Geir Hoff

Population-Based Surveillance by Colonoscopy: Effect on the Incidence of Colorectal Cancer: Telemark Polyp Study I

BACKGROUND Most cases of colorectal cancer (CRC) develop from adenomas. Polypectomy is believed to reduce the incidence of CRC, but this effect has never been explored in prospective controlled studies. The aim of the present study was to evaluate the effect of polypectomy on colorectal cancer incidence in a population-based screening program. METHODS In 1983, 400 men and women aged 50-59 years were randomly drawn from the population registry of Telemark, Norway. They were offered a flexible sigmoidoscopy and, if polyps were found, a full colonoscopy with polypectomy and follow-up colonoscopies in 1985 and 1989. A control group of 399 individuals was drawn from the same registry. In 1996 both groups (age, 63-72 years) were invited to have a colonoscopic examination. Hospital files and the files of The Norwegian Cancer Registry were searched to register any cases of CRC in the period 1983-96. RESULTS At screening endoscopy 324 (81%) individuals attended in 1983 and 451 (71%) in 1996. From 1983 to 1996, altogether 10 individuals in the control group and 2 in the screening group were registered to have developed CRC (relative risk, 0.2; 95% confidence interval (CI), 0.03-0.95; P = 0.02). A higher overall mortality was observed in the screening group, with 55 (14%) deaths, compared with 35 (9%) in the control group (relative risk, 1.57; 95% CI, 1.03-2.4; P = 0.03). CONCLUSION Endoscopic screening examination with polypectomy and follow-up was shown to reduce the incidence of CRC in a Norwegian normal population. The possible effect of screening on overall mortality should be addressed in larger studies.

Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial

Objective To determine the risk of colorectal cancer after screening with flexible sigmoidoscopy. Design Randomised controlled trial. Setting Population based screening in two areas in Norway—city of Oslo and Telemark county (urban and mixed urban and rural populations). Participants 55 736 men and women aged 55-64 years. Intervention Once only flexible sigmoidoscopy screening with or without a single round of faecal occult blood testing (n=13 823) compared with no screening (n=41 913). Main outcome measures Planned end points were cumulative incidence and mortality of colorectal cancer after 5, 10, and 15 years. This first report from the study presents cumulative incidence after 7 years of follow-up and hazard ratio for mortality after 6 years. Results No difference was found in the 7 year cumulative incidence of colorectal cancer between the screening and control groups (134.5 v 131.9 cases per 100 000 person years). In intention to screen analysis, a trend towards reduced colorectal cancer mortality was found (hazard ratio 0.73, 95% confidence interval 0.47 to 1.13, P=0.16). For attenders compared with controls, a statistically significant reduction in mortality was apparent for both total colorectal cancer (hazard ratio 0.41, 0.21 to 0.82, P=0.011) and rectosigmoidal cancer (0.24, 0.08 to 0.76, P=0.016). Conclusions A reduction in incidence of colorectal cancer with flexible sigmoidoscopy screening could not be shown after 7 years’ follow-up. Mortality from colorectal cancer was not significantly reduced in the screening group but seemed to be lower for attenders, with a reduction of 59% for any location of colorectal cancer and 76% for rectosigmoidal cancer in per protocol analysis, an analysis prone to selection bias. Trial registration Clinical trials NCT00119912.

Epidemiology of Polyps in the Rectum and Colon: Recovery and Evaluation of Unresected Polyps 2 Years after Detection

In an endoscopic population screening study for colorectal polyps among 200 men and 200 women, 50-59 years of age, 215 polyps less than 5 mm in diameter were left in situ for the present 2-year follow-up examination. The attendance rate was 102 of 106 (96%) for polyp patients and 77 of 90 (86%) in the control group. Of 194 polyps, 143 (74%) in the 102 polyp-bearing individuals were recovered for histological evaluation and 57 polyps were registered as new. Ninety-nine (50%) of the polyps were hyperplastic, 45 (23%) were adenomas, and 45 (23%) were mucosal tags. Both growth and regression of polyps were registered. Regression was commoner in the distal part of the rectum than in the proximal part or distal sigmoid colon. Growth was similar for recovered adenomas and hyperplastic polyps, whereas mucosal tags more often showed diminution in size. No polyp had reached a size of more than 5 mm in 2 years, and no case of severe dysplasia or carcinoma was registered. The estimated total polyp mass more than doubled both for adenomas and hyperplastic polyps. It is concluded that the time interval between initial examination with removal of polyps 5 mm or larger in diameter and the first follow-up examination may safely be set at 2 years.

