Narrow band imaging in Barrett's esophagus--where are we standing?
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Barrett Esophagus↗
Biomedical subjects
Helmut Messmann
Publications and source records attributed to Helmut Messmann.
Prospective, double-blind, placebo-controlled, multicenter, randomized phase III study with orally administered budesonide for prevention of irinotecan (CPT-11)-induced diarrhea in patients with advanced colorectal cancer.
BACKGROUND: Unpredictable and severe diarrhea (NCI grade > or =3) remains a life-threatening adverse event in patients treated with irinotecan (CPT-11). The aim of this study was to evaluate the efficacy and safety of orally administered budesonide for prevention of CPT-11-induced delayed diarrhea in patients with advanced colorectal cancer. PATIENTS AND METHODS: A total of 56 patients with advanced colorectal cancer receiving CPT-11 therapy (125 mg/m2 once weekly) were enrolled in this multicenter trial. Patients were randomly treated with 3 mg budesonide orally 3 times daily versus placebo. Detailed assessment of diarrhea by monitoring stool frequency, stool consistency and loperamide rescue medication was made by keeping a diary. RESULTS: Diarrhea, defined as number of stools >4 occurring on a single day during the study period, could be prevented in 58.3% of the budesonide-treated patients compared to 38.5% of the patients under placebo. Patients in the budesonide group had less episodes (0.7 vs. 2.2 episodes) and a considerably shorter total duration of diarrhea (1.8 vs. 4.2 days) episodes than patients in the placebo group. Loperamide use was more frequent in the placebo than in the budesonide arm (55.6 vs. 41.7%). Also, exposure to rescue medication of loperamide was higher for placebo (36.2 capsules) than for budesonide (24.9 capsules). A superior prevention of diarrhea was observed for budesonide compared to placebo in the first cycle (14 vs. 10; p = 0.257), with more failures observed in the placebo group (16 vs. 10). CONCLUSION: This double-blind randomized trial failed to show that budesonide has a significant benefit in preventing CPT-11-induced diarrhea. While a trend exists, further trials are warranted.
Administration, Oral↗
Are endoscopic antireflux procedures useful?
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Endoscopy, Gastrointestinal↗
Comparison of inpatient and outpatient upper gastrointestinal haemorrhage.
BACKGROUND AND AIMS: Inpatients developing upper gastrointestinal (GI) haemorrhage are at increased risk of death. This study was performed to elucidate differences in inpatients and outpatients. PATIENTS/METHODS: Three hundred and sixty-two patients who needed esophagogastroduodenoscopy for upper GI bleeding were identified from endoscopy charts. Patients' characteristics, bleeding parameters, clinical presentation, pre-existing medication, and laboratory data were compared between patients who were admitted because of upper GI bleeding and patients who developed bleeding while in hospital for other reasons. RESULTS/FINDINGS: Hospital mortality was 39.0% in inpatients vs. 11.1% in outpatients (p<0.01). Death due to bleeding was observed in 9.5% of inpatients vs. 2.5% of outpatients (p<0.01). Whereas peptic ulcer was the most common source of bleeding in both, variceal bleeding was the most common cause of death because of haemorrhage in both. Recurrent bleeding was associated with mortality in outpatients (p<0.001), but not in inpatients (p=0.11). Rates of bleeding recurrence and need for surgery was similar in both groups. Inpatients suffered more often from renal disease, pulmonary disease, diabetes mellitus, coagulopathy, or immunosuppression, and were treated more frequently with acetylsalicylic acid, glucocorticoids and heparin. The frequency of pre-existing disease was higher in inpatients. INTERPRETATION/CONCLUSION: Higher mortality after GI bleeding in inpatients than in outpatients is due to a generally higher prevalence of co-morbidity rather than a single or a few risk factors.
Adult↗
Bile salt-induced apoptosis in human colon cancer cell lines involves the mitochondrial transmembrane potential but not the CD95 (Fas/Apo-1) receptor.
