Search

We present an unusual case of Candida albicans costochondritis after a complicated Ivor Lewis esophagectomy. This case exhibits that pain, erythema, and swelling over the costal cartilages should alert the possibility of infective costochondritis, especially in a postoperative patient. If a fungal agent is identified, aggressive surgical debridement and early commencement of antifungal therapy are likely determinants for a satisfactory outcome.

Purpose: Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach., Methods: Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45-50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity., Results: Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significantly elevated (2.05-fold, p = 0.025) in the toxic group (n = 12) compared to the non-toxic group (n = 19). Nausea and vomiting was the most commonly documented severe toxicity. No associations between toxicity and response, age, sex, histology, or treatment were evident., Conclusions: This study supports evidence of TNF as a predictive biomarker in regimen-related gastrointestinal toxicity. Confirming these findings in a larger cohort is warranted.

Background: Previous trials show good outcomes following anterior and posterior partial versus Nissen fundoplication for gastro-oesophageal reflux. However, it is unclear which partial fundoplication performs best. This study compared anterior 180° versus posterior 270° fundoplication., Methods: At three hospitals, patients were randomized to anterior 180° versus posterior 270° partial fundoplication, and clinical outcomes were determined using a structured questionnaire at 3, 6 and 12 months. Heartburn, dysphagia and satisfaction were assessed using 0-10 analoue scales, and adverse outcomes and side effects were determined. Endoscopy, manometry and pH monitoring were performed 6 months after surgery., Results: Forty-seven patients were randomized to anterior (n = 23) versus posterior (n = 24) fundoplication. Clinical outcomes for 93-98% of patients were available at each follow-up point. At 12 months, the mean heartburn score was higher following anterior fundoplication (2.7 versus 0.8, P = 0.045), although differences were not significant at earlier follow-up. Conversely, following posterior fundoplication, patients were less able to belch at 3 (56% versus 16%, P = 0.013) and 6 months (43% versus 9%, P = 0.017). No significant differences were demonstrated for dysphagia. Both groups had high rates of satisfaction with the outcome - 85% versus 86% satisfied at 12 months follow-up., Conclusion: Both partial fundoplications are effective treatments for gastro-oesophageal reflux. Posterior partial fundoplication is associated with less reflux symptoms offset by more side effects., (© 2013 Royal Australasian College of Surgeons.)

Background: Radiological follow-up following repair of large hiatus hernias have identified recurrence rates of 20-30%, although most are small and asymptomatic. Whether patients will eventually develop clinical problems is uncertain. This study evaluated the outcome for individuals identified with an asymptomatic hiatus hernia following previous repair vs. asymptomatic controls., Methods: One hundred fifteen asymptomatic patients who had previously undergone sutured repair of a large hiatus hernia and then underwent barium meal X-ray 6-60 months after surgery within a clinical trial were identified and divided into two cohorts: with (n = 41) vs. without (n = 74) an asymptomatic hernia. Heartburn, dysphagia, and satisfaction with surgery were assessed prospectively using a standardized questionnaire applying analogue scales. Consumption of antisecretory medication and revision surgery were also determined. To determine the natural history of asymptomatic recurrent hiatus hernia, outcomes for the two groups were compared at 1 and 5 years and at most recent (late) follow-up., Results: Outcomes were available at 1 year for 98.2% and 5 years or the latest follow-up (range 6-237 months) for 100%. Heartburn and dysphagia scores were low and satisfaction scores high in both groups at all follow-up points, but heartburn scores and medication use were higher in the recurrent hernia group. At late follow-up, 94.6% of the recurrent hernia group vs. 98.5% without a hernia regarded their original decision for surgery to be correct. Two patients in recurrent hernia group underwent revision surgery., Conclusions: Patients with an initially asymptomatic recurrent hiatus hernia are more likely to report heartburn and use antisecretory medication at later follow-up than controls. However, overall clinical outcomes remain good, with high satisfaction and low surgical revision rates. Additional interventions to reduce the risk of recurrence might not be warranted.

Background: The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for improved detection methods. The potential for circulating microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating miRNAs have not been well characterized in esophageal adenocarcinoma. We investigated whether circulating exosomal miRNAs have potential to discriminate individuals with esophageal adenocarcinoma from healthy controls and non-dysplastic Barrett's esophagus., Methods: Seven hundred fifty-eight miRNAs were profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10 individuals with Barrett's esophagus, and 18 individuals with locally advanced esophageal adenocarcinoma. MiRNA expression was assessed using all possible permutations of miRNA ratios per individual. Four hundred eight miRNA ratios were differentially expressed in individuals with cancer compared to controls and Barrett's esophagus (Mann-Whitney U test, P < 0.05). The 179/408 ratios discriminated esophageal adenocarcinoma from healthy controls and Barrett's esophagus (linear regression, P < 0.05; area under receiver operating characteristic (ROC) > 0.7, P < 0.05). A multi-biomarker panel (RNU6-1/miR-16-5p, miR-25-3p/miR-320a, let-7e-5p/miR-15b-5p, miR-30a-5p/miR-324-5p, miR-17-5p/miR-194-5p) demonstrated enhanced specificity and sensitivity (area under ROC = 0.99, 95% CI 0.96-1.0) over single miRNA ratios to distinguish esophageal adenocarcinoma from controls and Barrett's esophagus., Conclusions: This study highlights the potential for serum exosomal miRNAs as biomarkers for the detection of esophageal adenocarcinoma.

Introduction: Laparoscopic surgery is the treatment of choice for repair of large hiatus hernia, but can be followed by recurrence. Repair with prosthetic mesh has been recommended to prevent recurrence, although complications following mesh repair have generated disagreement about whether or not mesh should be used. The early objective and clinical results of a randomized trial of repair with mesh versus sutures have been reported, and revealed few differences. In the current study, we evaluated quality of life outcomes within this trial at follow-up to 2 years., Methods: In a multicenter prospective double-blind randomized trial three methods for repair of large hiatus hernia were compared: sutures versus repair with absorbable mesh (Surgisis) versus non-absorbable (Timesh). Quality of life assessment using the Short-Form 36 (SF-36) questionnaire was undertaken at 3, 6, 12 and 24 months after surgery. SF-36 outcomes (8 individual scales and 2 composite scales) were determined for each group, and compared between groups, and across different follow-up points., Results: 126 patients were enrolled-43 sutures, 41 absorbable mesh and 42 non-absorbable mesh. 115 (91.3%) completed a preoperative questionnaire, and 113 (89.7%) completed the post-operative questionnaire at 3 months, 116 (92.1%) at 6 months, 114 (90.5%) at 12 months, and 91 (72.2%) at 24 months. The SF-36 Physical and Mental Component Scores (PCS and MCS) improved significantly following surgery, and this improvement was sustained across 24 months follow-up (p < 0.001 for PCS and MCS at each follow-up point). There were no significant differences between the groups for the component scores or the eight SF-36 subscale scores at each follow-up time. 29 individuals had a recurrence at 6 months follow-up, of which 9 were symptomatic. The PCS were higher in patients with recurrence versus without (p < 0.01), and in patients with a symptomatic recurrence versus asymptomatic recurrence versus no recurrence (p = 0.001)., Conclusion: SF-36 measured quality of life improved significantly after repair of large hiatal hernia at up to 2 years follow-up, and there were no differences in outcome for the different repair techniques. The use of mesh versus no mesh in repair of large hiatal hernia did not influence quality of life.

