Endoscopic vacuum-assisted closure therapy for leakage of the lower gastrointestinal tract: multicenter experiences.

Background and study aims Only a few studies are available regarding endoscopic vacuum-assisted closure (E-VAC) therapy for the post-surgery leakage of the lower gastrointestinal tract. Patients and methods In this multicenter German study, we retrospectively analyzed patients treated with E-VAC therapy due to post-surgery leakage of the lower gastrointestinal tract from 2000-2020 at Hannover Medical School, University Medical Center Schleswig-Holstein, Campus Luebeck, and Robert Koch Hospital Gehrden. Results Overall, 147 patients were included in this study. Most patients had undergone tumor resections of the lower gastrointestinal tract (n = 88; 59.9 %). Median time to diagnosis of leakage was 10 days (interquartile range [IQR] 6-19). Median duration of E-VAC therapy was 14 days (IQR 8-27). Increase of C-reactive protein (CRP) levels significantly correlated with first diagnosis of leakage ( P  < 0.001). E-VAC therapy led to closure or complete epithelialization of leakage in the majority of patients (n = 122; 83.0 %) and stoma reversal was achieved in 60.0 %. Stoma reversal was significantly more often achieved in patients with CRP levels ≤ 100 mg/L at first diagnosis compared to patients with CRP levels > 100 mg/L (78.4 % vs. 52.7 %; P  = 0.012). Odds ratio for failure of stoma reversal was 3.36 in cases with CRP values > 100 mg/L ( P  = 0.017). In total, leakage- and/ or E-VAC therapy-associated complications occurred in 26 patients (17.7 %). Minor complications included recurrent E-VAC dislocations and subsequent stenosis. Overall, 14 leakage- or E-VAC-associated deaths were observed most often due to sepsis. Conclusions E-VAC therapy due to post-surgery leakage of the lower gastrointestinal tract is safe and effective. High levels of CRP are a negative predictor of E-VAC therapy success.

Successful treatment of cervical esophageal leakage by endoscopic-vacuum assisted closure therapy.

AIM: To evaluate the efficacy and safety of endoscopic-vacuum assisted closure (E-VAC) therapy in the treatment of cervical esophageal leakage. METHODS: Between May and November 2012, three male patients who developed post-operative cervical esophageal leakage were treated with E-VAC therapy. One patient had undergone surgical excision of a pharyngo-cervical liposarcoma with partial esophageal resection, and the other two patients had received surgical treatment for symptomatic Zenker's diverticulum. Following endoscopic verification of the leakage, a trimmed polyurethane sponge was fixed to the distal end of a nasogastric silicone tube and endoscopically positioned into the wound cavity, and with decreasing cavity size the sponge was positioned intraluminally to cover the leak. Continuous suction was applied, and the vacuum drainage system was changed twice a week. RESULTS: The initial E-VAC placement was technically successful for all three patients, and complete closure of the esophageal leak was achieved without any procedure-related complications. In all three patients, the insufficiencies were located either above or slightly below the upper esophageal sphincter. The median duration of the E-VAC drainage was 29 d (range: 19-49 d), with a median of seven sponge exchanges (range: 5-12 sponge exchanges). In addition, the E-VAC therapy reduced inflammatory markers to within normal range for all three patients. Two of the patients were immediately fitted with a percutaneous enteral gastric feeding tube with jejunal extension, and the third patient received parenteral feeding. All three patients showed normal swallow function and no evidence of stricture after completion of the E-VAC therapy. CONCLUSION: E-VAC therapy for cervical esophageal leakage was well tolerated by patients. This safe and effective procedure may significantly reduce morbidity and mortality following cervical esophageal leakage.

Microbiologic analysis of peri-pancreatic fluid collected during EUS in patients with pancreatitis: impact on antibiotic therapy.

