Survival in patients with colorectal cancer diagnosed by screening colonoscopy.

BACKGROUND: In Germany, screening colonoscopy was first established in 2002 as part of the national cancer screening program. OBJECTIVE: To evaluate whether colorectal cancer (CRC) survival differs when CRC is diagnosed by screening colonoscopy (S-CRC) versus diagnostic colonoscopy (D-CRC). DESIGN: Long-term, retrospective, multicenter, observational study. SETTING: Study centers: 10 private gastroenterology practices in Germany. PATIENTS: A total of 60 patients diagnosed with CRC during screening colonoscopy and 252 patients during diagnostic colonoscopy in 2002, 2003, and 2004. INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Survival of patients up to December 2013. RESULTS: Mean (± standard deviation [SD]) follow-up time was 81.0 (± 40.1) months. Union Internationale Contre le Cancer (UICC) stages I and II were found more often in S-CRC (81.6%) compared with D-CRC (59.9%; P < .002). Kaplan-Meier analysis showed significantly reduced overall survival for patients with D-CRC (mean [± SD] 86.9 [± 3.0] months; 95% confidence interval [CI], 81.0-92.8) compared with S-CRC (mean [± SD] 107.1 [± 4.9] months; 95% CI, 97.4-116.9; P = .003). When deaths not related to CRC were excluded, survival was still shorter for D-CRC patients (mean [± SD] 89.4 [± 3.0] months; 95% CI, 83.5-95.4) compared with S-CRC (mean [± SD] 109.6 [± 4.7] months; 95% CI, 100.2-119.0; P = .004). LIMITATIONS: Retrospective study design. CONCLUSION: In this long-term, retrospective study, patients with CRC diagnosed during screening colonoscopy lived significantly longer when compared with patients with CRC diagnosed during diagnostic colonoscopy.

Respiratory complications in outpatient endoscopy with endoscopist-directed sedation.

BACKGROUND AND AIMS: Respiratory complications represent an important adverse event of endoscopic procedures. We screened for respiratory complications after endoscopic procedures using a questionnaire and followed-up patients suggestive of respiratory infection. METHOD: In this prospective observational, multicenter study performed in Outpatient practices of gastroenterology we investigated 15,690 patients by questionnaires administered 24 hours after the endoscopic procedure. RESULTS: 832 of the 15,690 patients stated at least one respiratory symptom after the endoscopic procedure: 829 patients reported coughing (5.28%), 23 fever (0.15%) and 116 shortness of breath (SOB, 0.74%); 130 of the 832 patients showed at least two concomitant respiratory symptoms (107 coughing + SOB, 17 coughing + fever, 6 coughing + coexisting fever + SOB) and 126 patients were followed-up to assess their respiratory complaints. Twenty-nine patients (follow-up: 22.31%, whole sample: 0.18%) reported signs of clinically evident respiratory infection and 15 patients (follow-up: 11.54%; whole sample: 0.1%) received therefore antibiotic treatment. Coughing or vomiting during the endoscopic procedure resulted in a 156.12-fold increased risk of respiratory complications (95% CI: 67.44 - 361.40) and 520.87-fold increased risk of requiring antibiotic treatment (95% CI: 178.01 - 1524.05). All patients of the follow-up sample who coughed or vomited during endoscopy developed clinically evident signs of respiratory infection and required antibiotic treatment while this occurred in a significantly lower proportion of patients without these symptoms (17.1% and 5.1%, respectively). CONCLUSIONS: We demonstrated that respiratory complications following endoscopic sedation are of comparably high incidence and we identified major predictors of aspiration pneumonia which could influence future surveillance strategies after endoscopic procedures.

Safety analysis of endoscopist-directed propofol sedation: a prospective, national multicenter study of 24 441 patients in German outpatient practices.

