EndoClot Polysaccharide Hemostatic System in Nonvariceal Gastrointestinal Bleeding: Results of a Prospective Multicenter Observational Pilot Study.

BACKGROUND AND STUDY AIMS: Hemostatic powders have been introduced to improve the management of gastrointestinal (GI) bleeding and to extend the variety of tools available for emergency endoscopy. The aim of the present pilot study was to evaluate the indication profiles and the short-term outcome of EndoClot. PATIENTS, MATERIALS AND METHODS: In a prospective observational pilot study patients with acute nonvariceal GI bleeding were included. Primary or secondary application of EndoClot was assessed. Hemoglobin, prothrombine time and platelets were documented before and after hemostasis. The efficacy of EndoClot was assessed 72 hours and 1 week after application. RESULTS: Seventy patients with acute GI bleeding were recruited into the study. Eighty-three percent (58/70) of the patients had upper and 17% (12/70) had lower GI bleeding. In the upper GI tract treatment success was achieved in 64% (30/47, 95% confidence interval, 50%-76%) after primary use and in all patients, when used after established techniques had failed (95% confidence interval, 70%-100%). In lower GI bleeding hemostasis was achieved in 83% of cases (10/12, 95% confidence interval 54%-97%). Rebleeding occurred in 11% (8/70), in 10% EndoClot served as a bridge to surgery (7/70). CONCLUSIONS: EndoClot expanded the therapeutic options in the management of GI bleeding. It was applicable as a monotherapy or in combination with other techniques from oozing bleeding type or lower. It was most effective in diffuse or extensive bleeding activity or when access to the bleeding vessel was difficult. EndoClot can be applied as a bridge to surgery when classical methods of hemostasis have failed.

EUS-guided Trucut needle biopsies as first-line diagnostic method for patients with intestinal or extraintestinal mass lesions.

INTRODUCTION: Fine-needle aspiration (FNA) is a well-established technique to obtain cytological specimens, but it does not permit the extraction of histological tissue-core samples, which, if available, may increase the yield and accuracy of the histopathological diagnosis. This prospective study was designed to assess the yield and diagnostic accuracy of endoscopic ultrasound (EUS)-guided Trucut needle biopsy (TNB) as first-line diagnostic method for suspected malignant lesions identified by upper gastrointestinal EUS. METHODS: In a prospective case series, 24 consecutive patients (14 women; median age, 68 (range, 38-84) years) with suspected malignancy underwent EUS-TNB with a 19-gauge needle. EUS was performed with a linear scanning echo endoscope. When the EUS-TNB device did not collect adequate samples, subsequent EUS-FNA was performed. The presence or absence of malignancy was confirmed by postoperative histopathology or diagnostic imaging follow-up for at least 9 months. RESULTS: Adequate tissue specimens were obtained in 20 of 24 (83%) patients by TNB. An accurate diagnosis was achieved in 19 of 20 (95%) patients in whom TNB was successful with a sensitivity and specificity of 93% and 100%, respectively. In 11 patients malignant disease was found, whereas 8 patients showed benign lesions on TNB-obtained histopathology. Thirteen patients underwent additional EUS-FNA. The diagnosis by TNB was confirmed in seven of nine (78%) patients with additional FNA. In three of four patients with inadequate TNB, the diagnosis was established by FNA. The overall accuracy of EUS-TNB was 79% (19/24) for all patients and 92% (22/24) with subsequent FNA. The positive and negative predictive values for the diagnosis of a malignant lesion by EUS-TNB were 57.9% and 88.9%, respectively. Neither method had any procedure-related complications. CONCLUSIONS: EUS-guided TNB is a safe and accurate technique to obtain core specimen for histopathologic diagnosis in patients with suspected malignancies on upper gastrointestinal EUS. FNA can serve as rescue technique and should be performed if TNB fails to obtain adequate tissue samples.

Predictors of clinical response to gluten-free diet in patients diagnosed with diarrhea-predominant irritable bowel syndrome.

