Anti-Inflammatory Agents/pharmacology , Benzopyrans/pharmacology , Catalase/metabolism , Colitis/chemically induced , Colitis/metabolism , Colon/drug effects , Colon/metabolism , Glutathione/metabolism , Malondialdehyde/metabolism , Mice, Inbred BALB C , Nitric Oxide/metabolism , Peroxidase/metabolism , Superoxide Dismutase/metabolism , Trinitrobenzenesulfonic Acid
8.
Gastrointest Endosc ; 83(5): 889-895.e1, 2016 May.
Article in English | MEDLINE | ID: mdl-26405045

ABSTRACT

BACKGROUND AND AIMS: Capsule endoscopy for visualization of the upper GI tract has thus far been experimental and potentially expensive. Our aim was to demonstrate the maneuverability and evaluate the ability to completely visualize and maintain views in the upper GI tract by using a simple magnetic-assisted capsule endoscopy (MACE) system. METHODS: Twenty-six volunteers were recruited. The hand-held magnet was placed at strategic points on the body surface and rotated to hold and maneuver the capsule. The ability to view the upper GI tract landmarks was noted: esophagogastric junction (EGJ), cardia, fundus, body, incisura, antrum, and pylorus. Control was assessed by the ability to hold the capsule for 1 minute at 5 positions: the lower esophagus and 4 designated positions in the proximal and distal stomach and also traversing the stomach and through the pylorus. Volunteers subsequently underwent a standard gastroscopy. RESULTS: The median data are as follows: age, 38 years (range 26-45 years); BMI, 24 (range 19-38); and procedure time, 24 minutes (range 12-39 minutes). Successful visualization of each landmark was EGJ, 92%; cardia, 88%; fundus, 96%; body, 100%; incisura, 96%; antrum, 96%; and pylorus, 100%; with fewer clear views of the EGJ and fundus. The capsule could be held in 88% of designated positions for 1 minute, moved from the fundus to the antrum in all cases, and traversed the pylorus in 50% (n = 13). An age of 40 years and older was associated with successful pyloric traversing (P = .04). There was positive concordance for 8 of 9 minor pathological findings on standard gastroscopy. CONCLUSION: MACE in the upper GI tract is feasible. There is a high degree of visualization and control, with some improvement required for optimizing proximal gastric views and traversing the pylorus.


Subject(s)
Capsule Endoscopy/instrumentation , Esophagus/diagnostic imaging , Magnets , Stomach/diagnostic imaging , Adult , Capsule Endoscopy/methods , Cardia/diagnostic imaging , Esophagogastric Junction/diagnostic imaging , Gastric Fundus/drug effects , Gastritis/diagnostic imaging , Gastroscopy , Healthy Volunteers , Humans , Male , Middle Aged , Pyloric Antrum/diagnostic imaging
10.
Endoscopy ; 47(11): 980-7, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26126159

ABSTRACT

BACKGROUND AND STUDY AIM: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. PATIENTS AND METHODS: Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. RESULTS: A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; P < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; P = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; P = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (P = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (P = 0.01). CONCLUSION: The Registry reports on endoscopic therapy for Barrett's neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.


Subject(s)
Adenocarcinoma/surgery , Barrett Esophagus/surgery , Catheter Ablation , Esophageal Neoplasms/surgery , Esophagus/surgery , Precancerous Conditions/surgery , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Barrett Esophagus/pathology , Esophageal Neoplasms/pathology , Esophagoscopy , Esophagus/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Mucous Membrane/pathology , Mucous Membrane/surgery , Precancerous Conditions/pathology , Registries , Treatment Outcome , United Kingdom
11.
Comput Biol Med ; 65: 359-63, 2015 Oct 01.
Article in English | MEDLINE | ID: mdl-25934086

ABSTRACT

Examination of the upper gastrointestinal tract by a standard endoscope is often thought as a daunting experience to many who have undertaken or are about to undergo the procedure. The overall perceived size of the gastroscope, unpleasantness of stimulation of the gag reflex and the need often for sedation is discouraging to many. A method to visualise the upper gastrointestinal mucosa which negates the need for sedation, the associated expensive decontamination costs and the possibility of having a community based examination would be particularly welcoming to this endoscopy field. Since the first swallow of a capsule endoscope by a human volunteer in 1999, their usage for examining the small bowel has exponentially grown to that of over a million patients worldwide. More recently, innovation in this field have shown plausibility for its use to visualise the upper gastrointestinal tract, with the integration of magnets within the capsule the most promising method.


