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.

Weekly High-dose 5-Fluorouracil as 24-hour Infusion Combined with Sodium Folinic Acid (AIO regimen) Plus Irinotecan in Second-line and Sequential Therapy of Metastatic Colorectal Cancer (CRC).

BACKGROUND/AIM: The aim of this work was to evaluate the efficacy and safety of second-line treatment with weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) combined with sodium folinic acid (FA) (AIO-regimen) plus irinotecan (Iri.) after pretreatment with AIO-regimen plus oxaliplatin (L-OHP). PATIENTS AND METHODS: Patients with non-resectable distant CRC metastases were enrolled in a prospective phase II study for palliative second-line treatment after previous progression of first-line treatment in accordance with the AIO-regimen plus oxaliplatin. On an outpatient basis, the patients received a treatment regimen comprising of weekly 80 mg/m2 irinotecan in the form of a 1-hour i.v. infusion and 2,000 mg/m2 5-FU combined with 500 mg/m2 sodium folinic acid administered as a 24-h infusion i.v. once weekly. RESULTS: During second-line treatment, a total of 59 patients received 520 chemotherapy applications. As the main higher-grade symptom of toxicity, diarrhea (NCI-CTC-toxicity grade 3) presented in 8 patients (13.6%, 95%CI=5.1-23.7), followed by leukocytopenia (CTC grade 3) in 3 patients (5.1%, 95%CI=0-11.9), followed by thrombocytopenia (CTC grade 3) in 1 patient (1.7%, 95%CI=0-5.1). Fifty-nine patients were evaluable for treatment response. The remission data can be summarized as follows: complete remission (CR); n=0; partial remission (PR); n=6 (10%; 95%CI=3.4-18.6); stable disease (SD); n=31 (53%; 95%CI=39.0-64.4); progressive disease (PD); n=19 (33%; 95%CI=20.3-44.1). The median progression-free survival (PFS) rate (n=59) was 4.2 months (range=3.8-5.8 months). The median survival time counted from the start of second-line treatment (n=59) 14.2 months (range 8.2-17.3 months) and the median survival time counted from the start of first-line therapy (n=59) 25 months (range 19-27 months). CONCLUSION: Palliative second-line treatment according to the AIO regimen plus irinotecan offers both a favourable toxicity profile and promising efficacy in second-line and palliative sequential therapy.

The impact of hospitalization on the performance of capsule endoscopy (CE).

BACKGROUND: For proper evaluation of capsule endoscopy (CE), a complete examination is necessary. AIM: We evaluated risk factors of an incomplete CE with focus on patient hospitalization. METHODS: We retrospectively evaluated 161 consecutive patients who underwent CE between 01.07.2013 and 13.03.2016. Main indications were active bleeding, iron deficiency anemia (IDA), inflammatory bowel disease (IBD), abdominal pain, and familial adenomatous polyposis (FAP). RESULTS: We report the results of 103 in-patients and 56 out-patients. Eighty-two patients were male, average age was 58.9 years (range 18-90). Indications for CE were active bleeding (103 patients), IDA and IBD (16 patients), and FAP, abdominal pain and others (eight examinations each). All FAP patients were out-patients, but showed the longest small bowel transit time (SBTT) of 443.6min (p=0.0001). The shortest SBTT was found in out-patients without FAP (267.5min, p<0.05). In the in-patient group, nine endoscopies did not record the entire small bowel (8.7%) due to battery depletion, compared with only one incomplete examination in the out-patients (1.8%, p=0.036). We found pathologic lesions in the last 30min of the SBTT in 43 patients, and this indicates the necessity for complete examination. Thirteen of these 43 patients showed major lesions such as ulcers or angiodysplasia in this last region alone. CONCLUSION: In-patients might require special treatment to ensure complete examination, since a considerable amount of pathologies can only be found in the ileum.

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.

Successful Multidisciplinary Treatment with Secondary Metastatic Liver Resection after Downsizing by Palliative Second-Line Treatment of Colorectal Cancer: A Curative Option.

INTRODUCTION: The prognostic outcome following progression after palliative first-line treatment for patients suffering from metastatic colorectal adenocarcinoma is generally poor. Long-term relapse-free survival with palliative second-line treatment may be achieved in only a limited number of individual cases. CASE REPORT: A 37-year-old patient presented with bilobar liver metastases of colon cancer confirmed by histology with wild-type K-RAS (exon 2). Due to progressive disease after eight cycles of first-line therapy with FOLFIRI plus cetuximab, second-line chemotherapy with modified FOLFOX4 (mFOLFOX4) plus bevacizumab was initiated. During four cycles of mFOLFOX4 plus bevacizumab (2 months), no higher-grade toxicity occurred. Liver MRI with contrast medium revealed downsizing of the segment II/III metastases, as well as regressive, small, faint, hardly definable lesions in segments VI and IVb. The interdisciplinary tumor board of the University of Erlangen thus decided to perform resection of the liver metastases. Segments II and III were resected, and the liver metastases in segments IVa and VI were excised (R0). Histopathology confirmed three of the R0-resected metastases to be completely necrotic, with residual scarring. As perioperative therapy, four additional cycles of mFOLFOX4 plus bevacizumab were administered postoperatively. No higher-grade toxicity was observed. Three years after the initial diagnosis, the patient is relapse free, professionally fully reintegrated, and has an excellent performance status. CONCLUSION: Patients suffering from metastatic colorectal cancer may benefit from multidisciplinary treatment with secondary metastatic liver resection after downsizing by palliative second-line treatment. In individual cases, patients may even have a curative treatment option, provided that close interdisciplinary collaboration exists.

