Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level.

Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine-mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 × 10-04 ) and on chromosome 8q24 at rs2585176 (P = 1.09 × 10-09 ). On chromosome 5p13 we found cis-eQTL effects with an upregulation of PTGER4 expression in GC risk allele carrier (P = 9.27 × 10-11 ). On chromosome 8q24 we observed cis-eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 × 10-47 ). In addition, we found trans-eQTL effects for the same variants on 8q24 with a downregulation of MBOAT7 expression in GC risk allele carrier (P = 3.11 × 10-09 ). In summary, we confirmed and refined the previously reported GC associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk-conferring GC pathomechanisms.

Intravenous vitamin C in the treatment of allergies: an interim subgroup analysis of a long-term observational study.

Objective Oxidative stress appears to be a key factor in the pathogenesis of allergic diseases and a potential therapeutic target in allergy treatment. Allergic diseases are reportedly associated with reduced plasma levels of ascorbate, which is a key physiological antioxidant. Ascorbate prevents excessive inflammation without reducing the defensive capacity of the immune system. Methods An interim analysis of a multicenter, prospective, observational study was conducted to investigate the change in disease-specific and nonspecific symptoms (fatigue, sleep disorders, depression, and lack of mental concentration) during adjuvant treatment with intravenous vitamin C (Pascorbin®; Pascoe, Giessen, Germany) in 71 patients with allergy-related respiratory or cutaneous indications. Results Between the start and end of treatment, the mean sum score of three disease-specific symptoms decreased significantly by 4.71 points and that of four nonspecific symptoms decreased significantly by 4.84 points. More than 50% of patients took no other allergy-related medication besides vitamin C. Conclusions Our observations suggest that treatment with intravenous high-dose vitamin C reduces allergy-related symptoms. Our observations form a basis for planning a randomized controlled clinical trial to obtain more definitive evidence of the clinical relevance of our findings. We also obtained evidence of ascorbate deficiency in allergy-related diseases. TRIAL REGISTRATION: Clinical Trials NCT02422901.

Plasma concentrations of ascorbic acid in a cross section of the German population.

Objectives Vitamin C deficiency is considered extremely rare in modern industrialized countries. This study was performed to assess vitamin C concentrations in the German population. Methods As part of a consultant-patient seminar on nutrition and food intolerances, patients were asked to participate in this study on a voluntary basis. Blood samples were taken for analysis of serum vitamin C concentrations, and all patients were asked to complete a questionnaire. The vitamin C concentration was determined by high-performance liquid chromatography. Results Of approximately 300 patients attending the seminar, 188 (62.6%) consented to vitamin C blood sample analysis and 178 (59.3%) answered the questionnaire. The mean vitamin C concentration was 7.98 mg/L (range, 0.50-17.40; reference range, 5-15 mg/L). A low plasma level with vitamin C insufficiency (<5 mg/L) was found in 31 patients (17.4%), and a potential scorbutogenic deficiency (<1.5 mg/L) was found in 6 (3.3%). Conclusions Potential vitamin C insufficiency and deficiency is common. It is therefore possible, even in modern developed populations, that certain individuals may require a higher intake of vitamin C.

The Application of Hemospray in Gastrointestinal Bleeding during Emergency Endoscopy.

Introduction. Gastrointestinal bleeding represents the main indication for emergency endoscopy (EE). Lately, several hemostatic powders have been released to facilitate EE. Methods. We evaluated all EE in which Hemospray was used as primary or salvage therapy, with regard to short- and long-term hemostasis and complications. Results. We conducted 677 EE in 474 patients (488 examinations in 344 patients were upper GI endoscopies). Hemospray was applied during 35 examinations in 27 patients (19 males), 33 during upper and 2 during lower endoscopy. It was used after previous treatment in 21 examinations (60%) and in 14 (40%) as salvage therapy. Short-term success was reached in 34 of 35 applications (97.1%), while long-term success occurred in 23 applications (65.7%). Similar long-term results were found after primary application (64,3%) or salvage therapy (66,7%). Rebleeding was found in malignant and extended ulcers. One major adverse event (2.8%) occurred with gastric perforation after Hemospray application. Discussion. Hemospray achieved short-term hemostasis in virtually all cases. The long-term effect is mainly determined by the type of bleeding source, but not whether it was applied as first line or salvage therapy. But, even in the failures, patients had benefit from hemodynamic stabilization and consecutive interventions in optimized conditions.

