Once in a Bile - the Incidence of Bile Reflux Post-Bariatric Surgery.

PURPOSE: Excellent metabolic improvement following one anastomosis gastric bypass (OAGB) remains compromised by the risk of esophageal bile reflux and theoretical carcinogenic potential. No 'gold standard' investigation exists for esophageal bile reflux, with diverse methods employed in the few studies evaluating it post-obesity surgery. As such, data on the incidence and severity of esophageal bile reflux is limited, with comparative studies lacking. This study aims to use specifically tailored biliary scintigraphy and upper gastrointestinal endoscopy protocols to evaluate esophageal bile reflux after OAGB, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). METHODS: Fifty-eight participants underwent OAGB (20), SG (15) or RYGB (23) between November 2018 and July 2020. Pre-operative reflux symptom assessment and gastroscopy were performed and repeated post-operatively at 6 months along with biliary scintigraphy. RESULTS: Gastric reflux of bile was identified by biliary scintigraphy in 14 OAGB (70%), one RYGB (5%) and four SG participants (31%), with a mean of 2.9% (SD 1.5) reflux (% of total radioactivity). One participant (OAGB) demonstrated esophageal bile reflux. De novo macro- or microscopic gastroesophagitis occurred in 11 OAGB (58%), 8 SG (57%) and 7 RYGB (30%) participants. Thirteen participants had worsened reflux symptoms post-operatively (OAGB, 4; SG, 7; RYGB, 2). Scintigraphic esophageal bile reflux bore no statistical association with de novo gastroesophagitis or reflux symptoms. CONCLUSION: Despite high incidence of gastric bile reflux post-OAGB, esophageal bile reflux is rare. With scarce literature of tumour development post-OAGB, frequent low-volume gastric bile reflux likely bears little clinical consequence; however, longer-term studies are needed. CLINICAL TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry number ACTRN12618000806268.

Quantification of fluoroscopic fundoplication anatomy: inter- and intraobserver reliability.

The etiology of postfundoplication dysphagia remains incompletely understood. Subtle changes of gastroesophageal junction (GEJ) anatomy may be contributory. Barium swallows have potential for standardization to evaluate postsurgical anatomical features. Using structured barium swallows, we aim to identify reproducible, objectively measured postfundoplication anatomical features that will permit future comparison between patients with/without dysphagia. At 6-12 months of postfundoplication, 31 patients underwent structured barium swallow with video-fluoroscopy recording: standing anteroposterior; standing oblique (×2); prone oblique (×2); and prone oblique with continuous free drinking. A primary observer recorded 11 variables of GEJ anatomy for each view, repeated 3 months later, forming two datasets to assess intraobserver consistency. Interobserver reliability was determined using a dataset each from the primary observer and two medical students (after training). Intraclass correlation coefficients (ICC) were based on two-way mixed-effects model (ICC agreement: 0.40-0.59 'fair'; 0.60-0.74 'good'; 0.75-1.00 'excellent'). Interobserver reliability was good-excellent for 47 of 66 measurements. Measures of maximal esophageal diameter cf. wrap opening diameter and posterior esophageal angle showed high interobserver reproducibility on all views (ICC range 0.84-0.91; 0.68-0.80, respectively). Interobserver agreement was good-excellent for 5/6 views when measuring anterior GEJ displacement and axis deviation (ICC range 0.56-0.79; 0.41-0.77, respectively). Measures of wrap length showed lower reproducibility. Prone oblique measurements showed highest reproducibility (good-excellent agreement in 19/22 measurements). Intraobserver consistency was excellent for 98% of measurements (ICC range 0.74-0.99). Objective measurements of postfundoplication GEJ anatomy using structured barium swallow are reproducible and may allow further interrogation of anatomical features contributing to postfundoplication dysphagia.

HIDA and Seek: Challenges of Scintigraphy to Diagnose Bile Reflux Post-Bariatric Surgery.

