Endoscopic rendez-vous reconstruction of complete biliary obstruction.

BACKGROUND AND STUDY AIMS: Complete biliary strictures normally require surgical intervention. We describe an alternative, minimally invasive endoscopic/percutaneous rendez-vous technique for the reconstruction of complete benign biliary strictures. PATIENTS AND METHODS: Complete biliary strictures were reconstructed in four patients using a rendez-vous percutaneous-endoscopic or percutaneous-percutaneous route guided by fluoroscopic and visual (transillumination) control. RESULTS: All four patients were treated successfully and safely with the rendez-vous technique. Complications were caused by the preliminary creation, dilatation and maturation of the percutaneous tract. CONCLUSION: This technique may offer a good alternative to surgical bilio-enteric anastomosis in experienced hands. The long term course of the patients treated remains to be seen.

Short-term effects and adverse events of endoscopically applied radiofrequency ablation appear to be comparable with photodynamic therapy in hilar cholangiocarcinoma.

BACKGROUND AND STUDY AIMS: Radiofrequency ablation (RFA) is a new endoscopic palliation therapy for malignant biliary obstruction. The aim of this study was to compare the short-term effects of biliary drainage and adverse events of this technique with the standard of endoscopical treatment of hilar cholangiocarcinoma, photodynamic therapy (PDT). PATIENTS AND METHODS: We retrospectively and since December 2012 prospectively investigated the efficacy and adverse events of RFA in patients with hilar cholangiocarcinoma in two tertiary referral centers between November 2011 and January 2013. The approach of the study was prospective, but because of the large amount of retrospectively included patients, the design of the study is overall retrospective. A group of 20 patients treated with PDT between April 2005 and May 2011 served as a historical control. RESULTS: Fourteen patients received 31 biliary RFAs and 20 patients received 36 PDTs. Within the RFA group, a significant decrease (p = 0.046) of the bilirubin level was seen 14 days after the first RFA (3.3 ± 3.9 (mg/dl) versus 2.3 ± 2.6 (mg/dl)). In the PDT group no significant decrease (p = 0.67) of the bilirubin level was obtained (4.1 ± 6.9 (mg/dl) versus 3.5 ± 5.3 (mg/dl)). In the PDT group (13/20, 65%) a significantly higher number of premature stent replacements (<3 months) after the first intervention was noticed in comparison with the RFA group (four of 14, 29%) (p < 0.01). Between the first and fifth procedure, post-interventional adverse events tend to occur more frequently in patients with PDT (eight of 20, 40%) than with RFA (three of 14, 21%) (p = 0.277). CONCLUSIONS: Looking at the short-term effects, we conclude that RFA may present a therapeutic alternative to PDT for palliative treatment of malignant biliary obstruction because of its simple feasibility and moderate adverse event rate. To provide a definitive evaluation of the long-term effects and of overall median survival, a controlled trial with PDT must follow.

Gastrointestinal stromal tumor as entry port for S. intermedius causing bacteremia and multiple liver abscesses. Case report and review of literature.

We report a case of a previously healthy 52-year-old man who presented with fever and liver lesions suspicious for metastatic disease, which proved subsequently to be abscesses. Further workup revealed a gastrointestinal stromal tumor (GIST) in the gastric corpus as entry port to Streptococcus intermedius-associated bacteremia and liver abscesses. After antibiotic treatment and surgical resection of the tumor, the patient recovered well. This unusual case indicates that gastrointestinal stromal tumors can remain undetected until they cause a life threatening infection. A review of recent literature pertaining to GIST and liver abscesses follows.

The use of proton pump inhibitors and the spectrum and number of biliary pathogens in patients with acute cholangitis.

