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1. COLONOSCOPY IN COLORECTAL -CANCER SCREENING FOR DETECTION OF ADVANCED NEOPLASIA -DR ADESH SOLANKI SENIOR RESIDENT DEPT. OF GEN. SURGERY

2. Authors: Jaroslaw Regula , Maceio Rupinski Ewa Kraszewska Marcin Polkowski Jack Pachlewski Eugeniusz Butruk PUBLISHED in New England Journal of Medicine (NEJM) The study was conducted in Poland in 2006.

3. INTRODUCTION: One of the most frequent cancer . One of the leading cause of the death . Hence, screening is essential – can lead to detection of PRE cancerous lesions and advanced lesion at an early stage and in turn decreased incidences of colorectal ca and death .

4. Screening Recommended to begin at 50 years age in population at average risk And at 40 years of age for at risk individuals. Age and family history taken into Consideration. Sex of the patient not considered. Method: Annual stool testing for occult blood. 5 yearly flex sigmoidoscopy 10 yearly colonoscopy

5. What is our study? Although it is generally accepted that the lifetime risk of colorectal cancer is similar among men and women , the prevalence of advanced neoplasia that is detected during colonoscopic screening has been found to be higher among men than in women. Despite this fact the current screening guidelines do not take sex into account. 2. The age for screening is 50 years or above , but it has been seen that certain groups of population have higher prevalence of advanced neoplasia in earlier age groups too.

6. AIM: To refine the recommendations for screening programmes for detection of advanced colorectal cancer by colonoscopies .

7. OBJECTIVES: To derive and validate a model for the detection of advanced neoplasia in the large bowel during screening colonoscopy. To determine the number of persons who would have to undergo colorectal cancer screening in order to detect one advanced neoplasia – the numbers needed to screen- in various age group. To compare these numbers in men and women .

8. Study type: A cross – sectional analysis of data from a national colonoscopy based screening program for colorectal ca in Poland.

9. METHODOLOGY:

10. INCLUSION CRITERIA: Age between 50-66 years . Age between 40-49 years if they had a family history of cancer of any type. Individual was in good health and colorectal cancer was not suspected. EXCLUSION CRITERIA: Recent changes in bowel habits anaemia, unexplained weight loss, bleeding in lower gastrointestinal tract not attributable to haemorrhoids. Characteristics that meet the criteria for hereditary non polyposis colorectal ca (HNPCC) ,familial adenosis polyposis (FAP) or inflammatory bowel disease. Colonoscopy within the preceding 10 years.

11. Screening program: Poland, October 2000 to 2004 Colonoscopy used as a primary screening tool. 40 different centres involved The following details were stored in central database demographic data participant questionnaires results of colonoscopy Histopathological analysis Follow up information

12. 2. SCREENING METHOD: Reviewed by institutional ethics committee . Written informed consent obtained from each patient. Recruitment method was same for men and women . Bowel prep- at home polyethylene glycol and cleansing phosphate enema 30 minutes before procedure . Video assisted colonoscopy performed. Sedation was performed according to local practice.

13. Advanced neoplasia defined as: Cancer or adenoma >10 mm diameter ( estimated in situ using biopsy forceps or determined after removal ) High grade dysplasia on histopathology. Villus or tubulovillous histologies characteristics Family history of cancer ( as reported by the patients) Two first degree relatives who had colorectal cancer ( did not meet criteria for HNPCC or FAP) One first degree relative under 60 years with colorectal ca. One first degree relative above 60 years with colorectal ca. Family history of others neoplasm.

14. 3. STATISTICAL ANALYSIS: Original data set was partitioned in the ratio 2:1 to create– DERIVATION GROUP and VALIDATION GROUP. A MULTIVARIATE LOGISTIC – REGRESSION MODEL was applied Dependent variable – advanced colorectal cancer present or absent. Independent / co variable- age, family history, sex. Backward selection procedure was used to include important factors with p <0.1. Predictions and estimated odds ratio from the derivation model were verified with the validation data set. The Hosmer - Lemeshow t est was used to check the Goodness – of- fit of the model

15. The point estimate of the numbers needed to screen were derived from the inverse of the point estimates for the prevalence of the finding. A p value of <0.05 was considered to be statistically significant . The analyses were computed with the use of Stata Statistical Software version 8 ( StataCorp ) SAMPLE SIZE: 50148 The large number of participants in the study allowed us to derive and validate the model to identify characteristics independently associated with advanced neoplasia.

