Colonoscopic Surveillance for Neoplasia in Ulcerative Colitis
Colonoscopic Surveillance for Neoplasia in Ulcerative Colitis
St Mark's Hospital is a tertiary referral center based in the United Kingdom, and it started colonoscopic surveillance program in 1971. Patients with endoscopic and histological evidence of UC proximal to the splenic flexure were traditionally offered annual to biannual surveillance colonoscopies from 8 to 10 years after onset of UC symptoms.
Segmental random biopsies were taken throughout the colon, with multiple targeted biopsies from any suspicious area of mucosa at each surveillance colonoscopy. In more recent years (from 2003 onwards), chromoendoscopy has been gradually implemented where pancolonic dye spray was used to highlight abnormal mucosa for targeted biopsy.
In our center, the management of a neoplastic lesion is based on its location within or outside of a diseased segment. Lesions arising proximal to the maximal extent of the colitis are considered sporadic and removed endoscopically. The management of lesions arising within the diseased segment has evolved over time.
Historically, colectomy was advised when the presence of dysplasia was confirmed and reviewed independently by two experienced pathologists. However, in our current policy, resectable dysplastic lesions are removed endoscopically and biopsies are taken from its surrounding mucosa with additional segmental biopsies taken from the colon. If the lesion is resected in full without evidence of further dysplasia elsewhere, the patient is usually advised to undergo close endoscopic surveillance, although the option of surgery is discussed. However, if complete resection cannot be achieved or if multifocal dysplasia is present, patients are advised to undergo colectomy.
Historically, lesion categorization into sporadic adenoma or UC-associated dysplasia was made on the basis of the endoscopic, histological, and immunohistochemical analysis. As there is no clearcut distinction between such lesions, the UC-associated dysplasia/adenoma categorization represented in this study reflects the clinical consensus made at the time of diagnosis.
Inclusion and Exclusion Criteria. All patients with a histological diagnosis of UC, with macroscopic and microscopic inflammation proximal to splenic flexure, were included. Index colonoscopy was defined as the first surveillance colonoscopy performed at our institution subsequent to the patient entering the surveillance program, occurring 8 to 10 years from onset of UC symptoms.
Patients were excluded from this study if they had the disease for <8 years, except for those considered to be at significant risk of CRC who began surveillance before 8 years from disease onset (e.g., patients with concomitant primary sclerosing cholangitis). Patients were excluded if they had a diagnosis of CRC before index colonoscopy or if they were referred from other centers with a diagnosis of dysplasia.
Data Collection. This study was approved by the Brent Research Ethics Committee and R&D Department at North West London Hospitals NHS Trust (reference number: 09/H0717/4). Patient data were obtained from the prospective UC surveillance database, clinical notes, endoscopy and histology reports, as well as surgical records. If a patient had died, death certificate information was reviewed. Data on the date, grade, and site of all episodes of neoplasia (sporadic adenoma, UC-associated dysplasia, or CRC) were collected. Each dysplasia was graded according to the 1983 Inflammatory Bowel Disease Dysplasia Morphology Study Group Classification of Dysplasia. Episodes of dysplasia occurring before 1983 had been previously reclassified according to these standardized criteria. All data were collected into a custom Microsoft Access 2010 database (Microsoft, Redmond, WA).
End Point Categorization. Primary end points: the primary study end points were the earliest occurring of the following: (i) death, (ii) colectomy, (iii) withdrawal from the surveillance program, or (iv) censor date (1 January 2013).
Secondary end point (postsurveillance follow-up): to ensure identification of all cancer cases in patients who had left the surveillance program, data were obtained from the UK National Cancer Registry. Secondary end points were as follows: (i) CRC diagnosed since leaving surveillance and (ii) no documented diagnosis of CRC since leaving surveillance.
Categorization of CRC Detection Modalities. Each CRC case was categorized into two groups based on how the cancer diagnosis was made, defined as follows.
Statistical Analysis. The data analysis was performed using the SPSS statistical software (version 20, IBM, Armonk, NY). All continuous variables are reported as medians with interquartile range (IQR). Study end points were examined using time-to-event analysis using Kaplan–Meier and Cox proportional hazard methods. A linear regression model was developed to determine time trends in CRC incidence. A P value of <0.05 was considered statistically significant.
Methods
Study Population
St Mark's Hospital is a tertiary referral center based in the United Kingdom, and it started colonoscopic surveillance program in 1971. Patients with endoscopic and histological evidence of UC proximal to the splenic flexure were traditionally offered annual to biannual surveillance colonoscopies from 8 to 10 years after onset of UC symptoms.