BACKGROUND AND AIMS: Depending on their physico-chemical characteristics, bile acids can be potent inducers of apoptosis in colon cancer cells. This observation contrasts with bile acids being promoters of colorectal cancer carcinogenesis. Our recent observation of caspase activation in deoxycholate (DC)-treated colon cancer cell lines prompted us to analyze the mechanisms of bile acid-induced colon cancer cell death. METHODS: CD95 expression was correlated to DC-induced cell death in four colon cancer cell lines. Mitochondrial transmembrane potential (MTP) was determined in whole cells as well as in isolated mitochondria. RESULTS: On 2 of the 4 human colon cancer cell lines investigated, no CD95 was detected. These data were supported by a lack of CD95 mRNA in those cell lines that did not express CD95 on their surface. The apoptotic response to bile acids did not correlate with CD95 receptor expression on the respective cell lines. Therefore, we analyzed the MTP after the addition of toxic bile acids. MTP was destabilized early after the addition of deoxycholate to SW480 cells. These data were confirmed in isolated mitochondria, which showed strong swelling after the addition of DC. Accordingly, release of cytochrome-c from the mitochondrial intermembrane space into the cytosol, indicating dissipation of the MTP, and subsequent caspase-3 cleavage were detectable as early as 3 min after the addition of DC. CONCLUSION: In contrast to hepatocytes and hepatic carcinoma cell lines, DC induces apoptosis in colon cancer cell lines via a CD95 receptor-independent mechanism. Direct induction of the mitochondrial permeability transition by toxic bile acids is suggested as the apoptosis-inducing mechanism in colon cancer cells.
Apoptosis↗
Risk factors for mortality in severe upper gastrointestinal bleeding.
BACKGROUND AND AIMS: Factors related to mortality after upper gastrointestinal (GI) bleeding may differ in importance in high- and low-risk populations. This retrospective study was undertaken to define risk factors of mortality in patients needing endoscopy for upper gastrointestinal bleeding at a tertiary care centre. PATIENTS/METHODS: Three hundred and sixty-two patients with upper gastrointestinal bleeding were identified from endoscopy charts. Patients' characteristics, bleeding parameters, clinical presentation, pre-existing medication and laboratory data were retrieved from hospital charts and patients who survived and those who died in hospital were compared. RESULTS/FINDINGS: The mean Rockall score was 6.6+/-1.3 with 92.5% of patients belonging to a Rockall high-risk group. In hospital, mortality was 26.5%, with 6.4% of patients dying as a direct consequence of bleeding. Variceal bleeding was associated with a high risk of recurrent bleeding and death. Renal disease, liver disease, coagulopathy and immunosuppression were more frequently found in non-survivors than in survivors. Accordingly, serological tests of renal or liver function and coagulation were more disturbed in non-survivors. On average, heart rate was higher, and blood pressure and haemoglobin levels lower in non-survivors. Heparin, glucocorticoids, and anti-ulcer drugs were more frequently used in patients dying in hospital. By logistic regression analysis, in-patient status at the time of bleeding, renal disease and coagulopathy, as well as glucocorticoid use, were risk factors for hospital mortality. INTERPRETATION/CONCLUSION: In tertiary care, a high mortality rate is observed in upper GI bleeding. Teams involved in treating such patients should be aware of the setting in which treatment is performed and its related risk factors.
Adult↗
Prevalence of familial pancreatic cancer in Germany.
Based on several case-control studies, it has been estimated that familial aggregation and genetic susceptibility play a role in up to 10% of patients with pancreatic cancer, although conclusive epidemiologic data are still lacking. Therefore, we evaluated the prevalence of familial pancreatic cancer and differences to its sporadic form in a prospective multicenter trial. A total of 479 consecutive patients with newly diagnosed, histologically confirmed adenocarcinoma of the pancreas were prospectively evaluated regarding medical and family history, treatment and pathology of the tumour. A family history for pancreatic cancer was confirmed whenever possible by reviewing the tumour specimens and medical reports. Statistical analysis was performed by calculating odds ratios, regression analysis with a logit-model and the Kaplan-Meier method. Twenty-three of 479 (prevalence 4.8%, 95% CI 3.1-7.1) patients reported at least 1 first-degree relative with pancreatic cancer. The familial aggregation could be confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3-2.4), by medical records in 9 of 23 patients (1.9%, 95% CI 0.9-3.5) and by standardized interviews of first-degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1-5.6), respectively. There were no statistical significant differences between familial and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis after palliative or curative treatment as well as associated tumours in index patients and families, respectively. The prevalence of familial pancreatic cancer in Germany is at most 3.5% (range 1.1-3.5%) depending on the mode of confirmation of the pancreatic carcinoma in relatives. This prevalence is lower than so far postulated in the literature. There were no significant clinical differences between the familial and sporadic form of pancreatic cancer.
Adult↗
Photodynamic diagnosis in the gastrointestinal tract.