BACKGROUND: Pancreatitis is a potentially life-threatening condition frequently accompanied by peri-pancreatic fluid collections (PPFC), such as pseudocysts or pancreatic necrosis. Aspiration of PPFCs during EUS interventions for microbiologic analysis is still rarely performed in clinical routine. OBJECTIVE: To evaluate the role of routine microbiologic analysis of PPFCs and its impact on antibiotic therapy in patients with pancreatitis. DESIGN: Prospective, observational, multicenter study. SETTING: Four treatment centers. PATIENTS: A total of 44 consecutive patients who presented for endoscopic treatment of PPFCs were included. INTERVENTION: Concomitantly, PPFC during intervention and concomitant blood cultures were obtained. MAIN OUTCOME MEASUREMENTS: Microbiologic examination of PPFCs and blood samples. RESULTS: Colonization of PPFCs was found in 59% of PPFC cultures, whereas all but 2 concomitant blood cultures showed no microbial growth. Risk factors for a colonization were the presence of necrosis (P = .006), acute pancreatitis (P = .033), leukocytosis (P = .001), elevated C-reactive protein levels (P = .003), fever (P = .02), turbid material (P = .031), and longer hospital stay (P = .003). In 23 patients with fluid colonization despite empiric antibiotic therapy, the treatment had to be adjusted in 18 patients (78%) according to the observed antibiotic susceptibility profile. LIMITATIONS: Contamination cannot be totally excluded. CONCLUSION: The microbiologic colonization of PPFCs in patients with pancreatitis is common. Only the direct microbiologic analysis of PPFCs, but not of blood cultures, is useful to optimize an effective antibiotic therapy in patients with pancreatitis.

Diagnostic value of ultrasound in detection of biliary tract complications after liver transplantation.

BACKGROUND: Biliary complications are significant source of morbidity after liver transplantation (LT). Cholangiography is the gold standard for diagnosis and specification of biliary complications. OBJECTIVES: Detailed analyses of ultrasound (US) as a safe imaging method in this regard are still lacking. Therefore we analyzed systematically the diagnostic value of US in these patients. PATIENTS AND METHODS: Retrospectively, 128 liver graft recipients and their clinical data were analyzed. All patients had a standardized US examination. The findings of US were compared to cholangiographic results in 42 patients. Following statistical analyses were performed: descriptive statistics, sensitivity, specificity, positive and negative predictive values (PPV, NPV). RESULTS: 42 patients had 54 different biliary complications (Anastomotic stenosis (AS) n = 33, ischemic type biliary lesions (ITBL) n = 18 and leakage n = 3). US detected n = 22/42 (52%) patients with biliary complications. The sensitivity, specificity, PPV and NPV of US were: 61%, 100%, 100%, 79% (95CI, 36-86%) for ITBL and 24%, 100, 100%, 31% (95CI, 9-46 %) for AS, respectively. CONCLUSIONS: US examination had no false positive rate. Therefore, it may be helpful as a first screening modality. But for the direct diagnosis of the biliary complication US is not sensitive enough.

Screening colonoscopy in liver transplant candidates: risks and findings.

The indication for mandatory screening colonoscopies in liver transplant candidates is controversial. Since the introduction of MELD-based allocation, patients with advanced liver disease and often severe comorbidities are prioritized for liver transplantation (LT). This study evaluated safety and outcome of colonoscopy in this high-risk patient group. During a two-yr period, we performed 243 colonoscopies in potential LT candidates. Endoscopic findings were registered in a standardized form, and correlations with biochemical or clinical parameters were analyzed using Mann-Whitney U-test and chi-square test. Only 57 patients (23.5%) had an endoscopically normal colon. Main findings were polyps (45.7%), hypertensive colopathy (24.3%), diverticulosis (21%), rectal varices (19.8%), and hemorrhoids (13.6%). In 21% of all patients, the removed polyps were diagnosed as adenomas. The prevalence of neoplastic polyps increased significantly with age: 13.6% (patients <50 yr) vs. 25% (patients ≥ 50 yr) (p = 0.03). Advanced neoplasia was found only in patients older than 40 yr. No major complications were observed; post-interventional hemorrhage was observed in 1.7% and controlled by clipping or injection therapy. In conclusion, lower gastrointestinal endoscopy is safe and effective in LT candidates. Due to the age dependency of neoplastic polyps, a screening colonoscopy should be performed in LT candidates older than 40 yr or with symptoms or additional risk factors.

Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders.

BACKGROUND: Diagnosis and curative treatment of cholangiocarcinoma (CC) often comes too late due to the lack of reliable tumour markers especially in patients with primary sclerosing cholangitis (PSC). The authors recently introduced bile proteomic analysis for CC diagnosis. Nevertheless, bile collection depends on invasive endoscopic retrograde cholangiography. The authors therefore evaluated urine proteomic analysis for non-invasive CC diagnosis. METHODS: Using capillary electrophoresis mass spectrometry the authors established a CC-specific peptide marker model based on the distribution of 42 peptides in 14 CC, 13 PSC and 14 benign biliary disorder (BBD) patients. RESULTS: In cross-sectional validation of 123 patients, the urine peptide marker model correctly classified 35 of 42 CC patients and 64 of 81 PSC and BBD patients with an area under the curve value of 0.87 (95% CI 0.80 to 0.92, p=0.0001, 83% sensitivity, 79% specificity). Evaluation of 101 normal controls resulted in 86% specificity. All 10 patients with CC on top of PSC were correctly classified. The majority of sequence-identified peptides are fragments of interstitial collagens with some of them also detected in blood indicating their extra-renal origin. Immunostaining of liver sections for matrix metallopeptidase 1 indicated increased activity of the interstitial collagenase in liver epithelial cells of CC patients. CONCLUSION: The urine test differentiates CC from PSC and other BBD and may provide a new diagnostic non-invasive tool for PSC surveillance and CC detection.

MicroRNA-146a-mediated downregulation of IRAK1 protects mouse and human small intestine against ischemia/reperfusion injury.

Intestinal ischemia/reperfusion (I/R) injury causes inflammation and tissue damage and is associated with high morbidity and mortality. Uncontrolled activation of the innate immune system through toll-like receptors (Tlr) plays a key role in I/R-mediated tissue damage but the underlying mechanisms have not been fully resolved. Here, we identify post-transcriptional upregulation of the essential Tlr signalling molecule interleukin 1 receptor-associated kinase (Irak) 1 as the causative mechanism for post-ischemic immune hyper-responsiveness of intestinal epithelial cells. Increased Irak1 protein levels enhanced epithelial ligand responsiveness, chemokine secretion, apoptosis and mucosal barrier disruption in an experimental intestinal I/R model using wild-type, Irak1(-/-) and Tlr4(-/-) mice and ischemic human intestinal tissue. Irak1 accumulation under hypoxic conditions was associated with reduced K48 ubiquitination and enhanced Senp1-mediated deSUMOylation of Irak1. Importantly, administration of microRNA (miR)-146a or induction of miR-146a by the phytochemical diindolylmethane controlled Irak1 upregulation and prevented immune hyper-responsiveness in mouse and human tissue. These findings indicate that Irak1 accumulation triggers I/R-induced epithelial immune hyper-responsiveness and suggest that the induction of miR-146a offers a promising strategy to prevent I/R tissue injury.

Transgastrically placed endoscopic vacuum-assisted closure system as an addition to transgastric necrosectomy in necrotizing pancreatitis (with video).

BACKGROUND: Endoscopic transluminal débridement of infected pancreatic necrosis has been proved to be an important alternative to surgical débridement. Recently, endoscopic vacuum-assisted closure (EVAC) has been described as a new effective treatment option in upper intestinal anastomotic leaks. OBJECTIVE: To test whether the EVAC can be applied to transgastrically accessible infected cavities. DESIGN: Single-center case study. SETTING: Academic medical center. PATIENTS: Two patients with necrotizing pancreatitis. MAIN OUTCOME MEASUREMENT: Successful closure of leak. RESULTS: We successfully applied EVAC to treat transgastrically accessible necrotic cavities. LIMITATIONS: Small case number. CONCLUSIONS: EVAC might be an important additional endoscopic treatment option for infected pancreatic necrosis, especially if established endoscopic treatment options fail.

Tolerability and efficacy of a low-volume enteral supplement containing key nutrients in the critically ill.