BACKGROUND AND AIM: Since 2008, there exists a German S3-guideline allowing non-anesthesiological administration of propofol for gastrointestinal endoscopy. In this prospective, national, multicenter study, we evaluated the safety of endoscopist-administered propofol sedation (EDP) in German outpatient practices of Gastroenterology. METHODS: In this multicenter survey of 53 ambulatory practices of Gastroenterology, we prospectively evaluated 24 441 patients that had received EDP. We recorded adverse events during the endoscopic procedure and additionally retrieved questionnaires investigating subjective parameters 24 h after the endoscopic procedure. RESULTS: In 24 441 patients 13 793 colonoscopies, 6467 esophagogastroduodenoscopies, and 4181 double examinations were performed. In this study, 52.1% of the patients received propofol mono-sedation, and 47.9% received a combination of midazolam and propofol. Major adverse events occurred in four patients (0.016%) enrolled to this study (three mask ventilations and one laryngospasm). Minor adverse events were observed in 112 patients (0.46%) with hypoxemia being the most common minor event. All patients with adverse events recovered without persistent impairment. Minor adverse events occurred more frequently in patients sedated with propofol mono compared to propofol and midazolam (P < 0.0001) and correlated with increasing propofol dosages (P < 0.001; Pearson correlation coefficient r = 0.044). Twenty-four hours after the endoscopy, patients sedated with propofol plus midazolam stated a significantly reduced sensation of pain (P < 0.01) and improved symptoms of dizziness, nausea and vomiting (P < 0.001) compared to patients having received propofol mono-sedation. CONCLUSION: Four years after the implementation of a German S3-Guideline for endoscopic sedation, we demonstrated that EDP is a safe procedure.

First clinical trial of a newly developed capsule endoscope with panoramic side view for small bowel: a pilot study.

BACKGROUND AND STUDY AIMS: Capsule endoscopy is the first-line diagnostic technique for the small bowel. However, the inability to visualize the duodenal papilla is an inherent limitation of this method. In the present study, we evaluated feasibility of a newly developed CapsoCam SV1 capsule. PATIENTS AND METHODS: This is a prospective dual center study of a newly developed video capsule CapsoCam SV1 from Capsovision, CA, providing panoramic 360° imaging. A high frequency of 20 frames occurs per second for the first 2 h and thereafter 12 frames/s, with a battery life of 15 h. We evaluated feasibility and completeness of small bowel examination together with secondary endpoints of duodenal papilla detection in 33 patients. Patients swallowed the capsules following colonoscopy or were prepared with 2 L of polyethylene glycol solution prior to the examination. All patients swallowed 20 mg of metoclopramide and 160 mg of simethicone 30 min before ingestion of the capsule. RESULTS: Thirty-one of the 33 patients' data could be evaluated. Small bowel examination was complete in all procedures. Mean time to pass the small bowel was 258 ± 136 min. Average small bowel cleanliness was 3.3 ± 0.5. In 71% of the patients, we identified the duodenal papilla. No adverse reaction in relation to the capsule examination was observed. CONCLUSIONS: CapsoCam SV1 is a safe and efficient tool in small bowel examination. The duodenal papilla as the only landmark in small bowel is detected in more than 70% of the patients.

Adverse events requiring hospitalization within 30 days after outpatient screening and nonscreening colonoscopies.

BACKGROUND: The incidence of adverse events (AEs) is a crucial factor when colonoscopy is considered for mass screening, but few studies have addressed delayed and non-GI AEs. OBJECTIVES: To investigate the risk of AEs requiring hospitalization after screening and nonscreening colonoscopies compared with control subjects who did not undergo colonoscopy. DESIGN: Retrospective matched cohort. SETTING: Statutory health insurance fund in Germany. PATIENTS: A total of 33,086 individuals who underwent colonoscopy as an outpatient (8658 screening, 24,428 nonscreening) and 33,086 matched controls who did not undergo colonoscopy. INTERVENTIONS: Outpatient screening and nonscreening colonoscopies. MAIN OUTCOMES MEASUREMENTS: Risk of AEs (perforation, bleeding, myocardial infarction, stroke, splenic injury, and others) requiring hospitalization within 30 days after colonoscopy/index date and risk differences between the group that underwent colonoscopy and the group that did not. RESULTS: The incidence of perforation was 0.8 (95% confidence interval [CI], 0.3-1.7) and 0.7 (95% CI, 0.4-1.1) per 1000 screening and nonscreening colonoscopies, respectively. Hospitalizations because of bleeding occurred in 0.5 (95% CI, 0.1-1.2) and 1.1 (95% CI, 0.8-1.7) per 1000 screening and nonscreening colonoscopies, respectively. The incidence of myocardial infarction, stroke, and other non-GI AEs was similar in colonoscopy and control groups. No splenic injury was observed. Those with AEs generally had a higher mean age and comorbidity rate than the overall study population. LIMITATIONS: The analysis relies on health insurance claims data. CONCLUSIONS: This study provides further evidence of the safety of colonoscopy in routine practice with regard to delayed and non-GI AEs. Hospitalizations because of the investigated AEs were uncommon or rare for both screening and nonscreening colonoscopies.