Significant disparities exist between genders for the development and progression of several gastro-intestinal (GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors (AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome - poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer.

Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability., (© 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Breast reconstruction has established psychosocial benefit compared to mastectomy alone. Evaluation of determinants of breast reconstruction outcome has previously been limited by lack of high quality, condition-specific, patient-reported outcomes measures. The BREAST-Q is such a measure and is well suited to comparison against objective measurements of reconstructed breasts such as volume and volume symmetry. A cohort of patients who had undergone breast reconstruction over a 14 year period underwent assessment of their breast reconstructions using a 3D laser scanning technique and at the same time completed the BREAST-Q patient reported outcomes measure. The objective data derived from the 3D laser scans were then compared to the quantitative data from the patient-reported outcomes measure. Internal comparisons between domains of the BREAST-Q were also examined. 119 patients completed the study. No correlation was found between objectively measured post-operative volume symmetry and patient reported satisfaction with breasts. Examination of a specific question of the BREAST-Q established that patients did notice if they had breast asymmetry but that this did not translate into dissatisfaction with the breasts overall. Patients who had second stage surgery to correct asymmetry, however, did have a statistically significant increase in satisfaction with breasts between pre and post-symmetrization measures. The strongest correlation for a high level of satisfaction with the reconstructed breast(s) was high level of satisfaction with pre-operative information given. Although symmetrization procedures are valuable for increasing satisfaction with breasts, breast volume symmetry is not a major determinant of outcome in breast reconstruction. The breast reconstruction 'process' is more important in determining patients' post-operative well-being and satisfaction with their overall outcome than the actual final 'product' of their reconstruction., (Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: Determine whether absorbable or nonabsorbable mesh in repair of large hiatus hernias reduces the risk of recurrence, compared with suture repair., Background: Repair of large hiatus hernia is associated with radiological recurrence rates of up to 30%, and to improve outcomes mesh repair has been recommended. Previous trials have shown less short-term recurrence with mesh, but adverse outcomes limit mesh use., Methods: Multicentre prospective double blind randomized controlled trial of 3 methods of repair: sutures versus absorbable mesh versus nonabsorbable mesh. Primary outcome-hernia recurrence assessed by barium meal radiology and endoscopy at 6 months. Secondary outcomes-clinical symptom scores at 1, 3, 6, and 12 months., Results: A total of 126 patients enrolled: 43 sutures, 41 absorbable mesh, and 42 nonabsorbable mesh. Among them, 96.0% were followed up to 12 months, with objective follow-up data in 92.9%. A recurrent hernia (any size) was identified in 23.1% after suture repair, 30.8% after absorbable mesh, and 12.8% after nonabsorbable mesh (P = 0.161). Clinical outcomes were similar, except less heartburn at 3 and 6 months and less bloating at 12 months with nonabsorbable mesh; more heartburn at 3 months, odynophagia at 1 month, nausea at 3 and 12 months, wheezing at 6 months; and inability to belch at 12 months after absorbable mesh. The magnitudes of the clinical differences were small., Conclusions: No significant differences were seen for recurrent hiatus hernia, and the clinical differences were unlikely to be clinically significant. Overall outcomes after sutured repair were similar to mesh repair.

Omental infarction can be difficult to diagnose preoperatively as imaging may be inconclusive and patients often present in a way that suggests a more common surgical pathology such as appendicitis. Here, a 40-year-old Caucasian man presented to casualty with shortness of breath and progressive right upper abdominal pain, accompanied with right shoulder and neck pain. Exploratory laparoscopy was eventually utilised to diagnose an atypical form of omental infarction that mimics cholecystitis. The vascular supply along the long axis of the segment was occluded initiating necrosis. In this case, the necrotic segment was adherent with the abdominal wall, a pathology not commonly reported in cases of omental infarction.

To identify novel non-invasive biomarkers for improved detection, risk assessment and prognostic evaluation of cancer, expression profiles of circulating microRNAs are currently under evaluation. Circulating microRNAs are highly promising candidates in this context, as they present some key characteristics for cancer biomarkers: they are tissue-specific with reproducible expression and consistency among individuals from the same species, they are potentially derived directly from the tumour and therefore might correlate with tumour progression and recurrence, and they are bound to proteins or contained in subcellular particles, such as microvesicles or exosomes, making them highly stable and resistant to degradation. The present review highlights the origin of circulating microRNAs, their stability in blood samples, and techniques to isolate exosomal microRNAs, and then addresses the current evidence supporting potential clinical applications of circulating miRNAs for diagnostic and prognostic purposes.

Background: The polymerase chain reaction amplifies and quantifies small amounts of DNA. It is a cyclic process, during each cycle of which each strand of template DNA is copied with probability approaching one: the amount of DNA approximately doubles and this amount can be estimated fluorimetrically each cycle, producing a set of fluorescence values hereafter referred to as the amplification curve. Commonly the biological question of relevance is one of the ratio of DNA concentrations in two samples: a ratio that is deduced by comparing the two amplification curves, usually by way of a plot of fluorescence against cycle number. Central to this analysis is measuring the extent to which one amplification curve is shifted relative to the other, a measurement often accomplished by defining a threshold or quantification cycle, C q , for each curve: the fractional cycle number at which fluorescence reaches some threshold or at which some other criterion (maximum slope, maximum rate of change of slope) is satisfied. We propose an alternative where position is measured relative to a reference curve; position equates to the cycle shift which maximizes the correlation between the reference and the observed fluorescence sequence. A key parameter of the reference curve is obtained by fixed-point convergence., Results: We consider the analysis of dilution series constructed for the estimation of qPCR amplification efficiency. The estimate of amplification efficiency is based on the slope of the regression line when the C q is plotted against the logarithm of dilution. We compare the approach to three commonly used methods for determining C q ; each is applied to publicly accessible calibration data sets, and to ten from our own laboratory. As in the established literature we judge their relative merits both from the standard deviation of the slope of the calibration curve, and from the variance in C q for replicate fluorescence curves., Conclusions: The approach does not require modification of experimental protocols, and can be applied retrospectively to existing data. We recommend that it be added to the methodological toolkit with which laboratories interpret their real-time PCR data.

