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The performance of endoscopic retrograde cholangiopancreaticography (ERCP) in patients with post-surgically altered anatomy is technically ambitious. Our study aimed at comparing a cohort of patients having successfully undergone single-balloon enteroscopy (SBE)-assisted ERCP to those in whom SBE-ERCP failed.This trial is a prospective single center cohort study. Participants included 30 patients (median age 69.5 years, range 20-86 years) with previous pancreaticobiliary surgery. First, a conventional ERCP approach was attempted in all patients. Additionally, those patients in whom prior conventional ERCP had failed underwent SBE-ERCP (n = 26). Patients' baseline characteristics were retrieved and patient cohorts with and without successful SBE-ERCPs were compared and analyzed. Statistical analysis was applied. Univariate analysis was performed to detect possible risk factors of SBE-ERCP failure.The overall success rate of SBE-ERCP, including two patients with percutaneous transhepatic cholangiography- assisted rendezvous technique was 65.4% (17/26). Patients with malignant obstructive cholestasis had a significantly higher failure rate compared to those with benign strictures (84.2% vs. 14.2%, p0.001).SBE-ERCP is a promising tool for diagnostic and therapeutic procedures in the pancreaticobiliary system of selected, previously operated patients with failure of conventional ERCP. However, higher failure rates in malignant biliary obstruction should be taken into account.

High calcium concentrations are an established risk factor for pancreatitis. We have investigated whether increasing magnesium concentrations affect pathological calcium signals and premature protease activation in pancreatic acini, and whether dietary or intraperitoneal magnesium administration affects the onset and course of experimental pancreatitis.Pancreatic acini were incubated with up to 10 mM magnesium; [Ca(2+)](i) (fura-2AM) and intracellular protease activation (fluorogenic substrates) were determined over 60 min. Wistar rats received chow either supplemented or depleted for magnesium (300 ppm to 30 000 ppm) over two weeks before pancreatitis induction (intravenous caerulein 10 µg/kg/h/4 h); controls received 1 µg/kg/h caerulein or saline. C57BL6/J mice received four intraperitoneal doses of magnesium (NaCl, Mg(2+) 55 192 or 384 mg/kg bodyweight) over 72 h, then pancreatitis was induced by up to eight hourly supramaximal caerulein applications. Pancreatic enzyme activities, protease activation, morphological changes and the immune response were investigated.Increasing extracellular Mg(2+) concentration significantly reduced [Ca(2+)](i) peaks and frequency of [Ca(2+)](i) oscillations as well as intracellular trypsin and elastase activity. Magnesium administration reduced pancreatic enzyme activities, oedema, tissue necrosis and inflammation and somewhat increased Foxp3-positiv T-cells during experimental pancreatitis. Protease activation was found in animals fed magnesium-deficient chow-even with low caerulein concentrations that normally cause no damage.Magnesium supplementation significantly reduces premature protease activation and the severity of pancreatitis, and antagonises pathological [Ca(2+)](i) signals. Nutritional magnesium deficiency increases the susceptibility of the pancreas towards pathological stimuli. These data have prompted two clinical trials on the use of magnesium in patients at risk for pancreatitis.

Bile duct stones that cannot be removed endoscopically are still a challenge in interventional gastroenterology. Extracorporeal shockwave lithotripsy (ESWL) with subsequent endoscopic extraction of residual fragments is an established treatment option if other endoscopic means are not successful. Our study aimed to investigate the efficacy and safety of ESWL for clearance of refractory bile duct stones.A total of 73 consecutive patients treated for refractory choledocholithiasis with ESWL were retrospectively analyzed. Success and complication rates were calculated.Complete stone clearance was achieved in 66 cases (90%). Patients with complete clearance had a significantly lower body mass index or BMI (25.55 ± 5.01 kg/m² vs. 31.60 ± 6.26 kg/m², p = 0.035) and needed less ESWL treatments (3.61 ± 1.87 vs. 5.00 ± 1.63, p = 0.048). A relevant drop of hemoglobin occurred significantly more often in the group with partial clearance (43% vs. 6%, p = 0.005).ESWL proves to be an excellent clearing approach to refractory bile duct stones with high success rates. However, obesity is one risk factor for ESWL failure and higher procedural hazard.

Background and Aims Pneumocystis jirovecii pneumonia also known as pneumocystis pneumonia (PCP) is an opportunistic respiratory infection in human immunodeficiency virus (HIV) patients that may also develop in non-HIV immunocompromised persons. The aim of our study was to evaluate mortality predictors of PCP patients in a tertiary referral centre. Methods Fifty-one patients with symptomatic PCP were enrolled in the study. The patients had either HIV infection (n = 21) or other immunosuppressive conditions (n = 30). Baseline characteristics (e.g. age, sex and underlying disease) were retrieved. Kaplan–Meier analysis was employed to calculate survival. Comparisons were made by log-rank test. A multivariate analysis of factors influencing survival was carried out using the Cox regression model. Chi-squared test and Wilcoxon–Mann–Whitney test was applied as appropriate. Results The median survival time for the HIV group was >120 months compared with 3 months for the non-HIV group (P = 0.009). Three-month survival probability was also significantly greater in the HIV group compared with the non-HIV group (90% vs 41%, P = 0.002). In univariate log-rank test, intensive care unit (ICU) necessity, HIV negativity, age >50 years, haemoglobin 5 mg/dL and multiple comorbidities were significant negative predictors of survival. In the Cox regression model, ICU and HIV statuses turned out to be independent prognostic factors of survival. Conclusion PCP is a serious problem in non-HIV immunocompromised patients in whom survival outcomes are worse than those in HIV patients.