Endoscopist-administered propofol sedation is safe - a prospective evaluation of 10,000 patients in an outpatient practice.

BACKGROUND & AIMS: Due to improved patient satisfaction and its pharmacological benefits, more endoscopic procedures are carried out with the use of propofol. However, recent rulings in the USA challenge endoscopist-administered propofol sedation. We evaluated the safety of endoscopist-administered propofol sedation in a German outpatient practice. METHODS: During a period of 65 months, we prospectively evaluated 10,000 patients who received endoscopic procedures. During 377 endoscopic procedures we performed extensive blood pressure observation. Propofol was administered via intermittent i.v. bolus titration by trained practice nurses under the supervision of the gastroenterologist. Oxygen saturation, heart rate and blood pressure were recorded constantly during the procedure and adverse cardiopulmonary events were monitored by the endoscopy team. A major respiratory event was defined as an episode of apnea or laryngospasm requiring assisted ventilation. RESULTS: 13,764 endoscopic procedures were recorded in 10,000 patients (7,349 esophago-gastro-duodenoscopies (ESD), 6,415 colonoscopies); 9,654 patients were sedated with propofol (ESD: 115 +/- 35; colonoscopy: 155 +/- 52; combined: 199 +/- 55 mg) and 346 patients had endoscopic examination without sedation. 0.03% of the patients received mask ventilation due to apnea and in 0.39% minor events of hypoxemia (oxygen saturation < 90%) were recorded. Bradycardia and arterial hypotension occurred in 0.07% and 0.24% of the patients. Patients with adverse events were significantly older than patients without (P < 0.001). CONCLUSION: The low number of adverse events recorded in this prospective study concludes that endoscopist-administered propofol sedation is a safe procedure. It does not seem likely that additional support of an anaesthetist would further improve patient's safety, and particularly cost-efficiency.

Capsule endoscopy compared with conventional colonoscopy for detection of colorectal neoplasms.

Colon capsule endoscopy (CCE) may be a means to overcome the low adherence to colorectal cancer screening. The device is an ingestible capsule with a video camera at both ends that can take photographs as it progresses through the gastrointestinal tract. PillCam colon (PCC1) may be used for structural evaluation of the large bowel following an adequate cleaning procedure. PCC1 measures 11 mm × 31 mm and has dual cameras that enable the device to acquire video images from both ends with a wide coverage area, automatic light control and a frame rate of four frames per second. The system includes a sensor array and data recorder connected to the patient during the procedure. The recorded data are downloaded to the Given Imaging Rapid workstation for review of the colon video. The second generation of PillCam Colon (PCC2) is similar to PCC1 and incorporates new developments. The angle of view has been increased to 172 degrees. It has an adaptive frame rate, alternating from 35 frames per second while in motion to 4 images when virtually stationary. The new RAPID(®) software now includes a simple graphic interface tool for polyp size estimation. The procedure of bowel cleansing until capsule ingestion is similar to that used for traditional colonoscopy. However it is more rigorous as the bowel cleanliness for capsule colonoscopy has to be excellent or at least good to result in an adequate sensitivity of the method. Briefly, it consists of 3.5-4 L of split dose polyethylene glycol. Oral NaP boosters are administered after 1-2 h if the capsule has entered the small bowel. Sodium phosphate (NaP) seems to be a necessary adjunct to the regimen because the total transit time is doubled without NaP. The cleansing level was considered to be good to excellent in 72%-88% in studies with PCC1. The sensitivity for significant polyps (> 6 mm or more than 3 polyps >3 mm) ranged from 63%-88% with specificities between 64%-94%. PCC2 showed an improved sensitivity of 89% and a specificity of 76%. CCE seems to be a safe and effective method of visualizing the colonic mucosa through colon fluids without the need for sedation or insufflation of air. The sensitivity of CCE to detect polyps, advanced adenomas and cancer is lower compared to optical colonoscopy but improvements will be made in the near future. With an increased recording duration, even a panenteric examination of the whole gastrointestinal tract may be possible.