BACKGROUND & AIMS: To compare early supplementation with antioxidants and glutamine using a low-volume enteral supplement containing key nutrients to an energy adjusted standard elementary diet and to investigate its effect on clinical efficacy and tolerability in critically ill patients with sepsis/SIRS. The primary endpoints were length of stay in the ICU and sufficient enteral feed. METHODS: This was a randomized, prospective, single-blind, controlled study in 58 critically ill patients (56.9% male, mean age 46.7 years, mean APACHE II score 21.6). They received either a low-volume enteral supplement containing key nutrients or a diluted standard nutrition solution. After 10 or 14 days inflammatory parameters, catecholamine need, and maximal enteral delivery were determined. RESULTS: Patients receiving a low-volume enteral supplement containing key nutrients did not reach sufficient enteral feed more often than controls (76 vs. 62%, respectively, p = 0.17). The difference in vitamin E and selenium uptake was higher in the treatment group than controls (12.4 vs. 3.7 and 54.7 vs. 16.3, respectively, p ≤ 0.011). Parameters such as fever, antibiotic treatment, artificial ventilation, and death were comparable. This was also true for days of ICU or hospital stay (33 ± 23 and 49 ± 34 days, respectively). CONCLUSIONS: The low-volume enteral supplement containing key nutrients was well tolerated and led to a better vitamin E and selenium supply. However, it did not affect length of ICU or hospital stay. Further studies are necessary to determine which disease-specific subgroups may benefit from this supplementation or which group may be harmed.

Bile proteomic profiles differentiate cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis.

UNLABELLED: Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes CC from nonmalignant lesions. We used capillary electrophoresis mass spectrometry (CE-MS) to identify disease-specific peptide patterns in patients with choledocholithiasis (n = 16), PSC (n = 18), and CC (n = 16) in a training set. A model for differentiation of choledocholithiasis from PSC and CC (PSC/CC model) and another model distinguishing CC from PSC (CC model) were subsequently validated in independent cohorts (choledocholithiasis [n = 14], PSC [n = 18] and CC [n = 25]). Peptides were characterized by sequencing. Application of the PSC/CC model in the independent test cohort resulted in correct exclusion of 12/14 bile samples from patients with choledocholithiasis and identification of 40/43 patients with PSC or CC (86% specificity, 93% sensitivity). The corresponding receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.93 (95% confidence interval [CI]: 0.82-0.98, P = 0.0001). The CC model succeeded in an accurate detection of 14/18 bile samples from patients with PSC and 21/25 samples with CC (78% specificity, 84% sensitivity) in the independent cohort, resulting in an AUC value of 0.87 (95% CI: 0.73-0.95, P = 0.0001) in ROC analysis. Eight out of 10 samples of patients with CC complicating PSC were identified. CONCLUSION: Bile proteomic analysis discriminates benign conditions from CC accurately. This method may become a diagnostic tool in future as it offers a new possibility to diagnose malignant bile duct disease and thus enables efficient therapy particularly in patients with PSC.

Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9.

UNLABELLED: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts. Both environmental and genetic factors contribute to its pathogenesis. To further clarify its genetic background, we investigated susceptibility loci recently identified for ulcerative colitis (UC) in a large cohort of 1,186 PSC patients and 1,748 controls. Single nucleotide polymorphisms (SNPs) tagging 13 UC susceptibility loci were initially genotyped in 854 PSC patients and 1,491 controls from Benelux (331 cases, 735 controls), Germany (265 cases, 368 controls), and Scandinavia (258 cases, 388 controls). Subsequently, a joint analysis was performed with an independent second Scandinavian cohort (332 cases, 257 controls). SNPs at chromosomes 2p16 (P-value 4.12 × 10(-4) ), 4q27 (P-value 4.10 × 10(-5) ), and 9q34 (P-value 8.41 × 10(-4) ) were associated with PSC in the joint analysis after correcting for multiple testing. In PSC patients without inflammatory bowel disease (IBD), SNPs at 4q27 and 9q34 were nominally associated (P < 0.05). We applied additional in silico analyses to identify likely candidate genes at PSC susceptibility loci. To identify nonrandom, evidence-based links we used GRAIL (Gene Relationships Across Implicated Loci) analysis showing interconnectivity between genes in six out of in total nine PSC-associated regions. Expression quantitative trait analysis from 1,469 Dutch and UK individuals demonstrated that five out of nine SNPs had an effect on cis-gene expression. These analyses prioritized IL2, CARD9, and REL as novel candidates. CONCLUSION: We have identified three UC susceptibility loci to be associated with PSC, harboring the putative candidate genes REL, IL2, and CARD9. These results add to the scarce knowledge on the genetic background of PSC and imply an important role for both innate and adaptive immunological factors.