Endoscopic ultrasound (EUS) is considered a gold standard in the initial staging of esophageal cancer. There is an ongoing debate whether EUS is useful for tumor staging after neoadjuvant chemotherapy (NAC). Ninety-five patients with esophageal cancer were retrospectively analyzed. In 45 patients, EUS was performed prior to and after NAC, while 50 patients had no induction therapy. Histological correlation through surgery was available. uT/uN classifications were compared to pT/pN stages. Statistical analysis included calculation of sensitivity, specificity, and accuracy rates. Agreement between endosonography and T staging was assessed with Cohen's kappa statistics. For those patients with prior NAC, overall accuracy of yuT and yuN classification was 29 and 62%, respectively. Sensitivity, specificity, and accuracy rates for local tumor extension after NAC were as follows (%): T1: –/97/84, T2: 13/76/53, T3:86/29/46, T4:20/100/91, T1/2: 27/83/56, T3/4: 89/31/56. Cohen's kappa indicated poor agreement (kappa = 0.129) between yuT classification and ypT stage. Relative to positive lymph node detection, sensitivity and specificity were 100 and 6%, respectively (kappa = 0.06). T stage was overstaged in 23 (51%) and understaged in seven (16%) patients. EUS is an unreliable tool for staging esophageal cancer after NAC. Overstaging of the T stage is common after NAC.

Zusammenfassung Grundlage fur die tabellarische Darstellung der fachspezifischen Differenzialdiagnosen ist die klinisch relevante Schmerzlokalisation. Sie erfolgt uber die Zuordnung der Schmerzsymptomatik zu den Regionen rechter Oberbauch, Epigastrium, linker Oberbauch, mittleres Abdomen, rechter Unterbauch, mittlerer Unterbauch, linker Unterbauch, Flanken sowie zum gesamten Abdomen. Da die Schmerzen auch in die Bauchdecken und in den Thorax ausstrahlen konnen, sind fur diese Bereiche ebenfalls die Differenzialdiagnosen aufgefuhrt. Innerhalb der jeweiligen Lokalisation sind die Differenzialdiagnosen, die entsprechenden wegweisenden Nebensymptome und Befunde sowie die Moglichkeiten zur Sicherung der Diagnose nochmals unterteilt. Praxisnah wird zwischen akuten, subakuten und chronischen Schmerzen und, soweit relevant, Schmerzsymptomen mit und ohne Abwehrspannung unterschieden.

BACKGROUND AND STUDY AIMS: Acute pancreatitis is considered a relevant major complication following endoscopic retrograde cholangiopancreatography (ERCP); according to literature data, the incidence varies between 1.5 % and 17 %. In the present study, we aimed to identify potentially new, hitherto unknown risk factors for post-ERCP pancreatitis. PATIENTS AND METHODS: A total of 2364 ERCP procedures performed in 1275 patients during the years 2004 - 2008 were included in the study. Post-ERCP pancreatitis was defined as acute abdominal pain within 48 hours following ERCP with at least 3-fold elevated levels of serum lipase and a requirement for analgesic drugs for at least 24 hours. The severity of the pancreatitis was determined using the Imrie score. RESULTS: In our cohort study a total of 54 different patients (2.3 %) developed post-ERCP pancreatitis. In 50 of these patients (92.6 %) the pancreatitis was mild; in 54 (7.4 %) it was severe. Patients with post-ERCP pancreatitis had highly significantly lower bilirubin levels than patients who did not have post-ERCP pancreatitis ( P < 0.001). Length of hospital stay, duration of analgesics, and need for analgesic drugs were significantly higher in patients suffering from severe pancreatitis ( P ≤ 0.01). In multivariate analysis, among other, already well-described risk factors we identified intraductal ultrasonography as another risk factor for post-ERCP pancreatitis, with a hazard ratio of 2.41 ( P = 0.004). CONCLUSIONS: According to our retrospective data, intraductal ultrasonography seems to be another independent risk factor for developing post-ERCP pancreatitis, which needs to be further elucidated in prospective studies.

Background and study aims Double-balloon enteroscopy (DBE) is the first choice endoscopic technique for small-bowel visualization. However, preparation and handling of the double-balloon enteroscope is complex. Recently, a single-balloon enteroscopy (SBE) system has been introduced as being a simplified, less-complex balloon-assisted enteroscopy system. Patients and methods This study was a randomized international multicenter trial comparing two balloon-assisted enteroscopy systems: DBE vs. SBE. Consecutive patients referred for balloon-assisted enteroscopy were randomized to either DBE or SBE. Patients were blinded with regard to the type of instrument used. The primary study outcome was oral insertion depth. Secondary outcomes included complete small-bowel visualization, anal insertion depth, patient discomfort, and adverse events. Patient discomfort during and after the procedure was scored using a visual analog scale. Results A total of 130 patients were included over 12 months: 65 with DBE and 65 with the SBE technique. Patient and procedure characteristics were comparable between the two groups. Mean oral intubation depth was 253 cm with DBE and 258 cm with SBE, showing noninferiority of SBE vs. DBE. Complete visualization of the small bowel was achieved in 18 % and 11 % of procedures in the DBE and SBE groups, respectively. Mean anal intubation depth was 107 cm in the DBE group and 118 cm in the SBE group. Diagnostic yield and mean pain scores during and after the procedures were similar in the two groups. No adverse events were observed during or after the examinations. Conclusions This head-to-head comparison study shows that DBE and SBE have a comparable performance and diagnostic yield for evaluation of the small bowel.

Cronkhite-Canada syndrome (CCS) is a rare non-familial disorder with multiple gastrointestinal polyps and ectodermal changes. Adenomatous and carcinomatous changes have been reported. Video capsule endoscopy is a useful non-invasive tool to reveal polypoid lesions of the gastrointestinal tract suspicious for malignancy. We report a case of a patient with CCS with excessively elongated intestinal villi resembling dense sea grass under water as well as multiple polyps of the intestinal mucosa revealed by video capsule endoscopy. This report presents for the first time small bowel video sequences of CCS qualifying video capsule endoscopy for screening purposes and early detection of malignancy.