Colon capsule endoscopy compared with conventional colonoscopy for the detection of colorectal neoplasms.

Given the low compliance with screening colonoscopy in countries with a national colorectal cancer screening program, noninvasive methods with an acceptable high rate of sensitivity and specificity are welcome to enlarge the array of screening tools. Colon capsule endoscopy seems to be a safe and effective method of visualizing the colonic mucosa without the need for sedation or insufflation of air. Bowel cleansing for colon capsule endoscopy is more rigorous as only excellent or good results can be accepted in order to obtain an adequate sensitivity. This restricts its application on persons who are able to drink 4 l of polyethylene glycol plus laxatives. The sensitivity of colon capsule endoscopy to detect polyps, advanced adenomas and cancer is lower compared with optical colonoscopy. It still seems to be an adequate alternative for patients reluctant to undergo colonoscopy. Conventional colonoscopy is still established as the gold standard in colorectal cancer screening and is used to evaluate positive screening tests of all programs. It is the only method with the ability to remove detected polyps and obtain biopsy specimens.

Is PillCam COLON capsule endoscopy ready for colorectal cancer screening? A prospective feasibility study in a community gastroenterology practice.

OBJECTIVES: Colorectal cancer (CRC) screening with colonoscopy was introduced into the National Cancer Prevention Program in Germany in 2002. As compliance for screening is low (around 3% per year), colon capsule endoscopy (CCE) could be an alternative approach. In this study, feasibility and performance of CCE were evaluated in comparison with colonoscopy in ambulatory patients with special attention to a short colon transit time. METHODS: CCE was prospectively tested in ambulatory patients enrolled for colonoscopy who presented for screening or with positive fecal occult blood test. Study subjects underwent colon preparation and ingested the capsule in the morning. Colonoscopy was performed after excretion of the capsule. Colonoscopy and CCE were performed by independent physicians who were blinded to the results. RESULTS: In total, 38 patients were included. One patient was excluded because the capsule remained in the stomach during the entire period of examination. Another patient had limited time and the procedure had to be stopped when the capsule was still in the transverse colon. We therefore report the results of 36 patients (30 men and 6 women; mean age 56 years, range 23-73 years) who successfully completed CCE and the conventional colonoscopy examination. The capsule was excreted within 6 h in 84% of the patients (median transit time 4.5 h). If oral sodium phosphate was excluded from the preparation, the colon transit time increased to a median of 8.25 h. In total, 7 of 11 small polyps (<6 mm) detected by colonoscopy were identified by CCE. One small polyp detected by CCE was not identified by colonoscopy. In this series, no large polyps were found. One CRC was detected by both methods. The mean rates of colon cleanliness (range from 1=excellent to 4=poor) in the cecum (2.1), transverse colon (1.6), and in the descending colon (1.5) were significantly better than in the rectosigmoid colon (2.6), and the overall mean rate during colonoscopy was significantly better than during CCE. No adverse effects occurred. CONCLUSIONS: CCE appears to be a promising new modality for colonic evaluation and may increase compliance with CRC screening. To achieve a short colon transit time, sodium phosphate seems to be a necessary adjunct during preparation. The short transit time is a prerequisite to abandon the delay mode of the capsule. With an undelayed PillCam COLON capsule, a "pan-enteric" examination of the gastrointestinal tract would be possible. Further studies are needed to improve the cleanliness, especially in the rectum and to evaluate the method as a potential screening tool.

Perspectives of colorectal cancer screening in Germany 2009.

Adequate screening methods can decrease colorectal cancer (CRC) mortality. The guaiac test for fecal occult-blood (FOBT) is part of the German CRC Screening Program since 1970 and has evidence level Ia. In randomized multicenter-studies FOBT has an average sensitivity of 24% and decreases CRC mortality up to 30%. Immunological tests for human haemoglobin (iFOBT) show better performance characteristics than guaiac FOBT, with augmented sensitivity and specificity. However, the single tests show wide differences in diagnostic performance and iFOBT is not yet covered by insurance companies although it should replace the guaiac test for CRC screening. Visual colonoscopy, which was introduced to the German National Cancer Screening Program in 2002, is the gold standard for the diagnosis of colorectal neoplasia. From 2003 to 2007 more than 2.8 million examinations have been documented in Germany. The prevalence of adenomas is around 20% and of CRC about 0.7% to 1.0% of the screenings. Seventy percent of the carcinomas detected during screening are in an early stage (UICC I and II). Furthermore, screening colonoscopy is a cost saving procedure with a low complication rate (0.25% overall). Insurance companies save 216€ for each screening colonoscopy mainly by prevention of neoplasia due to polypectomy. In Germany, virtual colonography by computed tomography (CT) or magnetic resonance imaging still lacks standardization of the hard and software. In experienced centres the sensitivity for CRC and large polyps of CT colonography is comparable to colonoscopy but in meta-analyses the ranking is lower. New technologies like computer-aided colonoscopies with sheath or double balloon techniques are coming up as well as capsule colonoscopy, which sensitivity for large polyps is about 70%. Advised by his physician, the patient can choose his most acceptable examination method from this whole set of screening tools.