Liver transplantation: A new risk factor for intestinal intussusceptions.

BACKGROUND: Intestinal intussusception in adults is associated with chronic inflammatory bowel disease, celiac disease, abdominal tumors or previous abdominal surgery but most often of unknown origin. AIM: The aim of our study was to evaluate circumstances and identify risk factors for intussusceptions. METHODS: All 65,928 abdominal ultrasound examinations performed at our tertiary medical center between January 2001 and June 2008 were analyzed retrospectively for the diagnosis "intussusception". After identifying individuals with sonographically proven intussusception we analyzed various patients' characteristics including age, gender and underlying disease as well as sonographic findings such as localization of the intussusception, absence or presence of ascites and lymph nodes. RESULTS: We identified 32 cases of intussusceptions [mean age 45 years (range 18 to 88); 18 patients were male]. Twelve patients (38%) had a history of abdominal surgery including 8 patients who had undergone liver transplantation (2 patients with primary sclerosing cholangitis, 1 patient with cystic fibrosis, 1 patient with sarcoidosis, 1 patient with hepatocellular carcinoma and HCV infection, 1 patient with autoimmune hepatitis, 1 patient with Crigler-Najar-syndrome and one patient with echinococcus). A hepaticojejunostomy had been performed in 4 of the patients after liver transplantation. Liver transplanted patients were significantly overrepresented in the intussusceptions group compared with the overall cohort of patients undergoing abdominal ultrasound examination (25% vs. 8%, Chi-Square-test, p = 0.0023). CONCLUSION: In our retrospective study liver transplantation, in particular with hepaticojejunostomy, was identified as a new major risk factor for intestinal intussusceptions

Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci.

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10⁻¹6 and P = 4.1 × 10⁻8, respectively).

Routine bile collection for microbiological analysis during cholangiography and its impact on the management of cholangitis.

BACKGROUND: Antibiotic treatment of cholangitis is often insufficient because of inappropriate antibiotic use or bacterial resistance. OBJECTIVE: To evaluate the role of routine bile collection during endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography for microbiological analysis in the antibiotic management of cholangitis and to identify risk factors of bacteriobilia. DESIGN: Prospective, observational, diagnostic study. SETTING: Hannover Medical School, Hannover, Germany. PATIENTS AND INTERVENTION: This study involved 243 consecutive patients undergoing endoscopic retrograde cholangiography/percutaneous transhepatic cholangiography for biliary complications after orthotopic liver transplantation (27%), malignancy (27%), primary sclerosing cholangitis (15%), benign strictures (11%), and choledocholithiasis (8%). MAIN OUTCOME MEASUREMENTS: Microbiological examination of bile samples. RESULTS: Patients with biliary stents or who were receiving repeated interventions after orthotopic liver transplantation were at increased risk of bacteriobilia (P < .05). The rate of gram-positive monomicrobial infection was higher in patients with primary sclerosing cholangitis (P < .01). In 40 examinations, patients presented with preprocedural cholangitis although they were receiving antibiotics. According to bile culture results, the antibiotic treatment was modified to a more specific therapy in 72.5% of patients. In patients who developed cholangitis after endoscopic retrograde cholangiography (27 examinations), specific antibiotic treatment was started or refined in 67% of cases, based on bile culture results. LIMITATIONS: Contamination of samples during intervention cannot be totally excluded. CONCLUSION: Orthotopic liver transplantation, biliary stenting, and repeated interventions are risk factors of bacteriobilia. In our patients with primary sclerosing cholangitis, gram-positive monomicrobial infections were more common. A bile sample collected during cholangiography for microbiological analysis is a simple, potentially valuable, diagnostic tool in patients with cholangitis. Each center should recognize its own patterns of infection to ensure ideal targeted therapy.

