Alterations of TGF-β signaling have been described in colorectal cancer, although the molecular consequences are largely unknown. By using transgenic mice overexpressing TGF-β or a dominant-negative ...TGF-βRII, we demonstrate that TGF-β signaling in tumor infiltrating T lymphocytes controls the growth of dysplastic epithelial cells in experimental colorectal cancer, as determined by histology and a novel system for high-resolution chromoendoscopy. At the molecular level, TGF-β signaling in T cells regulated STAT-3 activation in tumor cells via IL-6. IL-6 signaling required tumor cell-derived soluble IL-6R rather than membrane bound IL-6R and suppression of such TGF-β-dependent IL-6trans-signaling prevented tumor progression in vivo. Taken together, our data provide novel insights into TGF-β signaling in colorectal cancer and suggest novel therapeutic approaches for colorectal cancer based on inhibition of TGF-β-dependent IL-6trans-signaling.
Introduction: Chromoendoscopy allows more detailed inspection of superficial mucosal changes during colonoscopy. The aim of our prospective study was to look for such changes after intravital ...staining with indigocarmine (IC) and correlate staining patterns with histology. Methods: Since 5/99 60 unselected patients underwent high-resolution colonoscopy (CF 140, Olympus Co.). Visible lesions OR the distal rectosigmoid (in patients without visible lesions) were stained with 0.4% IC (1-15 ml) with a spraying catheter (Olympus PW-5L). The stained lesions were analyzed according to the Pit-Pattern (PP) Classification (Kudo et al., 1996). All stained lesions were biopsied or removed. Results: see table 45 patients had 79 lesions visible without chromoendoscopy (3-80 mm). After staining and biopsy/removal the incidence of dysplasia/carcinoma was: PPII 0%, PPIIIS 18%, PP IIIL 13%, PPIV 75%, PPV 83%. In 12 of 15 patients without lesions before staining, chromoendoscopy revealed 71 flat lesions (1-3 mm). 4 of these were adenomas with low grade dysplasia. Discussion: Chromoendoscopy with indigocarmine allows classification of mucosal changes according to the staining pattern (PP). Certain staining patterns (PPIV, PPV) seem to correlate with advanced neoplastic changes in histology. In addition, chromoendoscopy makes previously undetectable, small, flat adenomas visible. The clinical significance of the latter finding is the subject of ongoing studies.
Introduction: The purpose of this study was to assess patency rates, need for subsequent interventions, and survival after endoscopic placement of a new biliary stent made of Nitinol (Diamond stent®, ...Boston Scientific) versus standard plastic stent (PS,Wilson Cook) in patients with malignant biliary obstruction. Methods: Since 3/98, such patients were randomized to placement of PS (with side holes; at least 10 fr) or the new metal stent (MS). Follow-up was by calls to the referring MD and record review with regard to stent patency (recurrent cholestasis, cholangitis) and survival. ERCP's were done by 2 experienced endoscopists. Results: Data are available for 33 pts,(43-93y; mean 75.2 y; 30 pancreatobiliary tumors, 3 with metastases of other tumors). Stenting was successful on 1st attempt in 30, on 2nd attempt in 3 pts (1 had PTCD). Initial Bilirubin was 1.2-26.9 mg/dl (mean 10.6).In 2 pts no Bilirubin decrease occurred after stenting, these pts were not analysed further. 3 complications occurred: septicemia, arm fracture (after positioning), and slight hemoglobin decrease in 1 patient each. Table: STENT PERFORMANCE Conclusion: Stent occlusion occurred more often with use of a plastic stent, necessitating stent changes in these patients. Patency rate of the new Nitinol stent was excellent. Survival did not differ between the groups. A cost and quality of life analysis will follow.
