Rationalizing the formation of porosity in mechanochemically-synthesized polymers.

In this study, we present a matrix of 144 mechanochemically-synthesized polymers. All polymers were constructed by the solvent-free Friedel-Crafts polymerization approach, employing 16 aryl-containing monomers and 9 halide-containing linkers, which were processed in a high-speed ball mill. This Polymer Matrix was utilized to investigate the origin of porosity in Friedel-Crafts polymerizations in detail. By examining the physical state, molecular size, geometry, flexibility, and electronic structure of the utilized monomers and linkers, we identified the most important factors influencing the formation of porous polymers. We analyzed the significance of these factors for both monomers and linkers based on the yield and specific surface area of the generated polymers. Our in-depth evaluation serves as a benchmark study for future targeted design of porous polymers by the facile and sustainable concept of mechanochemistry.

Risk factors for bleeding from gastrointestinal angiodysplasia: a case-control study in patients with bleeding and non-bleeding angiodysplasia.

OBJECTIVES: Angiodysplasia (AD) is a common source of gastrointestinal bleeding. Yet, little is known about factors forwarding bleeding in these vascular malformations. The presented study aims to determine risk factors for bleeding that occurs only in patients with symptomatic, but not with asymptomatic, AD. METHODS: Case-control study in patients with AD and either a positive or a negative history of gastrointestinal bleeding in Munich, Germany. Groups were compared by clinical, laboratory, and endoscopic features. RESULTS: 80 patients with (58, f 31, med. age 72) or without bleeding AD (22, f 12, med. age 61) were included. Bleeding from AD was significantly associated with the total number of AD (OR 1.4 (95 % CI 1.1-1.7) p = 0.01) and closure time in PFA/collagen-epinephrine test (OR 1.0 (95 % CI 1.0-1.0) p < 0.01). The total number of AD correlated significantly with age (r = 0.36; p = 0.01). AD were mainly detected in the upper small intestine (> 30 %). Although patients with aortic stenosis suffered not significantly more frequently from bleeding from AD, they demonstrated a loss of high molecular multimers of VWF. CONCLUSIONS: The amount of AD is clearly correlated to the age of the patient. A higher number of ADs and inhibition of primary hemostasis increase the risk of bleeding.

Near-infrared fluorescence cholangiopancreatoscopy: initial clinical feasibility results.

BACKGROUND: The recent clinical propagation of targeted fluorescence agents brings a promising alternative in endoscopy by complementing visual disease detection with molecular biomarkers. OBJECTIVE: Development of near-infrared (NIR) fluorescence cholangiopancreatoscopy in real-time and validation of its clinical use. DESIGN: Feasibility study. SETTING: Tertiary referral center at a large university hospital. PATIENTS: Patients with pancreatic and biliary diseases. INTERVENTIONS: Routine cholangiopancreatoscopy with additional wide-field NIR fluorescence imaging. MAIN OUTCOME MEASUREMENTS: We adapted a miniature cholangioscope for real-time concurrent wide-field color and NIR fluorescence imaging. Illumination is provided through a custom-designed fiber bundle, and the acquired images are relayed via a dichroic beam splitter to 2 charge-coupled devices for simultaneous measurement. We characterize the sensitivity and resolution and demonstrate the clinical feasibility by detecting indocyanine green localization in 2 patients. RESULTS: A spatial optical resolution of approximately 50 µm was achieved, and fluorescent dye concentrations of 17.3 nM could be detected. Elevated fluorescence signals were detected during clinical measurements, and biopsy specimens confirmed the presence of malignancy in both patients. LIMITATIONS: Feasibility study, limited number of patients. CONCLUSIONS: The results demonstrate that real-time wide-field fluorescence detection in the NIR range is possible in humans by using adapted endoscopes. The feasibility of detecting indocyanine green in the pancreatobiliary ducts is verified, suggesting that cancer screening at a molecular level might play an increasingly important role in the future.

Nanoscale markers of esophageal field carcinogenesis: potential implications for esophageal cancer screening.