Lipopolysaccharide-mediated mast cell activation induces IFN-gamma secretion by NK cells.

Mast cells (MCs) that are well known for their important effector function in IgE-associated immune responses play a key role in innate immune defenses. In this study, we investigate the interaction between MCs and NK cells in vitro and in vivo. We show that mouse bone marrow-derived cultured MCs activated with LPS, polyinosinic-polycytidylic acid, or CpG can stimulate NK cells to secrete increasing concentrations of IFN-gamma. MCs induce a 20-fold increase in IFN-gamma release from NK cells after LPS stimulation. This enhancement of IFN-gamma secretion is cell contact dependent and TNF-alpha independent. Furthermore, we show that this interaction is in part mediated by OX40 ligand on MCs. NK cell-mediated cytotoxicity was not affected by the presence of MCs. Intracellular IFN-gamma levels in splenic NK cells are significantly decreased after i.p. injection of LPS in mast cell-deficient (C57BL/6 Kit(wsh/wsh)) mice in comparison with wild-type mice. In conclusion, our data show for the first time a direct mast cell-dependent NK cell activation. This interaction might play an important role in innate immune defense, as it is dependent on the presence of stimulators relevant in innate immune responses.

Management of major postsurgical gastroesophageal intrathoracic leaks with an endoscopic vacuum-assisted closure system.

BACKGROUND: Endoscopic treatment options for postsurgical intrathoracic leaks include injection of fibrin glue, clip application, and stent placement. Endoscopic vacuum-assisted closure (E-VAC) may be an effective treatment option. OBJECTIVE: To demonstrate that E-VAC is an effective endoscopic treatment option for closure of major intrathoracic postsurgical leaks. DESIGN AND SETTING: A prospective, single-center study at an academic medical center. PATIENTS: Eight consecutive patients with major intrathoracic postsurgical leaks. INTERVENTIONS: Endoscopic placement of transnasal draining tubes, armed with a size-adjusted sponge at their distal end, in the necrotic anastomotic cavities, followed by continuous suction. Sponge and drainage were changed twice weekly. Patients were followed-up for 193 +/- 137 days. MAIN OUTCOME MEASUREMENT: Successful leak closure. RESULTS: Successful closure of leaks was achieved in 7 of 8 patients (88%) after a mean of 23 +/- 8 days. A median of 7 endoscopic interventions was necessary. No major treatment-associated short-term or long-term (follow-up, 193 +/- 137 days) complications were noted. LIMITATIONS: Small sample size, single-center study, and lack of randomization. CONCLUSION: E-VAC is an effective endoscopic treatment modality for major postsurgical intrathoracic leaks. (This study is registered at Clinicaltrials.gov, identifier NCT00876551.).

Preserved Na(+)/H(+) exchanger isoform 3 expression and localization, but decreased NHE3 function indicate regulatory sodium transport defect in ulcerative colitis.