Introduction: Methodological/procedural risks of ERCP are well known, but cardiac risks have not been studied, specifically. Troponin I (TnI) is a cardio-selective enzyme that can aid in detection of ...even small amounts of myocardial damage. This prospective study examined the TnI levels of patients before and after ERCP to assess for cardiac injury, e.g. caused by administration of antimotility agents that can produce tachycardias (Scopolamine, Glucagon). Methods: 100 patients (57 f, 43 m, age 20-93, mean 62 y) were randomized prospectively to administration of Scopolamine or Glucagon as the antimotility agent during ERCP (30% diagnostic, 70% therapeutic). 65% of patients had one or more cardiovascular risk factors. TnI normal value 0-0.4 ng/ml was measured at baseline, at 8 h, and, if elevated, at 20 h post ERCP. Patients were sedated with Midazolam, Midazolam/Pentazocin or Propofol, given nasal O2(2 l/min), and were monitored during ERCP for heart rate, blood pressure, pulse oximetry. Results: Mean duration of ERCP was 28 min. 8 patients (5 with Scopolamine, 3 with Glucagon) had elevated TnI levels: 6 already had elevated levels at baseline (0.5-2.5ng/ml; mean 1.13), with subsequent decrease to normal in 4 patients over the 8/20 h after ERCP. The remaining 4 (2 with TnI elevations at baseline, 2 with normal TnI at baseline) had a rise in TnI levels from 0-1.3 (mean 0.47) ng/ml at baseline to 0.9-18.4 (mean 5.48) ng/ml at 8 h, to 0.6-7.8 (mean 2.75) ng/ml at 20 h after ERCP. 3 of these 4 patients had ERCP's of more than 30 min in duration (range 32-115 min). In the patients with a rise in TnI no cardiac symptoms or complication occurred during or after the ERCP. There was no correlation of an increase in TnI with tachycardias (pulse >120), hypoxic episodes (O2- Sat < 95%), or systolic BP elevations (>160 mm Hg). No difference was found between administration of Scopolamin versus Glucagon: Heartrates of >100/min and/or systolic BP >160 mm Hg occurred in 33 patients after Scopolamin and 34 patients after Glucagon without change in TnI. 22 patients had stable vital signs. Conclusions: In this study an increasing TnI level was observed in 4% of patients undergoing ERCP. This correlated only with duration of the procedure (>30 min). No difference was found with regard to choice of antimotility agent (Scopolamine versus Glucagon). No clinically relevant cardiac symptoms or cardiovascular problems resulted in any patient with TnI elevation. In this study ERCP appeared to be safe from a cardiovascular standpoint, even for multimorbid patients.
Worldwide, gastrointestinal endoscopies are predominantly performed under sedation. National and international guidelines and recommendations contain very different specifications for the use of ...sedation in gastrointestinal endoscopy. These differences come from specific requirements for staffing during endoscopy.
The aim of the study is to evaluate whether endoscopist-guided sedation without additional sedation assistance is not inferior to endoscopist-guided sedation with additional sedation assistance with respect to the rate of sedation-associated complications in a defined low-risk population (low-risk procedure and low-risk patient).
Prospective, multicenter, randomized study.
27 German study centers participated in the study. A total of 30 569 endoscopies were recorded during the study period from 1.8.2015 to 10.3.2020. The final data analysis included 28 673 examinations (64.1 % esophagosgastroduodenoscopies and 35.9 % colonoscopies). In 307 (1.1 %) examinations, 322 sedation-associated complications occurred. Of these, 321 (1.1 %) were minor complications and one (0.003 %) was a major complication. There was no statistically significant difference in the frequency of sedation-associated complications between endoscopist-guided sedation with versus without additional sedation assistance. Within the legal framework, a "shadow" sedation assistant was present in the study group without sedation assistance. This assistant intervened because of sedation-associated complications in 101 (0.7 %) of the endoscopies.
The study documents the safety of propofol-based endoscopist-guided sedation in a low-risk population. In 98.9 % of all endoscopies, no sedation-associated complication occurred or it was so minimal that no intervention (e. g., increase of oxygen supply) was necessary. The study cannot answer to what extent a serious complication was avoided by the active intervention of the "shadow" sedation assistance in the group without sedation assistance.The study proves in a randomized, prospective design that sedation in low-risk endoscopy (low-risk patient, low-risk procedure) can be performed as endoscopist-guided sedation without additional sedation assistance, without demonstrably accepting a reduction in safety.
Introduction: Bacterial ascension together with biliary obstruction can lead to acute cholangitis. The purpose of our prospective study was to examine the spectrum of bacterial colonisation of the ...bile during ERCP in patients with cholestasis. Methods: Since 8/99 50 patients with cholestasis(by ultrasound and bloodwork) underwent ERCP. After cannulisation of the common bile duct 10 ml of bile were aspirated and cultured. For positive results ( ≥ 104cfu/ml bile) MIC values were determined for Levofloxacin, Ceftriaxone, Piperacillin, Metronidazole. Within 15 minutes after the ERCP blood cultures were taken. Results: see table In all patients (27 m, 23 f, age 45-79 y) endoscopic drainage of the biliary obstruction could be achieved (41 benign, 9 malignant). 10 patients with positive bile cultures developed new or increasing fevers after ERCP and required antibiotic therapy. With negative bile cultures only 2 patients needed antibiotics. In vitro, all aerobic isolates were sensitive to Levofloxacin, all anaerobic flora to Metronidazole. Several isolates were resistant to Piperacillin and Ceftriaxone. Discussion: Cholangitis develops significantly more often in patients with positive bile cultures (≥ 104cfu/ml) even after complete drainage with ERCP, compared to patients with negative cultures. Antibiotic therapy with Levofloxacin/Metronidazole seems adequate coverage in these patients. Further study is needed to determine whether Levofloxacin reaches therapeutic levels in bile.
![TGF-[beta] Suppresses Tumor...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1074-7613/small "TGF-[beta] Suppresses Tumor Progression in Colon Cancer by Inhibition of IL-6 trans-Signaling")
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