Computed Tomography-Guided Percutaneous Gastrostomy/Jejunostomy for Feeding and Decompression.

BACKGROUND: An effective method for long-term enteral feeding or stomach decompression is the use of a percutaneous gastrostomy (PEG) or sometimes jejunostomy (PEJ). Under certain circumstances (eg, inadequate transillumination), endoscopic placement of PEG/PEJ tubes is impossible. In these cases, computed tomography (CT)-guided PEG/PEJ may represent an alternative technique. In this study, we evaluate indications, results, and complications of CT-guided PEG/PEJ. MATERIALS AND METHODS: A total of 102 consecutive referred patients were enrolled in the study. Patients came to the endoscopy unit of our department to undergo a CT-guided PEG/PEJ for long-term intragastric/intrajejunal feeding (n = 57) or decompression (n = 45). The majority (n = 98) received a pull-through PEG/PEJ with simultaneous gastroscopy/jejunoscopy. Dose length product and the effective dose for every patient were calculated. RESULTS: PEG/PEJ tube placement was successful in 87.3% (89 of 102). Feeding PEG/PEJ tube placement was successfully completed in 91.2% (52 of 57); decompressive PEG/PEJ tube placement was likewise successfully completed in 82.2% (37 of 45). No procedure-related mortality was observed. Minor complications (eg, tube dysfunction, local bleeding, minimal leakage, local skin infection) were observed in 13 patients. The complication rate was similar between the feeding and decompression groups ( P = .9). CONCLUSIONS: CT-guided PEG/PEJ is a feasible and safe method with a low procedure-related morbidity rate for patients where endoscopic placement via transillumination is not successful. Thus, the procedure is an attractive alternative to surgical tube placement. Long-term complications, mainly tube disturbances, can be treated easily.

Double-Balloon Enteroscopy-detected Lipid Islets in the Small Bowel are Strong Predictors of Cardiovascular Disease when associated with Angiectasia and Bleeding.

BACKGROUND AND AIMS: Double-balloon enteroscopy (DBE) is a sensitive and safe procedure for the detection and treatment of mid-gastrointestinal bleeding (MGIB). It combines the possibility of a panenteroscopy with the immediate chance for intervention. This study evaluates the yield of DBE for the detection and treatment of MGIB in an unselected patient cohort. METHODS: In a five-year period a total of 119 DBEs were carried out on 62 patients due to MGIB. Inclusion criteria were hematochezia, melena, anemia, positive hemoccult-test and iron deficiency. All pre-existing diseases or comorbidities were evaluated. Two main statistical methodologies were used in data analysis: descriptive statistics to describe the basic features of our data and Fisher's exact test for comparisons of proportions. RESULTS: The diagnostic yield was 69% (pathological findings in 43/62 patients) and the main diagnoses in all DBE-procedures were angiodysplasia (22%, 26/119 DBE), followed by lipid islets (18%, 21/119 DBE). In all patients with lipid islets this diagnosis was significantly connected with cardiovascular diseases. The combination of lipid islets and a relevant bleeding source appeared in 79% of the 19 patients with these findings. Of these, 53% had to be treated due to the bleeding event. The overall therapeutic intervention rate was 58%. Serious complications such as perforation or pancreatitis did not occur. CONCLUSION: Double-balloon enteroscopy as the gold standard for small bowel investigation in MGIB confirmed its high diagnostic yield in an unselected cohort of patients. A new strong combination of lipid islets with cardiovascular disease was revealed, with a high incidence of angiectasia bleeding. This combination should be evaluated in more detail as a new risk factor for MGIB, and should be regarded in this population when therapeutic anticoagulation is needed.

Jejunitis and brown bowel syndrome with multifocal carcinogenesis of the small bowel.

