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BACKGROUND: Esophageal and gastroesophageal junctional (GEJ) adenocarcinoma is one of the most fatal cancers and has the fastest rising incidence rate of all cancers. Identification of biomarkers is needed to tailor treatments to each patient's tumor biology and prognosis. METHODS: Gene expression profiling was performed in a test cohort of 80 chemoradiotherapy (CRTx) naïve patients with external validation in a separate cohort of 62 CRTx naïve patients and 169 patients with advanced stage disease treated with CRTx. RESULTS: As a novel prognostic biomarker after external validation CD151 showed promise. Patients exhibiting high levels of CD151 (=median) had a longer median overall survival than patients with low CD151 tumor levels (median not reached vs. 30.9 months; p = 0.01). This effect persisted in a multivariable Cox regression model with adjustment for tumor stage [adjusted hazard ratio (aHR) 0.33; 95 confidence interval (CI) 0.14 0.78; p = 0.01] and was further corroborated through immunohistochemical analysis (aHR 0.22; 95 CI 0.08 0.59; p = 0.003). This effect was not found in the separate cohort of CRTx exposed patients. CONCLUSION: Tumoral expression levels of CD151 may provide independent prognostic information not gained by conventional staging of patients with esophageal and GEJ adenocarcinoma treated by esophagectomy alone.

Background Epidemiological studies have identified obesity as a major risk factor for cancer in humans, and trials have demonstrated a significant reduction in the incidence of cancer after bariatric surgery. The rapidity of weight loss after bariatric surgery provides an opportunity to identify the molecular changes associated with effective obesity treatment. Indirectly, this may provide some insights into the mechanisms that drive the association between obesity and cancer. We sought to measure circulating cancer-associated proteins before and after laparoscopic sleeve gastrectomy (LSG). Methods We prospectively enrolled 15 patients undergoing LSG. Thirty-four plasma protein biomarkers thought to be associated with cancer processes were analyzed at baseline and following successful weight loss at 12 weeks using a multiplex bead-based assay. Results Mean excess body weight loss was 44 % at 12-week follow-up. After LSG, a significant reduction in circulating plasma levels was observed for half (17/34) of the proteins assessed: VEGF-A, VEGF-C, VEGF-D, endoglin, PLGF, sFASL, IGFBP-1, IL-18, prolactin, EGF, TGFα, sCD40L, IL-18, TNFα, IL-6, HB-EGF, and PAI-1. Nonsignificant decreases were found for the remaining proteins. Conclusions Circulating cancer-related biomarker levels were reduced by surgical weight loss, and this benefit was achieved as early as 3 months after operation. The observed reduction in cancer biomarkers may be related to the reported decrease in cancer incidence following bariatric surgery.

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.

Background Cathepsin E (CTSE), an aspartic proteinase, is differentially expressed in the metaplasia–dysplasia–neoplasia sequence of gastric and colon cancer. We evaluated CTSE in Barrett’s esophagus (BE) and cancer because increased CTSE levels are linked to improved survival in several cancers, and other cathepsins are up-regulated in BE and esophageal adenocarcinoma (EAC). Methods A total of 273 pretreatment tissues from 199 patients were analyzed [31 normal squamous esophagus (NE), 29 BE intestinal metaplasia, 31 BE with dysplasia (BE/D), 108 EAC]. CTSE relative mRNA expression was measured by real-time polymerase chain reaction, and protein expression was measured by immunohistochemistry. CTSE serum levels were determined by enzyme-linked immunosorbent assay. Results Median CTSE mRNA expression levels were ≥1,000-fold higher in BE/intestinal metaplasia and BE/D compared to NE. CTSE levels were significantly lower in EAC compared to BE/intestinal metaplasia and BE/D, but significantly higher than NE levels. A similar expression pattern was present in immunohistochemistry, with absent staining in NE, intense staining in intestinal metaplasia and dysplasia, and less intense EAC staining. CTSE serum analysis did not discriminate patient groups. In a uni- and multivariable Cox proportional hazards model, CTSE expression was not significantly associated with survival in patients with EAC, although CTSE expression above the 25th percentile was associated with a 41 % relative risk reduction for death (hazard ratio 0.59, 95 % confidence interval 0.27–1.26, p = 0.17). Conclusions CTSE mRNA expression is up-regulated more than any known gene in Barrett intestinal metaplasia and dysplasia tissues. Protein expression is similarly highly intense in intestinal metaplasia and dysplasia tissues. Electronic supplementary material The online version of this article (doi:10.1245/s10434-014-4155-y) contains supplementary material, which is available to authorized users.

Background: Endoscopic treatment by either radiofrequency (RFA) ablation or endoscopic mucosal resection (EMR) has become first line treatment for Barrett's esophagus (BE) with high grade dysplasia, while focal EMR and subsequent elimination of the residual segment by RFA or EMR is accepted therapy for intramucosal cancer (IMC). RFA and EMR are known to be clinically effective but the effect on the mRNA expression of molecular markers of disease stage, which may inform the long term risk of progression to adenocarcinoma, is unknown. We compared the mRNA expression profile in pre-treatment BE tissues biopsies and post-treatment neo-squamous tissues from the same level to provide a surrogatemolecular estimate of treatment effect. Methods: Paired pre-treatment BE tissues and post-treatment neosquamous biopsies were obtained from 38 patients treated by RFA (20 patients (3 IMC (prior EMR), 5 HGD, 12 LGD) or EMR (18 patients, 6 IMC, 12 HGD). mRNA expression of 16 genes significantly associated with different BE stages was measured using a multiplex tandem RT-PCR method with preand post-treatment tissues assessed simultaneously. Distal esophageal tissues from 12 patients with no history of GERD or BE were used as normal controls. Results: Endoscopic therapy resulted in a highly significant change in median values towards the normal squamous mucosa expression profile for all 16 genes on unpaired analysis. This change remained significant for 12 genes by paired analysis (t test). The only significant treatment differences in pre-post mean difference in gene expression were greater changes for RFA compared to EMR for 5 genes. The neosquamous expression profile was significantly different to the normal control profile for 9 of 16 genes. Conclusions: Both RFA and EMR result in marked changes in mRNA expression, with replacement of the highly disordered Barrett's dysplasia or IMC expression profile with a more "normal" expression profile. The neosquamous mucosa was significantly different to the normal control squamous mucosa for most genes but the significance of this finding is uncertain and may reflect confounding factors.

Background Alterations in gastrointestinal, pancreatic, and adipose hormone levels may have a greater role in weight loss than initially appreciated. The laparoscopic sleeve gastrectomy (LSG) operation is now the most frequently performed bariatric operation in many countries, but there are relatively few data regarding its molecular effects. We sought to characterize the effect of LSG on fasting plasma levels of selected hormones and on non-esterified fatty acids (NEFA), and to compare these to levels in non-obese control individuals. Materials and Methods The levels of nine plasma hormones were measured using a multiplex bead-based assay at baseline and at 3 months after operation in 11 obese patients undergoing LSG. NEFA levels were also measured. The levels were compared to those for 22 age- and sex-matched non-obese individuals. Results At baseline, obese patients showed significantly higher expression of C-peptide, insulin, and leptin and significantly lower ghrelin, glucose-dependent insulinotropic peptide (GIP), and resistin compared to non-obese controls (p