Evaluation of Midodrine Utilization in Patients with Cancer and Heart Failure.

PURPOSE: The purpose of this study was to evaluate safety and cardiovascular outcomes as well as overall survival of cancer patients with concomitant heart failure (HF) treated with midodrine for hypotension. METHODS: Adult patients diagnosed with cancer and HF who were treated with midodrine at a tertiary cancer center from 03/2013 to 08/2021 were identified. Demographic and clinical parameters were collected retrospectively. RESULTS: A total of 85 patients were included with a median age of 68 years (IQR: 60, 74; 33% female and 85% White). Of those, 31% had HFpEF (EF ≥ 50%), 42% HF with mildly reduced EF (HFmrEF; EF 41-49%), and 27% HFrEF (EF ≤ 40%). The most common indication for midodrine use was orthostatic hypotension (49%). Midodrine was continued for at least one month in 57% of the patients. Supine hypertension was the only side effect reported in 6% of patients. No statistically significant changes in NYHA class, guideline-directed medical therapy, cardiac biomarkers (NT-proBNP or troponin T), echocardiographic findings or cardiovascular hospitalizations were observed between patients who continued treatment with midodrine compared to those who stopped using midodrine over a median follow-up of 38 months. In the multivariable cox regression analysis, continuation of midodrine, compared to discontinuation, and use of midodrine for orthostatic hypotension, as opposed to other causes of hypotension, were not associated with an increased risk of mortality (HR 0.41, 95% CI 0.24-0.69, p < .0001; HR 0.34, 95% CI 0.18-0.64, p < .001, respectively). In contrast, elevated creatinine (> 1.3 for males and > 1.1 for females) was associated with an increased risk of mortality (HR 1.83, 95% CI 1.07-3.14). LVEF was not significantly associated with lower or higher risk of mortality. CONCLUSIONS: In our study, midodrine use in patients with cancer and HF was not associated with significant adverse effects, worse cardiovascular outcomes, or increased risk of mortality. Larger, prospective studies are needed to confirm these findings.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in µm), crypt depth (CrD, in µm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Anterior Glenoid Reconstruction With Distal Tibial Allograft: Biomechanical Impact of Fixation and Presence of a Retained Lateral Cortex.

BACKGROUND: Glenoid reconstruction with distal tibial allograft (DTA) is a known surgical option for treating recurrent glenohumeral instability with anterior glenoid bone loss; however, biomechanical analysis has yet to determine how graft variability and fixation options alter the torque of screw insertion and load to failure. HYPOTHESIS: It was hypothesized that retention of the lateral cortex of the DTA graft and the presence of a washer with the screw will significantly increase the maximum screw placement torque as well as the load to failure. STUDY DESIGN: Controlled laboratory study. METHODS: Whole, fresh distal tibias were used to harvest 28 DTA grafts, half of which had the lateral cortex removed and half of which had the lateral cortex intact. The grafts were secured to polyurethane solid foam blocks with a 2-mm epoxy laminate to simulate a glenoid with an intact posterior glenoid cortex. Grafts underwent fixation with 4.0-mm cannulated drills, and screws and washers were used for half of each group of grafts while screws alone were used for the other half, creating 4 equal groups of 7 samples each. A digital torque-measuring screwdriver recorded peak torque for screw insertion. Constructs were then tested in compression with a uniaxial materials testing system and loaded in displacement control at 100 mm/min until at least 3 mm of displacement occurred. Ultimate load was defined as the load sustained at clinical failure. RESULTS: The use of a washer significantly improved the ultimate torque that could be applied to the screws (+cortex and +washer = 12.42 N·m [SE, 0.82]; -cortex and +washer = 10.54 N·m [SE, 0.59]) (P < .0001), whereas the presence of the native bone cortex did not have a significant effect (+cortex and -washer = 7.83 N·m [SE, 0.40]; -cortex and -washer = 8.03 N·m [SE, 0.56]) (P = .181). CONCLUSION: In a hybrid construct of fresh cadaveric DTA grafts secured to a foam block glenoid model, the addition of washers was more effective than the retention of the lateral distal tibial cortex for both load to failure and peak torque during screw insertion. CLINICAL RELEVANCE: This biomechanical study is relevant to the surgeon when choosing a graft and selecting fixation options during glenoid reconstruction with a DTA graft.

Use of the Contralateral Glenoid for Calculation of Glenoid Bone Loss: A Cadaveric Anthropometric Study.