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.

Aim: To investigate expression of microRNA (miRNA) and potential targets in chemotherapy resistant esophageal cancer cell lines., Methods: An in-vitro model of acquired chemotherapy resistance in esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) cells was used, and microRNA expression profiles for cisplatin or 5-fluorouracil (5-FU) resistant variants vs chemotherapy sensitive controls were compared using microarray and quantitative real-time polymerase chain reaction (PCR). The expression of chemotherapy-relevant genes potentially targeted by the dysregulated microRNAs in the chemotherapy resistant variants was also evaluated., Results: Chemotherapy resistant sublines were found to have specific miRNA signatures, and these miRNA signatures were different for the cisplatin vs 5-FU resistant cells from the same tumor cell line, and also for EAC vs ESCC cells with resistance to the same specific chemotherapy agent. Amongst others, miR-27b-3p, miR-193b-3p, miR-192-5p, miR-378 a-3p, miR-125a-5p and miR-18a-3p were dysregulated, consistent with negative posttranscriptional control of KRAS, TYMS, ABCC3, CBL-B and ERBB2 expression via these miRNAs., Conclusion: The current study supports the hypothesis that microRNA expression has an impact on chemotherapy resistance in esophageal cancer.

Background: Antireflux surgery is effective for the treatment of gastroesophageal reflux, but not all patients benefit equally from it. The challenge is to identify the patients who will ultimately benefit from antireflux surgery. The aim of this study was to identify preoperative factors that predict clinical outcome after antireflux surgery, with special interest in the influence of socioeconomic factors., Methods: Preoperative clinical and socioeconomic data from 1,650 patients who were to undergo laparoscopic fundoplication were collected prospectively. Clinical outcome measures (persistent heartburn, dysphagia, satisfaction) were assessed at short-term (1 year) and longer-term (≥ 3 years) follow-up., Results: At early follow-up, male gender (relative risk [RR] 1.091, p < 0.001) and the presence of a hiatus hernia (RR 1.065, p = 0.002) were independently associated with less heartburn. Male gender was also associated with higher overall satisfaction (RR 1.046, p = 0.034). An association was found between postoperative dysphagia and age (RR 0.988, p = 0.007) and the absence of a hiatus hernia (RR 0.767, p = 0.001). At longer-term follow-up, only male gender (RR 1.125, p < 0.001) was an independent prognostic factor for heartburn control. Male gender (RR 0.761, p = 0.001), the presence of a hiatus hernia (RR 0.823, p = 0.014), and cerebrovascular comorbidities (RR 1.306, p = 0.019) were independent prognosticators for dysphagia at longer-term follow-up. A hiatus hernia was the only factor associated with better overall satisfaction. Socioeconomic factors did not influence any clinical outcomes at short- and longer-term follow-up., Conclusion: Male gender and hiatus hernia are associated with a better clinical outcome following laparoscopic fundoplication, whereas socioeconomic status does not influence outcome.

Summary: This is the first reported case of a patient who had a single-stage large-volume breast reconstruction with autologous fat grafting, following rotation flap approach (RoFA) mastectomy. The purpose of this case study was to evaluate the viability of reconstruction of the breast by autologous fat grafting alone, in the context of RoFA mastectomy. The hypothesis was that there would be minimal interval loss of autologous fat on the whole breast reconstruction side. Right RoFA mastectomy was used for resection of an invasive primary breast cancer and resulted in the right breast skin envelope. Eleven months later, the patient underwent grafting of 400 ml of autologous fat into the skin envelope and underlying pectoralis major muscle. Outcome was assessed by using a validated 3D laser scan technique for quantitative breast volume measurement. Other outcome measures included the BREAST-Q questionnaire and 2D clinical photography. At 12-month follow-up, the patient was observed to have maintenance of volume of the reconstructed breast. Her BREAST-Q scores were markedly improved compared with before fat grafting, and there was observable improvement in shape, contour, and symmetry on 2D clinical photography. The 2 new techniques, RoFA mastectomy and large-volume single-stage autologous fat grafting, were used in combination to achieve a satisfactory postmastectomy breast reconstruction. Novel tools for measurement of outcome were the 3D whole-body laser scanner and BREAST-Q questionnaire. This case demonstrates the potential for the use of fat grafting for reconstruction. Outcomes in a larger patient populations are needed to confirm these findings.

Objective: To perform long-term histopathological and clinical assessment of patients who have previously undergone cardiomyotomy for achalasia., Background: There are few studies on long-term outcome for patients treated by cardiomyotomy for achalasia. Recent publications suggest that these patients may be at high risk of both squamous cell carcinoma and adenocarcinoma of the esophagus., Methods: All patients, in whom at least 5 years had elapsed since laparoscopic cardiomyotomy for achalasia, were identified from a prospective database. Patients were invited to attend for endoscopy and clinical outcome was assessed by questionnaire., Results: Out of 171 patients identified, 2 had died from esophageal carcinoma. Of the remainder, 68 were recruited [mean age 52 years (range 26-72)]. Fifty-six percent reported minimal symptoms and 6% experienced frequent reflux symptoms. Almost all patients (93%) reported some dysphagia, but dysphagia scores remained significantly lower than preoperatively (P < 0.0001). Quality of life was comparable to normal subjects, and 97% of patients indicated they had made the correct decision to undergo surgery. At endoscopy 83% had evidence of chronic inflammation in the distal esophagus on histopathology, including 22% with moderate to severe esophagitis and 7% with Barrett's esophagus. Five patients showed esophageal candidiasis, and 2 had eosinophilic esophagitis. No dysplasia or malignancy was identified., Conclusions: The clinical outcome remains excellent in most patients at long-term follow-up after cardiomyotomy for achalasia. Surveillance endoscopy might identify high-risk patients but routine endoscopy in all patients is probably not necessary, particularly early after surgery.