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.

Primary Manifestation of Inflammatory Bowel Disease Following Subcutaneous Autovaccination.

Onset of inflammatory bowel disease [IBD] is nowadays seen as an interplay or a combination of genetic susceptibility, disturbed intestinal immunity, and environmental factors including gut microbiome. However, the initiation of inflammation and progression to IBD pathogenesis in a given individual is poorly understood. In this case report we describe the clinical course of a 17-year-old female patient developing symptoms suggestive of IBD after 'autovaccine therapy', in which sterilised samples of the patient's own stool were injected subcutaneously for improvement of her general immunity. The patient presented with a severe onset of disease, which was first suspected to be ulcerative colitis on outpatient examination and was later corrected to IBD with Crohn's-like features due to high systemic inflammation, mixed lymphocytic-granulocytic infiltrates in gastric biopsies, and further characteristics suggestive of Crohn's disease. A prolonged and complicated course was seen with intermittent steroid dependency in the long term. Numerous publications postulate that [auto-]immune reactions against resident bacterial stool flora may play a role in IBD. It is possible that in this patient tolerance to endogenous bacteria was disrupted by systemic pro-inflammatory mechanisms induced by autovaccination.

Excretion of urinary histamine and N-tele methylhistamine in patients with gastrointestinal food allergy compared to non-allergic controls during an unrestricted diet and a hypoallergenic diet.

BACKGROUND: Patients with gastrointestinal food allergy are characterised by increased production of mast cell derived mediators upon allergen contact and present often with unspecific symptoms. The aim of this study was to evaluate urinary histamine and methylhistamine excretion in patients with food allergy and to compare their values with food-tolerant controls. METHODS: In a retrospective case control study the urinary excretion parameters were analysed from 56 patients (40.9, 19 - 58 years) in whom later food challenge tests confirmed food allergy. During their diagnostic work-up urine was collected during a 12-h period under an unrestricted diet with staple foods and a hypoallergenic potato-rice-diet (each 2 days). Healthy controls underwent the same diet types to define normal excretion parameters. Urinary histamine and n-methylhistamine were determined by ELISA or tandem mass spectrometry, respectively, and were expressed as median (25 - 75% range, µg/mmol creatinine x m(2)BSA). RESULTS: During unrestricted diet urinary histamine was significantly higher in gastrointestinal food allergy than healthy controls (1.42, 0.9 - 2.7 vs 0.87, 0.4 - 1.3; p < 0.0001), while the difference between both groups became marginal during potato-rice diet (1.30, 0.7 - 2.1 vs 1.05, 0.5 - 1.5; p = 0.02). N-methylhistamine was found to be significantly elevated in gastrointestinal food allergy both during unrestricted diet (7.1, 5.0 - 11.2) and potato-rice diet (5.7, 3.7 - 8.7) compared to controls (p < 0.0001). Interestingly, urinary methylhistamine excretion (p < 0.004) and clinical symptom score (p < 0.02) fell significantly when the diet was switched from unrestricted to hypoallergenic food, but was not correlated with symptom scores. CONCLUSIONS: In gastrointestinal food allergy significantly higher levels of urine histamine and methylhistamine excretion were found under unrestricted diet, reflecting an increased secretion of histamine due to offending foods. Measurement of urinary n-methylhistamine levels may help to find out patients with increased histamine production and/or food-allergen induced clinical symptoms, respectively.

Arthroscopic treatment of bilateral snapping scapula syndrome: a case report and review of the literature.

Snapping scapula syndrome represents a rare entity in shoulder surgery. Clinically, it presents as shoulder pain and loud crepitus during shoulder movement. Moreover, glenohumeral bursitis can cause additional pain. Snapping scapula syndrome is caused by an increased angulation of the superomedial part of the scapula combined with bursitis. Other common causes such as subscapular osteochondroma or rib fracture non-unions were excluded. We report a 24-year-old female patient with persisting shoulder pain and disturbing crepitus during movement of the left shoulder. Radiographic examination revealed increased angulation of the superomedial scapula on both sides and MRI, bursitis of the left shoulder. The patient was successfully treated with minimally invasive arthroscopic trimming of the prominent osseous formation at the left scapula combined with bursectomy. Additionally, specific pain-adapted physiotherapeutic exercises of both shoulders were performed. The patient had a pain-free shoulder movement without crepitus on both sides at the 6th month follow-up.

Periprosthetic femoral fracture - an interdisciplinary challenge.

BACKGROUND: The increasing implantation rates of total hip and knee prostheses have been accompanied by a corresponding rise in periprosthetic fractures (PPF), most often affecting the femur. METHOD: This review is based on a selective search of the PubMed database for articles in English and German. The search was carried out with a set of pertinent medical subject headings (MeSH) and as a free text search employing a logical combination of search terms (evidence grade III-IV). RESULTS: Soft-tissue-sparing, stable-angle plate osteosynthesis with a firmly seated implant is a safe treatment of periprosthetic femoral fracture (PPFF). A correct assessment of the stability of the prosthesis is a prerequisite for the success of treatment. A loose prosthesis must be surgically revised, and a failed osteosynthesis can also necessitate revision of the prosthesis. The conservative management of PPFF is generally not indicated, as it has a high complication rate. CONCLUSION: The treatment of periprosthetic fractures requires competence, not just in osteosynthetic techniques, but also in endoprosthesis implantation and revision. Careful preoperative planning to select the proper treatment is essential, and the necessary equipment must be on hand.

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.