PURPOSE: The purpose of this study was to determine if there are significant side-to-side anthropometric differences between paired glenoids. METHODS: Forty-six matched-pair cadaver glenoids were harvested, and their glenoid heights (GHs) and glenoid widths (GWs) were measured with digital calipers. The glenoid surface area was calculated using the standard assumption that the inferior two-thirds of the glenoid is a perfect circle. RESULTS: There was a statistically significant difference between matched-pair GHs of 0.96 ± 3.07 mm (P = .020) and GWs of 0.46 ± 1.64 mm (P = .033). There was a significant difference of glenoid cavity area of 20.30 ± 81.53 mm2 (P = .044), or a difference of ∼3%. A total of 4 of 46 pairs of glenoids (8.6%) showed a difference in width >3 mm. CONCLUSIONS: This study demonstrates the fallacy of use of the contralateral glenoid in measuring glenoid bone loss. Although many paired samples exhibited similar side-to-side glenoid measurements, the number of cadaveric pairs that showed differences of >3 mm was substantial. Caution should be taken when using calculation methods that include this assumption for surgical decision making, as surface area, GW, and GH were all shown to have statistically significant side-to-side differences in their measurements. CLINICAL RELEVANCE: Many methods exist for measuring glenoid bone loss after anterior shoulder dislocation, but some of the current methods may be inaccurate and lead to unreliable estimations.

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

OBJECTIVES: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. DESIGN: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. RESULTS: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. CONCLUSION: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence.

A single nucleotide polymorphism in codon F31I and V57I of the AURKA gene in invasive ductal breast carcinoma in Middle East.

Although few studies have suggested a carcinogenic role for polymorphism of F31I and V57I codons of AURKA gene in invasive ductal carcinoma, contradictory results from different populations mandates regional investigations. We aimed to determine polymorphisms of F31I and V57I codons of AURKA gene and their association with cancer prognosis in patients compared with controls in an eastern population of Iran.A case-control study was conducted on specimens from 100 patients and 100 age- and gender-matched controls. DNA was extracted and the codons F31I and V57I were amplified. The different genotypes were analyzed by PCR-RFLP and electrophoresis.In codon F31I, the frequency of Phe/Ile was 70% and 82% in patients and healthy controls respectively, whereas (Ile/Ile) was 30% in patients and 18% in healthy (P = .047). Analyzing V57I genotypes showed a higher homozygote Val/Val genotype in patients compared with controls (76% vs 68%), whereas the frequency of heterozygous Val/Ile genotype was lower in patients (17%) than controls (30%), yielding a marginal association between breast cancer and Val/Val genotype (P = .048). No association was observed between SNPs of either F31I or V57I genotypes and histological grades. However, there was a significant association between tumor stages and F31I genotype (P for trend = .003).This is the first report of F31I and V57I polymorphisms in AURKA gene in breast cancer in Iran. Determination of allelic polymorphism of those codons will help to understand background genetic predisposition and could have prognostic value in management of breast cancer in the target population.

The role of perineural invasion in predicting survival in patients with primary operable colorectal cancer: A systematic review.

Perineural invasion is a clear route for cancer cell spread however, the role of nerves in cancer progression is relatively unknown. Recent work would suggest that nerves can actively infiltrate the tumour microenvironment and stimulate cancer cell growth. Therefore, the aim of the present study was to systematically review the identification and associations of perineural invasion and survival in patients with primary operable colorectal cancer. From initial search results of 912 articles, 38 studies were selected. Using H&E stains; five studies including 1835 patients reported on survival stratified by perineural invasion in colon cancer with weighted average detection rates of 26%; eleven studies including 3837 patients reported on rectal cancer with weighted average detection rates of 25% and; sixteen studies including 9145 patients reported on survival stratified by perineural invasion in colorectal cancer with weighted average detection rates of 17%. Using special techniques (S100), six studies including 1458 patients reported on the identification of perineural invasion in colorectal cancer. In comparison to H&E staining alone, the use of immunohistochemistry with S100 increased the detection of perineural invasion to approximately 70%. However, those studies did not examine the relationship with outcomes, so further research is required to establish the clinical significance of perineural invasion detected by immunohistochemistry. In conclusion, perineural invasion deserves special attention for improved prognostic stratification in patients with colorectal cancer. Further work is required to standardise pathology assessment and reporting of perineural invasion, in particular its definition, use of special stains and routine inclusion in pathology practice. Reliable assessment is required for investigations into mechanisms of perineural invasion, its role tumour spread and prognostic value.

Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux.

