Screening for Colorectal Cancer in Average and High Risk Population
Condition: Colorectal Neoplasms; Colorectal Cancer; Adenomatous Polyp of Colon
MeSH terms: Colorectal Neoplasms; Adenomatous Polyps; Colonic Polyps
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The existing evidence from epidemiological studies and randomized controlled trials has
      consistently assures the cost effectiveness and the influential role of screening in reducing
      incidence rates and deaths caused by Colorectal Cancer (CRC). Population based organized
      screening programmes, which should be considered an obligation that is not to be postponed,
      require valuable information that can be reliably extrapolated from well-designed pilot study
      conducted prior to programme implementation.

      The main objectives of the current pilot CRC screening project, named after "Al-Kindy College
      of Medicine", was to evaluate and explore the specific aspects of the intended
      population-based organized CRC screening programme, including: barriers affecting adherence
      to the programme, performance indicators of the proposed screening programme, the target
      population in which CRC screening is a legitimate healthcare priority, quality assurance of
      screening tests and colonoscopy services, and to propose an algorithm that will provide a
      clinically and logistically acceptable positivity rate.
    

Detailed description: 
      Screening Type and Setting :

      "Al-Kindy College Colorectal Cancer Screening Project", is proposed as an FIT-based
      colorectal cancer screening, with colonoscopy being used as the second stage investigation in
      those with a positive FIT result. This screening project was set as a 24 months pilot study,
      to be started in April 2015 and extended to May 2017. All the investigations and evaluation
      measures involved were performed in the scientific research laboratory and endoscopy unit of
      Al Kindy polyclinic at Al Kindy College of Medicine, University of Baghdad. Baghdad, Iraq.

      Study Protocol:

      Target Individuals and Eligibility:

      The target individuals of the present study are residents of Baghdad city being ≥45 years of
      age with stop age of 80 years. target individual with fulfill devoid of exclusion criteria is
      identified as eligible.

      Invitation of Eligible Individuals:

      Due to the lack of a population register, invitation for the proposed screening programme was
      based on two approaches, namely, household open invitation (HOI), and recommendation by
      physician (RBP).

        1. Household-Open Invitation (HOI): A survey sheet, which all together serves as an
           invitation letter, was assembled competently. The first part of the sheet, in Arabic
           language, included introductory information about CRC incidence and risk factors, CRC
           screening benefits and meaning of test results, along a briefly description for the
           potential diagnostic tests and treatment options. The second part aimed to document
           information about the invited families, including demographic data, the number of target
           individuals and their eligibility, as well as the prevalence of CRC risk factors
           including: body mass index (BMI), smoking and alcohol intake, type2 diabetes mellitus
           (T2DM) and family history of CRC. Total of 1000 survey sheets were delivered by 10
           teams, each team consist of 10 well-trained 4th stage students of Al Kindy College of
           Medicine, as part of their epidemiology training course. The dissemination was planned,
           in an order of 100 families per week, with as possible equity to ensure the coverage of
           all municipalities of Baghdad city. Students were requested to return the day next to
           delivery, to check for the eligibility of target individuals and participation consent.

        2. Recommendation By Physician (RBP): A random survey of 1000 outpatients, attending
           Endocrine Disease Treatment Center, Baghdad, Iraq, was arranged with the aim of
           encouraging patients who fulfil the criteria for eligibility to participate in the
           screening programme. Referral forma including participation consent was issued, as an
           act on acceptance, and the issued referral forma were documented to measure patients'
           compliance.

      Enrollment of Participants in the Proposed Screening Programme:

      Screenees' basic information and progressive examination outcomes were documented through a
      comprehensive "Audit and Tracking Sheet", divided into the following four major disciplines:

        1. Characteristics and Risk Stratification:

           To evaluate the impact of risk stratification on screenee's behavior and on the
           effectiveness of the screening project, participants were divided into three risk groups
           based on survey and medical record data: high-risk (history of polyps, and/or
           personal/family history of CRC, increased-risk (diabetes, obesity, and/or former or
           current smoking status), and average-risk (45 or older with no other risk factor).

        2. FIT and Colonoscopy Tracking Screening Schedule:

           After checking for sampling appropriateness, the received samples were analyzed by the
           FOB Gold/SENTiFOB method (Sentinel Diagnostics SpA, Milan, Italy), according to the
           previously validated procedural platform.

           In case of first FIT incompletion, the cause is identified and the screenees were
           encouraged for re-enrollment. Timely referral to colonoscopy was based on FIT level
           ≥75ng/ml in any of the two collected samples. Negative FIT-tested individuals with high
           risk stratification were also encouraged to be enrolled. On approval, after a brief
           elucidation for the pros and cons, screenees were scheduled for conventional
           colonoscopy.

           Considering the reported improved patient tolerance of sodium picosulphate preparations
           (PICOPREP, Ferring Pharmaceutical Co., Ltd., Zhongshan, China), this cleansing agent was
           preferentially prescribed.Detailed oral and written instructions on how to perform the
           bowel cleansing regimen was provided, with an excellent opportunity to answer any
           questions the screenee may have, to ensure that the process was appropriately
           understood.

           With the colonoscopists completely blinded regarding the FIT results, conventional
           colonoscopy examinations were conducted in the Endoscopy Unit of Al-Kindy Polyclinic.
           For non-compliance, the cause of cancelled appointment was identified, and screenees
           were reinvigorated for a rescheduled appointment. For attendants, on the other hands,
           the final examination report must verify the completeness of colonoscopy; otherwise, the
           report should point to the cause of incompleteness. The report should also document the
           number, size, type and anatomical location of any screen-detected lesions.