BACKGROUND & AIMS: Gluten sensitivity might cause abdominal symptoms in the absence of villous atrophy. We examined the prevalence of celiac disease-associated serum antibodies in diarrhea-dominant irritable bowel syndrome (d-IBS) patients and their efficacy in combination with HLA-DQ2 expression to predict the response to gluten-free diet. METHODS: HLA-DQA1*0501/DQB1*0201 expression and celiac disease-associated IgA and IgG serum antibodies against gliadin and tissue-transglutaminase were measured in 145 patients with d-IBS, 74 patients with untreated and treated celiac disease, and 57 patients with active IBD. Follow-up antibody levels, stool frequency, and gastrointestinal symptom scores were determined in 41 d-IBS patients (26 women, 15 men; median age, 46 years, range, 30-67 years) who participated in a nonrandomized evaluation of 6 months of gluten-free diet. RESULTS: Increased celiac disease-associated serum IgG, but not IgA, was found in the majority of patients with treated (55%) as in most patients with untreated celiac disease (97%). In d-IBS patients, celiac disease-associated serum IgG antibodies (37%) and HLA-DQ2 expression (39%) were more frequent than in IBD patients (18% and 23%, respectively). After 6 months of gluten-free diet, stool frequency and gastrointestinal symptom score returned to normal values in 60% of d-IBS patients who were positive and in 12% who were negative for HLA-DQ2 and celiac disease-associated serum IgG; both parameters combined yielded positive and negative predictive values of 56% (95% confidence interval, 30%-80%) and 88% (69%-97%), respectively. CONCLUSIONS: Celiac disease-associated serum IgG and HLA-DQ2 expression can identify likely responders to gluten-free diet in d-IBS patients.

Mutagenicity testing with transgenic mice. Part II: Comparison with the mouse spot test.

The mouse spot test, an in vivo mutation assay, has been used to assess a number of chemicals. It is at present the only in vivo mammalian test system capable of detecting somatic gene mutations according to OECD guidelines (OECD guideline 484). It is however rather insensitive, animal consuming and expensive type of test. More recently several assays using transgenic animals have been developed. From data in the literature, the present study compares the results of in vivo testing of over twenty chemicals using the mouse spot test and compares them with results from the two transgenic mouse models with the best data base available, the lacI model (commercially available as the Big Blue(R) mouse), and the lacZ model (commercially available as the Mutatrade mark Mouse). There was agreement in the results from the majority of substances. No differences were found in the predictability of the transgenic animal assays and the mouse spot test for carcinogenicity. However, from the limited data available, it seems that the transgenic mouse assay has several advantages over the mouse spot test and may be a suitable test system replacing the mouse spot test for detection of gene but not chromosome mutations in vivo.

Gd-EOB-DTPA-enhanced MR guidance in thermal ablation of liver malignancies.

OBJECTIVE: To evaluate the potency of Gd-EOB-DTPA to support hepatic catheter placement in laser ablation procedures by quantifying time-dependent delineation effects for instrumentation and target tumor within liver parenchyma. Monitoring potential influence on online MR thermometry during the ablation procedure is a secondary aim. MATERIALS AND METHODS: 30 cases of MR-guided laser ablation were performed after i.v. bolus injection of gadoxetic acid (0.025 mmol/Kg Gd-EOB-DTPA; Bayer Healthcare, Berlin, Germany). T1-weighted GRE sequences were used for applicator guidance (FLASH 3D) in the catheter placement phase and for therapy monitoring (FLASH 2D) in the therapy phase. SNR and consecutive CNR values were measured for elements of interest plotted over time both for catheter placement and therapy phase and compared with a non-contrast control group of 19 earlier cases. Statistical analysis was realized using the paired Wilcoxon test. RESULTS: Sustainable signal elevation of liver parenchyma in the contrast-enhanced group was sufficient to silhouette both target tumor and applicator against the liver. Differences in time dependent CNR alteration were highly significant between contrast-enhanced and non-contrast interventions for parenchyma and target on the one hand (p = 0.020) and parenchyma and instrument on the other hand (p = 0.002). Effects lasted for the whole procedure (monitoring up to 60 min) and were specific for the contrast-enhanced group. Contrasting maxima were seen after median 30 (applicator) and 38 (tumor) minutes, in the potential core time of a multineedle procedure. Contrast influence on T1 thermometry for real-time monitoring of thermal impact was not significant (p = 0.068-0.715). CONCLUSION: Results strongly support anticipated promotive effects of Gd-EOB-DTPA for MR-guided percutaneous liver interventions by proving and quantifying the delineating effects for therapy-relevant elements in the procedure. Time benefit, cost effectiveness and oncologic outcome of the described beneficiary effects will have to be part of further investigations.