Background: Endoscopic surveillance for non-dysplastic Barrett's esophagus (BE) is contentious and its cost effectiveness unclear., Objective: To perform an economic analysis of endoscopic surveillance strategies., Design: Cost-utility analysis by using a simulation Markov model to synthesize evidence from large epidemiologic studies and clinical data for surveillance, based on international guidelines, applied in a coordinator-managed surveillance program., Setting: Tertiary care hospital, South Australia., Patients: A total of 2040 patient-years of follow-up., Intervention: (1) No surveillance, (2) 2-yearly endoscopic surveillance of patients with non-dysplastic BE and 6-monthly surveillance of patients with low-grade dysplasia, (3) a hypothetical strategy of biomarker-modified surveillance., Main Outcome Measurements: U.S. cost per quality-adjusted life year (QALY) ratios., Results: Compared with no surveillance, surveillance produced an estimated incremental cost per QALY ratio of $60,858. This was reduced to $38,307 when surveillance practice was modified by a hypothetical biomarker-based strategy. Sensitivity analyses indicated that the likelihood that surveillance alone was cost-effective compared with no surveillance was 16.0% and 60.6% if a hypothetical biomarker-based strategy was added to surveillance, at an acceptability threshold of $100,000 per QALY gained., Limitations: Treatment options for BE that overlap those for symptomatic GERD were omitted., Conclusion: By using best available estimates of the malignant potential of BE, endoscopic surveillance of patients with non-dysplastic BE is unlikely to be cost-effective for the majority of patients and depends heavily on progression rates between dysplasia grades. However, strategies that modify surveillance according to cancer risk might be cost-effective, provided that high-risk individuals can be identified and prioritized for surveillance., (Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

The epidemiology of esophageal adenocarcinoma demonstrates a strong gender bias with a sex ratio of 8-9:1 in favor of males. A potential explanation for this is that estrogen might protect against esophageal adenocarcinoma. Estrogen has previously been shown to stimulate apoptosis in esophageal squamous cancer cells. However, the effect of estrogen on esophageal adenocarcinoma cells has not been determined. We used immunoblotting analysis to determine the expression of estrogen receptors, cell adhesion marker E-cadherin, and proliferation marker Ki-67 in cell lines derived from esophageal adenocarcinoma (OE-19, OE-33) and Barrett's esophagus (QhTRT, ChTRT, GihTRT). Estrogen and selective estrogen receptor modulator (SERM)-dependent effects on cell growth were determined by the CellTiter-96 Aqueous Proliferation Assay. Apoptosis was determined by Annexin V/Propidium Iodide cell labeling and flow cytometry. We detected that physiological and supra-physiological concentrations of 17β-estradiol and SERM decreased cell growth in esophageal adenocarcinoma cells. In Barrett's esophagus cells (QhTRT, ChTRT), decreased growth was also detected in response to estrogen/SERM. The level of estrogen receptor expression in the cell lines correlated with the level of anti-growth effects induced by the receptor agonists. Flow cytometry analysis confirmed estrogen/SERM stimulated apoptosis in esophageal adenocarcinoma cells. Estrogen/SERM treatments were associated with a decrease in the expression of Ki-67 and an increase in E-cadherin expression in esophageal adenocarcinoma cells. This study suggests that esophageal adenocarcinoma and Barrett's esophagus cells respond to treatment with selective estrogen receptor ligands, resulting in decreased cell growth and apoptosis. Further research to explore potential therapeutic applications is warranted., (© 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Objective: To investigate late objective outcomes 14 years after laparoscopic anterior 180-degree partial versus Nissen fundoplication., Background: Clinical outcomes from randomized clinical trials suggest good outcomes for anterior 180-degree partial fundoplication, with similar control of reflux symptoms and less side effects, compared with Nissen fundoplication. However, objective outcomes at late follow-up have not been reported., Methods: A subset of participants from a randomized trial of anterior 180-degree versus Nissen fundoplication underwent stationary esophageal high-resolution manometry and ambulatory 24-hour impedance-pH monitoring at 14 years' follow-up. The subset and other patients in the trial also completed a standardized clinical questionnaire to ensure that they were representative of the overall trial., Results: Eighteen patients (8 anterior, 10 Nissen) underwent objective testing and had a symptom profile similar to those who did not (n = 59) have testing. Total esophageal acid exposure time and the total number of acid and weakly acidic reflux episodes per 24 hours were higher after anterior fundoplication than after Nissen fundoplication. Proximal, midesophageal and distal reflux were proportionately increased after anterior 180-degree fundoplication. The number of liquid and mixed reflux episodes was also higher after anterior fundoplication, which was accompanied by higher clinical heartburn scores. There were no differences in gas reflux, gastric belches, and supragastric belches, which is in line with the observation that gas-related symptoms were similar for both groups. Mean LES resting and relaxation nadir pressure were lower after anterior fundoplication, which was reflected by lower dysphagia scores. Patient satisfaction was similar after both procedures., Conclusions: At 14 years after randomization, this study demonstrated that acid, weakly acidic, liquid and mixed reflux episodes are more common after anterior 180-degree fundoplication than after Nissen fundoplication. On the contrary, gas reflux and gastric belching and patient satisfaction are similar for both procedures. Mean LES resting and relaxation nadir pressure are lower after anterior fundoplication. Overall, these findings suggest less effective reflux control after anterior 180-degree partial fundoplication, offset by less dysphagia, leading to a clinical outcome that is equivalent to Nissen fundoplication at late follow-up.

Background: There is a learning curve associated with laparoscopic antireflux surgery which has an impact on patient outcomes. It is unclear, however, whether this can be eliminated by supervision of early cases by experienced surgeons. The aim of this study was to evaluate the impact of training under supervision on outcomes for laparoscopic fundoplication., Method: Patients undergoing primary laparoscopic antireflux surgery from 1995 to 2009 were identified from a prospective database. Patients were classified according to whether they were operated on by an experienced consultant or supervised trainee, and sub-categorised according to the presence of a very large hiatus hernia. A standardised questionnaire was used to assess outcomes for heartburn, dysphagia and satisfaction at 1 and 5 years follow-up. Outcomes for the study groups were compared., Results: One thousand seven hundred and ten patients underwent surgery; 1,112 were operated on by consultants and 598 by trainees. The peri-operative complication rate was not different between the groups, although in patients operated on by trainees, there were increased rates of endoscopic dilatation (9 vs. 5 % p = 0.014) and re-operation (9 vs. 6 %, p = 0.031), and a lower satisfaction rate (76 vs. 82 %, p = 0.044) within 5 years of surgery. All other outcomes were similar for trainees vs. consultants., Conclusion: The learning curve for laparoscopic fundoplication had a small, but statistically significant, impact on patient outcomes, with slightly lesser outcomes when surgery was undertaken by trainees, even when supervised by experienced surgeons. Although the differences were not large, they raise questions about equipoise and highlight ethical dilemmas with teaching new generations of surgeons.