BACKGROUND AND STUDY AIMS: Esophageal adenocarcinoma (EAC) has a dismal prognosis unless treated early or prevented at the precursor stage of Barrett's esophagus-associated dysplasia. However, some patients with cancer or dysplastic Barrett's esophagus (DBE) may not be captured by current screening and surveillance programs. Additional screening techniques are needed to determine who would benefit from endoscopic screening or surveillance. Partial wave spectroscopy (PWS) microscopy (also known as nanocytology) measures the disorder strength (Ld ), a statistic that characterizes the spatial distribution of the intracellular mass at the nanoscale level and thus provides insights into the cell nanoscale architecture beyond that which is revealed by conventional microscopy. The aim of the present study was to compare the disorder strength measured by PWS in normal squamous epithelium in the proximal esophagus to determine whether nanoscale architectural differences are detectable in the field area of EAC and Barrett's esophagus. METHODS: During endoscopy, proximal esophageal squamous cells were obtained by brushings and were fixed in alcohol and stained with standard hematoxylin and Cyto-Stain. The disorder strength of these sampled squamous cells was determined by PWS. RESULTS: A total of 75 patient samples were analyzed, 15 of which were pathologically confirmed as EAC, 13 were DBE, and 15 were non-dysplastic Barrett's esophagus; 32 of the patients, most of whom had reflux symptoms, acted as controls. The mean disorder strength per patient in cytologically normal squamous cells in the proximal esophagus of patients with EAC was 1.79-times higher than that of controls (P<0.01). Patients with DBE also had a disorder strength 1.63-times higher than controls (P<0.01). CONCLUSION: Intracellular nanoarchitectural changes were found in the proximal squamous epithelium in patients harboring distal EAC and DBE using PWS. Advances in this technology and the biological phenomenon of the field effect of carcinogenesis revealed in this study may lead to a useful tool in non-invasive screening practices in DBE and EAC.

Argon plasma coagulation of cervical heterotopic gastric mucosa as an alternative treatment for globus sensations.

BACKGROUND & AIMS: Ablation of gastric inlet patches (GIP) in the cervical esophagus by argon plasma coagulation (APC) can alleviate chronic globus sensations in the throat. We investigated the efficacy of this therapy in a randomized, controlled multicenter trial. METHODS: Patients with chronic globus sensations and GIP were randomly assigned 1:1 to groups that were treated with APC or a sham procedure (controls). Patients and their referring physicians were blinded to therapy. All patients completed a standardized questionnaire about symptoms before and 3 months after the procedure. Thereafter, control patients were eligible for cross-over therapy. Long-term efficacy was assessed in all patients >or=6 months after APC. RESULTS: Improvement of symptoms was reported in 9 (82%) of 11 patients who received APC, compared with 0 (0%) of 10 patients in the control group (P = .002). Nine (90%) of 10 patients treated with APC had per protocol healing, compared with 0 (0%) of 9 controls (P < .001). Scores for symptom/globus assessment significantly improved in patients in the APC group, whereas patients in the control group did not perceive any symptom relief. Eight of the 10 patients who started in the control group crossed over to the APC group. Long-term efficacy (after a median follow-up of 17 months) was documented in 13 (76%) of 17 treated patients. CONCLUSIONS: Ablation of gastric inlet patches appears to be an effective therapy for alleviation of associated globus sensations. This new treatment modality might change the paradigm for treatment of these patients.

Needle-based confocal endomicroscopy for in vivo histology of intra-abdominal organs: first results in a porcine model (with videos).

BACKGROUND: Probe-based confocal laser scanning endomicroscopy enables in vivo real time histopathology of the mucosa layer. Recently, a prototype of a new confocal miniprobe has been developed that is small enough to be introduced through a 22-gauge puncture needle. OBJECTIVE: The aim of this study was to evaluate the feasibility of such needle-based confocal laser scanning endomicroscopy (nCLE) for in vivo histology of various organs in a porcine model. DESIGN: Feasibility study. SETTING: Nonsurvival animal experiments with the animals under general anesthesia at three academic centers. INTERVENTIONS: Ten pigs were examined while they were under general anesthesia. Either EUS-guided organ puncture or natural-orifice transluminal endoscopic surgery (NOTES) procedure was used. The confocal miniprobe was inserted through the 22-gauge needle, and puncture of various intra-abdominal structures and organs was performed (lymph nodes, diaphragm, ovaries, liver, spleen, and pancreas) after intravenous injection of fluorescein (5-10 mL 1% or 2 mL 10% solution). Real-time sequences were recorded. Biopsy specimens were taken for standard histopathology. MAIN OUTCOME MEASUREMENTS AND RESULTS: It was technically feasible to introduce the needle-based confocal miniprobe into various organs at the time of EUS or NOTES procedures. The device enabled real-time in vivo collection of images at histologic resolutions and of acceptable image quality from several intra-abdominal organs interrogated. LIMITATIONS: Data were assessed in an experimental animal setting and on healthy organs only. CONCLUSIONS: Needle-based confocal laser endomicroscopy (CLE) of intra-abdominal organs is feasible in a porcine model. This innovative, minimally invasive technique has the potential to facilitate in vivo histology during EUS punctures or NOTES peritoneoscopy.