The association between IGF-I/IGFBP-3 and subclinical end points: epidemiology faces the limits.

BACKGROUND: The variation in laboratory measurements represents a challenge in clinical practice and epidemiological research. The use of different analytical platforms might have led to different results, which were often discussed in the interpretation of conflicting results. We aim to study the impact of two different IGF-I and IGF binding protein 3 assays on published epidemiological studies. METHODS: We compared epidemiological results based on the previous gold standard Nichols Advantage, which is no longer available, with these based on the IDS-iSYS assay. The latter follows the recently proposed Keswick criteria. We reinvestigated published association studies between IGF-I or IGF binding protein 3 and anthropometry, subclinical cardiovascular diseases including intima-media thickness or left ventricular mass index, and hard end points like mortality and single-nucleotide polymorphisms of our genome-wide association study in the Study of Health in Pomerania. RESULTS: We demonstrated that there are significant differences in the associations of IGF-I measured by the Nichols or IDS-iSYS assay and subclinical outcomes including intima-media thickness and left ventricular mass index. However, concerning hard outcomes like mortality or single-nucleotide polymorphisms, our analyses revealed similar results with comparable regression estimates. CONCLUSION: With our study we queried not only the accuracy of measurement but also the effect of different methods on study results. The establishment of laboratory standards like the Keswick criteria should be enforced to allow reliable comparisons of different methods and thus clinical and epidemiological studies. Single-center studies have to be interpreted carefully. Moreover, to assure the reliability of studies, their results should be replicated in a meta-analysis, and a generated hypothesis by epidemiology should be proven by intervention studies.

High rates of complications and substantial mortality in both types of refractory sprue.

INTRODUCTION: Refractory sprue (RS) is a rare malabsorption syndrome defined by persisting small bowel villous atrophy despite a strict gluten-free diet. The clinical picture and long-term outcome of RS is highly variable and is not well described. AIM: To define underlying and accompanying diseases and clinical outcome in consecutive patients with RS. PATIENTS AND METHODS: Clinical and histological data from patients with RS at our department were analyzed retrospectively. RS was defined as villous atrophy and malabsorption despite a strict gluten-free diet persisting without improvement for more than 6 months or requiring earlier therapeutic intervention. RESULTS: Thirty-two patients with RS were identified (23 RS type I, nine RS type II). Follow-up period was 55 (12-372) months. Two patients progressed from RS type I into type II. Thrombembolic events occurred in nine cases, and additional autoimmune diseases were found in 17 patients. Overt intestinal T-cell lymphoma developed in four patients with RS type II. Three patients with RS type II died during the observation period owing to intestinal T-cell lymphoma and four with RS type I owing to infectious complications. Five-year cumulative survival was 90% (95% confidence interval 76-100) in patients with RS type I and higher than in patients with RS type II (53%, 12-94%; P<0.05). CONCLUSION: RS comprises a very heterogenous group of patients with long-term survival seen even in single patients with RS type II. Overall, survival is shorter in RS type II in comparison with RS type I. Patients with RS type I, however, show similar rates of disease-related complications as well as substantial mortality.

Pancreatic pseudocysts: observation, endoscopic drainage, or resection?

BACKGROUND: Pancreatic pseudocysts are a common complication of acute and chronic pancreatitis. They are diagnosed with imaging studies and can be treated successfully with a variety of methods: endoscopic transpapillary or transmural drainage, percutaneous catheter drainage, laparoscopic surgery, or open pseudocystoenterostomy. METHODS: Relevant publications that appeared from 1975 to 2008 were retrieved from the MEDLINE, PubMed and EMBASE databases for this review. RESULTS: Endoscopic pseudocyst drainage has a high success rate (79.2%) and a low complication rate (12.9%). Percutaneous drainage is mainly used for the emergency treatment of infected pancreatic pseudocysts. Open internal drainage and pseudocyst resection are surgical techniques with high success rates (>92%), but also higher morbidity (16%) and mortality (2.5%) than endoscopic treatment (mortality 0.7%). Laparoscopic pseudocystoenterostomy, a recently introduced procedure, is probably similar to the endoscopic techniques with regard to morbidity and mortality. CONCLUSIONS: An interdisciplinary approach is best suited for the safe and effective stage-specific treatment of pancreatic pseudocysts. The different interventional techniques that are currently available have yet to be compared directly in randomized trials.