INTRODUCTION: Oesophageal bile reflux after bariatric surgery may trigger development of Barrett's oesophagus. Gastro-oesophageal reflux of bile is captured by hepatobiliary iminodiacetic acid (HIDA) scintigraphy; however, anatomical and physiological changes after bariatric surgery warrant protocol modifications to optimise bile reflux detection. METHODS: HIDA scintigraphy occurred 6 months after either sleeve gastrectomy, Roux-en-Y gastric bypass or one-anastomosis gastric bypass. Standard HIDA scanning involves (i) 6-h fast and 24-h abstinence from opioids; (ii) IV administration of 99mTc di-isopropyl iminodiacetic acid; and (iii) dual anterior/posterior 60-min dynamic scanning of the duodenum, stomach and oesophagus. Three challenges were identified, and modifications were implemented, namely, (1) anatomical localisation of refluxed bile on planar scintigraphy was improved by adding a SPECT/CT for 3D imaging; (2) impaired cholecystokinin-controlled gallbladder emptying, following bypassed duodenum, was addressed by ingestion of a 'fatty meal'; and (3) intestinal hypomotility after gastric bypass was counteracted by longer scan duration (75-90 min) to allow bile to pass beyond the gastro-jejunal anastomosis. RESULTS: HIDA scan was undertaken in 18 patients, 13 of whom underwent the modified protocol. The tailored protocol ameliorated issues identified with the standard HIDA scan protocol; thus, accurate anatomical localisation was achieved in all patients, no delayed gallbladder emptying was observed, and bile was observed beyond the gastro-jejunal anastomosis in all gastric bypass patients. The modified technique was well tolerated by patients. CONCLUSION: A tailored HIDA scan protocol with addition of a SPECT-CT scan, ingestion of a fatty meal and prolonged scanning duration results in enhanced bile reflux detection in post-bariatric surgical patients.

Detecting Bile Reflux-the Enigma of Bariatric Surgery.

Duodeno-gastro-esophageal reflux, or bile reflux, is a condition for which there is no diagnostic gold standard, and it remains controversial in terms of carcinoma risk. This is pertinent in the context of an increasingly overweight population who are undergoing weight-loss operations that theoretically further increase the risk of bile reflux. This article reviews investigations for bile reflux based on efficacy, patient tolerability, cost, and infrastructure requirements. At this time, whilst no gold standard exists, hepatobiliary scintigraphy is the least invasive investigation with good-patient tolerability, sensitivity, and reproducibility to be considered first-line for diagnosis of bile reflux. This review will guide clinicians investigating bile reflux.

Thiol surface functionalization via continuous phase plasma polymerization of allyl mercaptan, with subsequent maleimide-linked conjugation of collagen.

Thiol groups can undergo a large variety of chemical reactions and are used in solution phase to conjugate many bioactive molecules. Previous research on solid substrates with continuous phase glow discharge polymerization of thiol-containing monomers may have been compromised by oxidation. Thiol surface functionalization via glow discharge polymerization has been reported as requiring pulsing. Herein, continuous phase glow discharge polymerization of allyl mercaptan (2-propene-1-thiol) was used to generate significant densities of thiol groups on a mixed macrodiol polyurethane and tantalum. Three general classes of chemistry are used to conjugate proteins to thiol groups, with maleimide linkers being used most commonly. Here the pH specificity of maleimide reactions was used effectively to conjugate surface-bound thiol groups to amine groups in collagen. XPS demonstrated surface-bound thiol groups without evidence of oxidation, along with the subsequent presence of maleimide and collagen. Glow discharge reactor parameters were optimized by testing the resistance of bound collagen to degradation by 8 M urea. The nature of the chemical bonding of collagen to surface thiol groups was effectively assessed by colorimetric assay (ELISA) of residual collagen after incubation in 8 M urea over 8 days and after incubation with keratinocytes over 15 days. The facile creation of useable solid-supported thiol groups via continuous phase glow discharge polymerization of allyl mercaptan opens a route for attaching a vast array of bioactive molecules. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1940-1948, 2017.

