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Endoscopic mucosal resection (EMR) of early gastric and esophageal tumors is effective and avoids the morbidity and mortality of surgery. We report the long-term results of a consecutive series of 93 endoscopic resections, during a 7-year period, in a U.K. population. Eighty-eight patients with 93 lesions were included. EMR was performed for 64 and 29 malignant and benign lesions, respectively. Patients with malignant disease were subgrouped into “high risk” or “low risk” for recurrence. Of the 35 lesions in the low-risk group, local control was achieved in 31; 29 after 1 EMR session. Two had residual invasive carcinoma, one had treatment ceased due to pancreatic cancer, and one patient did not attend follow-up. Of the 29 lesions in the high-risk group, local control was achieved in 15; 13 after 1 EMR session. Median follow-up was 53 months. Cancer specific survival for the 45 invasive cancers (T1m and T1sm) was 93%; three patients died from their disease. This study has shown for the first time in a U.K. population that EMR is effective in controlling disease in patients with local high grade dysplasia (HGD) and early invasive carcinoma, with no mortality and low morbidity.

Studies have indicated that hypoalbuminemia is associated with decreased survival of patients with gastric cancer. However, the prognostic value of albumin may be secondary to an ongoing systemic inflammatory response. The aim of the study was to assess the relation between hypoalbuminemia, the systemic inflammatory response, and survival in patients with gastric cancer. Patients diagnosed with gastric carcinoma attending the upper gastrointestinal surgical unit in the Royal Infirmary, Glasgow between April 1997 and December 2005 and who had a pretreatment measurement of albumin and C-reactive protein (CRP) were studied. Most of the patients had stage III/IV disease and received palliative treatment. The minimum follow-up was 15 months. During follow-up, 157 (72%) patients died of their cancer. On univariate analysis, stage (p

Background: Peptic ulcer bleeding (PUB) is a serious and sometimes fatal condition. The outcome of PUB strongly depends on the risk of rebleeding. A recent multinational placebo-controlled clinical trial (ClinicalTrials.gov identifier: NCT00251979) showed that high-dose intravenous (IV) esomeprazole, when administered after successful endoscopic haemostasis in patients with PUB, is effective in preventing rebleeding. From a policy perspective it is important to assess the cost efficacy of this benefit so as to enable clinicians and payers to make an informed decision regarding the management of PUB. Objective: Using a decision-tree model, we compared the cost efficacy of high-dose IV esomeprazole versus an approach of no-IV proton pump inhibitor for prevention of rebleeding in patients with PUB. Method: The model adopted a 30-day time horizon and the perspective of third-party payers in the USA and Europe. The main efficacy variable was the number of averted rebleedings. Healthcare resource utilization costs (physician fees, hospitalizations, surgeries, pharmacotherapies) relevant for the management of PUB were also determined. Data for unit costs (prices) were primarily taken from official governmental sources, and data for other model assumptions were retrieved from the original clinical trial and the literature. After successful endoscopic haemostasis, patients received either high-dose IV esomeprazole (80 mg infusion over 30 min, then 8 mg/hour for 71.5 hours) or no-IV esomeprazole treatment, with both groups receiving oral esomeprazole 40 mg once daily from days 4 to 30. Results: Rebleed rates at 30 days were 7.7% and 13.6%, respectively, for the high-dose IV esomeprazole and no-IV esomeprazole treatment groups (equating to a number needed to treat of 17 in order to prevent one additional patient from rebleeding). In the US setting, the average cost per patient for the high-dose IV esomeprazole strategy was $US14 290 compared with $US14 239 for the no-IV esomeprazole strategy (year 2007 values). For the European setting, Sweden and Spain were used as examples. In the Swedish setting the corresponding respective figures were Swedish kronor (SEK)67 862 ($US9220 at average 2006 interbank exchange rates) and SEK67 807 ($US9212) [year 2006 values]. Incremental cost-effectiveness ratios were $US866 and SEK938 ($US127), respectively, per averted rebleed when using IV esomeprazole. For the Spanish setting, the high-dose IV esomeprazole strategy was dominant (more effective and less costly than the no-IV esomeprazole strategy) [year 2008 values]. All results appeared robust to univariate/threshold sensitivity analysis, with high-dose IV esomeprazole becoming dominant with small variations in assumptions in the US and Swedish settings, while remaining a dominant approach in the Spanish scenario across a broad range of values. Sensitivity variables with prespecified ranges included lengths of stay and per diem assumptions, rebleeding rates and, in some cases, professional fees. Conclusion: In patients with PUB, high-dose IV esomeprazole after successful endoscopic haemostasis appears to improve outcomes at a modest increase in costs relative to a no-IV esomeprazole strategy from the US and Swedish third-party payer perspective. Whereas, in the Spanish setting, the high-dose IV esomeprazole strategy appeared dominant, being more effective and less costly.

