Intertwining personal and reward relevance: evidence from the drift-diffusion model.

In their seminal paper 'Is our self nothing but reward', Northoff and Hayes (Biol Psychiatry 69(11):1019-1025, Northoff, Hayes, Biological Psychiatry 69(11):1019-1025, 2011) proposed three models of the relationship between self and reward and opened a continuing debate about how these different fields can be linked. To date, none of the proposed models received strong empirical support. The present study tested common and distinct effects of personal relevance and reward values by de-componenting different stages of perceptual decision making using a drift-diffusion approach. We employed a recently developed associative matching paradigm where participants (N = 40) formed mental associations between five geometric shapes and five labels referring personal relevance in the personal task, or five shape-label pairings with different reward values in the reward task and then performed a matching task by indicating whether a displayed shape-label pairing was correct or incorrect. We found that common effects of personal relevance and monetary reward were manifested in the facilitation of behavioural performance for high personal relevance and high reward value as socially important signals. The differential effects between personal and monetary relevance reflected non-decisional time in a perceptual decision process, and task-specific prioritization of stimuli. Our findings support the parallel processing model (Northoff & Hayes, Biol Psychiatry 69(11):1019-1025, Northoff, Hayes, Biological Psychiatry 69(11):1019-1025, 2011) and suggest that self-specific processing occurs in parallel with high reward processing. Limitations and further directions are discussed.

Early-stage adenocarcinoma of the esophagus with mid to deep submucosal invasion (pT1b sm2-3): the frequency of lymph-node metastasis depends on macroscopic and histological risk patterns.

The rate of lymph-node (LN) metastasis in early adenocarcinoma (EAC) of the esophagus with mid to deep submucosal invasion (pT1b sm2/3) has not yet been precisely defined. The aim of the this study was to evaluate the rate of LN metastasis in pT1b sm2/3 EAC depending on macroscopic and histological risk patterns to find out whether there may also be options for endoscopic therapy as in cancers limited to the mucosa and the upper third of the submucosa. A total of 1.718 pt with suspicion of EAC were referred for endoscopic treatment (ET) to the Dept. of Internal Medicine II at HSK Wiesbaden 1996-2010. In 230/1.718 pt, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of pT1b EAC (ER/surgery) was made. Of these, 38 pt had sm2 lesions, and 69 sm3. Rate of LN metastasis was analyzed depending on risk patterns: histologically low-risk (hisLR): G1-2, L0, V0; histologically high-risk (hisHR): ≥1 criterion not fulfilled; macroscopically low-risk (macLR): gross tumor type I-II, tumor size ≤2 cm; macroscopically high-risk (macHR): ≥1 criterion not fulfilled; combined low-risk (combLR): hisLR+macLR; combined high-risk (combHR): at least 1 risk factor. LN rate was only evaluated in pt who had proven maximum invasion depth of sm2/sm3, and who in case of ET had a follow-up (FU) by EUS of at least 24 months. 23/38 pt with pT1b sm2 lesions and 39/69 pt with sm3 lesions fulfilled our inclusion criteria. In the pT1b sm2 group, rate of LN metastasis in the hisLR, hisHR, combLR, and combHR groups were 8.3% (1/12), 36.3% (4/11), 0% (0/5), and 27.8% (5/18). In the pT1b sm3 group, rate of LN metastasis in the hisLR, hisHR, combLR and combHR groups were 28.6% (2/7), 37.5% (12/32), 25% (1/4), and 37.1% (13/35). 30-day mortality of surgery was 1.7% (1/58 pt). In EAC with pT1b sm2/3 invasion, the frequency of LN metastasis depends on macroscopic and histological risk patterns. Surgery remains the standard treatment, because the rate of LN metastasis appears to be higher than the mortality risk of surgery. Whether a highly selected group of pT1b sm2 patients with a favourable risk pattern may be candidates for endoscopic therapy cannot be decided until the results of larger case volumes are available.

[Microscopic colitis: clinical presentation, treatment and outcome of 494 patients]. / Mikroskopische Kolitis: klinische Manifestation, Therapie und Outcome in 494 Patienten.