This is the first report describing a case where prolonged, severe malabsorption from brown bowel syndrome progressed to multifocally spread small bowel adenocarcinoma. This case involves a female patient who was initially diagnosed with chronic jejunitis associated with primary diffuse lymphangiectasia at the age of 26 years. The course of the disease was clinically, endoscopically, and histologically followed for 21 years until her death at the age 47 due to multifocal, metastasizing adenocarcinoma of the small bowel. Multiple lipofuscin deposits (so-called brown bowel syndrome) and severe jejunitis were observed microscopically, and sections of the small bowel showed dense lymphoplasmacytic infiltration of the lamina propria as well as blocked lymphatic vessels. After several decades, multifocal nests of adenocarcinoma cells and extensive, flat, neoplastic mucosal proliferations were found only in the small bowel, along with a loss of the mismatch repair protein MLH1 as a long-term consequence of chronic jejunitis with malabsorption. No evidence was found for hereditary nonpolyposis colon carcinoma syndrome. This article demonstrates for the first time multifocal carcinogenesis in the small bowel in a malabsorption syndrome in an enteritis-dysplasia-carcinoma sequence.

Eosinophilic gastroenteritis with refractory ulcer disease and gastrointestinal bleeding as a rare manifestation of seronegative gastrointestinal food allergy.

Gastrointestinal bleeding and iron deficiency anaemia may cause severe symptoms and may require extensive diagnostics and substantial amounts of health resources.This case report focuses on the clinical presentation of a 22 year old patient with recurrent gastrointestinal bleeding from multilocular non-healing ulcers of the stomach, duodenum and jejunum over a period of four years. Extensive gastroenterological and allergological standard diagnostic procedures showed benign ulcerative lesions with tissue eosinophilia, but no conclusive diagnosis. Multiple diagnostic procedures were performed, until finally, endoscopically guided segmental gut lavage identified locally produced, intestinal IgE antibodies by fluoro-enzyme-immunoassay.IgE antibody concentrations at the intestinal level were found to be more-fold increased for total IgE and food-specific IgE against nuts, rye flour, wheat flour, pork, beef and egg yolk compared with healthy controls.Thus, a diet eliminating these allergens was introduced along with antihistamines and administration of a hypoallergenic formula, which resulted in complete healing of the multilocular ulcers with resolution of gastrointestinal bleeding. All gastrointestinal lesions disappeared and total serum IgE levels dropped to normal within 9 months. The patient has been in remission now for more than two years.Eosinophilic gastroenteritis (EG) is well known to induce refractory ulcer disease. In this case, the mechanisms for intestinal damage and gastrointestinal bleeding were identified as local gastrointestinal type I allergy. Therefore, future diagnostics in EG should also be focused on the intestinal level as identification of causative food-specific IgE antibodies proved to be effective to induce remission in this patient.

Outcome and complications of endoscopic balloon dilatations in various types of ileocaecal and colonic stenosis in patients with Crohn's disease.

AIM: We examined the outcome and the complications of endoscopic balloon dilatation (EBD) of ileocaecal and colonic strictures due to Crohn's disease. METHODS: We examined 237 dilatation procedures in 77 patients with symptomatic ileocaecal and colonic stenosis regarding outcome, individual perforation risk, the need for further interventions, and other complications within a 10 years observation period. RESULTS: In 50 of 77 patients (64.9%), endoscopic dilatation procedures were successful within a median follow-up period of 24 months (25th and 75th percentile 10-38.5 months). Thirty five patients (45.5%) were successfully dilated with only one endoscopic procedure, while the remaining patients required two or more EBDs. Albeit the EBD, 27 patients of the whole cohort (35.1%) underwent surgical repair of the stenosis in due course. Overall complication rate was 7.6%, with postdilatation bleeding in 1.7% and abdominal pain longer than 24 h in 4.2%. Perforation occurred in 4 of 77 patients (5.2%), resulting in a perforation rate of 1.7% per intervention, or, more importantly, for the individual patient in a long-term perforation rate of 5.2% per patient, respectively. DISCUSSION: Endoscopic balloon dilatation (EBD) is a safe and effective approach to ileocaecal and colonic stenosis in approximately 65% of Crohn's disease patients. Even in case of recurrence, further endoscopic treatments can be undertaken. The perforation rate depending on the number of interventions is low, but for the individual patient a cumulative per patient perforation risk of 5.2% in the long-term should be considered during patient information and decisions for or against surgical interventions.

Colon capsule endoscopy: detection of colonic polyps compared with conventional colonoscopy and visualization of extracolonic pathologies.