Through the endoscope balloon dilation of ileocolonic strictures: prognostic factors, complications, and effectiveness.

BACKGROUND/AIMS: About half of all Crohn's disease (CD) patients undergo surgery at some point, many because of strictures. An alternative possibility is to dilate strictures endoscopically. However, little is known about prognostic factors. PATIENTS AND METHODS: Thirty-two patients with primary CD (n=2), radiogenic strictures (n=1), or postoperative strictures (27 because of CD; 2 after resection because of cancer), were planned to undergo colonoscopic dilatation of which 25 patients were dilated (10 men; 15 women; median age 48). Length of stenosis, diameter of stricture, balloon size, smoking status, ulcer in the stricture, passage postdilatation, hemoglobin level, complications, redilatation, and subsequent surgery were recorded. Only patients with at least 6 months follow up were included. RESULTS: Five out of 32 patients had no stenosis, marked inflammation, or fistulas adjacent to the stricture. One patient each had a long stricture (8 cm) or a filiform stenosis ruling out dilatation [technical success, 25/27 (92.6%)]. Among these 25 patients, 39 colonoscopies with 51 dilatations were performed. After a single dilatation, 52% were asymptomatic while 48% needed another intervention, half of them surgery. Bleeding without need for transfusion occurred in 3 out of 39 colonoscopies and one perforation required surgery. Significant prognostic factors were smoking and ulcers in the stricture (P<0.05 each). Some ulcers led to intussusception requiring surgery in spite of good dilatation results. CONCLUSION: Through the endoscope balloon stricture dilatation is a relatively safe and often effective treatment modality in ileocolonic strictures. The presence of ulcers in the stricture have a worse outcome as do smokers.

Esophageal giant ulcer in primary human immunodeficiency virus infection is associated with an infiltration of activated T cells.

Primary human immunodeficiency virus (HIV) infection is a rarely diagnosed disease. The intestinal lymphocyte population represents a primary target of infection, virus replication, as well as cell infiltration and activation. The purpose of this study was to describe a patient suffering from esophageal giant ulcer as a clinical manifestation of primary HIV. In the present case of primary HIV infection a giant ulcer of the esophagus was diagnosed as the clinical manifestation. An upper endoscopy was performed and the biopsy specimens were further processed for immunohistochemical stainings characterizing the cellular infiltrate as well as cytokine production. In addition, seroconversion was documented and total viral load was determined. The esophageal ulceration presented the clinical manifestation of primary HIV infection since other causes of esophageal ulcerations could be excluded. The ulceration revealed an inflammatory infiltrate consisting of both CD4(+) and CD8(+) T cells. The vast majority of these cells expressed the activation marker CD38 and several cells showed interferon-gamma and interleukin-2 production. Furthermore, a substantial number of tissue infiltrating CD8(+) T cells expressed the cytotoxic molecule perforin. In addition, the HIV antigen p24 could be detected in the inflammatory infiltrate. Subsequent steroid treatment resulted in a relief of symptoms and healing of the ulcerations. These observations strongly suggest that infiltration of activated T cells plays a crucial role in the pathogenesis of giant ulcers during primary HIV infection.

Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum.