BACKGROUND: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic disorders characterized by watery diarrhea. AIM: To evaluate prospectively the clinical features, response to treatment and outcomes in a large group of patients with CC and LC. PATIENTS AND METHODS: Patients with histologically confirmed CC and LC were prospectively enrolled to complete a questionnaire on onset and duration of diarrhea, stool frequency and consistency, other gastrointestinal symptoms including weight loss, drug history, treatment success and concomitant diseases. RESULTS: A total of 494 patients (CC, n = 287, LC, n = 207) were available for analysis. The mean age at diagnosis was 65 in CC and 61 years in LC with a identically female predominance (76 % of patients) in both groups. Prior to diagnosis the mean duration of symptoms was 37 in CC and 23 months in LC. CC and LC patients share similar pattern of clinical symptoms. Concomitant autoimmune disorders were more common in CC patients (48.4 %) than in LC patients (29.6 %). Sustained clinical remission was reported by 35.5 % of CC and 38,6 % of LC, but more CC patients (47.7 %) received medication such as corticosteroids, antibiotics, bismuth or 5-aminosalicyclic than LC patients (16.9 %). 18.6 % of CC patients and 17.6 % of LC were regularly using NSAIDs. CONCLUSION: Collagenous and lymphocytic colitis are frequently diagnosed in elderly female patients. CC and LC share similar symptom pattern, but concomitant autoimmune disease were more common in CC than in LC patients.

The Churg-Strauss syndrome: diagnosed for the first time in a gastrectomy specimen.

The Churg-Strauss syndrome (CSS), first described in 1951 and characterised by eosinophilic inflammation and necrotising vasculitis in patients with asthma can in principle affect any organ. We report on a 47-year-old male patient, in whom the diagnosis of CSS was finally established for the first time on the basis of the histological work-up of a gastrectomy specimen. Endoscopic inspection had revealed a rigid gastric wall and a large irregularly shaped ulcer in the prepyloric antrum. Despite the fact that no carcinoma was demonstrable in the biopsy material, a gastrectomy was nevertheless performed since the endoscopic appearance was strongly suspicious for a carcinoma. The gastrectomy specimen revealed massive eosinophilic gastritis in combination with granulomas and necrotising vasculitis--localised mainly in the muscularis propria. In view of the subsequent information that the patient also suffered from asthma, the diagnosis of CSS (previously unrecognised) was established--for the first time--in the gastrectomy specimen.

Barrett's Adenocarcinomas are frequently underdiagnosed as "high grade intraepithelial neoplasia".

BACKGROUND: Relevant guidelines require that a primary histological diagnosis of high-grade intraepithelial neoplasia (HGIEN) in Barrett's oesophagus, be submitted to a second opinion by an expert gastroenterological pathologist. To date, however, no pertinent study of the outcome of such second-opinion diagnoses has been published. PATIENTS AND METHODS: Between 2001 and 2005, histological slides from 275 patients with the primary diagnosis HGIEN underwent a second-opinion review. The resulting diagnoses were checked by follow-up in 207 of these patients (75.3 %). RESULTS: The second-opinion diagnosis no IEN (n = 27) was confirmed in 85.2 % of the cases, 7.4 % had LGIEN, 3.7 % had HGIEN or a well-differentiated Barrett's adenocarcinoma (BCA) (1 patient, each). In the single patient with the second-opinion diagnosis LGIEN, endoscopic resection revealed a well-differentiated BCA, Follow-up examinations confirmed the second-opinion diagnosis BCA in 5 out of 12 patients, in 1 patient no IEN was found, and 6 patients had a BCA. The second-opinion diagnosis BCA was confirmed by follow-up-examinations in 145 patients (86.8 %), in 12 patients (7.2 %) follow-up revealed HGIEN and in 10 no neoplasia. CONCLUSION: The results of this study show that the demand for a second opinion from an expert gastroenterological pathologist is justified, and also that BCA is frequently underdiagnosed as HGIEN.

Misinterpretation of NSAID-induced Colopathy as Crohn's disease.