BACKGROUND: Conventional colonoscopy (CC) is the gold standard for diagnostic examination of the colon. However, the overall acceptance of this procedure is low due to patient fears of complications or embarrassment. Colon capsule endoscopy (CCE) represents a minimally invasive, patient-friendly procedure that offers complete visualization of the entire intestine. OBJECTIVE: To assess the PillCam Colon 2 (Given Imaging Ltd, Israel) capsule with regard to feasibility, sensitivity and specificity for the detection of colonic pathologies and additional recorded extracolonic findings. METHODS: CCE was performed before CC in patients indicated for CC for known or suspected colonic disease. The results of both techniques were compared with regard to polyp detection. Additionally, bowel preparation and extracolonic pathologies were analyzed. RESULTS: Twenty-four patients (mean age 51.1 years) were included in the analysis. Visualization of the colon was complete in 23 CCs and 17 CCEs. No adverse events or major technical failures occurred. CC detected 47 polyps and CCE detected 43 polyps of any size (per-finding sensitivity 90.9%, specificity 67.6%). The accuracy of CCE in detecting polyp carriers was 81.5% (per-patient analysis). On average, the colon was adequately cleansed in 90.1% of patients. CCE identified esophageal, gastric and small bowel pathologies in seven (24%), nine (38%) and 14 (58%) patients, respectively. CONCLUSIONS: CCE proved to be technically feasible and safe. Acceptable sensitivity and moderate specificity levels in polyp detection were recorded. Bowel preparation was adequate in most patients. Because extracolonic pathologies were effectively visualized, new indications for the PillCam Colon 2 may be defined.

QuickView video preview software of colon capsule endoscopy: reliability in presenting colorectal polyps as compared to normal mode reading.

OBJECTIVE. Colon capsule endoscopy (CCE) proved to be highly sensitive in detection of colorectal polyps (CP). Major limitation is the time-consuming video reading. The aim of this prospective, double-center study was to assess the theoretical time-saving potential and its possible impact on the reliability of "QuickView" (QV), in the presentation of CP as compared to normal mode (NM). METHODS. During NM reading of 65 CCE videos (mean patient´s age 56 years), all frames showing CPs were collected and compared to the number of frames presented by QV at increasing QV settings (10, 20, ... 80%). Reliability of QV in presenting polyps <6 mm and ≥6 mm (significant polyp), and identifying patients for subsequent therapeutic colonoscopy, capsule egestion rate, cleansing level, and estimated time-saving potential were assessed. RESULTS. At a 30% QV setting, the QV video presented 89% of the significant polyps and 86% of any polyps with ≥1 frame (per-polyp analysis) identified in NM before. At a 10% QV setting, 98% of the 52 patients with significant polyps could be identified (per-patient analysis) by QV video analysis. Capsule excretion rate was 74% and colon cleanliness was adequate in 85%. QV´s presentation rate correlates to the QV setting, the polyp size, and the number of frames per finding. CONCLUSIONS. Depending on its setting, the reliability of QV in presenting CP as compared to NM reading is notable. However, if no significant polyp is presented by QV, NM reading must be performed afterwards. The reduction of frames to be analyzed in QV might speed up identification of candidates for therapeutic colonoscopy.

Modern diagnosis of celiac disease and relevant differential diagnoses in the case of cereal intolerance.

At an incidence of 1:500, celiac disease (formerly sprue) is an important differential diagnosis in patients with malabsorption, abdominal discomfort, diarrhea and food intolerances. Celiac disease can induce a broad spectrum of both gastrointestinal and extraintestinal symptoms, e.g. dermatitis herpetiformis (Duhring's disease). A variety of oligo- and asymptomatic courses (e.g. anemia, osteoporosis, depression) through to refractory collagenic celiac disease are seen. In HLA-DQ2 and -8 predisposed individuals, celiac disease is provoked by contact with wheat gliadin fractions through a predominantly Th1 immune response and an accompanying Th2 response, which can eventually lead to villous atrophy. Using appropriate serological tests (IgA antibodies against tissue-transglutaminase, endomysium and deamidated gliadin peptides) under sufficient gluten ingestion, the diagnosis can be made more reliably today than previously. The same IgG-based serological tests should be used in the case of IgA deficiency. Diagnosis can either be made in children and adolescents with anti-transglutaminase titers exceeding ten times the standard for two of the above-mentioned serological markers and HLA conformity or it is made by endoscopy and histological Marsh classification in adults and in cases of inconclusive serology. If clinically tolerated, gluten challenges are indicated in patients that already have reduced gluten intake, in borderline serological results, discordance between serological and histological results or in suspected food allergy. The diagnosis of celiac disease needs to be definitive and robust before establishing a gluten-free diet, since lifelong abstention from gluten (gliadin < 20 mg/kg foodstuffs), cereal products (wheat, rye, barley and spelt) as well as from preparations and beverages containing gluten, is necessary. With effective elimination of gluten, the prognosis regarding complete resolution of small bowel inflammation is good. Refractory courses are seen only in rare cases, accompanied by enteropathy-associated T-cell lymphoma.