BACKGROUND: Knowledge of the bacterial spectrum for acute cholangitis is essential for adequate empiric antibiotic treatment. AIM: To analyse the relation of proton pump inhibitors (PPI) with biliary pathogens in patients with acute cholangitis. METHODS: This retrospective study identified 278 patients with 318 acute cholangitis episodes using an endoscopic database. The relationship between PPI and microbiological outcomes was assessed by logistic and poisson regression analysis for binary and count data. RESULTS: In total, 882 pathogens were isolated, of which, 120 cholangitis episodes occurred with PPI; 198 cholangitis episodes without PPI. Multivariate poisson regression analysis showed that PPI use resulted in a 23% increase in the number of biliary pathogens [3.14 vs. 2.55 (Δ = 0.59), P < 0.01], whereas stent therapy, previous interventional procedures (endoscopic retrograde cholangiography/percutaneous transhepatic cholangiography), genesis, age and sex showed no significant association with the number of biliary pathogens. Significantly, more cholangitis episodes with more than one pathogen isolated occurred during PPI treatment [103/120 (86%) vs. 151/198 (76%), P = 0.04]. Analysis of intrinsic anti-microbial resistance patterns was performed: Anti-microbial combination therapies were significantly more required to cover all isolated pathogens in cholangitis episodes with PPI than in cholangitis episodes without PPI (44/120 vs. 46/198, P = 0.01). Additionally, PPI use was associated with a significantly higher incidence of oropharyngeal flora in the biliary tract (53/120 vs. 61/198, P = 0.02). CONCLUSIONS: Proton pump inhibitors seem to influence biliary pathogens by increasing the number and broadening the spectrum of biliary pathogens. However, the findings of this hypothesis-generating study need to be tested by confirmatory studies.

Impact of cellular properties on red cell-red cell affinity in plasma-like suspensions.

The reversible aggregation of human red blood cells (RBC) by proteins or polymers continues to be of biological and biophysical interest, yet the mechanistic details governing this process are still being explored. In this report an approach is described to compute the interaction energy between RBC by considering cellular properties as well as polymer properties. Cell-cell affinities were calculated as functions of glycocalyx thickness and glycocalyx volume concentration as well as bulk polymer concentration. Our theoretical predictions show that cell-cell affinities do not monotonically increase with polymer size and concentration, but rather demonstrate an optimum dextran molecular mass and concentration which depends on cellular properties of RBC. These results show qualitative agreement with recent experimental observations. In conclusion, our model not only confirms the concept of a depletion mechanism for RBC aggregation but also provides new insights which should help understanding how cellular properties control in vivo RBC interactions.

Long-term follow-up of percutaneous transhepatic biliary drainage (PTBD) in patients with benign bilioenterostomy stricture.

BACKGROUND AND AIMS: Anastomotic strictures are well-known complications after bilioenterostomy. Endoscopic procedures are usually not possible in patients with a bilioenterostomy. Hence, percutaneous transhepatic biliary drainage (PTBD) has become the treatment of choice for the management of these patients. The main goal of the present study was to analyze the long-term follow-up of PTBD in such patients. METHODS AND PATIENTS: Between January 1996 and December 2006, 44 patients with benign anastomotic stricture after bilioenterostomy were identified by an analysis of the PTBD database, hospital charts, and cholangiograms. RESULTS: In 27/44 patients the percutaneous transhepatic biliary drain was successfully removed after 19.9 +/- 16.1 months (treatment success in 61.4 %). During a mean follow-up of 53.7 +/- 28.4 months after removal of the drain, no evidence was found of recurrent strictures in these patients. Ten out of 44 patients carry permanent drains (22.6 % of patients with ongoing treatment, mean follow-up 46.4 +/- 54.7 months) without the option for further surgery owing to concomitant disease (n = 2) or because they refused further surgery (n = 8). In 7 out of 44 patients (16 %) PTBD treatment was deemed to have failed and the patients underwent repeat operation. CONCLUSIONS: PTBD should be considered the treatment of choice in patients with benign anastomotic stricture after bilioenterostomy, especially after stricturing of a hepatojejunostomy.

RBC aggregation: laboratory data and models.