Hepatocellular carcinoma (HCC) is the most common tumor in cirrhotic patients with a median survival of only 8-10 months if untreated. Supraselective transarterial chemoembolization (STACE) is supposed to be a well-established method for treating HCC patients. In the present study, we evaluated the effect of STACE on post-transplant survival in patients with HCC.The charts of 53 HCC patients were retrospectively analyzed. Twenty-seven patients had STACE as a bridging therapy while 26 patients were scheduled for liver transplantation (LTX) without prior STACE therapy. A total of 53% of the patients who underwent LTX preoperatively fulfilled the Milan criteria, while 70.6% fulfilled the expanded University of California, San Francisco (UCSF) transplant criteria. Primary endpoint was the post-transplant survival. Statistical analysis included Kaplan-Meier-method, log rank, and chi square tests.Between the LTX groups (STACE vs. non-STACE), there was no significant difference in terms of age, Child classification, Okuda stage, co-morbidities, underlying disease, and post-transplant survival (p0.05). Independent of prior STACE, however, disease-free survival after LTX was highly significantly prolonged if LTX was performed within 3 months after initial diagnosis of HCC (p0.01) or if patients met the expanded transplant UCSF criteria (p = 0.02). Post-transplant survival did not depend on tumor size.We conclude that STACE performed prior to LTX does not secure any post-transplant survival benefit, while early LTX, i.e. within 3 months after HCC diagnosis, does improve survival regardless of whether STACE was performed or not. Additionally, fulfillment of the expanded transplant UCSF criteria leads to a prolonged post-transplant survival.

The potential role of kinesin and dynein in Golgi scattering and cytoplasmic vacuole formation during acute experimental pancreatitis

Double balloon enteroscopy (DBE) has evolved as one of the most innovative and fast spreading endoscopic procedures in the last decade. With increasing experience of performing endoscopic procedures in the mid gut outside the operating room it is necessary to investigate the effectiveness of DBE regarding therapeutic consequences, long-term efficacy as well as safety.To address this we retrospectively analyzed all DBE performed over a period of 2 years at our department. Furthermore, in order to evaluate long-term effectiveness of DBE procedures we performed a follow-up analysis on all patients, whose DBE procedure was at least 6 months ago. In addition, 100 consecutive patients who underwent DBE were questioned regarding procedure associated complaints using a standardized questionnaire.Retrospective analysis of all DBE procedures performed in our department before November 2006 (n = 545) revealed an overall diagnostic yield of 39.7% and a therapeutic yield of 31.1%. The overall number of major complications accounted to 0.9%. Follow-up analysis revealed a long-term effect of endoscopic interventions in more than 50%, while in those patients with an initially negative DBE long-term follow-up only revealed symptom explaining findings in 17% with the majority of the other patients being asymptomatic during follow-up. Regarding patient related complaints the prospective analysis showed that DBE procedures in general are well tolerated with the most common complaint being meteorism.DBE showed to be a relatively safe and well tolerated procedure. However, more sensitive algorithms are needed to enhance the therapeutic results.

Syndecan-1 (Sdc1) plays a major role in wound healing and modulates inflammatory responses. Sdc1 expression is reduced in lesions of patients with ulcerative colitis. The aim of this study was to investigate the role of Sdc1 in murine dextran sodium sulfate (DSS)-induced colitis. DSS colitis was induced in Sdc1-deficient (knockout (KO)) and wild-type mice by oral administration of 3% DSS. KO mice exhibited a significantly increased lethality as compared with wild-type controls (61 versus 5%, P < 0.05). Impaired mucosal healing and prolonged recruitment of inflammatory cells in KO mice were accompanied by significant up-regulation of tumor necrosis factor-alpha, CC chemokine ligand 3/macrophage inflammatory protein-1alpha, and vascular cell adhesion molecule-1, as determined by histological correlation between 0 and 15 days after colitis induction, TaqMan low-density array analysis, and quantitative real-time PCR. Treatment from days 7 through 14 with enoxaparin, a functional analogue of the Sdc1 heparan sulfate chains, significantly reduced lethality of KO mice due to DSS-induced colitis, which was correlated with improved mucosal healing. In vitro, Sdc1-deficient polymorphonuclear cells displayed increased adhesion to endothelial cells and intercellular adhesion molecule-1, and enoxaparin reverted adhesion to wild-type levels. Small interfering RNA-mediated knockdown of Sdc1 expression resulted in reduced basic fibroblast growth factor-mediated mitogen-activated protein kinase signaling and reduced Caco-2 cell proliferation. We conclude that Sdc1 has a protective effect during experimental colitis. The modification of missing Sdc1 function by heparin analogues may emerge as a promising anti-inflammatory approach.

Objectives To determine the prevalence of Raynaud's phenomenon (RP) in patients with primary Sjogren's syndrome (pSS) and to identify clinical and immunological characteristics associated with this manifestation. Since increased interferon-γ (INF-γ) has been associated with RP, we also compared the INF-γ production in pSS patients with or without RP. Methods RP was diagnosed if pSS patients presented with characteristic sequence of skin color changes of the digits. In uncertain cases noninvasive vascular tests were performed by ultrasound examination. The secretion of INF-γ by peripheral blood mononuclear cells was assessed by enzyme-linked immunospot analysis. Further, we examined the expression of different lymphocyte activation markers (CD25, CD45RO, CD69) on CD4+ T-cells by flow cytometric analysis. Results Thirty-six of 108 patients with pSS had RP. In these patients we found a significantly increased number of INF-γ-secreting peripheral blood mononuclear cells compared with patients without RP or to healthy controls. Further, in patients with RP a significantly increased percentage of CD25-positive T-helper cells was detectable. In addition we found an association of leukopenia, thyroiditis, and lower C3 levels with RP in pSS patients. Conclusions These results suggest a pathogenic role of INF-γ in pSS patients with RP. Whether the RP is immune-mediated or whether INF-γ directly causes vasospasm still remains to be elucidated.

Often long-term low-dosage glucocorticoid therapy cannot be terminated. This is due to the fact that even low doses which are within the physiological replacement range can cause a detectable, though clinically insignificant suppression of the adrenal gland function, resulting in "corticosteroid withdrawal syndrome". Another reason is the fact that it is necessary to be able to suppress undesirable inflammatory reactions caused by the underlying disease. ACTH testing of the adrenal capacity is widespread, but repeated testing may lead to undesirable side effects, such as allergic reactions. This study investigates the usefulness of testing the function of the pituitary-adrenal axis in predicting withdrawal problems. In 21 patients with chronic inflammatory disease who were treated with glucocorticoid doses of 5 to 10 mg prednisolone equivalent daily for a period of 2 to 131 months, stimulation with 100 microg hCRH (human corticotrophin-releasing hormone) was performed prior to the gradual withdrawal of medication. Blood samples were taken at baseline and after 45 minutes to measure ACTH and cortisol levels. Four weeks after steroid withdrawal the patients were reevaluated for signs of a relapse of the underlying disease in order to establish the necessity of reintroducing steroid therapy. This reevalution comprised clinical criteria, laboratory tests and the patients' own assessment of his/her well-being. In sixteen patients who later successfully withdrew from glucocorticoid therapy, a significant increase in cortisal levels was noticed after stimulation with CRH (p < 0.05). In five patients, with whom steroid withdrawal was not successful, baseline levels of cortisol were significantly lower than in the others (p < 0.05) and no sufficient increase was achieved after stimulation with CRH. These results show that successful withdrawal of a long-term low-dosage glucocorticoid therapy depends on the integrity of the pituitary-adrenal axis. Therefore CRH testing for evaluation of the pituitary-adrenal axis can be helpful in identifying patients in whom glucocorticoid withdrawal would be troublesome.