High-dose esomeprazole for treatment of symptomatic refractory gastroesophageal reflux disease--a prospective pH-metry/impedance-controlled study.

BACKGROUND/AIMS: Combined pH-metry/multichannel intraluminal impedance (pH/MII) measurement enables to measure gastroesophageal reflux despite ongoing proton pump inhibitor therapy. The aim of our study was to evaluate the influence of an escalating medical anti-reflux therapy with 40 mg esomeprazole, 80 mg esomeprazole and 80 mg esomeprazole plus baclofen for the treatment of refractory pathological reflux as determined by pH/MII. METHODS: Symptomatic patients under 40 mg esomeprazole were screened by pH/MII. Patients with normal values in pH/MII were excluded; all others received 2 x 40 mg esomeprazole for another 4 weeks. Thereafter, the treatment effect was controlled by pH/MII. In the case of persistent pathological reflux, therapy was further escalated by adding baclofen and controlled after 3 months by pH/MII. RESULTS: 45/138 (32.6%) patients showed pathological pH/MII despite ongoing therapy with 40 mg esomeprazole. In these, a significant reduction in liquid/mixed reflux events was observed after administering 2 x 40 mg (mean: 118.3 vs. mean: 66.6; p < 0.001), and pH/MII turned to normal in 32/45 (71.1%). Baclofen was additionally administered to 7/13 patients, which did not lead to a remarkable reduction in reflux events. CONCLUSION: In patients with abnormal pH/MII and persistent symptoms under 40 mg esomeprazole, we observed a significant reduction in liquid/mixed reflux events after increasing proton pump inhibitor dose up to 80 mg esomeprazole. Further escalation of therapy with baclofen has shown inconclusive results.

Detection of cholangiocarcinoma in vivo using miniprobe-based confocal fluorescence microscopy.

BACKGROUND & AIMS: The preoperative diagnosis of cholangiocarcinoma is associated with a low sensitivity. To overcome this limitation, a new imaging modality was evaluated to detect neoplasia in vivo in the biliary tract. METHODS: Fourteen patients with biliary strictures were examined. Mucosal imaging was performed with a miniaturized confocal laser scanning miniprobe introduced via the accessory channel of a cholangioscope. Thereafter, targeted biopsy specimens were taken from the same regions. RESULTS: All strictures could be reached. Presence of irregular vessels use confocal laser microscopy enabled prediction of neoplasia with an accuracy rate of 86%, sensitivity of 83%, and specificity of 88%. The respective numbers for standard histopathology were 79%, 50%, and 100%. The mean signal-to-noise-ratio of laser microscopic images acquired from malignant strictures differed significantly from those of benign origin (1.8 +/- 0.8 vs 2.6 +/- 1.0; P = .005). CONCLUSIONS: Miniprobe-based confocal laser scanning microscopy considerably increases sensitivity for the detection of biliary neoplasia and therefore represents a promising diagnostic approach.

Intravenous application of fluorescein for confocal laser scanning microscopy: evaluation of contrast dynamics and image quality with increasing injection-to-imaging time.