Effect of Flexible Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality A Randomized Clinical Trial

IMPORTANCE Colorectal cancer is a major health burden. Screening is recommended in many countries. OBJECTIVE To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 100,210 individuals aged 50 to 64 years, identified from the population of Oslo city and Telemark County, Norway. Screening was performed in 1999-2000 (55-64-year age group) and in 2001 (50-54-year age group), with follow-up ending December 31, 2011. Of those selected, 1415 were excluded due to prior colorectal cancer, emigration, or death, and 3 could not be traced in the population registry. INTERVENTIONS Participants randomized to the screening group were invited to undergo screening. Within the screening group, participants were randomized 1:1 to receive once-only flexible sigmoidoscopy or combination of once-only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants with positive screening test results (cancer, adenoma, polyp ≥10 mm, or positive FOBT) were offered colonoscopy. The control group received no intervention. MAIN OUTCOMES AND MEASURES Colorectal cancer incidence and mortality. RESULTS A total of 98,792 participants were included in the intention-to-screen analyses, of whom 78,220 comprised the control group and 20,572 comprised the screening group (10,283 randomized to receive a flexible sigmoidoscopy and 10,289 to receive flexible sigmoidoscopy and FOBT). Adherence with screening was 63%. After a median of 10.9 years, 71 participants died of colorectal cancer in the screening group vs 330 in the control group (31.4 vs 43.1 deaths per 100,000 person-years; absolute rate difference, 11.7 [95% CI, 3.0-20.4]; hazard ratio [HR], 0.73 [95% CI, 0.56-0.94]). Colorectal cancer was diagnosed in 253 participants in the screening group vs 1086 in the control group (112.6 vs 141.0 cases per 100,000 person-years; absolute rate difference, 28.4 [95% CI, 12.1-44.7]; HR, 0.80 [95% CI, 0.70-0.92]). Colorectal cancer incidence was reduced in both the 50- to 54-year age group (HR, 0.68; 95% CI, 0.49-0.94) and the 55- to 64-year age group (HR, 0.83; 95% CI, 0.71-0.96). There was no difference between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups. CONCLUSIONS AND RELEVANCE In Norway, once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening. Screening was effective both in the 50- to 54-year and the 55- to 64-year age groups. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00119912.

The Norwegian Colorectal Cancer Prevention (NORCCAP) screening study: baseline findings and implementations for clinical work-up in age groups 50-64 years.

Background: Randomized controlled trials of sufficient power testing the long-term effect of screening for colorectal neoplasia only exist for faecal occult blood testing (FOBT). There is indirect evidence that flexible sigmoidoscopy (FS) may have a greater yield. The aim of this study was to determine the diagnostic yield of screening with FS or a combination of FS and FOBT in an average-risk population in an urban and combined urban and rural population in Norway. Methods: 20,780 men and women (1:1), aged 50-64 years, were invited for once-only screening (FS only or a combination of FS and FOBT (1:1)) by randomization from the population registry. A positive FS was defined as a finding of any neoplasia or any polyp S 10 r mm. A positive FS or FOBT qualified for colonoscopy. Results: Overall attendance was 65%. Forty-one (0.3%) cases of CRC were detected. Any adenoma was found in 2208 (17%) participants and 545 (4.2%) had high-risk adenomas. There was no difference in diagnostic yield between the FS and the FS and FOBT group regarding CRC or high-risk adenoma. Work-up load comprised 2821 colonoscopies in 2524 (20%) screenees and 10% of screenees were recommended later colonoscopy surveillance. There were no severe complications at FS, but six perforations after therapeutic colonoscopy (1:336). Conclusions: The present study bodes well for future management of a national screening programme, provided that follow-up results reflect adequate proof of a net benefit. It is highly questionable whether the addition of once-only FOBT to FS will contribute to this effect.BACKGROUND Randomized controlled trials of sufficient power testing the long-term effect of screening for colorectal neoplasia only exist for faecal occult blood testing (FOBT). There is indirect evidence that flexible sigmoidoscopy (FS) may have a greater yield. The aim of this study was to determine the diagnostic yield of screening with FS or a combination of FS and FOBT in an average-risk population in an urban and combined urban and rural population in Norway. METHODS 20,780 men and women (1:1), aged 50-64 years, were invited for once-only screening (FS only or a combination of FS and FOBT (1:1)) by randomization from the population registry. A positive FS was defined as a finding of any neoplasia or any polyp > or = 10 mm. A positive FS or FOBT qualified for colonoscopy. RESULTS Overall attendance was 65%. Forty-one (0.3%) cases of CRC were detected. Any adenoma was found in 2208 (17%) participants and 545 (4.2%) had high-risk adenomas. There was no difference in diagnostic yield between the FS and the FS and FOBT group regarding CRC or high-risk adenoma. Work-up load comprised 2821 colonoscopies in 2524 (20%) screenees and 10% of screenees were recommended later colonoscopy surveillance. There were no severe complications at FS, but six perforations after therapeutic colonoscopy (1:336). CONCLUSIONS The present study bodes well for future management of a national screening programme, provided that follow-up results reflect adequate proof of a net benefit. It is highly questionable whether the addition of once-only FOBT to FS will contribute to this effect.