BACKGROUND AND AIMS: Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH. METHODS: We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro-oesophageal reflux disease with 15 controls matched for age, gender and body weight. Jumbo biopsies were taken across the squamocolumnar junction (SCJ). High-resolution pH metry (12 sensors) and manometry (36 sensors) were performed upright and supine, before and after a meal. The SCJ was marked with an endoscopically placed clip and visualised fluoroscopically. RESULTS: Cardiac mucosa was longer in volunteers with HH (3.5 vs 2.5 mm, p=0.01). There was no excessive acid reflux 5 cm above the upper border of the lower oesophageal sphincter (LOS) in either group but those with HH had short segment reflux 11 mm above the pH transition point after the meal when supine (pH<4 for 5.5% vs 0.3% of time, p=0.01). The SCJ and pH transition point were proximally displaced within the gastro-oesophageal junction in those with HH versus controls (p<0.05). The pH transition point was proximal to the peak LOS pressure point in HH subjects but distal to it in controls after the meal (p<0.05). When supine, the postprandial pH transition point crossed the SCJ in those with HH (p=0.03). CONCLUSIONS: Healthy volunteers with HH have increased intrasphincteric reflux and lengthening of cardiac mucosa in the absence of traditional transsphincteric reflux.

The gastric acid pocket is attenuated in H. pylori infected subjects.

OBJECTIVE: Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in Helicobacter pylori positive and negative volunteers in a Western population. DESIGN: We studied 31 H. pylori positive and 28 H. pylori negative volunteers, matched for age, gender and body mass index. Jumbo biopsies were taken at 11 predetermined locations from the gastro-oesophageal junction and stomach. Combined high-resolution pH metry (12 sensors) and manometry (36 sensors) was performed for 20 min fasted and 90 min postprandially. The squamocolumnar junction was marked with radio-opaque clips and visualised radiologically. Biopsies were scored for inflammation and density of parietal, chief and G cells immunohistochemically. RESULTS: Under fasting conditions, the H. pylori positives had less intragastric acidity compared with negatives at all sensors >1.1 cm distal to the peak lower oesophageal sphincter (LES) pressure (p<0.01). Postprandially, intragastric acidity was less in H. pylori positives at sensors 2.2, 3.3 and 4.4 cm distal to the peak LES pressure (p<0.05), but there were no significant differences in more distal sensors. The postprandial acid pocket was thus attenuated in H. pylori positives. The H. pylori positives had a lower density of parietal and chief cells compared with H. pylori negatives in 10 of the 11 gastric locations (p<0.05). 17/31 of the H. pylori positives were CagA-seropositive and showed a more marked reduction in intragastric acidity and increased mucosal inflammation. CONCLUSIONS: In population volunteers, H. pylori positives have reduced intragastric acidity which most markedly affects the postprandial acid pocket.

The Pretreatment Systemic Inflammatory Response is an Important Determinant of Poor Pathologic Response for Patients Undergoing Neoadjuvant Therapy for Rectal Cancer.

BACKGROUND: Not all patients respond equally to neoadjuvant chemoradiotherapy (nCRT), with subsequent effects on survival. The systemic inflammatory response has been shown to predict long-term outcomes in colorectal cancer. The current study examined the association between systemic inflammation and nCRT in patients with rectal cancer. METHODS: Between 1999 and 2010, patients who underwent nCRT were identified. Serum measurements of hemoglobin, C-reactive protein, albumin, modified Glasgow prognostic score (mGPS), and differential white cell counts were obtained before and after nCRT. The Rödel scoring system measured pathologic tumor regression, and magnetic resonance imaging and computed tomography determined radiologic staging. RESULTS: The study included 79 patients. Of these patients, 37% were radiologically downstaged, and 44% were categorized as showing a good pathologic response (Rödel scores 3 and 4). As a validated measure of the systemic inflammatory response, mGPS (P = 0.022) was associated with a poor pathologic response to nCRT. A radiologic response was associated with a good pathologic response to treatment (P = 0.003). A binary logistic regression model identified mGPS (odds ratio [OR] 0.27; 95% confidence interval [CI] 0.07-0.96; P = 0.043) and radiologic response (OR 0.43; 95% CI 0.18-0.99; P = 0.048) as strong independent predictors of a pathologic response to treatment. CONCLUSION: The current study showed that a systemic inflammatory response before nCRT is associated with a poor pathologic response. Further study in a prospective controlled trial setting is warranted.

The relationship between tumour budding, the tumour microenvironment and survival in patients with primary operable colorectal cancer.