Although NSAID-induced colonopathy characterised by erosions, ulcers, strictures and diaphragms has been known for quite some time, it is not infrequently misinterpreted endoscopically and histologically as Crohn's disease. This is exemplified by the present case history of a 39-year-old man with bloody diarrhoea and a stenosis in the transverse colon that was histologically interpreted as "consistent with Crohn's disease". Treatment with glucocorticoids, however, merely gave rise to adverse reactions. After surgical treatment of the stenosis, the episodes of bloody diarrhoea persisted, and endoscopy continued to reveal erosions and ulcers in the transverse colon. Changing treatment to azathioprine also failed to produce any positive response, merely causing side effects. Subsequent evaluation of the histological specimens by a consultant pathologist turned up the tentative diagnosis of NSAID-induced colonopathy. An analysis of the patient's medical history revealed that he was suffering from Bechterew's disease, for which he had long been taking diclofenac. This case history is a good example of the fact that NSAID-induced enterocolopathy is still too poorly recognised among internists, gastroenterologists and pathologists, and, on the basis of the discontinuous endoscopic and histological findings, is often misinterpreted as Crohn's disease.

Lymphocytic colitis under treatment with duloxetine.

Lymphocytic colitis is a disease characterised by chronic watery diarrhoea that can only be diagnosed histologically, since colonoscopy reveals macroscopically normal mucosa. A causal relationship to the administration of certain drugs has repeatedly been described. In this report we describe a case of lymphocytic colitis that developed after initiation of treatment with duloxetine - a selective serotonin- and noradrenaline-reuptake inhibitor - and remitted after discontinuation of the drug. Since a causal relationship between the onset of lymphocytic colitis and the use of duloxetine is highly probable, duloxetine should be included among those drugs capable of inducing lymphocytic colitis.

[Diagnosis of early neoplasia in Barrett's mucosa based on changes in surface structure. Comparative stereo-microscopic and histological investigations in 600 endoscopically resected specimens].

BACKGROUND: In view of the rapidly increasing incidence of Barrett's carcinoma, a desirable aim would be to detect intraepithelial neoplasia and mucosal carcinoma via the endoscope. Where something new is growing, it should give rise to visible changes in surface structure, in particular, in the case of the early Barrett's neoplasia. The present study was carried out to investigate this hypothesis. PATIENTS AND METHODS: A total of 600 formalin-fixed endoscopically resected specimens (317 patients) from Barrett's oesophagus were prospectively investigated by stereomicroscopy (magnification up to x 90). The surface structure was classified into regular (finely granulated or ridged gyriform) and irregular (coarsely granulated, polypoid elevated or depressed), and compared with the results of the histological evaluation. RESULTS: 88.5 % of the Barrett's carcinomas, and 76 % and 68 %, respectively, of the cases of high-grade and low-grade intraepithelial neoplasia were associated with an irregular surface structure. However, coarsely granulated mucosal surfaces, reflecting regenerative changes, were also found in 26 % of the cases of Barrett's mucosa without intraepithelial neoplasia. CONCLUSION: Despite formalin fixation, 68 - 88.5 % of the cases of early Barrett's neoplasia can be identified by stereo microscopy. This shows that high-resolution videoendoscopy or magnification endoscopy appears to be a highly suitable method for the targeted detection of early Barrett's neoplasia.

Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus.