Perforation during esophageal dilatation: a 10-year experience.

BACKGROUND & AIM: Esophageal stenosis can be caused by malignant, postsurgical, benign diseases etc. Endoscopic treatment options consist primarily of balloon dilatation and bougination. Both interventions carry a certain risk of further complications such as perforations. We aimed to evaluate this risk in our patients. METHODS: Frequency, perforation rates, further diagnostics, therapy, outcome and underlying diseases in 368 patients who underwent endoscopic dilatation or bougination in a 10 year period were evaluated. RESULTS: Overall, 1497 endoscopic interventions were performed for treatment of esophageal stricture, causing 8 perforations (0.53% per intervention, 2.17% per patient) and one lethal outcome (0.05% per intervention, 0.27% per patient). In 1286 bouginations, 8 perforations (0.62%) and one death occurred (0.08%), whilst no perforation was noted during 211 balloon dilatations. Outcome of the 8 perforations was greatly influenced by co-morbidities, causing a prolonged hospitalization and the death of one patient. CONCLUSION: Although complication rates are fairly small, patients should be under supervision or in contact for 24-72 hours after each intervention. In cases where perforation is suspected, radiological examinations should be conducted early. The perforation rate and mortality per patient may be used for patient information. Therapy and prognosis depend on the cause of perforation, localization and size of the perforation site as well as concomitant diseases.

Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases.

Histamine plays an important role in the development of symptoms in allergic, infectious, neoplastic and other diseases. Empirical findings have suggested beneficial effects of ascorbic acid supplementation in those diseases, and these effects are assumed to be related to a possible decrease in systemic histamine concentration. In the present study, we systematically investigated for the first time the effect of 7.5 g of intravenously administered ascorbic acid on serum histamine levels (as detected by ELISA) in 89 patients (19 with allergic and 70 with infectious diseases). When all patients were grouped together, there was a significant decline in histamine concentration from 0.83 to 0.57 ng/ml×m2 body surface area (BSA, p<0.0001). The decrease in serum histamine concentration in patients with allergic diseases (1.36 to 0.69 ng/ml×m2 BSA, p=0.0007) was greater than that in patients with infectious diseases (0.73 to 0.56 ng/ml×m2 BSA, p=0.01). Furthermore, the decline in histamine concentration after ascorbic acid administration was positively correlated with the basal, i.e. pre-therapeutic, histamine concentration. Intravenous infusion of ascorbic acid clearly reduced histamine concentrations in serum, and may represent a therapeutic option in patients presenting with symptoms and diseases associated with pathologically increased histamine concentration.

Metastatic insulinoma - prolonged survival after multimodal approach.

BACKGROUND: Metastatic insulinoma is a disease associated with a poor life expectancy. CASE REPORT: The case of a presently 68 year old female with malignant, metastatic insulinoma is reported. Due to severe clinical symptoms surgical tumor mass reduction was conducted. Furthermore the patient underwent a chemotherapy using streptozotocine and fluorouracil. After two years without any symptoms, the remaining hepatic metastases increased in size and again hypoglycemias occurred. To reachieve an asymptomatic state and further reduction in tumor mass, the decision was made for transarterial chemoembolization with streptozotocine. After the first treatment the patient was hypoglycemia - free for 3 months, after another more extensive chemoembolization the patient is presently symptom free for 8 months. CONCLUSIONS: Since the diagnosis of extended disease was established, the patient has survived for 36 months. We regard this as the result of a multimodal approach and the extensive use of local tumor therapy. The different therapeutic options for local tumor therapy are reported and discussed.