Objective: To compare short- and long-term outcome after 180-degree laparoscopic anterior fundoplication (180-degree LAF) with laparoscopic Nissen fundoplication (LNF)., Summary of Background Data: LNF is currently the most frequently performed surgical therapy for gastroesophageal reflux disease. Alternatively, 180-degree LAF has been alleged to reduce troublesome dysphagia and gas-related symptoms, with similar reflux control., Methods: MEDLINE, EMBASE, Cochrane Library, and web of Knowledge CPCI-S were searched for randomized clinical trials comparing primary 180-degree LAF with LNF. The methodological quality was evaluated to assess bias risk. Primary outcomes were esophageal acid exposure, esophagitis, heartburn score, dilatation for dysphagia, modified Dakkak dysphagia score (0-45), and reoperation rate. Meta-analysis was conducted at 1 and 5 years., Results: Five distinct randomized clinical trials comparing 180-degree LAF (n = 227) with LNF (n = 231) were identified. At 1 year, the Dakkak dysphagia score [2.8 vs 4.8; weighted mean difference: -2.25; 95% confidence interval (CI): -2.66 to -1.83; P < 0.001], gas bloating [11% vs 18%; relative risk (RR) 0.59; 95% CI: 0.36-0.97; P = 0.04], flatulence (14% vs 25%; RR: 0.57; 95% CI: 0.35-0.91; P = 0.02), inability to belch (19% vs 31%; RR: 0.63; 95% CI: 0.40-0.99; P = 0.05), and inability to relieve bloating (34% vs 44%; RR: 0.74; 95% CI: 0.55-0.99; P = 0.04) were lower after 180-degree LAF. Esophageal acid exposure (standardized mean difference: 0.19; 95% CI: -0.07 to 0.46; P = 0.15), esophagitis (19% vs 13%; RR: 1.42; 95% CI: 0.69-2.91; P = 0.34), heartburn score (standardized mean difference: 1.27; 95% CI:-0.36 to 2.90; P = 0.13), dilatation rate (1.4% vs 2.8%; RR: 0.60; 95% CI: 0.19-1.91; P = 0.39), reoperation rate (5.7% vs 2.8%; RR: 2.08; 95% CI: 0.80-5.41; P = 0.13), perioperative outcome, regurgitation, proton pump inhibitor (PPI) use, lower esophageal sphincter pressure, and patient satisfaction were similar after 180-degree LAF and LNF. At 5 years, the Dakkak dysphagia score, flatulence, inability to belch, and inability to relieve bloating remained lower after 180-degree LAF. The 5-year heartburn score, dilatation rate, reoperation rate, PPI use, and patient satisfaction were similar., Conclusions: At 1 and 5 years, dysphagia and gas-related symptoms are lower after 180-degree LAF than after LNF, and esophageal acid exposure and esophagitis are similar, with no differences in heartburn scores, patient satisfaction, dilatations, and reoperation rate. These results lend level 1a support for the use of 180-degree LAF for the surgical treatment of gastroesophageal reflux disease.

Evaluation of: Ko MA, Zehong G, Virtanen C et al. miRNA expression profiling of esophageal cancer before and after induction chemoradiotherapy. Ann. Thorac. Surg. 94(4), 1094-1103 (2012). Most patients undergoing surgery for esophageal cancer are treated before surgery with chemotherapy and radiotherapy. However, some tumors respond poorly to these treatments. The article under evaluation profiled miRNA levels in esophageal cancers from patients who did respond to chemoradiotherapy versus those who did not. A large number of miRNAs were differentially expressed between responders versus nonresponders, and patients with either decreased miR-135b or increased miR-145 expression in cancer tissue had improved disease-free survival. Although this study has several limitations, including a mixed cohort of patients with adenocarcinoma and squamous cell carcinoma, and the absence of a validation set of patients, the results do suggest that a miRNA profiling approach may be able to circumvent one of the primary challenges for biomarker development, molecular heterogeneity.

Background: Ulceration of the oesophageal squamous mucosa (ulcerative oesophagitis) is a pathological manifestation of gastro-oesophageal reflux disease, and is a major risk factor for the development of Barrett's oesophagus. Barrett's oesophagus is characterised by replacement of reflux-damaged oesophageal squamous epithelium with a columnar intestinal-like epithelium. We previously reported discovery of microRNAs that are differentially expressed between oesophageal squamous mucosa and Barrett's oesophagus mucosa. Now, to better understand early steps in the initiation of Barrett's oesophagus, we assessed the expression, location and function of these microRNAs in oesophageal squamous mucosa from individuals with ulcerative oesophagitis., Methods: Quantitative real-time PCR was used to compare miR-21, 143, 145, 194, 203, 205 and 215 expression levels in oesophageal mucosa from individuals without pathological gastro-oesophageal reflux to individuals with ulcerative oesophagitis. Correlations between microRNA expression and messenger RNA differentiation markers BMP-4, CK8 and CK14 were analyzed. The cellular localisation of microRNAs within the oesophageal mucosa was determined using in-situ hybridisation. microRNA involvement in proliferation and apoptosis was assessed following transfection of a human squamous oesophageal mucosal cell line (Het-1A)., Results: miR-143, miR-145 and miR-205 levels were significantly higher in gastro-oesophageal reflux compared with controls. Elevated miR-143 expression correlated with BMP-4 and CK8 expression, and elevated miR-205 expression correlated negatively with CK14 expression. Endogenous miR-143, miR-145 and miR-205 expression was localised to the basal layer of the oesophageal epithelium. Transfection of miR-143, 145 and 205 mimics into Het-1A cells resulted in increased apoptosis and decreased proliferation., Conclusions: Elevated miR-143, miR-145 and miR-205 expression was observed in oesophageal squamous mucosa of individuals with ulcerative oesophagitis. These miRNAs localised to the basal layer of the oesophageal epithelium. They reduced proliferation and increased apoptosis, and may play roles in regulating epithelial restoration in response to injury caused by gastro-oesophageal reflux.

There are several microRNAs that have been consistently reported to be differentially expressed in esophageal squamous cell carcinoma vs. normal squamous tissue, with prognostic associations for miR-21 (invasion, positive nodes, decreased survival), miR-143 (disease recurrence, invasion depth), and miR-375 (inversely correlated with advanced stage, distant metastasis, poor overall survival, and disease-free survival). There is also evidence that miR-375 regulates gene expression associated with resistance to chemotherapy. Hence, microRNA expression assays have the potential to provide clinically relevant information about prognosis and potential response to chemotherapy in patients with esophageal squamous cell carcinoma. Results are inconsistent, however, for microRNAs across different studies for esophageal adenocarcinoma (EAC) vs. its precursor lesion Barrett's esophagus. These inconsistencies may partly result from pathological and/or molecular heterogeneity in both Barrett's esophagus and EAC, but may also result from differences in study designs or different choices of comparator tissues. Despite these inconsistencies, however, several mRNA/protein targets have been identified, the cancer related biology of some of these targets is well understood, and there are clinico-pathological associations for some of these mRNA targets. MicroRNAs also have potential for use in therapy for esophageal cancers. The development of new delivery methods, such as minicells and autologous microvesicles, and molecular modifications such as the addition of aromatic benzene pyridine analogs, have facilitated the exploration of the effects of therapeutic microRNAs in vivo. These approaches are producing encouraging results, with one technology in a phase I/IIa clinical trial.