OBJECTIVE: Endoscopic therapy is increasingly being used in the treatment of high-grade intraepithelial neoplasia (HGIN) and mucosal adenocarcinoma (BC) in patients with Barrett's oesophagus. This report provides 5 year follow-up data from a large prospective study investigating the efficacy and safety of endoscopic treatment in these patients and analysing risk factors for recurrence. DESIGN: Prospective case series. SETTING: Academic tertiary care centre. PATIENTS: Between October 1996 and September 2002, 61 patients with HGIN and 288 with BC were included (173 with short-segment and 176 with long-segment Barrett's oesophagus) from a total of 486 patients presenting with Barrett's neoplasia. Patients with submucosal or more advanced cancer were excluded. INTERVENTIONS: Endoscopic therapy. MAIN OUTCOME MEASURES: Rate of complete remission and recurrence rate, tumour-associated death. RESULTS: Endoscopic resection was performed in 279 patients, photodynamic therapy in 55, and both procedures in 13; two patients received argon plasma coagulation. The mean follow-up period was 63.6 (SD 23.1) months. Complete response (CR) was achieved in 337 patients (96.6%); surgery was necessary in 13 (3.7%) after endoscopic therapy failed. Metachronous lesions developed during the follow-up in 74 patients (21.5%); 56 died of concomitant disease, but none died of BC. The calculated 5 year survival rate was 84%. The risk factors most frequently associated with recurrence were piecemeal resection, long-segment Barrett's oesophagus, no ablative therapy of Barrett's oesophagus after CR, time until CR achieved >10 months and multifocal neoplasia. CONCLUSIONS: This study showed that endoscopic therapy was highly effective and safe, with an excellent long-term survival rate. The risk factors identified may help stratify patients who are at risk for recurrence and those requiring more intensified follow-up.

Correlation of T cell response and bacterial clearance in human volunteers challenged with Helicobacter pylori revealed by randomised controlled vaccination with Ty21a-based Salmonella vaccines.

BACKGROUND: Helicobacter pylori remains a global health hazard, and vaccination would be ideal for its control. Natural infection appears not to induce protective immunity. Thus, the feasibility of a vaccine for humans is doubtful. METHODS: In two prospective, randomised, double-blind, controlled studies (Paul Ehrlich Institute application nos 0802/02 and 1097/01), live vaccines against H pylori were tested in human volunteers seronegative for, and without evidence of, active H pylori infection. Volunteers (n = 58) were immunised orally with Salmonella enterica serovar Typhi Ty21a expressing H pylori urease or HP0231, or solely with Ty21a, and then challenged with 2x10(5) cagPAI(-) H pylori. Adverse events, infection, humoral, cellular and mucosal immune response were monitored. Gastric biopsies were taken before and after vaccination, and postchallenge. Infection was terminated with antibiotics. RESULTS: Vaccines were well tolerated. Challenge infection induced transient, mild to moderate dyspeptic symptoms, and histological and transcriptional changes in the mucosa known from chronic infection. Vaccines did not show satisfactory protection. However, 13 of 58 volunteers, 8 vaccinees and 5 controls, became breath test negative and either cleared H pylori (5/13) completely or reduced the H pylori burden (8/13). H pylori-specific T helper cells were detected in 9 of these 13 (69%), but only in 6 of 45 (13%) breath test-positive volunteers (p = 0.0002; Fisher exact test). T cells were either vaccine induced or pre-existing, depending on the volunteer. CONCLUSION: Challenge infection offers a controlled model for vaccine testing. Importantly, it revealed evidence for T cell-mediated immunity against H pylori infection in humans.

Comparison of histological parameters for the diagnosis of eosinophilic oesophagitis versus gastro-oesophageal reflux disease on oesophageal biopsy material.

AIMS: Eosinophil infiltration of the oesophageal epithelium is the cardinal pathomorphological finding in eosinophilic oesophagitis (EO), but gastro-oesophageal reflux disease (GORD) is also associated with increased eosinophils. The aim was to compare histological parameters for the diagnosis of EO versus GORD on routinely taken biopsy specimens. METHODS AND RESULTS: One hundred and five routine biopsy specimens with EO (n = 62), GORD (n = 24) and probable EO (n = 19) from 74 patients (52 men, 22 women; mean age 43.7 years) were analysed for numbers of eosinophils, mast cells, degranulation and qualitative changes of oesophageal epithelium using immunohistochemistry with monoclonal antibodies against eosinophil peroxidase and eosinophil major basic protein and mast cell tryptase. Eosinophil infiltration was significantly higher in EO than in GORD both on haematoxylin and eosin staining (54.8 versus 9.1; P < 0.05) and immunohistochemistry (77.5 versus 24.7; P < 0.05). Eosinophil degranulation was significantly more intense in EO than in GORD (1.16 versus 0.41; P < 0.05). Furthermore, eosinophilia-codependent secondary qualitative changes of squamous epithelium in EO were generally more extensive than those in GORD. CONCLUSIONS: Histological differential diagnosis of EO and GORD should be based on eosinophil counts, secondary morphological changes of eosinophils and oesophageal squamous epithelium, especially in cases suspicious of EO.