Clinical staging in patients with gastro-oesophageal cancer, is of crucial importance in determining the likely benefit of treatment. Despite recent advances in clinical staging, overall survival remains poor. The aim of the present study was to examine the relationship between pre-treatment clinical prognostic factors and cancer-specific survival. Two hundred and seventeen patients, undergoing staging investigations including host factors (Edinburgh Clinical Risk Score (ECRS)) and the systemic inflammatory response (Glasgow Prognostic score (mGPS)), in the upper GI surgical unit at Glasgow Royal Infirmary, were studied. During the follow-up period, 188 (87%) patients died; 178 of these patients died from the disease. The minimum follow-up was 46 months, and the median follow-up of the survivors was 65 months. On multivariate survival analysis of the significant factors, only cTNM stage (HR 1.84, 95% CI 1.56–2.17, p

It remains unclear whether any aspect of quality of life has a role in predicting survival in an unselected cohort of patients with gastro-oesophageal cancer. Therefore the aim of the present study was to examine the relationship between quality of life (EORTC QLQ-C30), clinico-pathological characteristics and survival in patients with gastro-oesophageal cancer. Patients presenting with gastric or oesophageal cancer, staged using the UICC tumour node metastasis (TNM) classification and who received either potentially curative surgery or palliative treatment between November 1997 and December 2002 (n=152) participated in a quality of life study, using the EORTC QLQ-C30 core questionnaire. On univariate analysis, age (P

Summary Background A limited number of trials have investigated the efficacy of proton pump inhibitors for peptic ulcer bleeding, and some study design issues have been identified. Aim To present the design of a large trial evaluating the effects of intravenous esomeprazole on clinical outcomes in high-risk patients who have undergone endoscopic haemostasis for peptic ulcer bleeding. Methods The Peptic Ulcer Bleed study is an international, randomized, double-blind, placebo-controlled trial comparing either esomeprazole 80 mg intravenous bolus infusion for 30 min followed by esomeprazole 8 mg/h intravenously for 71.5 h, or placebo infusion for 72 h, after successful endoscopic haemostasis in patients with peptic ulcer bleeding and associated high-risk stigmata. All patients will receive once daily oral esomeprazole 40 mg for 27 days after intravenous therapy. The primary end point is the rate of clinically significant re-bleeding during the first 72 h after endoscopy. Secondary end points include: rate of re-bleeding during the first 7 and 30 days after treatment; length of hospitalization; mortality; blood transfusion; endoscopic re-treatment and surgery. Results Expected 2008. Conclusions The carefully designed protocol and quality control measures represent a pragmatic approach to contemporary challenges in peptic ulcer bleeding management and, it is hoped, qualify the Peptic Ulcer Bleed study as a new standard for future interventional studies.

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of tumours. The aim of the present study was to examine the relationship between clinico-pathological status, preoperative C-reactive protein concentration and cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer. One hundred and twenty patients attending the upper gastrointestinal surgical unit in the Royal Infirmary, Glasgow, who were selected for potentially curative surgery, were included in the study. Laboratory measurements of haemoglobin, white cell, lymphocyte and platelet counts, albumin and C-reactive protein were carried out at the time of diagnosis. All patients underwent en-bloc resection with lymphadenectomy and survived at least 30 days following surgery. On multivariate analysis, only the positive to total lymph node ratio (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.44-2.84, P0.001) and preoperative C-reactive protein concentration (HR 3.53, 95% CI 1.88-6.64, P0.001) were independent predictors of cancer-specific survival. The patient group with no evidence of a preoperative systemic inflammatory response (C-reactive proteinor =10 mg l(-1)) had a median survival of 79 months compared with 19 months in the elevated systemic inflammatory response group (P0.001). The results of the present study indicate that in patients selected to undergo potentially curative resection for gastro-oesophageal cancer, the presence of an elevated preoperative C-reactive protein concentration is an independent predictor of poor cancer-specific survival.