Segmental random biopsies were taken throughout the colon, with multiple targeted biopsies from any suspicious area of mucosa at each surveillance colonoscopy. In more recent years (from 2003 onwards), chromoendoscopy has been gradually implemented where pancolonic dye spray was used to highlight abnormal mucosa for targeted biopsy.
Dysplasia Management Protocol
In our center, the management of a neoplastic lesion is based on its location within or outside of a diseased segment. Lesions arising proximal to the maximal extent of the colitis are considered sporadic and removed endoscopically. The management of lesions arising within the diseased segment has evolved over time.
Historically, colectomy was advised when the presence of dysplasia was confirmed and reviewed independently by two experienced pathologists. However, in our current policy, resectable dysplastic lesions are removed endoscopically and biopsies are taken from its surrounding mucosa with additional segmental biopsies taken from the colon. If the lesion is resected in full without evidence of further dysplasia elsewhere, the patient is usually advised to undergo close endoscopic surveillance, although the option of surgery is discussed. However, if complete resection cannot be achieved or if multifocal dysplasia is present, patients are advised to undergo colectomy.
Historically, lesion categorization into sporadic adenoma or UC-associated dysplasia was made on the basis of the endoscopic, histological, and immunohistochemical analysis. As there is no clearcut distinction between such lesions, the UC-associated dysplasia/adenoma categorization represented in this study reflects the clinical consensus made at the time of diagnosis.
Study Protocol
Inclusion and Exclusion Criteria. All patients with a histological diagnosis of UC, with macroscopic and microscopic inflammation proximal to splenic flexure, were included. Index colonoscopy was defined as the first surveillance colonoscopy performed at our institution subsequent to the patient entering the surveillance program, occurring 8 to 10 years from onset of UC symptoms.
Patients were excluded from this study if they had the disease for <8 years, except for those considered to be at significant risk of CRC who began surveillance before 8 years from disease onset (e.g., patients with concomitant primary sclerosing cholangitis). Patients were excluded if they had a diagnosis of CRC before index colonoscopy or if they were referred from other centers with a diagnosis of dysplasia.
Data Collection. This study was approved by the Brent Research Ethics Committee and R&D Department at North West London Hospitals NHS Trust (reference number: 09/H0717/4). Patient data were obtained from the prospective UC surveillance database, clinical notes, endoscopy and histology reports, as well as surgical records. If a patient had died, death certificate information was reviewed. Data on the date, grade, and site of all episodes of neoplasia (sporadic adenoma, UC-associated dysplasia, or CRC) were collected. Each dysplasia was graded according to the 1983 Inflammatory Bowel Disease Dysplasia Morphology Study Group Classification of Dysplasia. Episodes of dysplasia occurring before 1983 had been previously reclassified according to these standardized criteria. All data were collected into a custom Microsoft Access 2010 database (Microsoft, Redmond, WA).
End Point Categorization. Primary end points: the primary study end points were the earliest occurring of the following: (i) death, (ii) colectomy, (iii) withdrawal from the surveillance program, or (iv) censor date (1 January 2013).
Secondary end point (postsurveillance follow-up): to ensure identification of all cancer cases in patients who had left the surveillance program, data were obtained from the UK National Cancer Registry. Secondary end points were as follows: (i) CRC diagnosed since leaving surveillance and (ii) no documented diagnosis of CRC since leaving surveillance.
Categorization of CRC Detection Modalities. Each CRC case was categorized into two groups based on how the cancer diagnosis was made, defined as follows.
Per-Protocol Surveillance (PPS) CRC: cancer detected in patients who had good compliance to the surveillance program, where they had a regular surveillance with recommended interval. These are subdivided into two groups.
Surveillance CRC: cancer detected in a planned surveillance procedure or colectomy performed for dysplasia, in otherwise asymptomatic patients.
Interval CRC: cancer detected in symptom-driven investigations or surgery before the next scheduled surveillance procedure.
Non-Per-Protocol Surveillance (NPPS) CRC: cancer detected at least 6 months after the date of originally planned surveillance procedures. These are subdivided into two groups.
Defaulted: cancer detected in poorly compliant patients who failed to attend scheduled surveillance before cancer diagnosis.
Non-defaulted: cancer detected after the patients were transferred to another hospital for their care or whose surveillance was terminated because of their age or comorbidities.
Statistical Analysis. The data analysis was performed using the SPSS statistical software (version 20, IBM, Armonk, NY). All continuous variables are reported as medians with interquartile range (IQR). Study end points were examined using time-to-event analysis using Kaplan–Meier and Cox proportional hazard methods. A linear regression model was developed to determine time trends in CRC incidence. A P value of <0.05 was considered statistically significant.
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