Invisible gastric carcinoma detected by random biopsy: long-term results after photodynamic therapy.

BACKGROUND AND STUDY AIMS: Gastric cancer diagnosed from routine gastric biopsies without any evidence of a visible lesion and negative repeated biopsies is an infrequent but serious clinical problem for which gastrectomy has usually been recommended, even if operative specimens do not show cancer either. We report on a series of 22 such patients undergoing long-term follow-up after attempted treatment with photodynamic therapy (PDT). PATIENTS AND METHODS: 22 patients with invisible gastric cancer (IGC) who presented during a 10-year period (10 men, mean age 56 +/- 15 years) were prospectively included. Initial histopathological findings confirmed by second opinion included 10 well-differentiated adenocarcinomas and 12 signet ring cell carcinomas. After two negative state-of-the art endoscopic reassessments, a single session of PDT using 5-delta-aminolevulinic acid (ALA) was performed in the area from which the biopsy was taken, and patients were followed up regularly. RESULTS: After a mean follow-up period of 56.2 +/- 27.6 months, three patients had died of causes unrelated to gastric cancer, four had developed mucosal cancer that was successfully treated endoscopically after 4 - 38 months, and the remaining 15 patients remained without evidence of recurrent gastric cancer, lymph-node involvement, or metastases during a follow-up period of 54 +/- 26 months. CONCLUSIONS: Our results suggest that gastrectomy may not be the only option for IGC, which might follow an uneventful natural course provided careful follow-up is scheduled. The role of PDT in this setting remains unclear and should be studied further.

High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome.

BACKGROUND: In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown. METHODS: Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS. RESULTS: By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis of the PTEN gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients (5%). SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) than did patients with BMPR1A mutations (8%) (p<0.001); all seven cases of gastric cancer occurred in families with SMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without (p<0.001). In 22% of the 23 unrelated SMAD4 mutation carriers, hereditary hemorrhagic telangiectasia (HHT) was also diagnosed clinically. The documented histologic findings encompassed a wide distribution of different polyp types, comparable with that described in hereditary mixed polyposis syndromes (HMPS). CONCLUSIONS: Screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. A strong genotype-phenotype correlation for gastric polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted.

Adenocarcinoma developing in de novo Barrett's mucosa in the remnant esophagus after esophagectomy: clinical and molecular assessment.

For many patients after subtotal esophagectomy and gastric pull-up, reflux of gastric contents to the esophageal stump is the leading clinical problem. Besides symptoms such as heartburn and regurgitation, de novo formation of columnar mucosa in the esophageal remnant is a well-known and frequent phenomenon. In this context, the remnant supra-anastomotic esophagus serves as an in vivo model for the study of Barrett's carcinogenesis. We present a retrospective case analysis of a patient who developed de novo Barrett's metaplasia followed by de novo invasive carcinoma 28 months after gastric pull-up by assessing clinical and molecular parameters.

Critical reappraisal of current surveillance strategies for Barrett's esophagus: analysis of a large German Barrett's database.

Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE). Based on a large database, gathered from predominantly community-based practices in Germany, we aimed to investigate the time-course of malignant progression and apply these findings to current clinical practice. Data of 1438 patients with BE from a large German BE database were analyzed. Patients with at least one follow-up endoscopy/biopsy were included. Detection of 'malignant Barrett' (either high-grade intra-epithelial neoplasia or invasive adenocarcinoma) was considered as study end-point. Of 1438 patients with BE, 57 patients had low-grade intra-epithelial neoplasia (LG-IN) on initial biopsy and 1381 exhibited non-neoplastic BE. 'Malignant Barrett' was detected in 28 cases (1.9%) during a median follow-up period of 24 months (1-255), accounting for an incidence of 0.95% per patient year of follow-up. The frequency of 'malignant Barrett' was significantly higher (P < 0.001, chi(2)-test) in the LG-IN group (n = 11, 19.3%) compared with the non-neoplastic BE group (n = 17, 1.2%). In the non-neoplastic BE group, 'malignant Barrett' was predominantly found during re-endoscopy within the first year of follow-up (12 of 17; 70.6%), in contrast to the LG-IN group, in which 'malignant Barrett' was observed predominantly after a time exceeding 12 months (8 of 11, 72.7%; P = 0.05, Fisher's exact test). Initial endoscopic evaluations seem to play the most crucial role in managing BE. After 1 year of follow-up, endoscopic surveillance should be focused on patients with LG-IN. In patients with repeatedly proven non-neoplastic BE, elongation of the follow-up intervals to the upper limit of current guidelines, that is, 5 years, might be justified.

Long-term treatment of patients with gastro-oesophageal reflux disease in routine care - results from the ProGERD study.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a common condition frequently requiring long-term pharmacological treatment. AIM: To describe the long-term pattern of GERD medication use in GERD patients receiving routine care. METHODS: Patients were recruited as part of the ongoing ProGERD study, a 10-year-cohort study including 6215 patients at baseline. GERD medication and symptoms were assessed with patient questionnaires. During follow-up, medical treatment was prescribed by participating primary care physicians. Associations between patient characteristics and medication were analysed by logistic regression. RESULTS: The percentage of patients who reported using any GERD medication remained constant from year 1 to year 4 (74%, 74%, 73% and 71%). Of patients who reported using GERD medication, the majority were taking proton pump inhibitors (PPI) (79%, 84%, 85%, and 87%). Continuous PPI intake was the predominant prescription pattern (53%, 49%, 56% and 56%), followed by on-demand treatment (26%, 35%, 29% and 29%). Continuous PPI intake was strongly associated with the presence of erosive GERD. CONCLUSION: Three-quarters of the GERD population in our study reported long-term treatment with a PPI. Continuous PPI intake was the predominant treatment pattern, and the proportion of patients taking a PPI on a continuous basis remained constant over time.

Analysis of symptoms and endoscopic findings in 117 patients with histological diagnoses of eosinophilic esophagitis.

BACKGROUND AND STUDY AIMS: Although eosinophilic esophagitis has been increasingly diagnosed over recent years, little is known about this disease. In this study, symptoms, accompanying allergic disorders, and endoscopic findings in 117 patients with eosinophilic esophagitis were analyzed retrospectively. PATIENTS AND METHODS: The physicians who had treated the 117 patients (mean age 42.2 years; 9 children, 108 adults; male patients 71.8%) with the histological diagnosis of eosinophilic esophagitis were asked to provide data on symptoms, accompanying allergic disorders, and endoscopic findings. RESULTS: In 82.2% of the patients symptoms appeared in adulthood, predominantly between the ages of 21 and 30 years. The average duration of symptoms until final diagnosis of eosinophilic esophagitis was 4.2 years (range 0-44 years). The most frequent symptom was dysphagia (70.1%), followed by heartburn (47%), chest pain (29%), epigastric pain (29%), and a combination of dysphagia and heartburn (29%). Allergic disorders were seen in 48.7% of our patients. The most frequent endoscopic findings were stipple-like exudates (25.6%), linear fissures (25.6%), and reddening (25.6%), followed by rings (18.8%) and strictures (16.2%) of the esophagus. The esophageal mucosa was regarded as "normal" in 24.8% of the patients. CONCLUSION: Dysphagia in the second or third decade of life may suggest eosinophilic esophagitis. Symptoms of eosinophilic esophagitis may be indistinguishable from those of gastroesophageal reflux disease. The endoscopic appearance is not specific. Biopsies taken from multiple locations in the esophageal mucosa are essential for diagnosis of eosinophilic esophagitis.

Prospective evaluation of the macroscopic types and location of early Barrett's neoplasia in 380 lesions.