BACKGROUND: Confocal laser scanning microscopy (CLSM) is reported to be a promising tool for in vivo histopathology during an endoscopy. The most commonly used fluorophore is fluorescein sodium given intravenously. However, so far, there are no objective data on contrast dynamics and image quality over time after injection of the substance. OBJECTIVE: We aimed to investigate the ideal time period for the best CLSM imaging when using fluorescein sodium. DESIGN: The proximal stomachs of 4 anesthetized pigs were examined via standard endoscopes with a portable confocal miniprobe. After injection of 1% fluorescein intravenously (0.1 mL/kg body weight), consecutive sequences were recorded after 1, 2, 3, 5, 8, 20, 30, 40, 50, and 60 minutes. After the procedure, histograms, which represented signal intensity of 20 images (at respective time points), were analyzed from representative regions of interest (ROI). The mean (standard deviation [SD]) pixel value of the pixel values in the ROI were noted. A signal-to-noise ratio (SNR), defined as the ratio between the mean and the SD, was calculated. In addition, 5 images per time period were put into a random order and then blindly evaluated by 2 endoscopists. RESULTS: A total of 560 histograms from selected ROIs were analyzed. The SNR decreased significantly after 8 minutes, with the lowest values being reached after 30 minutes. Subjective evaluation of still images also demonstrated a continuous decrease, with the lowest image quality after 30 minutes. A slight increase of image quality after 40 minutes occurred because of extramucosal leakage of fluorescein, with fluorophore deposits in the crypt orifices. CONCLUSIONS: In the pig model, fluorescein-based CLSM of the GI tract delivered the best contrast and image quality within the first 8 minutes after injection of the fluorophore. These data might facilitate standardization of the procedure for research purposes but may also help when applying this new technology in a daily routine manner.

Sorbitol malabsorption in patients with abdominal discomfort.

BACKGROUND: The role of sorbitol malabsorption in patients with functional abdominal discomfort has not been finally clarified yet. Therefore, aim of this study was to evaluate the clinical significance of sorbitol malabsorption, diagnosed by sorbitol hydrogen breath testing in these patients. METHODS: Data of all patients referred to our hospital for hydrogen breath testing between May 1st, 2013 and December 31st, 2014 were retrospectively collected and analyzed. Patients with confirmed sorbitol malabsorption completed a symptom-based questionnaire before and after nutritional counseling. RESULTS: Five hundred and ten patients with functional abdominal discomfort (65.5% female, 34.5% male; mean age 45±16.4 years) were referred to our hospital for hydrogen breath testing. H2-sorbitol breath tests were performed in 252 of these patients. In 122 of them (48%), sorbitol-malabsorption was diagnosed. In 66 of these patients (54%), the results of the symptom-based questionnaire showed a significant improvement of the frequency of abdominal discomfort (P<0.001) and of the influence of these symptoms on daily life (P<0.001) after sorbitol testing/nutritional counseling. CONCLUSIONS: Sorbitol malabsorption is a common finding in patients with functional abdominal discomfort. Dietary intervention positively affects abdominal symptoms in these patients.

In vivo histopathology for detection of gastrointestinal neoplasia with a portable, confocal miniprobe: an examiner blinded analysis.

BACKGROUND & AIMS: Confocal fluorescence microscopy (CFM) has been mentioned to be a promising tool for in vivo histology. Recently, a portable confocal miniprobe has been developed. Our aim was to evaluate the potential benefit of CFM for detection of gastrointestinal neoplasia. METHODS: A total of 47 patients with known or suspected neoplasia in the upper (n = 34) or lower gastrointestinal tract (n = 13) were examined with standard endoscopes. After mucolyis with 5-10 mL of acetic acid 1.5%, chromoendoscopy with 2-5 mL cresyl violet 0.25% was performed, with the substance also being used as a fluorophore for CFM. Real-time video sequences were recorded. Thereafter, biopsies were taken or mucosectomy/polypectomy was performed from the same examined area. All stored sequences were put into a random order and assessed by a pathologist and a gastroenterologist both blinded to any data. RESULTS: A total of 119 CFM video sequences were recorded of 85 benign or 34 neoplastic areas. Quality of CFM images was regarded too low in 24 (pathologist) and 14 sequences (gastroenterologist). For the pathologist, accuracy of CFM detecting neoplasia was 92.6% (suitable images) and 73.9% (intention to diagnose). The respective accuracy values for the gastroenterologist were 92.4% (suitable images) and 81.5% (intention to diagnose). Agreement between CFM and histopathology was excellent (kappa values, 0.821 and 0.817). CONCLUSIONS: We have demonstrated that CFM with a miniprobe has the potential to diagnose neoplasia during ongoing endoscopy. This system has the advantage that it can be used with standard endoscopes. Further studies are warranted for validation.

Combined pH-metry/impedance monitoring increases the diagnostic yield in patients with atypical gastroesophageal reflux symptoms.