BACKGROUND: Giardia lamblia causes infection of the small intestine, which leads to malabsorption and chronic diarrhoea. AIM: To characterise the inherent pathomechanisms of G lamblia infection. METHODS: Duodenal biopsy specimens from 13 patients with chronic giardiasis and from controls were obtained endoscopically. Short-circuit current (I(SC)) and mannitol fluxes were measured in miniaturised Ussing chambers. Epithelial and subepithelial resistances were determined by impedance spectroscopy. Mucosal morphometry was performed and tight junction proteins were characterised by immunoblotting. Apoptotic ratio was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling staining. RESULTS: In giardiasis, mucosal surface area per unit serosa area was decreased to 75% (3%) of control, as a result of which epithelial resistance should increase. Instead, epithelial resistance of giardiasis biopsy specimens was decreased (19 (2) vs 25 (2) Omega cm(2); p<0.05) whereas mannitol flux was not significantly altered (140 (27) vs 105 (16) nmol/h/cm(2)). As structural correlate, reduced claudin 1 expression and increased epithelial apoptosis were detected. Furthermore, basal I(SC) increased from 191 (20) in control to 261 (12) microA/h/cm(2) in giardiasis. The bumetanide-sensitive portion of I(SC) in giardiasis was also increased (51 (5) vs 20 (9) microA/h/cm(2) in control; p<0.05). Finally, phlorizin-sensitive Na(+)-glucose symport was reduced in patients with giardiasis (121 (9) vs 83 (14) microA/h/cm(2)). CONCLUSIONS: G lamblia infection causes epithelial barrier dysfunction owing to down regulation of the tight junction protein claudin 1 and increased epithelial apoptoses. Na(+)-dependent d-glucose absorption is impaired and active electrogenic anion secretion is activated. Thus, the mechanisms of diarrhoea in human chronic giardiasis comprise leak flux, malabsorptive and secretory components.

Diagnostic value of endoscopy for the diagnosis of giardiasis and other intestinal diseases in patients with persistent diarrhea from tropical or subtropical areas.

OBJECTIVE: Upper endoscopy has been suggested as a valuable tool in the diagnosis of giardiasis. The aim of this study was to compare two methods based on endoscopy, i.e. microscopy of duodenal fluid and histology, with a fluorescent-antibody assay for the detection of Giardia lamblia cysts in stool specimens. The role of endoscopy in the identification of other causes of chronic diarrhea acquired during travel abroad was also evaluated. MATERIAL AND METHODS: Thirty-one patients (9 F, 22 M, median age 39 years, range 19-63 years) with persistent diarrhea after returning from tropical or subtropical areas agreed to undergo upper gastrointestinal endoscopy before and after treatment. Lower gastrointestinal endoscopy was subsequently performed. Three stool samples from each patient were examined using the direct fluorescent-antibody assay (DFA) for the detection of G. lamblia, and by routine methods for other protozoal and bacterial enteric pathogens. Each patient underwent upper endoscopy and biopsies and duodenal fluid samples were taken. In 12 patients a further lower endoscopy was performed. RESULTS: In 16 patients G. lamblia was detected in stool samples by DFA (relative sensitivity: 100%). Histology of duodenal biopsies and microscopy of duodenal fluids allowed diagnosis of giardiasis to be made in only 8, and 3 patients, respectively (relative sensitivities: 21% and 44%). Besides giardiasis, upper endoscopic examination revealed an alternative diagnosis (tropical sprue), whereas six additional diagnoses were made by colonoscopy. In six patients the cause of chronic diarrhea remained unclear. CONCLUSIONS: Compared to stool examinations using DFA, upper endoscopy is less sensitive for the diagnosis of giardiasis. In patients with negative stool examinations, lower endoscopy yields relevant diagnoses more often than upper endoscopy.

The fine structure of the lateral-line organs of larval Ichthyophis (Amphibia: Gymnophiona).

Light and electron microscopic observations of the lateral-line organs of larval Ichthyophis kohtaoensis confirmed earlier reports of the occurrence of two different types of lateral-line organs. One type, the ampullary organ, possesses 15-26 egg-shaped sensory cells. Each sensory cell extends a single kinocilium surrounded by a few microvilli into the ampullary lumen. This is in contrast to the ampullary organs of urodele amphibians that contain only microvilli. The second type of organ, the ordinary neuromast, has 15-24 pear-shaped sensory cells arranged in two to three rows. Each sensory cell shows a kinocilium that is asymmetrically placed with respect to both a basal plate and approximately 60 stereovilli. The sensory cells of ampullary organs are always separated by supporting cells; those of neuromasts are occasionally in contact with one another. Numerous (neuromasts) or few (ampullary organs) mantle cells separate the organs from the epidermal cells. Only afferent synapses are found in the ampullary organs whereas vesicle-filled fibers together with afferent nerve terminals are found in neuromasts. Both organs contain similarly sized presynaptic spheres adjacent to the afferent fibers. It is suggested that the neuromasts have a mechanoreceptive function, whereas the ampullary organs have an electroreceptive one.