Laparoscopic Nissen fundoplication is the standard operation for the surgical control of gastro-oesophageal reflux in many centres. However, in some patients, it can be followed by troublesome side effects, and to minimise the risk of these, partial fundoplications have been recommended. One approach is to construct an anterior 180° partial fundoplication. Randomised trials and a large outcome study have confirmed that in most patients, this approach achieves effective reflux control, as well as a reduced incidence of side effects. In this paper, we describe our approach to this procedure. The procedure entails full dissection of the oesophageal hiatus, hiatal repair with posteriorly placed sutures and then construction of an anterior 180° partial fundoplication using three sutures to attach the anterior gastric fundus to the oesophagus and right hiatal pillar, and two further sutures between the fundus and the apex of the hiatus.

Background: Barrett's oesophagus develops in some individuals with gastro-oesophageal reflux and is the precursor to oesophageal adenocarcinoma. Proton pump inhibitors (PPIs) suppress gastric acid production and are used to treat reflux. Clinical trials suggest that cyclooxygenase (COX) inhibitors might prevent oesophageal cancer, although PPIs could offset this by increasing COX-2 expression in Barrett's oesophagus. To investigate this, we evaluated the impact of a PPI on COX expression in oesophageal mucosal cells., Methods: The effect of the PPI esomeprazole on COX-1 and COX-2 mRNA levels in oesophageal cells was determined. Oesophageal cell lines OE33 (adenocarcinoma-derived) and HET-1A (immortalized squamous cells) and a control intestinal cell line HT29 (colon carcinoma) were treated for 24 h, with increasing concentrations of the esomeprazole., Results: COX-2, but not COX-1, mRNA levels dose-dependently increased in OE33 and HET-1A cells versus esomeprazole concentration. COX-2 mRNA levels did not increase in HT29 cells., Conclusions: Exposure to esomeprazole increases COX-2 mRNA in oesophageal cells. This might contribute to the lack of benefit for COX inhibitors for oesophageal cancer prevention in recent clinical studies., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Background: There are few reports of large patient cohorts with long-term follow-up after laparoscopic antireflux surgery. This study was undertaken to evaluate changes in surgical practice and outcomes for laparoscopic antireflux surgery over a 20-year period., Methods: A standardized questionnaire, prospectively applied annually, was used to determine outcome for all patients undergoing laparoscopic fundoplication in two centres since commencing this procedure in 1991. Visual analogue scales ranging from 0 to 10 were used to assess symptoms of heartburn, dysphagia and satisfaction with overall outcome. Data were analysed to determine outcome across 20 years., Results: From 1991 to 2010, 2261 consecutive patients underwent laparoscopic fundoplication at the authors' institutions. Follow-up ranged from 1 to 19 (mean 7.6) years. Conversion to open surgery occurred in 73 operations (3.2 per cent). Revisional surgery was performed in 216 patients (9.6 per cent), within 12 months of the original operation in 116. There was a shift from Nissen to partial fundoplication across 20 years, and a recent decline in operations for reflux, offset by an increase in surgery for large hiatus hernia. Dysphagia and satisfaction scores were stable, and heartburn scores rose slightly across 15 years of follow-up. Heartburn scores were slightly higher and reoperation for reflux was more common after anterior partial fundoplication (P = 0.005), whereas dysphagia scores were lower and reoperation for dysphagia was less common (P < 0.001). At 10 years, satisfaction with outcome was similar for all fundoplication types., Conclusion: Laparoscopic Nissen and partial fundoplications proved to be durable and achieved good long-term outcomes. At earlier follow-up, dysphagia was less common but reflux more common after anterior partial fundoplication, although differences had largely disappeared by 10 years., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. Endoscopic interventions that ablate Barrett's esophagus mucosa lead to replacement with a new squamous (neosquamous) mucosa, but it can be difficult to achieve complete ablation. Knowing whether cancer is less likely to develop in neosquamous mucosa or residual Barrett's esophagus after ablation is critical for determining the efficacy of treatment. This issue can be informed by assessing biomarkers that are associated with an increased risk of progression to adenocarcinoma. Although there are few postablation biomarker studies, evidence suggests that neosquamous mucosa may have a reduced risk of adenocarcinoma in patients who have been treated for dysplasia or cancer, but some patients who do not have complete eradication of nondysplastic Barrett's esophagus may still be at risk. Biomarkers could be used to optimize endoscopic surveillance strategies following ablation, but this needs to be assessed by clinical studies and economic modeling.

Barrett's oesophagus is the major risk factor for the development of oesophageal adenocarcinoma. The management of Barrett's oesophagus entails treating reflux symptoms with acid-suppressing medication or surgery (fundoplication). However, neither form of anti-reflux therapy produces predictable regression, or prevents cancer development. Patients with Barrett's oesophagus usually undergo endoscopic surveillance, which aims to identify dysplastic changes or cancer at its earliest stage, when treatment outcomes should be better. Alternative endoscopic interventions are now available and are suggested for the treatment of early cancer and prevention of progression of Barrett's oesophagus to cancer. Such treatments could minimize the risks associated with oesophagectomy. The current status of these interventions is reviewed. Various endoscopic interventions have been described, but with long-term outcomes uncertain, they remain somewhat controversial. Radiofrequency ablation of dysplastic Barrett's oesophagus might reduce the risk of cancer progression, although cancer development has been reported after this treatment. Endoscopic mucosal resection (EMR) allows a 1.5-2 cm diameter piece of oesophageal mucosa to be removed. This provides better pathology for diagnosis and staging, and if the lesion is confined to the mucosa and fully excised, EMR can be curative. The combination of EMR and radiofrequency ablation has been used for multifocal lesions, but long-term outcomes are unknown. The new endoscopic interventions for Barrett's oesophagus and early oesophageal cancer have the potential to improve clinical outcomes, although evidence that confirms superiority over oesphagectomy is limited. Longer-term outcome data and data from larger cohorts are required to confirm the appropriateness of these procedures., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Demographic and lifestyle factors, in particular tobacco smoking and alcohol, are well established causes of esophageal squamous cell carcinoma (ESCC); however, little is known about the effect of these factors on survival. We included all 301 patients with incident ESCC, recruited into a population-based case-control study of esophageal cancer in Australia. Detailed information about demographic and lifestyle factors was obtained at diagnosis, and deaths were identified using the National Death Index. Median follow-up for all-cause mortality was 6.4 years. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated from Cox proportional hazards models, adjusted for age, sex, pretreatment AJCC tumor stage, treatment and presence of comorbidities. Two hundred and thirteen patients (71%) died during follow-up. High lifetime alcohol consumption was independently associated with poor survival. Relative to life-long nondrinkers and those consuming<1 drink/week, the HRs for those with average consumption of 7-20 drinks/week or ≥21 drinks/week were 2.21 (95% CI=1.27-3.84) and 2.08 (95% CI=1.18-3.69), respectively. There was a suggestion of worse survival among current smokers (HR=1.42, 95% CI=0.89-2.28); however, the risk of early death was greatest among current smokers who reported regularly (≥7 drinks/week) consuming alcohol (HR=3.84, 95% CI=2.02-7.32). Other lifestyle factors putatively associated with risk of developing ESCC were not associated with survival. In addition to increasing disease risk, heavy alcohol consumption may be independently associated with worse survival among patients with ESCC. Future clinical follow-up studies should consider alcohol as a potential prognosticator, in addition to known clinicopathologic factors., (Copyright © 2011 UICC.)