BACKGROUND: Tumour budding has been reported to reflect invasiveness, metastasis and unfavourable prognosis in colorectal cancer. The aim of the study was to examine the relationship between tumour budding and clinicopathological characteristics, tumour microenvironment and survival in patients with primary operable colorectal cancer. METHODS: A total of 303 patients from a prospective data set of patients with primary operable colorectal cancer were included in the study. The presence of budding was determined through assessment of all tumour-containing H&E slides and the number of tumour buds was counted using a 10 high-powered field method. Routine pathologic sections were used to assess: tumour necrosis, the tumour inflammatory cell infiltrate using Klintrup-Makinen (KM) grade and tumour stroma percentage (TSP) combined as the Glasgow Microenvironment Score (GMS). RESULTS: High-grade tumour budding was present in 39% of all tumours and in 28% of node-negative tumours respectively. High-grade budding was significantly associated with T stage (P<0.001), N stage (P<0.001), TNM stage (P<0.001), serosal involvement (P<0.001), venous invasion (P<0.005), KM grade (P=0.022), high tumour stroma (P<0.001) and GMS (P<0.001). Tumour budding was associated with reduced cancer-specific survival (CSS) (HR=4.03; 95% confidence interval (CI), 2.50-6.52; P<0.001), independent of age (HR=1.47; 95% CI, 1.13-1.90; P=0.004), TNM stage (HR=1.52; 95% CI, 1.02-2.25; P=0.040), venous invasion (HR=1.73; 95% CI, 1.13-2.64; P=0.012) and GMS (HR=1.54; 95% CI, 1.15-2.07; P=0.004). CONCLUSIONS: The presence of tumour budding was associated with elements of the tumour microenvironment and was an independent adverse prognostic factor in patients with primary operable colorectal cancer. Specifically high tumour budding stratifies effectively the prognostic value of tumour stage, venous invasion and GMS. Taken together, tumour budding should be assessed routinely in patients with primary operable colorectal cancer.

Worldwide Inverse Association between Gastric Cancer and Esophageal Adenocarcinoma Suggesting a Common Environmental Factor Exerting Opposing Effects.

OBJECTIVES: The incidence of esophageal adenocarcinoma (EAC) is increasing while adenocarcinoma of the stomach is decreasing. We have investigated whether the incidences of these two cancers and their time trends might be inversely related pointing to a common environmental factor exerting opposite effects on these cancers. METHODS: For cross-sectional analyses data were abstracted from "Cancer Incidence in Five Continents" (CI5) Volume X and GLOBOCAN 2012. Relevant ICD-10 codes were used to locate esophageal and gastric cancers anatomically, and ICD-O codes for the histological diagnosis of EAC. For longitudinal analyses, age standardized rates (ASRs) of EAC and total gastric cancer (TGC) were extracted from CI5C-Plus. RESULTS: Estimated (2012) ASRs were available for 51 countries and these showed significant negative correlations between EAC and both TGC (males: correlation coefficient (CC)=-0.38, P=0.006, females: CC=-0.41, P=0.003) and non-cardia gastric cancer rates (males: CC=-0.41, P=0.003 and females: CC=-0.43, P=0.005). Annual incidence trends were analyzed for 38 populations through 1989-2007 and showed significant decreases for TGC in 89% and increases for EAC in 66% of these, with no population showing a fall in the latter. Significant negative correlation between the incidence trends of the two cancers was observed in 27 of the 38 populations over the 19-50 years of available paired data. Super-imposition of the longitudinal and cross-sectional data indicated that populations with a current high incidence of EAC and low incidence of gastric cancer had previously resembled countries with a high incidence of gastric cancer and low incidence of EAC. CONCLUSIONS: The negative association between gastric cancer and EAC in both current incidences and time trends is consistent with a common environmental factor predisposing to one and protecting from the other.

Microscopic enteritis: Bucharest consensus.

Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5(th) International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity.