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients with advanced cancer. The aim of the present study was to examine whether an inflammation-based prognostic score (Glasgow Prognostic score, GPS) was associated with survival, in patients with inoperable gastro-oesophageal cancer. Patients diagnosed with inoperable gastro-oesophageal carcinoma and who had measurement of albumin and C-reactive protein concentrations, at the time of diagnosis, were studied (n=258). Clinical information was obtained from a gastro-oesophageal cancer database and analysis of the case notes. Patients with both an elevated C-reactive protein (>10 mg l−1) and hypoalbuminaemia (

According to the published medical literature to date, prophylactic gastrectomy undertaken in the context of carriage of a germline truncating E-cadherin mutation and an appropriate positive family history will lead to the discovery of occult foci of adenocarcinoma in all gastrectomy specimens. We describe the first published case of a patient whose prophylactic gastrectomy in this setting failed to reveal any dysplastic or malignant foci. Furthermore the patient's nephew, who was found to carry an identical E-cadherin mutation on family screening and also underwent prophylactic gastrectomy, was shown to have multi-focal diffuse adenocarcinoma after analysis of the gastrectomy specimen. Both patients were also found to have penetrant genetic haemochromatosis. Within this case, we discuss the clinical manifestations and penetrance of germline E-cadherin mutations and the difficult decisions facing both clinicians and families with this mutation. We also speculate on how these patients' undiagnosed genetic haemochromatosis may have influenced the pathology encountered.

beta-galactosidase activity at pH 6 is associated in vitro with senescence and cellular death, but in vivo data are sparse. This study undertook firstly to map 'senescence-associated' beta-galactosidase activity (SAbetaG) at pH 6 in normal epithelia and mucosae of the upper gastrointestinal tract. As escape from senescence confers a proliferative advantage, a reduction in SAbetaG activity might be predicted in neoplasia and their precursors in vivo. This prediction was tested in metaplastic, dysplastic, and neoplastic epithelium of the upper gastrointestinal tract. Histochemical staining for SAbetaG was performed at pH 6 on cryostat sections of 350 endoscopic biopsies from sites including oesophagus, stomach, and duodenum of 46 patients: 28 with Barrett's oesophagus (two with adenocarcinoma), 15 with gastric adenocarcinoma, and three with oesophageal squamous cancer. A staining score (range 0-6) was assigned to epithelial cells in all mucosae and scores were calculated for surface (luminal), intermediate, and deep (basal) layers. The strongest SAbetaG activity was in surface lurninal cells of normal duodenal mucosa (mean score 3.6 +/- 0.5; n = 19), 'specialized' Barrett's mucosa (mean 2.2 +/- 0.12; n = 105), and intestinal metaplasia in the stomach (mean 2.4 +/- 0.40; n=16). Squamous epithelium was consistently negative for SAbetaG activity. Low- and high-grade Barrett's dysplasia showed no decrease in SAbetaG activity, but reduced activity was seen in gastric and oesophageal adenocarcinomas (mean 1.24 +/- 0.29; n=17; p=0.012). In six gastric adenocarcinomas, there was no detectable activity. Whether SAbetaG is truly a marker of cellular senescence in vivo remains to be determined. Activity is low in mucosal proliferation compartments and increases with cellular differentiation, especially in native or metaplastic intestinal mucosae. SAbetaG activity persists in dysplastic mucosae but may show some reduction or loss in adenocarcinomas (p=0.0012). Loss of SAbetaG activity is not, therefore, an early event in glandular dysplasianeoplasia of the upper gastrointestinal tract.

Background: Telomerase is detectable in 85% of cancers, but is largely repressed in normal tissues. Human telomerase RNA (hTR) inhibition is a promising anti-cancer strategy, but requires differential expression between malignant and normal tissue. Method: Archival paraffin sections from 48 oral squamous cell carcinomas (SCC) (23 floor of mouth, 25 tongue) and 56 oesophageal carcinomas (41 SCC, 15 adenocarcinomas) were evaluated for hTR expression using a radiolabelled riboprobe. Results were compared with expression in controls and adjacent histologically normal tissue. Statistical analysis was by the χ2 test. Results: hTR was detectable in 76% of oral SCC overall (floor of mouth 65%, tongue 88%, P=0.61), and in 54% of oesophageal cancers (SCC 51%, adenocarcinoma 60%, P=0.56). Detectable hTR expression was significantly more frequent in oral SCC than oesophageal SCC (P=0.01). hTR expression was only detected in normal tissue at low levels in basal squamous epithelium. There was agreement of hTR expression between 8/9 surgically excised carcinomas and their initial diagnostic biopsies. Conclusion: Tumour-specific hTR expression confirms hTR inhibition as a possible therapeutic strategy in some if not all oesophageal and oral cancers. Generally concordant hTR status between biopsy and resection suggest that biopsy may have a role in selecting candidates for telomerase inhibition therapy.