Objective: This study aims to synthesize cost and health outcomes for current treatment pathways for esophageal adenocarcinoma and high-grade dysplasia (HGD) and to model comparative net clinical and economic benefits of alternative management scenarios., Methods: A decision-analytic model of real-world practices for esophageal adenocarcinoma treatment by tumor stage was constructed and validated. The model synthesized treatment probabilities, survival, quality of life, and resource use extracted from epidemiological datasets, published literature, and expert opinion. Comparative analyses between current practice and five hypothetical scenarios for modified treatment were undertaken., Results: Over 5 years, outcomes across T stage ranged from 4.06 quality-adjusted life-years and costs of $3,179 for HGD to 1.62 quality-adjusted life-years and costs of $50,226 for stage T4. Greater use of endoscopic mucosal resection for stage T1 and measures to reduce esophagectomy mortality to 0-3 % produced modest gains, whereas a 20 % reduction in the proportion of patients presenting at stage T3 produced large incremental net benefits of $4,971 (95 % interval, $1,560-8,368)., Conclusion: These findings support measures that promote earlier diagnosis, such as developing risk assessment processes or endoscopic surveillance of Barrett's esophagus. Incremental net monetary benefits for other strategies are relatively small in comparison to predicted gains from early detection strategies.

Background: Some patients develop troublesome dysphagia after laparoscopic antireflux surgery, and a proportion require further intervention. The management of this problem was evaluated., Methods: Patients who underwent intervention for dysphagia after laparoscopic fundoplication were identified from a database. Outcomes were prospectively determined from a standardized questionnaire that evaluated symptoms scores for dysphagia for solids and liquids, as well as patient satisfaction with the overall outcome. Outcomes 1 year after reintervention, and at the most recent follow-up were evaluated., Results: From 1994 to 2009, 121 (6.6%) of 1,821 patients who underwent laparoscopic fundoplication for gastroesophageal reflux also underwent endoscopic or surgical reintervention for dysphagia. Of these 121 patients, 56 underwent endoscopic dilatation, and 24 were satisfied with the outcome of dilatation; 18 progressed to surgery, and dysphagia persisted in 14 of them. Overall, 83 patients underwent revisional surgery, and 47 (62.7%) were satisfied with the outcome. Compared to patients who did not undergo any intervention for dysphagia, patients who underwent reintervention had lower satisfaction scores and higher dysphagia scores., Conclusions: Approximately two thirds of patients with troublesome post-fundoplication dysphagia have a satisfactory outcome following either endoscopic dilatation or revisional surgery. However, approximately one third continue to be troubled by symptoms, despite further intervention.

Purpose: Patients diagnosed with esophageal adenocarcinoma (EAC) or gastroesophageal junction adenocarcinoma (GEJAC) have poor survival. We investigated the possible influence of pre-morbid lifestyle factors on survival for these lethal cancers., Methods: This study included a population-based cohort of patients with EAC (n = 362) and GEJAC (n = 421) tumors. Detailed information about demographic and lifestyle factors was obtained around the time of diagnosis, and deaths were identified using the National Death Index. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated from Cox proportional hazards models, adjusted for age, sex, pre-treatment American Joint Committee on Cancer tumor stage, treatment and presence of comorbidities., Results: Median follow-up for mortality was 6.4 years. Five-year survival rates were 27 and 33% for EAC and GEJAC, respectively. As expected, tumor and treatment characteristics were the strongest predictors of survival for both cancer sites. Among patients diagnosed with GEJAC tumors, those who were older (≥ 70 years, adjusted HR = 1.70, 95% CI 1.24-2.32) and those who reported being current smokers (adjusted HR = 1.45, 95% CI 1.02-2.06) fared worse. Other lifestyle factors putatively associated with risk of developing GEJAC including body mass index, gastroesophageal reflux symptoms, alcohol, and use of non-steroidal anti-inflammatory drugs were not associated with survival. Likewise, after adjusting for stage and treatment, no clear associations were detected between lifestyle factors and survival among patients with EAC tumors. We found similar results for analyses restricted to patients treated surgically., Conclusions: Overall, our data suggest that lifestyle factors do not appear to unduly influence survival for these cancers.

Objective: To compare longer term (5-year) outcomes for reflux control and postsurgery side effects after laparoscopic anterior (90° and 180°) partial versus Nissen fundoplication for gastroesophageal reflux., Background: Laparoscopic Nissen fundoplication is the most frequently performed surgical procedure for gastroesophageal reflux. It achieves excellent control of reflux, but in some patients it is followed by troublesome side effects. To reduce the risk of side effects laparoscopic anterior partial fundoplication variants have been advocated, although some studies suggest poorer reflux control., Methods: From 1995 to 2003, 461 patients with gastroesophageal reflux were enrolled in 4 randomized controlled trials comparing anterior partial versus Nissen fundoplication. Two trials evaluated anterior 180° and 2 anterior 90° partial fundoplication. The original trial data were combined, and a reanalysis from original data was undertaken to determine outcomes at 5 years follow-up. Reflux symptom control and side effects were evaluated in a blinded fashion using standardized questionnaires, including 0 to 10 analog scores (0 = no symptoms, 10 = severe symptoms)., Results: At 5 years, patients who underwent an anterior 90° or 180° partial fundoplication had less side effects than those who underwent Nissen fundoplication and were equally satisfied with the overall outcome. Reflux control, measured by heartburn scores and antisecretory medication use, was similar for anterior 180° partial versus Nissen fundoplication, but inferior after anterior 90° partial versus Nissen fundoplication., Conclusions: Anterior 180° partial fundoplication achieves durable control of reflux symptoms and fewer side effects compared with Nissen fundoplication. Reflux control after anterior 90° partial fundoplication appears less effective than after Nissen fundoplication. This data supports the use of anterior 180° partial fundoplication for the surgical treatment of gastroesophageal reflux.