Surface-bound collagen 4 is significantly more stable than collagen 1.

Collagen 1 (C1) is commonly used to improve biological responses to implant surfaces. Here, the stability of C1 was compared with collagen 4 (C4) on a mixed macrodiol polyurethane, both adsorbed and covalently bound via acetaldehyde glow discharge polymerization and reductive amination. Substrate specimens were incubated in solutions of C1 and C4. The strength of conjugation was tested by incubation in 8 M urea followed by enzyme linked immunosorbent assays to measure residual C1 and C4. The basal lamina protein, laminin-332 (L332) was superimposed via adsorption on C4-treated specimens. Keratinocytes were grown on untreated, C1-treated, C4-treated, and C4 + L332-treated specimens, followed by measurement of cell area, proliferation, and focal adhesion density. Adsorbed C4 was shown to be significantly more stable than C1 and covalent conjugation conferred even greater stability, with no degradation of C4 over twenty days in 8 M urea. Cell growth was similar for C1 and C4, with no additional benefit conferred by superimposition of L332. The greater resistance of C4 to degradation may be consequent to cysteine residues and disulphide bonds in its non-collagenous domains. The use of C4 on implants, rather than C1, may improve their long-term stability in tissues. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1364-1373, 2017.

Toward a skin-material interface with vacuum-integrated capped macroporous scaffolds.

Avulsion, epidermal marsupialization, and infection cause failure at the skin-material interface. A robust interface would permit implantable robotics, prosthetics, and other medical devices; reconstruction of surgical defects, and long-term access to blood vessels and body cavities. Torus-shaped cap-scaffold structures were designed to work in conjunction with negative pressure to address the three causes of failure. Six wounds were made on the backs of each of four 3-month old pigs. Four unmodified (no caps) scaffolds were implanted along with 20 cap-scaffolds. Collagen type 4 was attached to 21 implants. Negative pressure then was applied. Structures were explanted and assessed histologically at day 7 and day 28. At day 28, there was close tissue apposition to scaffolds, without detectable reactions from defensive or interfering cells. Three cap-scaffolds explanted at day 28 showed likely attachment of epidermis to the cap or cap-scaffold junction, without deeper marsupialization. The combination of toric-shaped cap-scaffolds with negative pressure appears to be an intrinsically biocompatible system, enabling a robust skin-material interface. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1307-1318, 2017.

Australian and New Zealand Audit of Surgical Mortality: concordance between reported and audited clinical events and delays in management in surgical mortality patients.

BACKGROUND: The Australian and New Zealand Audit of Surgical Mortality (ANZASM) is a nationwide confidential peer review of deaths associated with surgical care. This study assesses the concordance between treating surgeons and peer reviewers in reporting clinical events and delays in management. METHODS: This is a retrospective cross-sectional analysis of deaths in 2009 and 2010. Cases that went through the process of submission of details by the surgeon in a structured surgical case form (SCF), first-line assessment (FLA) and a more detailed second-line assessment (SLA) were included. Significant clinical events reported for these patients were categorized and analysed for concordance. RESULTS: Of the 11,303 notifications of death to the ANZASM, 6507 (57.6%) were audited and 685 (10.5%) required the entire review process. Nationally, the most significant events were post-operative complications, poor preoperative assessment and delay to surgery or diagnosis. The SCF submissions reported 338 events, as compared with 1009 and 985 events reported through FLA and SLA, respectively (P = 0.01). Treating surgeons and assessors attributed 29-30% of events to factors outside the surgeon's control. Surgeons felt that delay to surgery or diagnosis was a significant event in 6.6% of cases, in contrast to 20% by assessors (P = 0.01). Preoperative management could be improved in 19% of cases according to surgeons, compared with 45 and 36% according to the assessors (P < 0.001). CONCLUSION: There is significant discordance between treating surgeons and assessors. This suggests the need for in-depth analysis and possible refinement of the audit process.