BACKGROUND AND STUDY AIMS: The macroscopic appearance of early gastric cancers, classified according to the Japanese criteria, has been shown to be an important prognostic factor for local endoscopic therapy. No prospective data about the distribution of macroscopic types and their location in early Barrett's neoplasia are available, however. The present study was conducted to evaluate the clinical applicability of this macroscopic classification and to analyze the relative proportions of the different gross types in early Barrett's neoplasms and the correlation between the macroscopic classification and the stage or grade of differentiation. PATIENTS AND METHODS: A total of 344 patients with 380 Barrett's neoplastic lesions who were referred between October 1996 and September 2005 for endoscopic therapy of early Barrett's high-grade intraepithelial neoplasia and carcinoma were prospectively included in the study. Routine endoscopy prior to endoscopic resection in our center included assessment of the macroscopic type (according to the Japanese classification) and documentation of the radial location of the neoplastic lesions. Images were recorded which were later assessed by six independent reviewers; intra- and interobserver agreement for the assessment of the macroscopic type were calculated using kappa statistics. RESULTS: The distribution of the lesions by gross type was as follows: type I, n = 49 (13 %); type IIa, n = 139 (37 %); type IIb, n = 106 (28 %); type IIc, n = 17 (4 %); type IIa + c, n = 62 (16 %); type III, n = 7 (2 %). Type IIb lesions seem to be the most favorable type with regard to differentiation and T category ( P < 0.05). The mean kappa value for the interobserver agreement was 0.86 and the mean kappa value for the intraobserver agreement was 0.89. Most lesions were found at the 12 o'clock and 3 o'clock positions. CONCLUSIONS: Assessment of the macroscopic type may provide important information about the possibility of endoscopic treatment. The harder-to-detect flat lesions are by far the most frequent macroscopic type of neoplastic lesion in Barrett's esophagus.

Self-bias modulates saccadic control.

We present novel data on the role of attention in eliciting enhanced processing of stimuli associated with self. Participants were required to make pro- or anti-saccades according to whether learned shape-label pairings matched or mismatched. When stimuli matched participants were required to make an anti-saccade, and when the stimuli mismatched a pro-saccade was required. We found that anti-saccades were difficult to make to stimuli associated with self when compared to stimuli associated with a friend and a stranger. In contrast, anti-saccades to friend-stimuli were easier to make than anti-saccades to stranger-stimuli. In addition, a correct anti-saccade to a self-associated stimulus disrupted subsequent pro-saccade trials, relative to when the preceding anti-saccade was made to other stimuli. The data indicate that self-associated stimuli provide a strong cue for explicit shifts of attention to them, and that correct anti-saccades to such stimuli demand high levels of inhibition (which carries over to subsequent pro-saccade trials). The self exerts an automatic draw on attention.

Acetylsalicylic acid enhances antiproliferative effects of the EGFR inhibitor gefitinib in the absence of activating mutations in gastric cancer.

The epidermal growth factor receptor (EGFR) is highly expressed in gastric cancer indicating its suitability as a target for receptor tyrosine kinase (RTK) inhibitors. In the current study we explored the role of EGFR and its potential use as a therapeutic target in gastric cancer. First we analyzed 66 gastric cancer samples of Asian and Caucasian patients for the presence of EGFR mutations. No activating EGFR mutations were found and gefitinib alone was only weakly effective in gastric cancer cell lines. However, acetylsalicylic acid (ASA) significantly enhanced the inhibitory effects of gefitinib indicating synergistic action. Whole genome expression profiling indicated significant regulation of 120 genes in the case of co-administration of gefitinib and ASA (32 induced, 88 repressed) in gastric adenocarcinoma cells. Further analyses indicated that several important signalling pathways were effectively inhibited by simultaneous exposure to gefitinib and ASA. Our findings indicate that although gastric cancer does not seem to harbour mutations which render the cancer cells constitutively susceptible to gefitinib, the co-administration of ASA can strengthen RTK inhibitor activity in adenocarcinoma cells by EGFR activation. This is the first report of effective modulation of EGFR-inhibition activity in cancer.