Background: Patients may be unwilling to participate in clinical trials if they perceive risks. Outcomes were evaluated following surgery for gastro-oesophageal reflux in patients recruited to randomized trials compared with patients not in trials., Methods: This study compared outcomes of patients who had surgery for reflux within or outside randomized trials between 1994 and 2009. The choice of procedure outside each trial was according to surgeon or patient preference. Clinical outcomes were determined 1 and 5 years after surgery using a standardized questionnaire, with analogue scales to assess heartburn, dysphagia and overall satisfaction. Subgroup analysis was undertaken for those aged less than 75 years undergoing laparoscopic Nissen fundoplication., Results: Some 417 patients entered six randomized trials evaluating surgery for reflux and 981 underwent surgery outside the trials. The trial group contained a higher proportion of men and younger patients, and patients in trials were more likely to have undergone Nissen fundoplication. At 1 year, patients in the trials had slightly lower heartburn scores and less abdominal bloating, but otherwise similar outcomes to those not in the trials. At 5 years there were no differences, except for a slightly higher dysphagia score for liquids in the trial group. For the subgroup analysis, demographic data were similar for both groups. There were no differences at 1 year, but at 5 years patients enrolled in the trials had higher scores for dysphagia for liquids and heartburn. All of the statistically significant differences were thought unlikely to be clinically relevant., Conclusion: Participation in a randomized trial assessing surgery for reflux did not influence outcomes., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Laryngopharyngeal reflux is a controversial but increasingly made diagnosis used in patients with a collection of often non-specific laryngeal symptoms. It is a clinical diagnosis, and its pathophysiology is currently poorly understood. Previous reflux research has focused on injurious agents, acid, pepsin and biomarker expression. Failure of intrinsic defences in the larynx may cause changes in laryngeal epithelia, particularly alterations in carbonic anhydrases and E-cadherin. Carbonic anhydrase III levels vary in the larynx in response to laryngopharyngeal reflux, depending on location. Expression of E-cadherin, a known tumour suppressor, is reduced in the presence of reflux. Mucin expression also varies according to the severity of reflux. Further research is required to define the clinical entity of laryngopharyngeal reflux, and to identify a definitive mechanism for mucosal injury. Understanding this mechanism should allow the development of a comprehensive model, which would enable future diagnostic and therapeutic interventions to be developed.

Background: This study examined the interaction between natural history, current practice patterns in diagnosis, monitoring and treatment of oesophageal cancer, and associated health resource utilization and costs., Methods: A cost analysis of a prospective population-based cohort of 1100 patients with a primary diagnosis of oesophageal cancer was performed using chart review from the Australian Cancer Study Clinical Follow-Up Study. The analysis enabled estimation of healthcare resources and associated costs in 2009 euros by stage of disease and treatment pathway., Results: Most patients (88·5 per cent) presented with stage II, III or IV cancer; 61·1 per cent (672 of 1100) were treated surgically. Overall mean costs were €37,195 (median €29,114) for patients undergoing surgery and €17,281 (median €13,066) for those treated without surgery. Surgery contributed 66·4 per cent of the total costs (mean €24,697 per patient) in the surgical group. In the non-surgical group, use of chemotherapy was more prevalent (81·9 per cent of patients) and contributed 61·1 per cent of the total costs. Other important cost determinants were gastro-oesophageal junction tumours, treatment location and tumour stage. Mean costs of those monitored for Barrett's oesophagus (7·3 per cent of patients) were lower, although about one-third still presented with advanced-stage cancer., Conclusion: Overall costs for managing oesophageal cancer were high and dominated by surgery costs in patients treated surgically and by chemotherapy costs in patients treated without surgery. Radiotherapy, treatment location and cancer subtype were also important. Monitoring for Barrett's oesophagus and earlier-stage detection were associated with lower management costs, but the potential net benefit from surveillance strategies needs further investigation.

Background: Previous research suggests that females have a poorer outcome than do males after surgery for gastroesophageal reflux., Objective: To evaluate reflux and esophageal symptoms in males and females in a community sample and in patients undergoing antireflux surgery., Design: Face-to-face interview., Setting: A South Australian community., Participants: Random sample of 2973 individuals from the community and 2153 patients presenting for antireflux surgery., Main Outcome Measures: In a random sample of 2973 individuals from the community, the prevalence of reflux and other esophageal symptoms was determined and compared with symptoms in 2153 patients presenting for antireflux surgery. Identical questions were used to assess frequency and severity of heartburn and dysphagia and medication use. Analog scales assessed heartburn and dysphagia (0 indicating no symptoms and 10, severe symptoms). Outcomes for males vs females were compared across both groups., Results: In the community, females were more likely to report heartburn, and when reported, symptom severity was higher. The prevalence of dysphagia was similar for males and females, although females reported higher dysphagia scores for solid foods. A similar proportion of males and females took antireflux medications. Females presenting for antireflux surgery were, on average, 7 years older than males, had a higher body mass index, and had higher heartburn and dysphagia symptom scores. At endoscopy, men were more likely to have ulcerative esophagitis and Barrett esophagus, and at surgery they were less likely to have a hiatal hernia., Conclusions: Significant differences were noted between males and females in the frequency and severity of gastroesophageal reflux-associated symptoms in the community and in patients presenting for surgery. These might reflect differences in symptom perception, which explain previously reported better outcomes in men undergoing antireflux surgery.

Background: Acute respiratory distress syndrome (ARDS) is a major contributor to respiratory morbidity and mortality after oesophagectomy. Several pre-, intra- and post-operative factors are thought to predispose to its development in the post-oesophagectomy period. The aim of this study was to determine factors predisposing to ARDS in the post-oesophagectomy period., Methods: A total of 112 patients who underwent elective oesophagectomy for oesophageal cancer (gastro-oesophageal adenocarcinoma and high-grade dysplasia, 93; oesophageal squamous cell carcinoma, 16; oesophageal oat cell tumour, 1; oesophageal anaplastic carcinoma, 1; oesophageal colloid carcinoma, 1) between 1 January 2003 and 31 December 2006 formed the study group in this retrospective study. The pre-, intra and post-operative data for these patients (male : female = 89:23, mean age 60.8 years) were collected from an oesophagectomy database and hospital medical records., Results: The incidence of ARDS was 13%. The in-hospital mortality among ARDS cases was 20% and 1-year mortality was 40%. Various factors such as preoperative chronic respiratory disease (P-value = 0.000, odds ratio = 17.76), smoking pack-years (P-value = 0.045, odds ratio = 1.02), abnormal preoperative forced expiratory volume in 1 s (P-value = 0.009, odds ratio = 7.97), high percentage of oxygen in inspired air (P-value = 0.041, odds ratio = 1.24) and use of perioperative inotropes (P-value = 0.021, odds ratio = 4.26) were associated with ARDS., Conclusions: Preoperative physiological status as indicated by a preoperative history of chronic respiratory disease and preoperative pulmonary function influenced the post-operative outcome in our patients. The use of perioperative inotropes suggests perioperative cardiorespiratory instability, and could also predispose to the development of ARDS in the post-operative period.