This paper examines and analyzes the stylized facts of the contemporary transition economies, specifically the initial decline and subsequent variable recovery of real gross domestic product. We test the argument that a major source of observed differences in magnitude and duration of decline is the extent of initial disequilibrium of these economies. We specify and estimate a simple econometric model relating the observed pattern of decline to important pre-transition disequilibrium forces, especially macroeconomic distortions. Microeconomic distortions, conceptual, and measurement issues are considered as well. The transition experiences of former Soviet republics are compared with those of countries in Eastern Europe. Journal of Economic Literature, Classification Numbers: O10, P20, P50. 6 figures, 1 table, 21 references.

The aim of this study was to investigate the origin of globus pharyngis with particular reference to esophageal disorders such as gastroesophageal reflux disease (GERD), motility disorders, structural abnormalities, other gastrointestinal tract diseases, and psychological profile. Previous studies on this subject using 24-hour pH monitoring give conflicting results and are hampered by the high background prevalence of asymptomatic GERD in the normal Western population. The local Chinese population is known to have a very low background level of GERD and therefore is an ideal study population. Twenty-six patients with globus pharyngis underwent 24-hour ambulatory pH monitoring, esophageal manometry, and esophagogas-troduodenoscopy with lower esophageal biopsy. A control group of 20 patients presenting with non-ulcer dyspepsia was similarly investigated. Personality profiles of the globus pharyngis subjects and an appropriate control group were assessed. Eight of the globus pharyngis group (30.7%) had evidence of GERD, whereas only one of the controls (5%) demonstrated GERD on 24-hour esophageal pH monitoring (P < 0.05). The manometric and personality profile studies did not show significant differences between study and control groups. We concluded that the finding of GERD in patients with globus pharyngis is not a coincidental finding but that there is a true association between GERD and globus pharyngis.

This paper utilizes the Soviet Interview Project (SIP) and the 1990 U.S. census to identify and to track a sample of Soviet emigres. After examining basic descriptive statistics on income mobility, we specify and estimate earnings functions to examine the impact of a variety of explanatory factors on household earnings in the Soviet Union and in the United States. We find that while the household income of emigres from the Soviet Union increased, the degree of inequality increased significantly as did the share of this population experiencing poverty as defined by U.S. poverty norms.

Background Gastric outlet obstruction secondary to chronic duodenal ulceration is an indication for surgery as conservative management with balloon dilatation frequently fails. The standard operation is truncal vagotomy and a drainage procedure. However, development of minimally invasive surgery has revolutionized the surgical approach to this clinical problem. Methods Twelve male patients with pyloric stenosis secondary to duodenal ulceration underwent laparoscopic truncal vagotomy and gastrojejunostomy. The perioperative and long term outcome of this group of patients were analyzed. Results The median operating time was 210 (range 180 to 240) minutes. Median postoperative stay was 6 (range 4 to 41) days. Conversion to laparotomy was necessary in one patient. Delayed gastric emptying occurred in two patients but resolved on conservative measures. At a median postoperative followup of 6 (range 1 to 12) months all patients had a good symptomatic outcome (Visick grades I or II). Conclusions Laparoscopic truncal vagotomy and gastrojejunostomy is a feasible technique. Intermediate followup shows good symptomatic results when used for pyloric stenosis.

"In spite of extensive literature on migration in the Soviet Union, we know little about household-level decisions. This study specifies and estimates those variables important to understanding the migration decision. Using data from the Soviet Interview Project (SIP), we examine the forces influencing the decision to migrate or not to migrate, and in addition, for those who did migrate, the forces influencing the locational choices made. The results indicate that, while some of the traditional factors influencing migration are important, others are not, suggesting that in the post-Soviet era, differentiating the persistence of Soviet-type forces from emerging market-type forces will be important for an understanding of urban to urban migration."

Background & Aims Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett's esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. Methods We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. Results Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. Conclusions We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.