Subject(s)
Capsule Endoscopy/instrumentation , Capsule Endoscopy/methods , Magnetic Phenomena , Humans
12.
Indian J Pharmacol ; 47(2): 153-9, 2015.
Article in English | MEDLINE | ID: mdl-25878373

ABSTRACT

OBJECTIVES: To study the effects of two different classes of drugs in sephadex-induced lung inflammation using rats and explore the potential mechanism (s). MATERIALS AND METHODS: Effects of dexamethasone (0.3 mg/kg, p.o.) and rosiglitazone (10 mg/kg, p.o.) treatments were evaluated up to 3 days in sephadex challenged rats. 72 h postsephadex administration, broncho-alveolar lavage fluid (BALF) was collected for cell count and cytokine estimation. Lung tissues were harvested for gene expression and histopathology. RESULTS: Dexamethasone treatment resulted in significant inhibition of lymphocytes, monocytes, eosinophils and neutrophils, whereas rosiglitazone inhibited eosinophils and neutrophils only. Further, dexamethasone reduced the elevated levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) after sephadex challenge while rosiglitazone significantly reduced the PGE2 levels without altering LTB4 in the BALF. Hydroxyproline content in rat lung homogenate was significantly reduced with dexamethasone treatment but not with rosiglitazone. Both the drugs were found to suppress matrix metallo proteinase 9, whereas only dexamethasone showed inhibition of tumor necrosis factor-alpha and up-regulation of tissue inhibitor of metalloproteinase 3 (TIMP-3) expression and preserved the broncho-alveolar microstructure. CONCLUSIONS: Our results revealed that up-regulation of TIMP-3 corroborated well with dexamethasone mediated inhibition of collagen degradation and restoration of alveolar micro-architecture.


Subject(s)
Dexamethasone/therapeutic use , Dextrans/administration & dosage , Lung/drug effects , Pneumonia/drug therapy , Thiazolidinediones/therapeutic use , Tissue Inhibitor of Metalloproteinase-3/metabolism , Animals , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Cytokines/analysis , Dexamethasone/administration & dosage , Disease Models, Animal , Gene Expression/drug effects , Hydroxyproline/metabolism , Leukocyte Count , Lung/immunology , Lung/metabolism , Male , PPAR gamma/agonists , Pneumonia/chemically induced , Pneumonia/enzymology , Rats, Wistar , Receptors, Glucocorticoid/agonists , Reverse Transcriptase Polymerase Chain Reaction , Rosiglitazone , Thiazolidinediones/administration & dosage , Tissue Inhibitor of Metalloproteinase-3/genetics
13.
Eur J Gastroenterol Hepatol ; 27(4): 460-6, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25874522

ABSTRACT

BACKGROUND AND AIMS: This study used computed tomography modelling of the abdomen to determine the optimal placements of a magnetic capsule endoscope in the stomach that allows complete mucosal visualization and determined the optimal placement of the handheld magnet to aid pyloric traversing. MATERIALS AND METHODS: Using multiplanar reformatting, 100 abdominal computed tomography scans were analysed to assess gastric luminal visualization by a capsule endoscope from five fixed stations throughout the stomach. From each station, we assessed the ability of a capsule endoscope to visualize six gastric landmarks. The pyloric canal angles were calculated to create a vector. We mapped the position of this vector on the patient to determine the optimal placement of the magnet that would aid pyloric traversing. RESULTS: Complete visualization of the stomach (viewing all landmarks) was only achievable in up to 29% of cases when viewed from a sole station. Maximal visualization required combining stations. Fundal dependent (station 1) and opposite antral dependent (station 4) was the best, achieving visualization in 85% (P<0.01). The optimal positioning of the magnet to aid pyloric traversing was posteriorly between vertebrae T5 and L2 in an area 10 cm to the left and 18 cm to the right (83% cases). Age older than 55 years (P=0.03) and the ability to view the pylorus from station 3 (P=0.04) were associated with an extreme pyloric vector. CONCLUSION: Although there is some extreme variation in the upper gastrointestinal anatomy, the majority of cases will allow the use of a single standard method in performing MACE, which may be very useful for screening purposes.