NORCCAP (Norwegian colorectal cancer prevention): a randomised trial to assess the safety and efficacy of carbon dioxide versus air insufflation in colonoscopy

Background: To eliminate the risk of combustion during electrosurgical procedures and to reduce patient discomfort, carbon dioxide (CO2) insufflation has been recommended during colonoscopy. However, air insufflation is still the standard method, perhaps due to the lack of suitable equipment and shortage of randomised studies. Aims: This randomised controlled trial was conducted to assess patient tolerance and safety when using CO2 insufflation during colonoscopy. Patients: Over an eight month period a successive series of patients referred for a baseline colonoscopy due to findings in a flexible sigmoidoscopy screening trial were randomly assigned to the use of either air or CO2 insufflation during colonoscopy. Methods: End tidal CO2 (ETCO2), a non-invasive parameter of arterial pCO2, was registered before and repeatedly during and after the examination. The patients experience of pain during and after the examination was registered using a visual analogue scale (VAS). Sedation was not used routinely. Results: CO2 insufflation was used in 121 patients (51%) and air in 119 patients (49%). The groups were similar in age, sex, and caecal intubation rate. No rise in ETCO2 was registered. There were statistically significant differences in VAS scores between the groups with less pain reported when using CO2. Conclusions: This randomised study of unsedated patients shows that CO2 insufflation is safe during colonoscopy with no rise in ETCO2 level. CO2 was found to be superior to air in terms of pain experienced after the examination.

The NordICC Study: rationale and design of a randomized trial on colonoscopy screening for colorectal cancer.

BACKGROUND AND STUDY AIM While colonoscopy screening is widely used in several European countries and the United States, there are no randomized trials to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on colorectal cancer (CRC) incidence and mortality. This paper describes the rationale and design of the NordICC trial. STUDY DESIGN Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up. POWER ANALYSIS: We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance, yielding a 25 % mortality reduction among those invited to screening. For 90 % power and a two-sided alpha level of 0.05, using a 2:1 randomization, 45 600 individuals will be randomized to control, and 22 800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up. CONCLUSIONS The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population.

Epidemiology of Polyps in the Rectum and Sigmoid Colon

Epidemiological studies have suggested an association between diet and colorectal cancer. Case/control studies, however, have been scarce, and studies based on interview with cancer patients who have symptoms from their cancer are inevitably prone to bias. An endoscopic population screening study for detection of colorectal adenomas enabled a double-blind registration of diet during 5 consecutive weekdays. Neither the participant nor the dietitian was informed of the findings at endoscopy. The estimation of 23 nutritional components was based on analysis of local commercial food and on the composition of foods in Norway. Results showed increasing consumption of fat and decreasing consumption of fiber and cruciferous vegetables in the presence of increasing neoplastic changes. The present material will form the basis for dietary-related follow-up studies.

Long-Term Colorectal-Cancer Mortality after Adenoma Removal

BACKGROUND Although colonoscopic surveillance of patients after removal of adenomas is widely promoted, little is known about colorectal-cancer mortality among these patients. METHODS Using the linkage of the Cancer Registry and the Cause of Death Registry of Norway, we estimated colorectal-cancer mortality among patients who had undergone removal of colorectal adenomas during the period from 1993 through 2007. Patients were followed through 2011. We calculated standardized incidence-based mortality ratios (SMRs) using rates for the Norwegian population at large for comparison. Norwegian guidelines recommended colonoscopy after 10 years for patients with high-risk adenomas (adenomas with high-grade dysplasia, a villous component, or a size ≥10 mm) and after 5 years for patients with three or more adenomas; no surveillance was recommended for patients with low-risk adenomas. Polyp size and exact number were not available in the registry. We defined high-risk adenomas as multiple adenomas and adenomas with a villous component or high-grade dysplasia. RESULTS We identified 40,826 patients who had had colorectal adenomas removed. During a median follow-up of 7.7 years (maximum, 19.0), 1273 patients were given a diagnosis of colorectal cancer. A total of 398 deaths from colorectal cancer were expected and 383 were observed, for an SMR of 0.96 (95% confidence interval [CI], 0.87 to 1.06) among patients who had had adenomas removed. Colorectal-cancer mortality was increased among patients with high-risk adenomas (expected deaths, 209; observed deaths, 242; SMR, 1.16; 95% CI, 1.02 to 1.31), but it was reduced among patients with low-risk adenomas (expected deaths, 189; observed deaths, 141; SMR, 0.75; 95% CI, 0.63 to 0.88). CONCLUSIONS After a median of 7.7 years of follow-up, colorectal-cancer mortality was lower among patients who had had low-risk adenomas removed and moderately higher among those who had had high-risk adenomas removed, as compared with the general population. (Funded by the Norwegian Cancer Society and others.).

Epidemiology of polyps in the rectum and sigmoid colon: evaluation of nutritional factors

Epidemiological studies have suggested an association between diet and colorectal cancer. Case/control studies, however, have been scarce, and studies based on interview with cancer patients who have symptoms from their cancer are inevitably prone to bias. An endoscopic population screening study for detection of colorectal adenomas enabled a double-blind registration of diet during 5 consecutive weekdays. Neither the participant nor the dietitian was informed of the findings at endoscopy. The estimation of 23 nutritional components was based on analysis of local commercial food and on the composition of foods in Norway. Results showed increasing consumption of fat and decreasing consumption of fiber and cruciferous vegetables in the presence of increasing neoplastic changes. The present material will form the basis for dietary-related follow-up studies.