BACKGROUND: A major causative factor of diarrhea in ulcerative colitis (UC) patients is the loss of Na(+) absorptive capacity of the inflamed colonic mucosa. Potential contributing mechanisms include reduced driving force for active transport, and impaired expression, mislocalization, or defective transport function of Na(+) absorptive proteins. We therefore studied the expression, brush border membrane (BBM) localization, and transport capacity of the major intestinal Na(+) absorptive protein, the Na(+)/H(+) exchanger isoform 3 (NHE3) in biopsies from UC patients. METHODS: In UC and control biopsies, inflammation was graded histologically, NHE3, tumor necrosis factor alpha (TNF-alpha), villin, as well as other housekeeping genes were analyzed by quantitative real-time polymerase chain reaction (PCR), BBM localization of NHE3 determined by immunohistochemistry, and confocal microscopy. Na(+) absorptive capacity was assessed by (22)Na(+) isotope fluxes and NHE3 transport activity measured microfluorometrically in BCECF-loaded surface colonocytes within isolated crypts. RESULTS: In mildly, moderately, and severely inflamed sigmoid colon of UC patients, neither NHE3 mRNA expression nor the abundance of NHE3 in the BBM was significantly altered compared to other structural components of the BBM. However, Na(+) absorption was strongly reduced by approximately 80% and acid-activated NHE3 transport activity was significantly decreased in the surface cells of sigmoid colonic crypts even in moderately inflamed mucosa. CONCLUSIONS: In the colonic mucosa of patients with active UC, NHE3 transport capacity was found significantly decreased despite correct NHE3 location and abundance in the brush border, independent of current treatment. These findings suggest functional NHE3 transport as a novel factor for inflammatory diarrhea in UC patients.

Clinical relevance of transjugular liver biopsy in comparison with percutaneous and laparoscopic liver biopsy.

BACKGROUND: Transjugular liver biopsy (TJLB) is frequently used to obtain liver specimens in high-risk patients. However, TJLB sample size possibly limits their clinical relevance. METHODS: 102 patients that underwent TJLB were included. Clinical parameters and outcome of TJLB were analyzed. Control samples consisted of 112 minilaparoscopic liver biopsies (mLLBs) and 100 percutaneous liver biopsies (PLBs). RESULTS: Fewer portal tracts were detected in TJLB (4.3 +/- 0.3) in comparison with PLB (11.7 +/- 0.5) and mLLB (11.0 +/- 0.6). No difference regarding the specification of indeterminate liver disease and staging/grading of chronic hepatitis was observed. In acute liver failure (n = 32), a proportion of hepatocellular necrosis beyond 25% was associated with a higher rate of death or liver transplantation. CONCLUSIONS: Despite smaller biopsy samples the impact on the clinical decision process was found to be comparable to PLB and mLLB. TJLB represents a helpful tool to determine hepatocellular necrosis rates in patients with acute liver failure.

Quantification of cytomegalovirus DNA levels in intestinal biopsies as a diagnostic tool for CMV intestinal disease.

BACKGROUND: CMV intestinal disease (CMV-ID) is a serious complication in immunocompromised patients and mainly diagnosed by clinical, endoscopic and histopathologic findings, whereas qualitative CMV-PCR in tissue samples is not recommended for diagnosis due to its low positive predictive value (PPV). OBJECTIVES: To study the interpretation and diagnostic use of CMV-quantification by PCR in intestinal tissue biopsies to recognize CMV-ID. To develop cut-off intestinal CMV-loads attributing illness to CMV. STUDY DESIGN: CMV-genome copies in 163 biopsies from the lower intestinal tract of immunocompromised patients were determined by quantitative real-time PCR, normalized to the cell number, and retrospectively compared to histopathological analysis, clinical findings and occurrence of CMV-antigenemia. Two cut-off intestinal CMV-loads, cut-off(histo) and cut-off(clin), were defined using histopathological or clinical criteria as gold standard, respectively. RESULTS: CMV was detected in 32.5% of biopsies with a more than six log range of CMV-concentrations (1 x 10(-4)-1.4 x 10(2)copies/cell). Notably, biopsies with histopathologically or clinically confirmed CMV-ID had a significantly higher CMV-load (p<0.001). Cut-off(histo) and cut-off(clin) were defined at the intestinal CMV-load of 0.14 and 0.01 copies/cell, respectively, and improved the PPV. However, cut-off(histo) showed a decreased sensitivity for clinically defined CMV-ID cases. Interestingly, many patients with CMV-ID showed no concomitant CMV-antigenemia, suggesting a localized intestinal CMV-replication. CONCLUSIONS: Quantification of CMV in intestinal biopsies is a useful diagnostic tool allowing the definition of cut-off values that can predict CMV-ID more accurate than qualitative PCR results. Further prospective studies have to clarify wether these cut-offs can improve diagnostics and treatment of CMV-ID in day-to-day clinical practice.