INTRODUCTION: Recently, we showed that the length of cardiac mucosa in healthy volunteers correlated with age and obesity. We have now examined the immunohistological characteristics of this expanded cardia to determine whether it may be due to columnar metaplasia of the distal oesophagus. METHODS: We used the squamocolumnar junction (SCJ), antral and body biopsies from the 52 Helicobacter pylori-negative healthy volunteers who had participated in our earlier physiological study and did not have hiatus hernia, transsphincteric acid reflux, Barrett's oesophagus or intestinal metaplasia (IM) at cardia. The densities of inflammatory cells and reactive atypia were scored at squamous, cardiac and oxyntocardiac mucosa of SCJ, antrum and body. Slides were stained for caudal type homeobox 2 (CDX-2), villin, trefoil factor family 3 (TFF-3) and liver-intestine (LI)-cadherin, mucin MUC1, Muc-2 and Muc-5ac. In addition, biopsies from 15 Barrett's patients with/without IM were stained and scored as comparison. Immunohistological characteristics were correlated with parameters of obesity and high-resolution pH metry recording. RESULTS: Cardiac mucosa had a similar intensity of inflammatory infiltrate to non-IM Barrett's and greater than any of the other upper GI mucosae. The immunostaining pattern of cardiac mucosa most closely resembled non-IM Barrett's showing only slightly weaker CDX-2 immunostaining. In distal oesophageal squamous mucosa, expression of markers of columnar differentiation (TFF-3 and LI-cadherin) was apparent and these correlated with central obesity (correlation coefficient (CC)=0.604, p=0.001 and CC=0.462, p=0.002, respectively). In addition, expression of TFF-3 in distal oesophageal squamous mucosa correlated with proximal extension of gastric acidity within the region of the lower oesophageal sphincter (CC=-0.538, p=0.001). CONCLUSIONS: These findings are consistent with expansion of cardia in healthy volunteers occurring by squamo columnar metaplasia of distal oesophagus and aggravated by central obesity. This metaplastic origin of expanded cardia may be relevant to the substantial proportion of cardia adenocarcinomas unattributable to H. pylori or transsphincteric acid reflux.

Aneusomy detected by fluorescence in-situ hybridization has high positive predictive value for Barrett's dysplasia.

AIMS: The goal of this study was to pilot a commercial four-colour fluorescence in-situ hybridization (FISH) probe set as a marker of dysplasia in surveillance biopsies. METHODS AND RESULTS: FISH probes to 9p12 (CDKN2A), 17q11.2-12 (HER2), 8q24.12-13 (CMYC) and 20q13.2 (ZNF217) in 20 cases of Barrett's oesophagus. Dysplastic and non-dysplastic mucosa were compared for each case. Two observers independently counted 50 cells in each region of interest (ROI), and the mean score taken. Wilcoxon's signed-rank test was used to determine the significance of differences between dysplastic and non-dysplastic tissue. Predictive power was determined by logistic regression and receiver operator characteristic (ROC) curves were plotted to examine sensitivity and specificity of each gene to detect dysplasia. Interobserver agreement was excellent. HER2, CMYC and ZNF217 showed significant (P < 0.0005) increases in copy number in dysplastic mucosa; CDKN2A had an insignificant (P = 0.852) decrease when compared to non-dysplastic mucosa. While aneusomy was strongly predictive of dysplasia, eusomy did not rule it out. CONCLUSIONS: Increased HER2, CMYC and ZNF217 copy number distinguished dysplastic from non-dysplastic mucosa, but non-detection of aneusomy did not exclude dysplasia. Further studies are justified to determine whether FISH-positive dysplasia might justify earlier treatment by radio-frequency ablation.

Gastric neo-adenocarcinoma arising in a gastric tube after Ivor Lewis oesophagectomy for oesophageal adenocarcinoma.

A 69-year-old man, seven years post Ivor-Lewis oesophagectomy for oesophageal adenocarcinoma, was diagnosed to have a moderately differentiated 4 cm, malignant ulcer within the gastric tube remnant on an endoscopic biopsy. His original presentation was with a T1N0 oesophageal adenocarcinoma, histologically intestinal in type with inflammatory features. He presented with anaemia and melena due to a malignant ulcer in the mid body of his gastric tube on an endoscopy which was confirmed to be a gastric neo-adenocarcinoma on biopsy. He underwent right posterolateral thoracotomy and a wedge resection of the gastric tube including the tumour. Pathology confirmed a T3 N0 (0/7 lymph nodes) with clear margins moderately differentiated adenocarcinoma of intestinal phenotype with papillary features and was reported to be a histopathologically new tumour. Proposed surgical treatments in such patients are dependent on patient's fitness for major resection and may vary from Endoscopic Mucosal Resection to partial resection with preservation of right gastroepiploic vessels or total gastrectomy with intestinal interposition via a retromediastinal route. We suggest that regular endoscopic surveillance may be indicated in such post-oesophagectomy patients as the number of patients developing gastric tube cancers may increase with improve survival of those patients.