The regulated secretion of pancreatic zymogens depends on a functional cytoskeleton and intracellular vesicle transport. To study the dynamics of tubulin and its motor proteins dynein and kinesin during secretion in pancreatic acinar cells, we infused rats with 0.1 mug/kg/h caerulein. Electron and fluorescence microscopy detected neither dynein nor kinesin at the apical secretory pole, nor on the surface of mature zymogen granules. After 30 min of secretagogue stimulation, kinesin and the Golgi marker protein 58 K were reallocated towards the apical plasma membrane and association of kinesin with tubulin was enhanced. Disruption of acinar cell microtubules had no effect on initial caerulein-induced amylase release but completely blocked secretion during a second stimulus. Our results suggest that mature zymogen granule exocytosis is independent of intact microtubules, kinesin and dynein. However, microtubule-dependent mechanisms seem to be important for the replenishment of secretory vesicles by redistribution of Golgi elements towards the apical cell pole.

Lymph nodes (LNs) are important sentinel organs where antigen-presenting cells interact with T cells to induce adaptive immune responses. In cutaneous infection of mice withLeishmania major, resistance depends on the induction of a T-helper-cell-1 (Th1)-mediated cellular immune response in draining, peripheral LNs. We investigated whether draining, peripheral LNs are absolutely required for resistance againstL. majorinfection. We investigated the course of experimental leishmaniasis in wild-type (wt) mice lacking peripheral LNs (pLNs), which we generated by in utero blockade of membrane-bound lymphotoxin, and in mice lacking pLNs or all LNs due to genetic deletion of lymphotoxin ligands or receptors. wt mice of the resistant C57BL/6 strain without local skin-draining LNs were still able to generate specific T-cell responses, but this yielded Th2 cells. This switch to a Th2 response resulted in severe systemic infection. We also confirmed these results with mice lacking pLNs due to genetic depletion of lymphotoxin-β. The complete absence of LNs due to a genetic depletion of the lymphotoxin-β receptor also resulted in a marked deterioration of disease and a Th2 response. Thus, in the absence of pLNs, anL. major-specific Th2 response is induced in the remaining secondary lymphoid organs, such as the spleen and non-skin-draining LNs. This indicates a critical requirement for pLNs to induce protective Th1 immunity and suggests that whether Th1 or Th2 priming to the same antigen occurs depends on the site of the primary antigen recognition.

Increasing evidence supports the concept of macrophage migration inhibitory factor (MIF) as a central proinflammatory cytokine in autoimmune diseases. To further evaluate its role in systemic sclerosis (SSc), serum levels of MIF were determined by enzyme-linked immunoassay, and correlations to clinical manifestations were analyzed in 43 patients. MIF levels were significantly increased in patients (median, 18.8; range

The purpose of this study was to characterize the action of exogenous PYY, an ileocolonic peptide released by fatty meal, and that released by Heal perfusion with oleate on intestinal and gallbladder motility patterns and the posssible role of the adrenergic pathway in this action. Dogs were equipped with chronic duodenal electrodes for recording myoelectric activity and with a cannula in the gallbladder fundus for measuring the gallbladders intraluminal pressure and volume and calculating its motility index (MI) and emptying rate. After intravenous infusion of PYY, there was a dose-dependent prolongation of the migrating motor complex (MMC) interval and almost complete abolition of the contractions and emptying of gallbladder during the duodenal activity front. After meat feeding or during intravenous infusion of cerulein, 50 pmol/(kg · h), the MMC was interrupted and replaced by irregular spike activity, accompanied by a marked increase in the gallbladder MI and about 80% to 90% reduction of its volume. PYY, 200 pmol/(kg · h), reduced significantly the meal- or cerulein-induced duodenal spike activity but failed to affect the MI and volume of the gallbladder. Similar changes in fasted and fed patterns of motility were observed after Heal oleate (16 mM/h), producing plasma PYY levels in a range similar to that observed after infusion of exogenous PYY. The inhibitory effects of PYY or Heal fat on intestinal myoelectric activity were reversed in part by α-adrenergic blockade (phentolamine). We conclude that exogenous PYY or endogenous hormone released by Heal oleate inhibits the interdigestive and postprandial motility pattern of the small bowel but does not affect gallbladder motility, and that the inhibition of intestinal motility involves, at least in part, the adrenergic pathway.

Manometric investigations of patients with irritable colon show an undisturbed cyclic course of interdigestive motility studies of the rectosigmoid in patients with irritable colon show a spectrum of variable frequency of slow membrane potential changes with predominance of a frequency of 3/min. In addition, after a 1000 calorie test meal, patients with irritable colon showed a significantly prolonged increase of motility. As functional disturbances of irritable colon are mainly diagnosed by exclusion of organic changes, further development and rational use of colonic myoelectric methods promises future possibilities for objective diagnosis and control of treatment.

Endoscopic examination of the colon was performed in 405 patients (125 without, 217 with benign, and 63 with malignant colorectal diseases), and the serum levels of the tumour-associated antigens CEA and CA 19-9 were determined. On comparing both markers, the specificity of CA 19-9 (96% correctly normal values) was found to be higher in benign colorectal diseases than that of CEA (92% with a cut-off limit of 5 ng/ml for CEA). On the other hand, the sensitivity of CA 19-9 in colorectal carcinomas was only about 25% and thus much lower than that of CEA (52% correctly pathological values). The sensitivity of both markers was particularly low in the initial stages of carcinoma (in Dukes A: CEA 20%, CA 19-9 0%). If the cut-off limit for CEA was raised to 10 ng/ml, the specificity was increased to 99%, whereas the sensitivity was markedly reduced to 25%. The diagnostic accuracy of CEA in colorectal carcinomas was not surpassed by CA 19-9. There was no obvious advantage in simultaneous determination of CEA and CA 19-9.