Symptoms, investigations and management of patients with cancer of the oesophagus and gastro-oesophageal junction in Australia.

OBJECTIVE: To document presenting symptoms, investigations and management for Australian patients with oesophageal adenocarcinoma (OAC), gastro-oesophageal junction adenocarcinoma (GOJAC) and oesophageal squamous cell carcinoma (OSCC). DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of a population-based sample of 1100 Australian patients aged 18-79 years with histologically confirmed oesophageal cancer diagnosed in 2002-2005, using data from cancer registries and treatment centres, supplemented with clinical information collected through medical record review in 2006-2007 and mortality information collected in 2008. MAIN OUTCOME MEASURES: Prevalence of primary symptoms, and staging investigations and treatment modalities used. RESULTS: The primary presenting symptom was dysphagia, which was self-reported by 41%, 39% and 48% of patients with OAC, GOJAC and OSCC, respectively. Less common symptoms were reflux, chest pain, bleeding and weight loss. All patients underwent endoscopy, most had a staging computed tomography scan (OAC 93%, GOJAC 95% and OSCC 93%), and about half had positron emission tomography scans (OAC 51%, GOJAC 44% and OSCC 42%). Pretreatment tumour stage was reported in 25% of records, and could be derived from results of investigations in a further 23%, but the remaining half lacked sufficient information to ascribe a pretreatment stage. Curative treatments were attempted for 60% of OAC, 88% of GOJAC and 65% of OSCC patients. Surgery was performed on 52% of OAC, 83% of GOJAC and 41% of OSCC patients. About two-thirds of surgical patients received additional therapies. CONCLUSIONS: With anticipated increases in oesophageal cancer incidence, the resources required to diagnose and manage patients with oesphageal cancer are also likely to rise. Our data provide a baseline from which to plan for the future care of patients with cancers of the oesophagus.

Tissue compatibility of biomaterials: benefits and problems of skin biointegration.

The integration of biomaterials with skin is necessary to enable infection-free access to vasculature and body cavities. Also, integrating plastics and metals with skin increases options for the reconstruction of surgical and traumatic defects and enables the permanent implantation of robotic and electronic devices. Until now, attempts to integrate biomaterials with skin permanently have failed because of epidermal marsupialization and infection. This article reviews the general properties required of biomaterials to optimize integration with body tissues, the modifications that increase biocompatibility, focusing particularly on surface functionalization and the specific requirements for biomaterial integration into skin. Critical pathophysiological processes relating to biocompatibility are discussed with particular emphasis on the skin-biomaterial interface. Future directions are speculated on, in particular, the specific utility of subatmospheric pressure dressings in facilitating tissue integration into biomaterials.

Improvement of respiratory symptoms following laparoscopic Nissen fundoplication.

BACKGROUND: Laparoscopic fundoplication has become the standard of care for the management of symptomatic gastro-oesophageal reflux disease (GORD). Although atypical and respiratory symptoms are frequently described in standard texts in association with reflux, the response of respiratory symptoms to management of GORD has not been extensively studied. METHODS: Herein is reported a prospective series of 29 patients who presented with predominantly respiratory symptoms. Typical and respiratory symptoms were graded according to a standard scale. All patients had preoperative investigations confirming GORD. These patients were treated by a laparoscopic Nissen fundoplication and followed up for a minimum of 14 months (range: 14-48 months). Patients were contacted and interviewed by an independent observer. RESULTS: Conversion to open surgery was necessary in three patients. There were four significant complications. Ultimately control of typical reflux symptoms was achieved in 88%. Cough was completely relieved in 81% and improved in a further 13%. Wheeze and nocturnal bronchospasm was completely relieved in 50% and improved in the balance. Dysphagia remains a significant problem, with only 42% of patients completely free of trouble. CONCLUSIONS: Overall the respiratory symptoms were improved in the majority of patients, with cough responding somewhat better than wheeze. Appropriate patient selection remains the greatest challenge when a patient with cough or wheeze that is considered to be due to GORD is referred for surgery.