Subject(s)
Capsule Endoscopes , Capsule Endoscopy/methods , Magnets , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Anatomic Landmarks , Capsule Endoscopy/instrumentation , Female , Humans , Male , Middle Aged , Retrospective Studies , Stomach/anatomy & histology , Stomach/diagnostic imaging
14.
World J Gastrointest Endosc ; 7(3): 169-82, 2015 Mar 16.
Article in English | MEDLINE | ID: mdl-25789087

ABSTRACT

Since the first report of use of endoscopy in children in the 1970s, there has seen an exponential growth in published experience and innovation in the field. In this review article we focus on modern age therapeutic endoscopy practice, explaining use of traditional as well as new and innovative techniques, for diagnosis and treatment of diseases in the paediatric upper gastrointestinal tract.

15.
Indian J Pharmacol ; 47(1): 80-5, 2015.
Article in English | MEDLINE | ID: mdl-25821316

ABSTRACT

OBJECTIVES: The aim was to investigate the nephroprotective effect of combination of aliskiren (ASK), a direct renin inhibitor and pentoxifylline (PTX), inhibitor of tumor necrotic factor-alpha (TNF-alpha), in rat remnant kidney model of chronic kidney disease (CKD). MATERIALS AND METHODS: Nephrectomized (NPX) rats were treated with ASK (10 mg/kg, p.o.), PTX (100 mg/kg, p.o.), and combination of PTX + ASK once daily for 28 days. We have performed analysis of various renal injury parameters after 4 weeks of treatment. RESULTS: Treatment with PTX, ASK and combination showed significant improvement in urea, creatinine and total protein in plasma when compared with vehicle treated group in NPX rats. ASK and combination of PTX + ASK elicited significant reduction in blood pressure but PTX alone did not produce blood pressure reduction. ASK treatment showed significant elevation in TNF-alpha, whereas PTX and ASK + PTX showed significant reduction in TNF-alpha in plasma. Histopathologically, the extent of the kidney injury was similar in NPX + vehicle and NPX + ASK-treated rats. PTX and ASK + PTX-treated group showed lesser extent of kidney injury. There was good correlation of mRNA expression levels of kidney injury molecule-1 and bradykinin B1 receptor data with histopathological findings in kidney samples and elevated TNF-alpha levels in plasma. CONCLUSIONS: We conclude that combination of PTX + ASK may be better therapeutic intervention for nephroprotection in CKD patients.


Subject(s)
Amides/pharmacology , Fumarates/pharmacology , Kidney Failure, Chronic/drug therapy , Kidney/drug effects , Nephrectomy , Pentoxifylline/pharmacology , Animals , Arterial Pressure/drug effects , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Creatinine/blood , Disease Models, Animal , Drug Therapy, Combination , Kidney/metabolism , Kidney/pathology , Kidney/physiopathology , Kidney Failure, Chronic/genetics , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/physiopathology , Male , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Receptor, Bradykinin B1/genetics , Receptor, Bradykinin B1/metabolism , Renin/antagonists & inhibitors , Renin/metabolism , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/blood , Urea/blood
16.
Endoscopy ; 47(7): 650-3, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25625696

ABSTRACT

BACKGROUND AND STUDY AIMS: Capsule endoscopy is well tolerated but control of its movement is needed in order to visualize the whole gastric surface. Technological developments have produced an external magnet to allow manipulation of the capsule within the gastric cavity. The aim of this study was to compare magnetically steerable gastric capsule endoscopy (MSGCE) with flexible endoscopy for the detection of beads in a porcine stomach. MATERIALS AND METHODS: Beads were sewn onto the mucosal surface of 12 ex vivo porcine stomachs. Each model was examined by flexible endoscopy and MSGCE by two blinded investigators. MSGCE was performed according to a protocol using positional changes and magnetic steering. Outcome measures were number and location of beads identified, and duration of procedure. RESULTS: Flexible endoscopy identified 79 /90 beads (88 %), and MSGCE identified 80 /90 (89 %). The difference in sensitivities was 1.11 (95 % confidence interval 0.06 - 28.26). Thus, MSGCE was noninferior to flexible endoscopy. Mean examination times for flexible endoscopy and MSGCE were 3.34 minutes and 9.90 minutes, respectively. CONCLUSION: MSGCE was equivalent to conventional flexible endoscopy in the detection of beads in a porcine stomach model.