Piezoelectric lithotripsy was undertaken on 50 patients with gallbladder stones, none of them requiring anaesthesia, analgetics or sedatives. Stone fragmentation was achieved in all patients during the first treatment. In 44 patients the maximum fragment size was less than 50% of the initial stone diameter. The mean maximum fragment size after the first treatment was 4.3 mm (+/- 3.3 mm). After a follow-up of 0-2 months in 14 of the 50 patients and of 2-4 months in 6 of 13 patients, no more stones could be seen by ultrasonography. After an average period of 8 weeks, 17 of 50 patients were free of stones. Piezoelectric lithotripsy did not have any severe side effects besides a mild pancreatitis in one patient.

A 44-year-old man, a known alcoholic and heavy smoker, was hospitalized with high fever and respiratory failure which a few hours later required intubation and artificial ventilation, although the chest x-ray had been unremarkable. Later serial chest x-ray films showed intrapulmonary infiltrations, while Legionella Bozemanii was demonstrated by direct immunofluorescence. Cranial computed tomography was unremarkable, despite the onset of tetraparesis and a severe midbrain syndrome. Cerebrospinal fluid contained merely mild lymphocytic pleocytosis. However, magnetic resonance imaging revealed symmetrical demyelinization foci in the brainstem as a sign of encephalitis. The neurological deficits regressed almost completely after several weeks of antibiotic treatment and rehabilitation measures over several months.

Self-expanding, wire-mesh stents, 10 mm in diameter, were implanted retrogradely through the papilla of Vater via an endoscopically introduced catheter system in 14 patients (9 females, 5 males, mean age 70.2 [44-85] years) with stenosis of the common bile duct by malignant tumour. Postimplantation examinations revealed no complications caused by the stent. Two of the patients have since died from their underlying disease, the others have survived an average of 10.8 weeks with markedly reduced clinical symptoms, neither jaundice nor signs of cholestasis having recurred. Serum bilirubin concentration had fallen from a mean of 8.2 mg/dl to 1.7 mg/dl 12 weeks after the procedure. Serum alkaline phosphatase activity had similarly fallen, from 515 to 330 U/l. No increase in serum amylase activity was recorded, either initially or in the course of follow-up.

BASIC PROBLEM AND OBJECTIVE OF STUDY The power of resolution of conventional imaging methods is too low for the diagnosis of very small pancreaticobiliary tumours. High-frequency ultrasound transducers (20 MHz), adapted to the dimensions of the pancreaticobiliary systems (2 mm diameter), make intraductal ultrasound examination possible during endoscopic retrograde cholangiopancreatography (ERCP). In a prospective study the invasiveness and diagnostic value of intraductal ultrasound (IDUS) was compared with ERCP, endosonography (ES) and computed tomography (CT). PATIENTS AND METHODS During ERCP in 51 consecutive patients an intraductal ultrasound transducer was introduced into the pancreaticobiliary duct system, the results being compared with those obtained with the other imaging modalities and histopathological findings, if available. RESULTS IDUS of the pancreatic and bile duct systems is a rapid, simple and reliable method during ERCP and provides valuable additional information on periductal tissues. In the diagnosis of carcinoma of the pancreas its sensitivity was 75% (six of eight cases), that of ERCP 37% (3/8), ES 50% (4/8) and CT 37% (3/8). In the diagnosis of biliary tract tumour the sensitivity of the different modalities (in the above order) was 89% (8/9), 78% (7/9), 33% (3/9) and 33% (1/3). Specificity was 67% (2/3), 67% (2/3), 67% (2/3) and 33% (3/9); predictability 89%, 88%, 75% and 60%. CONCLUSIONS The use of small ultrasound catheter transistor system in the biliary and pancreatic ducts, introduced during ERCP, is technically simple and has few complications. It is a valuable addition to ERCP in the precise diagnosis of small pancreaticobiliary lesions.

Tumour-associated antigens CA 50 and CA 19-9 were determined in serum of 208 patients. Specificity of both neo-antigens as tumour markers was equally good, at 100% and 95%, in patients without malignancy or gastrointestinal disease, respectively, using an upper limit of normal of 17 U/ml for CA 50 and 37 U/ml for CA 19-9. Benign diseases of the upper gastrointestinal tract, such as pancreatitis, cholestasis or cirrhosis of the liver, reduce the specificity of CA 50 more than of CA 19-9. For example, specificity of CA 50 is only 33% for choledocholithiasis, but 74% with CA 19-9. The sensitivity of both closely related sialogangliosides in malignancies of the upper GI tract is similar, with the usual normal limits: in pancreas carcinoma 77% for CA 50, 81% for CA 19-9; in biliary tract carcinoma 80% for CA 50, 90% for CA 19-9; in gastric carcinoma 40% for CA 50, 50% for CA 19-9. But if one equalizes the upper limits of normal for both markers to a common 95% specificity, the tumour-indicating sensitivity of CA 19-9 clearly surpasses that of CA 50. Malignant tumours not recognized by increased levels of CA 19-9 also escape serological diagnosis with CA 50.

Tumour-associated antigen CA 19-9 was determined in serum from 166 patients (30 without gastro-intestinal disease, 32 with liver cirrhosis, 9 with choledocholithiasis, 65 with acute or chronic pancreatitis and 30 with malignant tumors in the region of pancreas and bile passages). The specificity of CA-19-9 as tumour marker was 97% in patients without gastro-intestinal disease, but in those with liver cirrhosis or choledocholithiasis it was only 56% and 44%, respectively. In particular, cholestasis reduced specificity. Acute pancreatitis in its initial attack gave false-positive CA 19-9 values in 27% of cases, repeated bouts in chronic recurrent pancreatitis in as many as 50%. In chronic pancreatitis the specificity was 90%. Malignant tumours of pancreas and bile ducts were diagnosed with a sensitivity of 80%. Determination of CA 19-9 in pure pancreatic secretion failed to differentiate between the control group (30), chronic pancreatitis (21) and carcinoma of the pancreas (22).