        3. Histological Report of Lesion Biopsies and Resections:

           Histopathological examinations of screen-detected lesions were performed by skilled
           pathologists in gastrointestinal disease with specific emphasis on colorectal cancer,
           along a good expertise in the preparation and interpretation of biopsies and endoscopic
           polypectomy specimens.

           Classification of adenomas included grading of neoplasia was accomplished according to
           the revised Vienna classification that has been modified for the European Guidelines to
           obtain a two- tiered system of low-grade and high-grade neoplasia.. Furthermore, and
           whenever applicable, the correlation between histological diagnosis of biopsy and
           resection specimens were included in the final examination reports.

           If more than one lesion is found, lesion with the worst prognosis is indicated as the
           final colonoscopic outcome and will be used for evaluation purposes. Based on the number
           and characteristics of adenomas detected at baseline colonoscopy, screenees were
           stratified into low, intermediate, and high risk polyp for the development of colorectal
           cancer. Screenees with intermediate and high risk were referred to a follow-up
           surveillance programme. Positive FIT results in participants who were identified with no
           adenomas, advance adenomas, or adenocarcinomas on subsequent colonoscopies are
           considered False-positive fecal immunochemical tests (FP-FIT) results.

        4. Quality Assurance of Screening Programme:To ensure a potential benefit of colorectal
           cancer screening, quality assurance of the programme was assessed at every step in the
           process, including the FIT sampling regimen, precolonoscopy cleansing regimen, bowel
           preparation quality using the Ottawa bowel preparation scale (OBPS), as well as
           colonoscopy quality with special emphasis on colonic mucosa inspection and the safety
           and tolerance of colonoscopy.

      Data Processing and Statistical Analysis:

      All Data analysis was processed by the statistical package SPSS version 21.0 (SPSS, Inc.).
      Descriptive and categorical variables were presented as frequencies and percentages, and
      Fischer's exact test was performed to inspect any association between these variables.
      Indicators of screening performance for FIT (including participation rate, and positivity
      rate) and colonoscopy (including compliance rate, completion rate, lesions detection rate,
      adenoma detection rate, advanced adenoma detection rate, and cancer detection rate), in
      addition to the positive predictive value (PPV) for detection of lesions, adenoma, advanced
      adenoma, and cancer, were all calculated according to the European guidelines for quality
      assurance in colorectal cancer screening and diagnosis.
    

Intervention name(s): FIT; Precolonoscopy cleansing regimen; Conventional Colonoscopy; Histopathological examinations of screen-detected lesions; Tribenoside 400 mg + lidocaine 40 mg suppositories; Diltiazem hydrochloride 2%/Nitroglycerin rectal ointment
Intervention type(s): Diagnostic Test; Procedure; Procedure; Diagnostic Test; Drug; Drug
Intervention description(s): Screenees were supplied with two fecal collection devices and asked to collect two specimens from two consecutive Different Bowel Movement Samples (DBMS) or, in case of infrequent bowel movements, from the Same Bowel Movement Sample (SBMS).Instruction stressed that after collection the device must be stored in refrigerator and transported in an iced pack within no more than 48h from sampling. After checking for sampling appropriateness, the received samples were analyzed by the FOB Gold/SENTiFOB method (Sentinel Diagnostics SpA, Milan, Italy), according to the previously validated procedural platform; Laxative stimulant two days prior to the cleansing regimen involves the intake of one 10 mg tablet of bisacodyl (Dulcolax, Sanofi,UK) at 18:00 for two consecutive nights.The evening before colonoscopy cleansing started with 2 doses (at 16:00 and 20:00) of one sachet Sodium picosulphate preparations (PICOPREP, Ferring Pharmaceutical Co., Ltd., Zhongshan, China), dissolved in150 mL of cold water, followed with five 240 mL portions of clear liquids within 3 h. The third dose is taken in the morning about 5 h prior to colonoscopy, followed with at least three 240 mL portions of clear liquids no later than 2 h before colonoscopy.; With the colonoscopists completely blinded regarding the FIT results, conventional colonoscopy examinations were conducted in the Endoscopy Unit of Al-Kindy Polyclinic. According to the five levels of competency proposed by the European guidelines, this unit is assigned as level 2, with the possibility of removing polypoid and sessile lesions <25 mm, providing there is good access. For flat lesions, larger sessile and polypoid lesions, and smaller lesions with more difficult access, the lesions were documented appropriately with the patients referred to higher competent units in order to be safely and expertly removed.; Adenomas were classified according to the modified revised Vienna classification for the European Guidelines. Advanced adenoma was defined as the presence of one of the following features: >10 mm diameter, tubulovillous or villous structure, and high-grade neoplasia. Polypoid adenocarcinomas were reported according to the TNM classification, while colorectal cancer associated with flat and/or depressed lesions were reported as non-polypoid lesions, and further classified by the Paris classification. Pathologic results of hyperplastic polyps, sessile serrated lesions or post inflammatory polyps were considered normal findings.; Treatment of hemorrhoids was initiated with tribenoside 400 mg + lidocaine 40 mg suppositories, once daily for up to 2 weeks.; Treatment of anal fissure was initiated with Diltiazem hydrochloride 2%/Nitroglycerin rectal ointment applied every 12 hours, for up to six weeks.
Other intervention name(s): Fecal Immunochemical Test (FIT); Fecal occult blood tests (FOBT); FOB Gold/SENTiFOB (Sentinel Diagnostics SpA, Milan, Italy); PICOPREP- Adjuvant Bisacodyl Regimen; Optical Colonoscopy; Histological examinations of Lesion Biopsies and Resections; PROCTO-GLYVENOL; Topical calcium channel blockers/nitrates
Intervention MeSH terms: Tribenoside; Lidocaine; Diltiazem; Calcium Channel Blockers; Nitroglycerin; Bisacodyl
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: Colorectal cancer; Screening; Fecal Immunochemical Test