Clinical data on photodynamic diagnosis for the detection of premalignant and malignant lesions in the gastrointestinal tract are encouraging so far. A major benefit of using autofluorescence is the lack of side effects because no sensitizer has to be applied.However, highly sophisticated detection systems are needed to enhance the weak autofluorescence-based fluorescent signal. New prototypes of autofluorescence video endoscopes are under way and will be decisive for further clinical use, especially because results of recently published studies have been disappointing.
Aminolevulinic Acid↗
Low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.
BACKGROUND: Studies suggest that heparin has anti-inflammatory effects that could prevent acute post-ERCP pancreatitis. The aim of this investigator-initiated, prospective, randomized, double-blind, multicenter study was to determine whether low-molecular-weight heparin can prevent acute post-ERCP pancreatitis. METHODS: Patients at increased risk for acute post-ERCP pancreatitis based on assessment of known risk factors were randomized to receive low-molecular-weight heparin (Certoparin 3000 IU subcutaneously) or placebo (saline solution 0.3 mL subcutaneously) the day before ERCP. The drug was given 2 hours before and 22 hours after ERCP. Documentation and follow-up included patient history, risk factors for acute post-ERCP pancreatitis, procedure-related data, assessment of pain (visual analogue scale, need for pain medication), laboratory findings before and after ERCP (0, 4, and 24 hours), as well as post-ERCP complications. The two-sided Fisher exact test was used for statistical comparison, and a p value < or =0.05 was considered significant. RESULTS: A total of 458 patients were enrolled in the study. Data from 10 patients could not be evaluated, leaving 221 patients in the low-molecular-weight heparin group and 227 in the placebo group (total 448 patients; 135 men, 313 women; mean age 58 [15] years). Low-molecular-weight heparin and placebo groups were comparable with regard to risk factors for acute post-ERCP pancreatitis (gender distribution, age <65 years, history of pancreatitis, pancreas divisum, disorders of sphincter of Oddi) and procedure-related data (difficult cannulation, diagnostic or therapeutic ERCP, needle-knife papillotomy, endoscopic sphincterotomy, biliary or pancreatic procedure, pancreatic contrast injection, success and final diagnosis of ERCP). Acute post-ERCP pancreatitis occurred in 8.5% (38/448), with one death resulting from severe pancreatitis. Low-molecular-weight heparin offered no benefit compared with placebo based on the frequency of acute post-ERCP pancreatitis (low-molecular-weight heparin, 18/221 vs. placebo, 20/227; p=0.87) and the severity of acute post-ERCP pancreatitis (low-molecular-weight heparin, 14 mild, 3 moderate, one severe; placebo, 18 mild, two moderate, 0 severe). The 24-hour serum amylase values and 24-hour pain scores did not differ significantly between the low-molecular-weight heparin group and the placebo group. Bleeding complications occurred in two patients, both in the low-molecular-weight heparin group (one mild, one moderate). CONCLUSIONS: Prophylactic subcutaneous administration of low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.
Acute Disease↗
Comparison of interobserver agreement for different scoring systems for reflux esophagitis: Impact of level of experience.
BACKGROUND: The Savary-Miller, the Los Angeles, and the MUSE (metaplasia, ulcer, stricture, erosion) scoring systems have been developed to assess esophageal lesions related to GERD. Interobserver agreement for these systems was compared, with particular reference to the experience of the endoscopist. METHODS: By using videoendoscopes, videotapes were made of the gastroesophageal junction of 60 patients who presented with symptoms suggestive of GERD. The Savary-Miller, the Los Angeles, and the MUSE systems were used to score all video clips by 9 endoscopists who were subgrouped by level of experience (3 levels, 3 endoscopists per level). Agreement was assessed by using weighted kappa statistics (kappa). RESULTS: The Savary-Miller scoring system revealed moderate agreement for the experienced group (kappa=0.41) but performed poorly when applied by inexperienced raters (kappa=0.16). The Los Angeles system was most reproducible in all subgroups, irrespective of the level of experience (kappa=0.49 to 0.65). The MUSE scoring system was highly similar to the Los Angeles scoring system with respect to erosions and, in addition, allowed assessment of complications of GERD. CONCLUSIONS: The Los Angeles and the MUSE scoring systems are most reliable for the assessment of erosions caused by GERD. Because of low reliability, use of the Savary-Miller scoring system is not recommended. For all scoring systems, interobserver agreement varies with the level of experience in the performance of upper endoscopy.
Endoscopy, Gastrointestinal↗
Obstructive jaundice in AIDS: diagnosis of biliary tuberculosis by ERCP.