In a randomized, endoscopically controlled double-blind trial the effectiveness of a single oral, morning dose of 40 mg omeprazole was compared with a twice daily oral dose of 150 mg ranitidine given to 334 ambulatory patients with duodenal ulcers. Under omeprazole 105 of 146 duodenal ulcers were demonstrated to have healed within 14 days (72%), compared with 95 of 160 (59%) on ranitidine. The difference is statistically significant (P = 0.0121). After 14 days smaller ulcers healed more quickly than large ones, regardless of the drug used: 80 of 110 with diameter 3-5 mm (73%); 48 of 90 with diameter more than 8 mm (53%). Smoking delayed healing [healing rate among non-smokers, 87 of 117 (74%); among smokers, 113 of 189 (60%)]. Healing rates among smokers receiving omeprazole and non-smokers receiving ranitidine were nearly identical. After 4 weeks, at 96 and 92% respectively, there was no difference in regard to healing rate. Both drugs had a similar influence on the symptoms. Thus, for the first time it has been demonstrated that omeprazole is superior to ranitidine after 14-day treatment of duodenal ulcer.

The effectiveness of omeprazole (20 mg orally each morning) or ranitidine (150 mg orally twice daily) in the treatment of gastric ulcer was compared in 184 out-patient in a randomized, endoscopically controlled multi-centre double-blind ("double dummy") trial. Healing rates with omeprazole after two, four and eight weeks were 43, 81 and 95%, respectively, those with ranitidine were 45, 80 and 90%, a statistically not significant difference. Independently of medication, small ulcers (less than 8 mm diameter) healed more quickly than larger ones. Ulcers in the body of the stomach responded poorest to both drugs. Smoking had no statistically significant effect on healing rate. Omeprazole and ranitidine had similarly favourable effects on symptoms. Neither side effects nor changes in biochemical parameters could be ascribed to omeprazole. Both drugs had equivalent effects on the healing of gastric ulcers in the stated dosages.

BACKGROUND AND OBJECTIVE Nowadays ultrasonic endoscopy is accepted as the most accurate method in the preoperative TNM staging of oesophageal tumour. At the time a diagnosis of oesophageal is made, 25-62% of patients have marked oesophageal stricture due to an advanced stage of the tumour. As a result, it is often impossible to pass a conventional endoscope and the examination is incomplete or a dilator has to be introduced at high risk of perforation or other complications. An ultrasonic oesophagoprobe (Olympus MH 908) with a diameter of 7.9 mm, its tip acting as a dilator has been developed so that even in high-grade oesophageal stricture a complete and low-risk investigation can be undertaken. The value of this instrument has been compared prospectively with that of a standard ultrasonic endoscope in patients with oesophageal stricture due to carcinoma and in relation to the postoperative histology. PATIENTS AND METHODS Between May 1996 and February 1997, 62 patients (55 men, 7 women; average age 55.8 [41-82] years) with suspected or histologically confirmed oesophageal carcinoma were examined with the standard ultrasonic endoscope and the new oesophagoprobe. The two independent results were related to the postoperative histology. RESULTS It was possible to compare the endoscopic results with the postoperative histology in 47 patients. In 55.8% it was not possible to pass the stricture with the standard ultrasonic endoscope (SE) so that an accuracy of only 41% was obtained in the T stage and 56.4% in the N stage. But with the oesophagoprobe (OP) an accuracy of 74.5% in the T stage and of 63% in the N stage were achieved. The difference in the findings between the two instruments was highly significant (p < 0.001) in those patients in whom the SE could not be passed through the stricture. For the T stage the accuracy was 14.3% vs. 76.2% (SE vs. OP); in the N stage it was 38.1% and 57.2%, respectively. When both instruments could be passed the results were comparable. CONCLUSIONS Examination with the ultrasonic oesophagoprobe is a reliable and accurate method free of complications for the preoperative assessment of oesophageal carcinoma with stricture.

Background: Despite some progress in recent years, the options for treating inflammatory bowel disease (IBD) are still dissatisfying, and surgery rates are still high. The anti-inflammatory effects of melanocortin peptides such as alpha-melanocyte-stimulating hormone (α-MSH) have been described recently in, for example, dextran sodium sulfate (DSS) colitis in mice. The aim of this study was to investigate the therapeutic potential of the melanocortin-derived tripeptide α-MSH(11–13) (KPV) and its mode of action in 2 models of intestinal inflammation. Methods: The anti-inflammatory activity of KPV was analyzed in 2 well-described models of IBD: DSS colitis, and CD45RBhi transfer colitis. Furthermore, animals expressing a nonfunctional melanocortin-1 receptor (MC1Re/e) received DSS for induction of colitis and were treated with KPV. The course of inflammation was monitored by weight loss and histological changes in the colon as well as by myeloperoxidase (MPO) activity. Results: In the DSS-colitis model, treatment with KPV led to earlier recovery and significantly stronger regain of body weight. Histologically, inflammatory infiltrates were significantly reduced in KPV-treated mice, which was confirmed by the significant reduction of MPO activity in colonic tissue after KPV treatment. Supporting these findings, KPV treatment of transfer colitis led to recovery, regain of body weight, and reduced inflammatory changes histologically. In MC1Re/e mice, KPV treatment rescued all animals in the treatment group from death during DSS colitis. Conclusions: The melanocortin-derived tripeptide KPV showed significant anti-inflammatory effects in 2 murine models of colitis. These effects seem to be at least partially independent of MC1R signaling. In conclusion, our data suggest KPV as an interesting therapeutic option for the treatment of IBD. (Inflamm Bowel Dis 2007)

M cells, specialized cells within Peyer's patches (PPs), are reduced in number in chemokine receptor 6 (CCR6)-deficient mice. The pathogenic microorganism Yersinia enterocolitica exploits M cells for the purpose of mucosal tissue invasion exclusively through PPs. The aim of this study was to evaluate the course of yersiniosis in CCR6-deficient mice and to investigate whether these mice might be used as an in vivo model to determine M-cell function. After oral challenge with Y. enterocolitica, control mice suffered from lethal septic infection whereas CCR6-deficient mice showed very limited symptoms of infection. Immunohistochemical analysis demonstrated PP invasion by Y. enterocolitica in control mice whereas no bacteria could be found in CCR6-deficient mice. In addition, a significant induction of proinflammatory cytokines could be found in control mice whereas proinflammatory cytokine levels in CCR6-deficient mice remained unchanged. In contrast, intraperitoneal infection resulted in severe systemic yersiniosis in both mouse groups. Abrogated oral Y. enterocolitica infection in CCR6-deficient mice demonstrates the importance of CCR6 expression in the physiological and pathological immune responses generated within PPs by influencing M-cell differentiation, underscoring the important role of M cells in the process of microbial uptake. CCR6-deficient mice may therefore represent a suitable model for the study of M-cell function in vivo.