The reversible aggregation of red blood cells (RBC) into linear and three-dimensional structures continues to be of basic science and clinical interest: RBC aggregation affects low shear blood viscosity and microvascular flow dynamics, and can be markedly enhanced in several clinical states. Until fairly recently, most research efforts were focused on relations between suspending medium composition (i.e., protein levels, polymer type and concentration) and aggregate formation. However, there is now an increasing amount of experimental evidence indicating that RBC cellular properties can markedly affect aggregation, with the term "RBC aggregability" coined to describe the cell's intrinsic tendency to aggregate. Variations of aggregability can be large, with some changes of aggregation substantially greater than those resulting from pathologic states. The present review provides a brief overview of this topic, and includes such areas as donor-to-donor variations, polymer-plasma correlations, effects of RBC age, effects of enzymatic treatment, and current developments related to the mechanisms involved in RBC aggregation.

A prospective multicenter clinical and endoscopic follow-up study of patients with gastroesophageal reflux disease.

BACKGROUND: Despite its high prevalence, data on the course of gastroesophageal reflux disease (GERD) are still sparse. There is also an ongoing debate on the natural history of its various manifestations, i.e., non-erosive reflux disease (NERD) vs. erosive reflux disease (ERD) vs. Barrett's esophagus (BE). PATIENTS AND METHODS: This study was conducted within the framework of a prospective multicenter study on the course and prevalence of intestinal metaplasia at the gastroesophageal junction. 1014 dyspeptic patients were screened by the means of upper GI endoscopy. Clinical data were recorded by the use of a questionnaire. At least 15 months after the initial examination, all patients were invited for follow-up (FU) examination. Patients were analyzed separately with respect to their clinical and endoscopic findings. For the latter, only patients without any treatment with proton-pump-inhibitors (PPI) prior to initial and follow-up examinations were included. Patients were categorized as GERD positive if typical symptoms were present and/or proton pump inhibitors were used. RESULTS: Sufficient clinical and/or endoscopic data were available in 590 GERD patients with heartburn at least once a week. Follow-up data could be obtained in 320 patients (clinical FU: n = 304; endoscopic FU: n = 52) after a mean follow-up period of 35 months (18-48 months). 96 of 144 previously asymptomatic patients (67%) remained asymptomatic at follow-up, the rest (n = 48) were symptomatic. 143 of 304 previously symptomatic patients (47%) were symptom-free at follow-up, and only 161 patients (53%) remained symptomatic or had concomitant therapy with proton-pump-inhibitors (PPI). For follow-up endoscopy in patients off PPI (n = 52), ERD was no longer confirmed in 7/12 ERD patients (58%), whereas progress to ERD was found in 3/34 patients (9%) in the NERD group. BE was newly diagnosed in two NERD patients but could no longer be detected in 2 of 6 patients with an initial diagnosis of BE. CONCLUSIONS: With respect to its clinical as well as its endoscopic manifestations, gastroesophageal reflux disease does not appear to be very stable over time. However, in most cases this is due to regression rather than progression of the disease.

Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection.

BACKGROUND AND AIMS: Recent studies linked cytokine gene polymorphisms to H pylori related gastric cancer development. The current study evaluated the role of cytokine gene polymorphisms for mucosal cytokine expression, the gastric inflammatory response, and bacterial colonisation during H pylori infection. PATIENTS AND METHODS: In 207 H pylori infected patients with chronic gastritis, polymorphisms at different loci of the interleukin (IL)-10, IL-1B, IL-1 receptor antagonist (IL-1RN), tumour necrosis factor (TNF)-A, and interferon (IFN)-G genes were genotyped by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) analysis, and allelic discriminating TaqMan PCR. Mucosal cytokine mRNA copy numbers were determined by real time quantitative PCR. Presence of bacterial virulence factors was investigated by cagA, vacAs1/2, and babA2 PCR. Biopsies were assessed with regard to the degrees of granulocytic/lymphocytic infiltration and the presence of intestinal metaplasia (IM) and atrophic gastritis (AG). RESULTS: Proinflammatory IL-1 polymorphisms (IL-1RN*2(+)/IL-1B-511T/-31C(+)) were associated with increased IL-1beta expression, more severe degrees of inflammation, and an increased prevalence of IM and AG. Carriers of the IL-10-1082G/-819C/-592C alleles (GCC haplotype) had higher mucosal IL-10 mRNA levels than ATA haplotype carriers and were associated with colonisation by more virulent cagA(+), vacAs1(+), and babA2(+) H pylori strains. The TNF-A-307(G/A) and IFN-G+874(A/T) polymorphisms did not influence mucosal cytokine expression or the inflammatory response to H pylori. CONCLUSIONS: Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and the long term development of precancerous lesions in H pylori infection. Host polymorphisms are associated with certain bacterial strain types, suggesting host specific colonisation or adaptation. These findings contribute to the understanding of the complex interplay between host and bacterial factors involved in the development of gastric pathology.