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Acquired Immunodeficiency Syndrome↗
Hexaminolevulinate-induced fluorescence endoscopy in patients with rectal adenoma and cancer: a pilot study.
BACKGROUND: Fluorescence endoscopy is a promising new method for detection and treatment of premalignant and malignant lesions. The aim of this pilot study was to investigate the feasibility of hexaminolevulinate-based photodetection of rectal adenoma and cancer, including safety, dose finding, and efficacy. METHODS: Ten patients with known rectal adenoma or cancer were sensitized by instillation of 3.2 mM of hexaminolevulinate as an enema. Fluorescence endoscopy was performed after retention of the enema for 30 to 60 minutes, followed by a rest time of up to 30 minutes before endoscopy. Biopsy specimens were taken from fluorescent and non-fluorescent areas and fluorescence microscopy studies were performed to assess the distribution of protoporphyrin IX fluorescence in different tissue layers. Adverse events were reported by direct questioning of all patients; skin photosensitivity, changes in biochemical tests of liver function, blood pressure and heart rate, and the occurrence of GI symptoms (nausea, vomiting) were recorded for 5 patients. OBSERVATIONS: Hexaminolevulinate-induced fluorescence endoscopy produced selective fluorescence of all rectal adenomas with intraepithelial neoplasia. For rectal cancer, there was only weak fluorescence or none at all. No hexaminolevulinate-induced side effect was observed. In two patients, fluorescence differentiated adenomas and hyperplastic polyps. CONCLUSIONS: Hexaminolevulinate-based fluorescence endoscopy (3.2 mM administered as an enema) in patients with rectal cancer and adenoma was well tolerated and produced no significant skin sensitivity or other side effects. The optimal duration of application is 30 to 45 minutes, with a rest time of 30 minutes. Selective fluorescence of adenoma with intraepithelial neoplasia suggests that hexaminolevulinate-based fluorescence endoscopy may be useful for detection of premalignant lesions.
Adenoma↗
Detection of dysplastic lesions by fluorescence in a model of chronic colitis in rats after local application of 5-aminolevulinic acid and its esterified derivatives.
5-Aminolevulinic acid (ALA) and ALA ester-induced protoporphyrin IX (PPIX) fluorescence are used for photodynamic diagnosis and therapy with promising results. The aim of the present study was to investigate the detection of dysplastic lesions by fluorescence after topical application of ALA and different esterified derivatives in a model of chronic colitis in rats. In female CD rats chronic colitis was induced by oral application of 5% dextrane sulfate sodium. ALA was used at different concentrations (0.072 and 0.036 mol/L). ALA-methylester (m-ALA), ALA-hexylester (h-ALA) and ALA-benzylester (b-ALA) were used at a concentration of 0.003, 0.002 and 0.002 mol/L, respectively. Fluorescence was examined under blue light, and histological findings of fluorescent and nonfluorescent biopsy specimens were recorded. Using ALA at a concentration of 0.072 mol/L, all dysplastic lesions (8/8) showed fluorescence (sensitivity 100%). Specificity was low at 57%. Reducing the concentration to 0.036 mol/L resulted in a sensitivity of only 56% (5/9) with an increase in specificity to 76%. On using h-ALA, sensitivity was 60% (3/5) with a specificity of 51%. Using m-ALA and b-ALA, sensitivity values were 25% and 33%, and values for specificity were 62% and 63%, respectively. Despite a low number of dysplastic lesions, the results of this study indicate that ALA ester-induced PPIX fluorescence has the potential for the detection of premaligant lesions but was not superior to ALA. ALA esters were used in 18- to 36-fold lower concentrations compared with ALA.
Administration, Topical↗
Lower gastrointestinal bleeding--the role of endoscopy.
Endoscopy is the method of choice in diagnosing the cause of lower gastrointestinal bleeding, and it offers the opportunity to treat patients suffering from lower gastrointestinal bleeding. Endoscopic procedures must be integrated with other approaches to reach a correct diagnosis rapidly, safely, and economically. In all patients, evaluation begins with a history and physical examination. The sequence of other tests depends on many factors, especially the rate of bleeding. New technologies such as wireless capsule endoscopy will influence the management of patients with lower gastrointestinal bleeding.
Angiodysplasia↗
Intracellular localization is a cofactor for the phototoxicity of protoporphyrin IX in the gastrointestinal tract: in vitro study.