BACKGROUND: Globus sensations, hoarseness and chronic cough are suggested to be atypical manifestations of Gastroesophageal Reflux Disease (GERD). The aim of the study was to investigate whether combined pH-metry and multichannel intraluminal impedance monitoring increases the diagnostic yield. METHODS: 41 patients with atypical GERD symptoms were included in the study. Globus sensation was the dominant symptom in 23 patients (56.1%). The remaining 18 patients (43.9%) complained mainly about hoarseness or chronic cough. All patients were examined by endoscopy, dual-channel pH-metry and impedance monitoring off-therapy with proton pump inhibitors (PPI). Diagnostic yield of the respective method was determined. RESULTS: A total of 26 patients (63.4%) had pathological findings in any method. The highest diagnostic yield was achieved by combined 24-h pH-metry/impedance measurement (61.0%), followed by solely impedance measurement (48.8%), distal pH-metry (29.3%), endoscopy (22.8%) and proximal pH-metry (17.1%). All patients with a positive PPI-test and 25% of patients (5/20) with a negative PPI-test had a pathological result in pH-metry/impedance. CONCLUSION: Multichannel intraluminal impedance monitoring increases the diagnostic yield for objective detection of atypical manifestation of GERD. Combined 24-h pH-metry/impedance measurement has the best diagnostic yield for detection of gastroesophageal reflux and has therefore the potential to represent a new diagnostic gold standard.

Pharyngeal pH monitoring in gastrectomy patients - what do we really measure?

AIM: Diagnosis of laryngopharyngeal reflux (LPR) has dramatically increased over the last years. For diagnosis of gastroesophageal reflux, a newly designed pharyngeal probe (Dx-pH) was recently introduced. It is also recommended to guide therapy decision in antireflux surgery. However, diagnostic results are questionable. Therefore, we establish a reliable reference group with asymptomatic patients after total gastrectomy and, thus, complete extinction of gastric acid production. METHODS: Pharyngeal pH monitoring was performed in 10 consecutive patients with history of total gastrectomy. All patients were off proton pump inhibitor (PPI) therapy and followed a non-acid diet during the complete measurement period. RESULTS: All procedures were performed without any complication. Six of the 10 asymptomatic gastrectomy patients (60%) had pathological results derived from the validated reference values (Ryan score) in pharyngeal pH monitoring. CONCLUSION: Pathological pH values assessed by the Dx-pH device, usually interpreted as pathological aerosolized acidic gastroesophageal and/or laryngopharyngeal reflux, are obviously dissociated from gastric acid production. Further studies are required to determine diagnostic value of the new system. Therefore, the pharyngeal pH monitoring system seems currently not to be useful to guide any diagnostic or therapeutic decisions, in particular if surgical therapy is considered.

pH/multichannel impedance monitoring in patients with laryngo-pharyngeal reflux symptoms - Prediction of therapy response in long-term follow-up.

BACKGROUND AND STUDY AIM: Optimal therapy concepts in patients with laryngo-pharyngeal reflux (LPR) are still under discussion. Aim of this study was to evaluate long term symptom relief according to results in combined pH/multichannel impedance (MII) monitoring to predict therapy response and symptom relief during long term follow-up. PATIENTS AND METHODS: In patients with predominant LPR symptoms, pH/MII monitoring and subsequent proton pump inhibitor (PPI) therapy were evaluated retrospectively after a minimum follow-up period of 36months. Patients were asked to complete symptom based questionnaires. RESULTS: 45 patients were evaluated and classified according to results of pH/MII. Twenty one patients showed a pathological finding in pH/MII. These patients reported significantly higher LPR-symptom intensity scores and a significantly higher LPR symptom-induced impairment of everyday life scores compared to patients with normal pH/MII monitoring at baseline and at follow-up. PPI associated symptom relief was significantly higher in patients with pathologic pH/MII monitoring (p=0.003). CONCLUSION: In conclusion, combined pH/MII monitoring can reliably predict therapy response to PPIs in LPR patients. With negative results, PPI therapy should be avoided. This approach should be assessed in future prospective clinical trials.

Developments in flexible endoscopic surgery: a review.