The recent introduction of laparoscopy into the armamentarium of the general surgeon has revolutionized many aspects of surgical practice. The repair of perforated peptic ulceration is ideally suited to a laparoscopic approach. An accurate diagnosis is obtained, and closure of the perforation with thorough peritoneal toilet safely can be undertaken. The main advantages include the avoidance of a major incision and the reduction of postoperative pain. This may benefit the patient with associated respiratory disease in particular. Although mobilization may be improved, early discharge from the hospital is unlikely because the patient must recover from the peritonitis and associated ileus. The main drawback is a longer operating time caused by technical difficulty with laparoscopic suturing. Many innovative techniques have been described to simplify the procedure. The reported experience with laparoscopic repair of perforated peptic ulcers is encouraging, and randomized trials comparing it with open surgery are eagerly awaited.

Efficacy of a continuous high-dose intravenous infusion of esomeprazole, followed by an oral regimen after successful endoscopic therapy for peptic ulcer bleeding (PUB) was established in the PUB study (ClinicalTrials. gov identifier: NCT00251979). Mortality rates and detailed safety and tolerability results from this study are reported here. This was a double-blind, randomized study in patients a parts per thousand yen18 years with overt signs of upper gastrointestinal bleeding, following endoscopic diagnosis of a single gastric or duodenal ulcer (a parts per thousand yen5 mm) with stigmata indicating current/ recent bleeding (Forrest class Ia, Ib, IIa, or IIb). Postendoscopic hemostasis, patients received intravenous esomeprazole (80 mg/30 minutes, then 8 mg/hour for 71.5 hours) or placebo. Postinfusion, all patients received open-label oral esomeprazole 40 mg once daily for 27 days. Mortality rates were analyzed using Fisher's exact test; other safety variables were analyzed descriptively. A total of 767 patients were randomized; 764 comprised the safety analysis set (375 patients received esomeprazole, 389 placebo). Baseline characteristics were similar across the two treatment groups. Three deaths from the esomeprazole treatment group and eight from the placebo group occurred during the trial (0.8% versus 2.1%; P=0.22). From these 11 all-cause deaths, one (esomeprazole group; rebleeding from duodenal ulcer) occurred during the 72-hour intravenous treatment phase. Adverse event (AE) frequency was similar for the two groups over the intravenous treatment phase (esomeprazole, 39.2%; placebo, 41.9%), with gastrointestinal disorders being most commonly reported (12.3% and 19.8%, respectively). Serious AEs were mostly related to bleeding events. Infusion-site reactions (mild, transient) were reported in 4.3% of esomeprazole-treated patients versus 0.5% of placebo patients. These did not lead to treatment discontinuation. Esomeprazole, given as a continuous high-dose intravenous infusion followed by an oral regimen after successful endoscopic therapy for PUB, was well tolerated, with no apparent safety concerns from either the high-dose intravenous treatment or oral phases.

Background: Variceal bleeding is an acute medical emergency with high mortality. Although less common than oesophageal variceal haemorrhage, gastric variceal bleeding is more severe and more difficult to control. The optimal therapy for gastric variceal bleeding remains unclear although endoscopic injection of N -Butyl-2-Cyanoacrylate (Histoacryl) glue is often used. However, its long-term efficacy is poorly described. We studied the immediate and long-term effects of Histoacryl glue injection as treatment for bleeding gastric varices in a large UK hospital. Method: Endoscopy records and case notes were used to identify patients receiving Histoacryl injection for gastric variceal bleeding over a 4-year period. Results: Thirty-one patients received Histoacryl for gastric variceal bleeding. Seventy-four per cent patients had alcohol-related liver disease and 61% of cirrhotics were Childs Pugh grade B or C. Fifty-eight per cent were actively bleeding during the procedure with 100% haemostasis rates achieved. Two patients developed pyrexia within 24 h of injection settling with antibiotics. No other complications were encountered. Mean overall follow-up was 35 months, with mean follow-up of survivors 57 months. Forty-eight per cent patients had endoscopic ultrasound assessment of varices during follow-up with no effect on rebleeding rates. Thirteen per cent required subsequent transjugular intrahepatic portosystemic shunt placement. Gastric variceal rebleeding rate was 10% at 1 year and 16% in total. One- and two-year mortality was 23% and 35%, respectively. Conclusion: Endoscopic injection of Histoacryl glue appears to be a safe and effective treatment for gastric variceal bleeding. Further data are required to compare it with other therapies in this situation.