Subject(s)
Capsule Endoscopy/methods , Gastroscopy/methods , Magnets , Animals , Capsule Endoscopy/instrumentation , Gastroscopy/instrumentation , Random Allocation , Single-Blind Method , Swine
17.
World J Gastrointest Endosc ; 7(19): 1306-10, 2015 Dec 25.
Article in English | MEDLINE | ID: mdl-26722611

ABSTRACT

Methods to assess, access and treat pathology within the gastrointestinal tract continue to evolve with video endoscopy replacing radiology as the gold standard. Whilst endoscope technology develops further with the advent of newer higher resolution chips, an array of adjuncts has been developed to enhance endoscopy in other ways; most notable is the use of magnets. Magnets are utilised in many areas, ranging from endoscopic training, lesion resection, aiding manoeuvrability of capsule endoscopes, to assisting in easy placement of tubes for nutritional feeding. Some of these are still at an experimental stage, whilst others are being increasingly incorporated in our everyday practice.

18.
Gastroenterology ; 148(2): 367-78, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25447851

ABSTRACT

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.


Subject(s)
Barrett Esophagus/genetics , Bone Morphogenetic Proteins/genetics , Genetic Predisposition to Disease , Growth Differentiation Factors/genetics , Polymorphism, Single Nucleotide , T-Box Domain Proteins/genetics , Barrett Esophagus/etiology , Esophageal Neoplasms/genetics , Genome-Wide Association Study , Humans , Risk
19.
Gut ; 63(1): 7-42, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24165758

ABSTRACT

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia.


Subject(s)
Barrett Esophagus , Ablation Techniques , Adenocarcinoma/diagnosis , Adenocarcinoma/economics , Adenocarcinoma/etiology , Adenocarcinoma/therapy , Barrett Esophagus/complications , Barrett Esophagus/diagnosis , Barrett Esophagus/economics , Barrett Esophagus/therapy , Biopsy , Cost-Benefit Analysis , Decision Support Techniques , Early Detection of Cancer/economics , Early Detection of Cancer/methods , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/economics , Esophageal Neoplasms/etiology , Esophageal Neoplasms/therapy , Esophagectomy , Esophagoscopy/economics , Esophagoscopy/methods , Esophagus/pathology , Esophagus/surgery , Humans , Risk Assessment/methods , Risk Factors , United Kingdom , United States
20.
Eur J Gastroenterol Hepatol ; 25(7): 778-83, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23739279

ABSTRACT

OBJECTIVES: Diagnostic gastroscopy provides a unique opportunity to diagnose early oesophagogastric neoplasia; however, intraluminal mucus and bile can obscure mucosal visualization. The aim of this study was to determine whether the use of a premedication solution containing the mucolytic agent N-acetylcysteine and the surfactant simethicone improves mucosal visualization within a UK diagnostic gastroscopy service. MATERIALS AND METHODS: A total of 75 consecutive patients were recruited from a single (S.J.) endoscopist's diagnostic gastroscopy list. They were randomized into three treatment groups: (a) standard control=clear fluids only for 6 h, nil by mouth for 2 h; (b) water control=standard control+100 ml sterile water (given 20 min before gastroscopy); and (c) solution=standard control+100 ml investigated solution (20 min before gastroscopy). The endoscopist was blinded to patient preparation. Inadequate mucosal visualization was defined as fluid/mucus during gastroscopy that could not be suctioned and required flushing with water. The volume of flush, the site at which it was used and the total procedure times were recorded. RESULTS: All three groups showed no statistical difference for age, sex ratio, procedure priority or indication. The mean volume of flush required to obtain clear mucosa was significantly less in the solution group compared with the other groups. The mean overall procedure time was also less in the solution group compared with the other groups. DISCUSSION: Premedication with N-acetylcysteine and simethicone markedly improves mucosal visibility during gastroscopy. It also reduces the time taken for the procedure. This low-cost and well-tolerated intervention may improve detection of early neoplasia.


Subject(s)
Acetylcysteine/administration & dosage , Duodenum/pathology , Endoscopy, Digestive System , Esophagogastric Junction/pathology , Expectorants/administration & dosage , Gastric Mucosa/pathology , Intestinal Mucosa/pathology , Premedication , Simethicone/administration & dosage , Surface-Active Agents/administration & dosage , Acetylcysteine/adverse effects , Adult , Aged , Chi-Square Distribution , Duodenum/metabolism , England , Esophagogastric Junction/metabolism , Expectorants/adverse effects , Female , Gastric Mucosa/metabolism , Humans , Intestinal Mucosa/metabolism , Male , Middle Aged , Mucus/metabolism , Predictive Value of Tests , Premedication/adverse effects , Simethicone/adverse effects , Surface-Active Agents/adverse effects , Therapeutic Irrigation , Time Factors , Young Adult
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