Leukocyte infiltration is an early and critical event in the development of acute pancreatitis. However, the mechanism of leukocyte transmigration into the pancreas and the function of leukocytes in initiating acute pancreatitis are still poorly understood. Here, we studied the role of S100A9 (MRP14), a calcium binding protein specifically released by polymorph nuclear leukocytes (PMN), in the course of acute experimental pancreatitis. Acute pancreatitis was induced by repeated supramaximal caerulein injections in S100A9 deficient or S100A9 wild-type mice. We then determined S100A9 expression, trypsinogen activation peptide (TAP) levels, serum amylase and lipase activities, and tissue myeloperoxidase (MPO) activity. Cell-cell contact dissociation was analyzed in vitro with biovolume measurements of isolated acini after incubation with purified S100A8/A9 heterodimers, and in vivo as measurement of Evans Blue extravasation after intravenous application of S100A8/A9. Pancreatitis induced increased levels of S100A9 in the pancreas. However, infiltration of leukocytes and MPO activity in the lungs and pancreas during acute pancreatitis was decreased in S100A9-deficient mice and associated with significantly lower serum amylase and lipase activities as well as reduced intrapancreatic TAP-levels. Incubation of isolated pancreatic acini with purified S100A8/A9-heterodimers resulted in a rapid dissociation of acinar cell-cell contacts which was highly calcium-dependent. Consistent with these findings, in vivo application of S100A8/A9 in mice was in itself sufficient to induce pancreatic cell-cell contract dissociation as indicated by Evans Blue extravasation. These data show that the degree of intrapancreatic trypsinogen activation is influenced by the extent of leukocyte infiltration into the pancreas which, in turn, depends on the presence of S100A9 that is secreted from PMN. S100A9 directly affects leukocyte tissue invasion and mediates cell contact dissociation via its calcium binding properties.

Members of the interleukin (IL)-12 family constitute subunits of IL-12, -23, and -27. These ILs represent pivotal mediators in the regulation of cell-mediated immune responses and in animal models of human inflammatory bowel disease. Recent work has suggested that intestinal endothelial cells might serve as a second line of defense in bacterial sensing of invading pathogens. The purpose of this study was to examine the production of IL-12 family members in intestinal endothelial cells (HIMEC). HIMEC were stimulated with proinflammatory agents (TNF-alpha, IFN-gamma, IL-1beta) and microbial antigens [LPS, lipoteichoic acid, peptidoglycan, CpG-DNA, flagellin, poly(I:C)]. Expression of IL-12 family members and of Toll-like receptor (TLR)3 in HIMEC was assessed by real-time RT-PCR, immunostaining, flow cytometry, and immunoblot analysis. HIMEC display an induction of Epstein-Barr virus-induced gene 3 (EBI3), IL-12p35, and IL-23p19, whereas no expression of IL-12p40 and IL-27p28 was detectable. The strongest induction was induced by proinflammatory factors known to utilize the NF-kappaB pathway, and expression of EBI3 and IL-23p19 was diminished by an NF-kappaB inhibitor. HIMEC display regulated expression of TLR3. Adhesion and transmigration assays showed proinflammatory responses after HIMEC stimulation. HIMEC are capable of producing IL-12 family members as a response to microbial stimuli. The TLR3 agonist, poly(I:C), was shown to enhance leukocyte adhesion in vitro in HIMEC. Our data suggest that the intestinal microvasculature is responsive to ligands of TLR3 expressed on intestinal endothelial cells, thereby adding to the regulation of adaptive immunity and leukocyte recruitment.

A variety of physical and biochemical cell properties depends on the function and integrity of the actin cytoskeleton. The actin cytoskeleton mediates crucial cellular functions as migration, intracellular transport, exocytosis, endocytosis, cell stiffness and force generation. Highly dynamic actin fibers are therefore targets for several drugs and toxins. However, the study of actin interfering processes by standard microscopy techniques fails in the detailed resolution of dynamic spatial alterations required for a deeper understanding of toxic or drug effects. Here we applied digital holographic microscopy in the online functional analysis of the actin cytoskeleton changes of a highly differentiated and a dedifferentiated pancreas tumor cell line induced by the marine toxin Latrunculin B. Scanning electron microscopy (SEM) and fluorescence microscopy showed rapid Latrunculin B induced alterations in cell morphology and actin fiber degradation in both pancreatic tumor cell lines. In contrast digital holographic in vivo analysis of the drug dependent dynamic cellular processes revealed unequal changes in cell morphology. While tumor cells with a low metastatic potential showed Latrunculin B induced cell collapse within 4 h the metastatic tumor cells were resistant to Latrunculin B treatment. Spatial resolution of morphological alterations by digital holography detected so far unknown differences in the actin cytoskeleton stability of highly differentiated and dedifferentiated pancreas tumor cell lines. These data demonstrate that marker-free, non-destructive online analysis of cellular morphology and dynamic spatial processes in living cells by digital holography offers new insights in actin dependent cellular mechanisms. Digital holographic microscopy was shown to be a versatile tool in the screening of toxic drug effects and cancer cell biology.