Flexible endoscopy is increasingly developing into a therapeutic instead of a purely diagnostic discipline. Improved visualization makes early lesions easily detectable and allows us to decide ad hoc on the required treatment. Deep enteroscopy allows the exploration of even the small bowel - for long a "white spot" for gastrointestinal endoscopy - and to perform direct treatment. Endoscopic submucosal dissection is a considerable step forward in oncologically correct endoscopic treatment of (early) malignant lesions. Though still technically challenging, it is increasingly facilitated by new manipulation techniques and tools that are being steadily optimized. Closure of wall defects and hemostasis could be improved significantly. Even the anatomy beyond the gastrointestinal wall is being explored by the therapeutic use of endoluminal ultrasound. Endosonographic-guided surgery is not only a suitable fallback solution if conventional endoscopic retrograde cholangiopancreatography fails, but even makes necrosectomy procedures, abscess drainage, and neurolysis feasible for the endoscopist. Newly developed endoscopic approaches aim at formerly distinctive surgical domains like gastroesophageal reflux disease, appendicitis, and cholecystitis. Combined endoscopic/laparoscopic interventional techniques could become the harbingers of natural orifice transluminal endoscopic surgery, whereas pure natural orifice transluminal endoscopic surgery is currently still in its beginnings.

New aspects in the pathomechanism and diagnosis of the laryngopharyngeal reflux-clinical impact of laryngeal proton pumps and pharyngeal pH metry in extraesophageal gastroesophageal reflux disease.

AIM: To determine the laryngeal H+K+-ATPase and pharyngeal pH in patients with laryngopharyngeal reflux (LPR)-symptoms as well as to assess the symptom scores during PPI therapy. METHODS: Endoscopy was performed to exclude neoplasia and to collect biopsies from the posterior cricoid area (immunohistochemistry and PCR analysis). Immunohistochemical staining was performed with monoclonal mouse antibodies against human H+K+-ATPase. Quantitative real-time RT-PCR for each of the H+K+-ATPase subunits was performed. The pH values were assessed in the aerosolized environment of the oropharynx (DxpH Catheter) and compared to a subsequently applied combined pH/MII measurement. RESULTS: Twenty patients with LPR symptoms were included. In only one patient, the laryngeal H+K+-ATPase was verified by immunohistochemical staining. In another patient, real-time RT-PCR for each H+K+-ATPase subunit was positive. Fourteen out of twenty patients had pathological results in DxpH, and 6/20 patients had pathological results in pH/MII. Four patients had pathological results in both functional tests. Nine out of twenty patients responded to PPIs. CONCLUSION: The laryngeal H+K+-ATPase can only be sporadically detected in patients with LPR symptoms and is unlikely to cause the LPR symptoms. Alternative hypotheses for the pathomechanism are needed. The role of pharyngeal pH-metry remains unclear and its use can only be recommended for patients in a research study setting.

Evaluation of isolated lung perfusion as neoadjuvant therapy of lung metastases using a novel in vivo pig model: II. High-dose cisplatin is well tolerated by the native lung tissue.

OBJECTIVE: Efficacy of in vivo isolated lung perfusion (ILP) with cisplatin could be shown in different rodent tumor models. Despite the use of this alternative therapeutical strategy in very few patients with lung metastases, there are no systematic studies regarding the tolerance of the native lung tissue in large animal models or humans. METHODS: In a novel ILP pig model, groups with two different concentrations of cisplatin (group CP150: 150 mg/m(2) cisplatin, n=5; group CP300: 300 mg/m(2) cisplatin, n=5) were compared with a control group (n=5) and a Sham group (n=5) concerning the influence on hemodynamic, ventilatory and gas exchange parameters as well as on structural integrity of the lung. In the additional CP300-HT group the potentially cumulative effect of hyperthermia and high-dose cisplatin perfusion was evaluated (300 mg/m(2) cisplatin, 41.5 degrees C, n=5). Following the ILP of the left lung for 40 min, right main bronchus and right pulmonary arteries were clamped and survival as well as lung function parameters were dependent on the previously perfused lung for the 6-h-reperfusion period. Quantification of histological acute lung injury was performed using the score of Chiang. ANOVA, ANOVA with repeated measures and Pearson's correlation estimation were applied for statistical evaluation. RESULTS: All animals survived ILP and the entire reperfusion period. Platinum levels of the perfusate and lung tissue showed a significant correlation with the dose given (P<0.001) but no correlation with the very low plasma levels in all groups (P=0.825). ILP resulted in a slight deterioration of most functional parameters compared to the Sham group. Although there were no differences between the perfusion groups regarding hemodynamic and ventilatory parameters, gas exchange parameters (pO(2)/FiO(2)-index, pCO(2), AADO(2)) demonstrated a trend toward dose-related functional impairment. Histological evaluation confirmed a dose-depending damage of lung tissue (P<0.001, correlation coefficient 0.670). The hyperthermic ILP with high-dose cisplatin led to improved gas exchange parameters and a reduction of morphological lung damage. CONCLUSIONS: In vivo ILP with high-dose cisplatin represents a safe procedure in this pig model. Hyperthermic perfusion up to 41.5 degrees C was beneficial to reduce the acute lung injury. The promising results of this study might be used for initiation of clinical trials as an alternative treatment in patients with a very poor prognosis.