Influence of cell-specific factors on red blood cell aggregation.

The reversible aggregation of red blood cells (RBC) into linear and three-dimensional structures continues to be of basic science and clinical interest: RBC aggregation affects low shear blood viscosity and microvascular flow dynamics, and can be markedly enhanced in several clinical states. Until fairly recently, most research efforts were focused on relations between suspending medium composition (i.e., protein levels, polymer type and concentration) and aggregate formation. However, there is now an increasing amount of experimental evidence indicating that RBC cellular properties can markedly affect aggregation, with the term "RBC aggregability" coined to describe the cell's intrinsic tendency to aggregate. Variations of aggregability can be large, with some changes of aggregation substantially greater than those resulting from pathologic states. The present review provides a brief overview of this topic, and includes such areas as donor-to-donor variations, polymer-plasma correlations, effects of RBC age, effects of enzymatic treatment, and current developments related to the mechanisms involved in RBC aggregation.

Is esophageal capsule endoscopy feasible? Results of a pilot.

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) has been shown to be accurate in the evaluation of small-bowel bleeding and possibly also other small-bowel disorders. It is commonly believed that other organs are not suitable for CE. We report here on our experience in studying the distal esophagus using CE under various conditions. PATIENTS AND METHODS: A prospective evaluation of CE was carried out in three groups: evaluation of the distal esophagus in routine patients (n = 58) mostly examined for suspected small-intestinal bleeding (group 1); in eight patients with signs of grade I - II reflux esophagitis on upper gastrointestinal endoscopy, who were examined in a supine position for esophageal passage (group 2); and in four volunteers who swallowed the capsule attached to a string (group 3). RESULTS: In 62 routine patients initially included in group 1, the median CE exposure time was 2 s (range 0 - 217 s; median of four pictures, range 0 - 434), excluding four patients with extremely delayed esophageal transit (esophageal times: 45 - 226 min); at least one image of the Z line was obtained in 24.1 % of cases, but adequate assessment of 50 % and 100 % of the circumference of the distal esophagus was possible in only 10.4 % and 0 % of these cases, respectively. In group 2, the values were better (adequate visibility rates of 50 % and 100 % in 12.5 % and 37.5 % of the eight patients, respectively), but the correct diagnosis of reflux lesions was obtained in only three of the eight. In group 3, the visibility of the Z line was good, but all four volunteers experienced the procedure with the attached string as being quite unpleasant. CONCLUSIONS: Distal esophageal assessment by CE with the aim of providing an easy screening method for reflux lesions is not at present feasible. Technical developments will be necessary to achieve this.

Reduced incidence of radiocontrast-induced nephropathy in ICU patients under theophylline prophylaxis: a prospective comparison to series of patients at similar risk.