Background: Exposure to bacterial antigens and other environmental factors in combination with a genetic susceptibility have been implicated in the etiology of inflammatory bowel disease (IBD). As certain perinatal circumstances, e.g., delivery by cesarean section, predispose to a different intestinal colonizations the aim of this analysis was to define a potential influence on the development of IBD in later life. Methods: In a case-control study design, birth data were recorded from patients diagnosed with IBD (Crohn's disease [CD], n = 1096; ulcerative colitis [UC], n = 763) and healthy controls ([C], n = 878) by a self-administered questionnaire. Results: Preterm birth (CD: odds ratio [OR] 1.5 [95% confidence interval 1.1–2.0], UC: OR 1.3 [0.9–1.9]), mother's disease during pregnancy (CD: OR 1.9 [1.3–2.9], UC: OR 1.6 [1.0–2.4]), and disease in the first year of life (CD: OR 2.2 [1.6–2.9], UC: OR 1.7 [1.3–2.3]) are associated with the development of IBD in later life. No significant associations were found for the mode of delivery and breast feeding. In a logistic regression analysis female sex, smoking, appendectomy, maternal IBD, and disease in the first year of life were independently associated with CD. Female sex, appendectomy, and disease in the first year of life were independently associated with UC. Conclusions: Preterm birth and other perinatal circumstances are associated with the development of IBD, of which disease in the first year of life is an independent risk factor in multivariate analysis. (Inflamm Bowel Dis 2007)

Joint involvement is the most frequent extraintestinal manifestation of inflammatory bowel diseases (IBDs). Arthralgias are common and spondyloarthropathy may affect peripheral joints and the axial skeleton, as well as the tendons. The broad spectrum of joint manifestations requires a therapeutic concept that takes the potential influence of agents on the underlying bowel disease into consideration. This review will focus on the current therapeutic approach to the different manifestations of IBD-related joint disease and will outline baseline treatment, the use of conventional agents and biologicals. TNF antagonists have dramatically changed the care of patients. In particular, TNF antagonists have emerged as the most effective treatment for ankylosing spondylitis, which has often been refractory to therapy in the past. For patients who fail to respond to TNF antagonists, several novel agents will provide more treatment choices in the future. Recent insights into disease mechanisms of IBD have revealed at...

Thin spin-coated films of polystyrene-block-poly(tert-butyl acrylate) (PS690-b-PtBA1210) on various substrates are introduced as versatile, robust reactive platform for the immobilization of (bio)molecules for the fabrication of tailored biointerfaces. The films are characterized by high stability and (bio)reactivity due to the presence of a glassy PS and a reactive PtBA block, respectively. The selective deprotection of the tert-butyl-ester groups in the PtBA skin layer by hydrolysis under acidic conditions, the activation with N-hydroxysuccinimide and the subsequent derivatization with amino functionalized (bio)molecules were investigated. Based on contact angle, FTIR spectroscopy and XPS, fluorescence microscopy and AFM data, it was shown that the (bio)molecules were coupled covalently to the polymer films and that high molecular coverages up to 2.4 poly(ethylene glycol) (PEG) molecules per nm2 (Mn = 500 g/mol) were obtained. Organic dyes, polyamidoamine dendrimers, polypeptides, proteins and amino end-functionalized DNA were efficiently and homogeneously immobilized on the PS-PtBA platforms. Grafting of ω-amino functionalized PEG afforded surfaces with substantially reduced non-specific adsorption of proteins and DNA. Owing to the glassy nature of PS and the covalent amide linkages, the derivatized films showed excellent stability under a broad range of processing conditions. Finally, the viability of PS690-b-PtBA1210 platforms as versatile biointerfaces was demonstrated in DNA hybridization experiments, as well as cell-surface interaction studies using pancreatic cancer and K562 cells.

Background: Pulmonary arterial hypertension (PAH) is a severe complication of systemic rheumatic diseases. Exact prevalence data of PAH in rheumatic disorders are not yet available. Improved therapy options like antagonizing endothelin-1 receptor or inhibiting phosphodiesterase-type 5 account for increasing efforts to diagnose PAH at an earlier stage. We performed an echocardiographic screening for PAH at our outpatient clinic for rheumatology in Munster, Germany.Materials and methods: Between November 2002 and March 2006, a total of 256 echocardiographic examinations were performed in 63 patients with systemic lupus erythematosus (SLE), 24 with progressive systemic sclerosis (PSS), 21 with CREST syndrome, 19 with rheumatoid arthritis, 15 with systemic vasculitides, 35 with other connective tissue diseases and five with other forms of systemic arthritis. Pulmonary arterial hypertension was assumed if peak tricuspid regurgitation jet velocity (TRV) exceeded 3 m/s. Symptomatic patients were subseque...

In the present in-vitro study we investigated the possible role of the calmodulin-antagonistic drugs loperamide and calmidazolium in the regulation of transepithelial Ca2+ transport of human duodenum. Brush border membrane vesicles and basolateral membrane vesicles were simultaneously prepared from surgically resected pieces of morphologically intact human duodenum with a modified Percoll-gradient centrifugation method. Brush border and basolateral membrane vesicles were characterized using enzyme marker analysis and electron microscopy: alkaline phosphatase was enriched 20-fold in brush border membrane vesicles, whereas [Na+ + K+]-stimulated adenosine triphosphatase was enriched 15-fold in basolateral membrane vesicles. Calmodulin activity was determined by a specific radioimmunoassay after solubilizing brush border and basolateral membrane vesicles in 1% Triton X-100. In basolateral membrane vesicles, we found no calmodulin activity. In brush border membrane vesicles calmodulin activity was impaired by 50% after pre-incubation with loperamide or calmidazolium. We measured calcium, sodium, D-glucose and D-mannitol uptake with a rapid filtration technique. Before the transport experiments, brush border and basolateral membrane vesicles were pre-incubated with 5 microM loperamide or 5 microM calmidazolium for 60 min at 5 degrees C. In drug-pretreated, brush border membrane vesicles calcium uptake was significantly reduced after 1 min incubation (-25% +/- 5%, P less than 0.05); this effect was completely reversed in the presence of 5 microM calmodulin. In basolateral membrane vesicles, we found two Ca2+ transport systems: (1) Na+/Ca2+ exchange and (2) ATP-dependent Ca2+ transport. In basolateral membrane vesicles loperamide had no effect. Calmidazolium had no effect on Na+/Ca2+ exchange, but significantly inhibited ATP-dependent Ca2+ transport. This effect could not be reversed by calmodulin.