Evaluation of isolated lung perfusion as neoadjuvant therapy of lung metastases using a novel in vivo pig model: I. Influence of perfusion pressure and hyperthermia on functional and morphological lung integrity.

OBJECTIVE: Despite favorable experimental results and an encouraging early experience in humans, isolated lung perfusion (ILP) for treatment of metastases is still not established clinically. The complexity of the procedure as well as poor knowledge regarding the technical necessities of lung perfusion represents major limitations. METHODS: In this novel in vivo pig model, ILP of the left lung was performed for 40 min followed by the exclusion of the right lung. Survival and all monitored parameters of hemodynamics, ventilation and gas exchange were exclusively dependent on the previously perfused left lung for the 6-h reperfusion period. Furthermore, histological examination was assessed. In the first protocol influence of different perfusion pressures (PP) on the native lung tissue was investigated (LPG, n=6, PP<25 mmHg; HPG, n = 8, PP> or =25 mmHg). In the second protocol the influence of normothermic (T-38; n=5; t=38 degrees C), mild (T-40; n=5; t=40 degrees C) and moderate hyperthermic (T-41.5; n=5; t=41.5 degrees C) perfusion temperature was evaluated. Results were compared to those of a sham-operated control group (SG, n=5). RESULTS: ILP led to a slight deterioration of all functional as well as histological parameters in all groups. HPG resulted in impairment regarding all monitored parameters compared to LPG and SG. Significant differences between HPG and SG were found for cardiac index (P=0.026) and pulmonary vascular resistance index (PVRI, P=0.026). Histological scoring revealed significantly higher grade of lung injury for HPG animals (P=0.001). Functional parameters did not differ between normothermic and hyperthermic perfusion groups. However, animals of the T-38 group demonstrated significantly increased PVRI (P=0.004). Histological examination revealed significantly higher scores of acute lung injury for all perfusion groups compared to the Sham group (P<0.001). CONCLUSIONS: The results of this novel large animal model represent the first available demonstration that increased PP in a setting of ILP will result in deleterious effects on lung function and morphology. However, mild to moderate hyperthermia is well tolerated by the native lung tissue.

Prucalopride reduces the number of reflux episodes and improves subjective symptoms in gastroesophageal reflux disease: a case series.

INTRODUCTION: Treatment of persistence to proton pump inhibitors or non-acid reflux episodes in patients with gastroesophageal reflux disease is challenging. Prucalopride, a selective high affinity serotonin (5-HT4) receptor agonist, might offer a possible new therapeutic alterative. CASE PRESENTATIONS: We report four chronically constipated female gastroesophageal reflux disease-patients with reflux symptoms and an increased number of reflux episodes in combined esophageal pH and multichannel impedance monitoring treated with prucalopride (2mg per day). Symptoms were persistent to proton pump inhibitors and ranitidine. Gastroesophageal reflux was detected by pH or multichannel impedance (MII) monitoring. Numbers of all reflux episodes as well as non-acid reflux episodes were reduced in all of our patients. The objective findings were concordant with subjective reports of symptom relief. There were no major adverse events in any patient during therapy with prucalopride. CONCLUSION: Administration of prucalopride showed promising results in the treatment of persisting or weakly and/or non-acid reflux episodes in our case series in four constipated patients. Therefore, prucalopride can be regarded as a possible therapeutic option in the treatment of standard proton pump inhibitor-persistent reflux in the chronically constipated patient. However, further prospective trials are needed to prove our findings.

Small bowel pleomorphic liposarcoma: a rare cause of gastrointestinal bleeding.

In this case report we present a 60-year-old male patient with overt midgastrointestinal bleeding of a primary ileal pleomorphic liposarcoma diagnosed by video capsule endoscopy (VCE). Clinical work-up for final diagnosis and the pathological background of this uncommon tumorous entity of the small bowel will be discussed in this paper.