Insufficient vitamin D supply as a possible co-factor in colorectal carcinogenesis.

Vitamin D, the "sunshine vitamin", may play a role in the development of colorectal cancer. In a prospective open study, the plasma levels of 25-hydroxyvitamin D [25(OH)D], the marker for sufficient or insufficient vitamin D supply, were determined in three groups of patients whose diagnoses were confirmed by colonoscopy: healthy individuals (n = 239), patients with colorectal adenoma (n = 203) and with carcinoma (n = 98). In order to assess other factors such as nutrition, sunlight exposure and physical activity as co-variates for the risk of colorectal cancer, the individuals completed a questionnaire. Patients with colorectal cancer (CRC) had significantly decreased plasma 25(OH)D levels (p < 0.001) compared to the controls in contrast to patients with adenomas, who had lower levels exclusively in the winter (p = 0.01). When analyzed by the Kruskal-Wallis test, the groups of patients with adenomas (p = 0.03) and colorectal carcinomas (p < 0.0001) had significantly different mean plasma values compared to the controls. The plasma 25(OH)D levels showed an inverse correlation to the UICC stages of CRC; however, the differences were not significant. Patients with CRC were significantly older than the controls, but regression analysis showed no significant correlation between the plasma 25(OH)D levels and age, and the influence of age on the plasma levels of 25(OH)D was minimized in a group of individuals over 65 years of age, in which the patients with CRC had significantly decreased plasma levels of 25(OH)D in the winter. About one-half of the individuals with normal colonic mucosa had plasma 25(OH)D levels below 25 microg/l (the normal range) and one-third even had plasma levels below 20 microg/l. Regression analysis showed a significant influence of age on plasma 25(OH)D levels in healthy individuals, of physical activity in patients with adenomas and of season in patients with CRC. Other covariates, such as nutrition or sunlight exposure, had no significant influence on plasma 25(OH)D. In conclusion, an insufficient vitamin D supply might act as a co-factor in colorectal carcinogenesis.

Relevance of underlying disease and bacterial vacA and cagA status on the efficacy of Helicobacter pylori eradication.

AIM: To study the effects of Helicobacter pylori associated diseases and the bacterial vacA and cagA statuses on the efficacy of H. pylori eradication. METHODS: A prospective study in a consecutive series of outpatients of a gastroenterological institution and of a primary practice. A series of 146 H. pylori positive patients with peptic ulcer disease (PUD; n = 40) or nonulcer dyspepsia (NUD; n = 106) were evaluated. H. pylori vacA genotpyes and cagA status were determined directly in gastric biopsy specimens by polymerase chain reaction. The patients were treated with triple-therapy regimens consisting of a proton pump inhibitor and two antibiotics twice daily for 7 days. Reevaluation of H. pylori was determined 4-5 weeks later by endoscopy or 13C urea breath test. RESULTS: 123 patients completed the study. In 8 patients, colonization with two or more H. pylori strains was found. The overall cure rate was 84.6% (104/123). The eradication rates were significantly higher in patients with PUD (94.4%, 34/36) than in those with NUD (81.6%, 71/87; p < 0.05). In patients with cagA-positive H. pylori strains, the eradication rate was 89.0% (73/82) as compared with 78.8% (26/33) in those with cagA-negative strains (p = 0.15). The vacA genotype had no effect on the efficacy of H. pylori eradication. CONCLUSION: Using 1-week triple-therapy regimens, treatment of H. pylori infection is more effective in patients with PUD than in those with NUD.