16. RESULTS:

17. A total of 50148 people participated with there being 32136 ( 64.1%) women and 18012 (35.9%) men. The mean age for males and females was 55 years More women than men -sex structure of the population asked to undergo screening (patients visiting family / general practitioners for various reasons) Sex related differences in agreeing to undergo screening. However no recruitment bias as fraction of cancer was similar in birth sexes .

18. Among the participants 14.2% belonged to the age group of 40-49 yrs and 85.8% belonged to the age group 50-66 yrs of age. Participants in the age group of 50-66 yrs had 13.3% and those in the 40-49 yrs had 66.3 % family history of colorectal ca.

19. Intravenous sedation was required for 31.3% women and 26.9 % men Caecal intubation could be achieved in 89.5% women and 93.9 % men. Clinically significant complications post colonoscopy was seen in 0.1% population Perforation 5 cases Bleeding 13 episodes Cardiovascular events 22 . No deaths occurred. Thus we can say that colonoscopy is a safe study

20. A total of 2796 out of 50,148 had advanced neoplasia 5.9% of people of 50-66yrs had advanced neoplasia. 3.4% of people of 40-49 had advanced lesions.

21. The following was the MODEL created to detect advance colorectal neoplasia on screening by using the LOGISTIC REGRESSION MODEL. Derivation set consists of 33,431 participants. Validation set contains 16,717 participants. INDEPENDENT predictors of advanced neoplasia included: age more than 49 years, family history of colorectal ca, male sex. Hosmer lame showing goodness of fit testing of the model in derivation and validation data sets confirmed its validity .

22. This model showed that male sex was independently associated with advanced neoplasia Odds ratio 1.73; 95% confidence interval , 1.52-1.98; p< 0.001

23. Numbers needed to screen with colonoscopy to detect advanced neoplasia in the large bowel , according to age , sex Age No. Screened No needed to screen to detect advanced neoplasia 40-49 yrs. : Male Female 2646(5.3) 4460(8.9) 23 36 50-54 Male Female 5564(11.1) 10401(20.7) 17 28 55-59 Male Female 4941(9.9) 8068(16.1) 12 22 60-64 Male Female 4861(9.7) 8068(16.1) 10 18

24. In each age group ( 40-49, 50-59, 60-66). The number of persons needed to detect advanced neoplasia was significantly lower in men than in females ( 23vs 36, 17vs 28, 12 vs 22, 10 vs 18)

25. Numbers needed to screen with colonoscopy to detect advanced neoplasia in the large bowel , according to age , sex based on fam story : Age No needed to screen to detect advanced neoplasia in patients with family history of colorectal cancer No needed to screen to detect advanced neoplasia in patients with no family history of colorectal cancer 40-49 yrs. : Male Female 20 32 30 52 50-54 Male Female 13 20 18 31 55-59 Male Female 8 18 12 23 60-64 Male Female 6 16 10 19

26. Participants of 40-49 yrs of age with family history of CRC- numbers needed to screen Two first degree relatives with CRC Male Female 11 16 One first degree relative < 60 yrs of age with CRC Male Female 17 27 One first degree relative >60 yrs of age with CRC Male Female 23 37

27. Limitations: We analysed data from a screening program that included only people who were offered and agreed for colonoscopy . Thus our results cannot be generalised to population – based screening programs. Women outnumbered Men by 3 to 2, though both were recruited by a similar manner.

28. 3. The numbers needed to screen can be the basis for modification of screening test but we did not evaluate the effect of potential changes in screening recommendations on COST EFFECTIVENESS. SOLUTIONS a. TO RECOMMEND screening only in groups with numbers needed to treat below a certain threshold Eg: keep recommended age at first screening for males at 50 yrs and females at 60 years . b. Perform colonoscopies only in people who are at risk of proximal neoplasia and perform flexible sigmoidoscopy in others : Imperial et al. Proposed an index to stratify at risk individuals. From proximal neoplasia . Male factor was an important factor. Anderson et al. Suggested age > 60 and smoking are predictors of isolated proximal advanced malignancies.

29. 4. In our study the prevalence of colorectal carcinoma in participants aged 50-66 neoplasia was 5.9% which was less compared to that in the united states( 10.6%) Reasons : Poland has less incidence of ca colorectal region. We did not study participants older than 66 years of age Women were more than men.

30. CONCLUSION : Sex is an independent predictor of the detection of advanced neoplasia during colonoscopy screening . Different rates of detection of advanced neoplasia for men and women and lesser number needed to screen in males warrant a refinement of screening recommendations to include sex along with age and family history. A family history of colorectal ca i s an important predictor of advanced neoplasia. colonoscopy is a safe and effective method for screening purposes.

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