OBJECTIVE: To investigate whether the adenosine-antagonist theophylline reduces the incidence of contrast-induced nephropathy (CIN). DESIGN AND SETTING: Prospective, comparison to series of patients at similar risk of CIN in a university hospital medical ICU. PATIENTS: 78 ICU patients with at least one risk factor for CIN undergoing 150 consecutive contrast examinations. INTERVENTIONS: Administration of 200 mg theophylline/70 kg BW intravenously 30 min before that of 100 ml or more low-osmolarity contrast medium (CM). MEASUREMENTS AND RESULTS: Concentrations of serum creatinine and blood urea nitrogen (BUN), urine volume, fluid balance, and the incidence of CIN [increase in creatinine > or =20.5 mg/dl (= 44.2 micromol/l) within 48 h] were monitored for 48 h. Despite the large number of risk factors (6.8 per patient) including a high dose of CM (169.4 ml), impaired renal function (51%), diabetes (38%), aminoglycosides (61%), vancomycin (53%), catecholamines (52%), creatinine concentrations were not increased 24 h (1.40+/-0.92 mg/dl) or 48 h (1.38+/-0.88 mg/dl) after CM [1.47+/-1.0 mg/dl (= 130+/-88 micromol/l)] vs. baseline. The fluid balance was not different before (+3 ml/h) and after CM (-9 ml/h). The urine volume slightly increased after CM and theophylline (184 ml/h vs. 164 ml/h). Only three patients (2%) developed CIN. The incidence was significantly lower than that of 14% (78/565) in the control series with patients at comparable risk of CIN (p < 0.0001). CONCLUSIONS: Using a theophylline prophylaxis the incidence of CIN in patients with increased risk of CIN is as low as 2%.

Electrophoretic and aggregation behavior of bovine, horse and human red blood cells in plasma and in polymer solutions.

The electrophoretic mobility of native and glutaraldehyde-fixed bovine, human, and horse red blood cells (RBC) was investigated as a function of ionic strength (5-150 mM) and concentration of 464 kDa dextran (2 and 3 g/dl); RBC aggregation in autologous plasma and in dextran solutions was also measured. In agreement with previous observations, human and horse RBC form stable rouleaux whereas bovine RBC do not aggregate in either plasma or in dextran 464 kDa solutions. Electrophoretic measurements showed a species-dependent adsorption and depletion of dextran that can be theoretically evaluated. Adsorption of polymer is not a prerequisite for RBC aggregation (bovine RBC show the highest amount of adsorbed dextran yet do not aggregate). Aggregate formation thus occurs as long as the Gibbs free energy difference, given by the osmotic pressure difference between the bulk phase and the polymer-depleted region between two RBC, is larger than the steric and electrostatic repulsive energy contributed by the macromolecules present on the RBC surface. With increasing bulk-phase polymer concentration the depletion layer thickness decreases and the amount of adsorbed macromolecules increases, thereby resulting in an increase of the repulsive component of the interaction energy and decreased aggregation. We thus view electrophoretic measurements of RBC in various media as an important tool for understanding polymer behavior near the red cell surface and hence the mechanisms involved in RBC aggregation.

Aggregation of human RBC in binary dextran-PEG polymer mixtures.

The present study was prompted by prior reports suggesting that small polymers can affect RBC aggregation induced by large macromolecules. Human RBC were washed and re-suspended in isotonic buffer solutions containing 72.5 kDa dextran (DEX 70, 2 g/dl) or 35.0 kDa poly(ethylene glycol) (PEG 35, 0.35 g/dl), then tested for aggregation in these solutions with and without various concentrations of smaller dextrans (10.5 and 18.1 kDa) or PEGs (3.35, 7.5 and 10.0 kDa). RBC aggregation was measured at stasis and at low shear using a photometric cone-plate system (Myrenne Aggregometer) and RBC electrophoretic mobility (EPM) in the various polymer solutions via an automated system (E4, HaSoTec GmbH). Our results indicate: (1) a heterogeneous effect with greater reduction of aggregation for small PEGs added to DEX 70 or for small dextrans added to PEG 35 than for small polymers of the same species; (2) for cells in DEX 70, aggregation decreased with increasing molecular mass and concentration of the small dextrans or PEGs; (3) for cells in PEG 35, small dextrans decreased aggregation with increasing molecular mass and concentration, whereas small PEGs had minimal effects with a minor influence of concentration and an inverse association between molecular mass and inhibition of aggregation. RBC EPM results indicated the expected polymer depletion for cells in DEX 70 or PEG 35, and that small PEGs yielded greater EPM values than small dextrans for cells in PEG 35 whereas the opposite was true for cells in DEX 70. Interpretation of our results in terms of the depletion model for RBC aggregations appears appropriate, and our findings are consistent with the assumption that inhibition of aggregation occurs because of an increase of small molecules in the depletion region. Our results thus suggest the merit of further studies of red blood cell aggregation in binary polymer systems.