Photodynamic therapy (PDT) is a new treatment modality for solid tumors as well as for flat lesions of the gastrointestinal tract. Although the use of 5-aminolevulinic acid-induced protoporphyrin IX (PPIX) shows important advantages over other photosensitizers, the main mechanisms of phototoxicity induced are still poorly understood. Three human colon carcinoma cell lines with variable degrees of differentiation and a normal colon fibroblast cell line were used to generate a suitable in vitro model for investigation of photosensitizer concentration as well as the applied light dose. Also, the effects of intracellular photosensitizer localization on efficiency of PDT were examined, and cellular parameters after PDT (morphology, mitochondrial transmembrane potential, membrane integrity and DNA fragmentation) were analyzed to distinguish between PDT-induced apoptosis from necrosis. The fibroblast cell line was less affected by phototoxicity than the tumor cells to a variable degree. Well-differentiated tumor cells showed higher toxicity than less-differentiated cells. After irradiation, cell lines with cytosolic or mitochondrial PPIX localization indicate a loss of mitochondrial transmembrane potential resulting in growth arrest, whereas membrane-bound PPIX induces a loss of membrane integrity and consequent necrosis. Although the absolute amount of intracellular photosensitizer concentration plays the main determining role for PDT efficiency, data indicate that intracellular localization has additional effects on the mode of cell damage.
Adenocarcinoma↗
Clinical determinants for the recovery of fungal and mezlocillin-resistant pathogens from bile specimens.
We conducted a retrospective analysis of all bile specimens obtained for routine cultures from January 1995 through December 1999 at our tertiary care hospital. Results of microbiologic testing were linked to clinical parameters gathered by means of chart review. A total of 722 isolates were cultured from 345 of 454 bile specimens obtained from 288 individual patients. Prior receipt of a >7-day course of antibiotics (odds ratio [OR], 5.7), extensive leukocytosis (leukocyte count, >20,000 cells/microL) on admission (OR, 7.8), endoscopic or percutaneous biliary manipulation during the previous 14 days (OR, 2.9), and treatment in an internal medicine ward (OR, 2.5) were independent factors significantly associated (Pless-than-or-eq, slant.05) with recovery of Candida species from bile specimens. Culture of mezlocillin-resistant bacteria from bile specimens was independently associated with the specimen having been obtained >1 week after admission (OR, 3.8), lack of history of endoscopic biliary drainage (OR, 3.2), and high serum aspartate aminotransferase levels (>72 U/L) on admission (OR, 2.6). Prospective studies are warranted to evaluate accordingly adjusted empiric therapies for biliary infections.
Bacteria↗
A laparoscopic approach for the treatment of lower third esophageal diverticula.
Diverticula in the middle and lower thirds of the esophagus are a rare disorder, frequently associated with esophageal motility disturbances. For symptomatic patients transthoracic diverticulectomy with or without Heller's myotomy is recommended. Here we report two cases of symptomatic esophageal diverticula which were both treated successfully by a laparoscopic transhiatal approach.
Aged↗
Metabolic characterization of tumor cell-specific protoporphyrin IX accumulation after exposure to 5-aminolevulinic acid in human colonic cells.
5-Aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) fluorescence has been shown to have high tumor cell selectivity in various organs, including the gastrointestinal (GI) tract. To better understand and to possibly find new approaches to therapeutic application, we investigated the uptake kinetics and consequent metabolism of ALA and PPIX, respectively. Three colon carcinoma (CaCo2, HT29, SW480) and a stromal cell line (fibroblast, CCD18) were chosen to mimic important aspects of malignant mucosa of the GI tract. Because differential PPIX concentrations in these cell lines represented the in vivo observations (ratio tumor vs normal 10:1-20:1), we analyzed the ALA uptake, mitochondrial properties and key molecules of PPIX metabolism (porphobilinogen deaminase [PBGD], ferrochelatase [FC], iron content, transferrin receptor content). The tumor-preferential PPIX accumulation is strongly influenced, but not solely determined, by activity differences between the PPIX-producing PBGD and the PPIX-converting FC, when compared with fibroblasts. Tumor-specific PPIX accumulation is generated by ALA conversion rather than by initial ALA uptake because no significant overall difference in uptake (about 0.6 microg ALA/mg protein) of ALA is seen. In conclusion, further research of tumor cell selectivity of PPIX fluorescence should focus on the mechanisms responsible for an altered PPIX metabolism to find tumor-specific target molecules, thus leading to an improved clinical practicability of ALA application and consequent endoscopy.
Adenocarcinoma↗