Serrated Epithelial Changes in Chronic Colitis
Serrated Epithelial Changes in Chronic Colitis
Figure 1 diagrams the flow of patients identified, excluded, re-classified and diagnosed. A total of 79 patients with SEC and 10 with SSP were identified and the number of cases was reported by year (Figure S1). A total of 4208 unique IBD patients underwent colonoscopy between 2010 and 2012. During the same time period, a total of 43 cases of SEC and 9 cases of SSP were found, for an estimated detection rate of 10 per 1000 (95% CI, 8–14) for SEC and 2 per 1000 (1–4) for SSP, respectively.
(Enlarge Image)
Figure 1.
Flow diagram of patient selection: (a) Characteristics of chronic colitis patients with serrated epithelial changes (SEC) or sessile serrated polyp (SSP), 2006–12 (Table 1); (b) patients included in detection rate calculation; (c) characteristics of serrated epithelial change (SEC) patients and randomly selected control IBD patients undergoing colonoscopy between 2010–12 (Table 2); (d) patients included in time to event analysis (Table 3, Table 4 and Figure 2); SNO-Med, systematised nomenclature of medicine; CPT, current procedural terminology (American Medical Association); ICD-9, international classification of diseases (9th Edition); SEC, serrated epithelial change; SSP, sessile serrated polyp; IBD, inflammatory bowel disease; TSA, traditional serrated adenoma. * Non-dysplastic indications; †Immediately after index - Lymphoma; ¥ Ovarian cancer metastatic to the colon.
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Figure S1.
Serrated epithelial change (SEC) and sessile serrated polyp (SSP) diagnoses by year, 2006–2012.
Median ages at index were 57 years [interquartile range, (IQR) 48–65] and 48 years (IQR 42–57) for the SEC and SSP groups respectively ( Table 1 ). CUC was the predominant form of IBD in SEC (84%) but was less common among SSP cases (40%) (P = 0.005). Median disease duration was longer in the SEC group compared to the SSP group at 18 (IQR 10.5–29) and 9.5 (IQR 1.5–22.5) years, respectively. Overall, the median age at IBD diagnosis was 34 years (IQR 25.5–46.5) in SEC and 34.5 years (31–44.75) in SSP. Proportions of patients with extensive disease were similar, 77% in SEC and 70% in SSP. PSC was found in 23 of SEC patients (29%), but was not seen in the SSP cohort. CRN was diagnosed prior to (n = 19) or synchronous with (n = 8) index lesions in 27 of SEC patients (34%). Six of 27 (22%) had both prior and synchronous dysplasia at index. SEC occurred in the same side of the colon (proximal or distal to splenic flexure) as prior dysplasia in 8 of 19 (42%), and in 11 of 14 (79%) of those with synchronous lesions. In SSP patients, CRN was diagnosed prior to (n = 2) or synchronous with (n = 4) in 6 of the 10 patients (60%). All SSP lesions were visible and therefore targeted at index colonoscopy; however, only 38% of SEC patients were diagnosed with targeted biopsies, despite similar use of chromoendoscopy (20%) at index in each group. Because only 10 SSP patients were found during the entire study period, outcome analyses were not performed on this group.
The sub-set of IBD patients diagnosed with SEC between 2010 and 2012 was compared to a random sample of IBD patients who had colonoscopy during the same time period (Figure 1c, Table 2 ). A total of 52 records were reviewed to obtain 50 control patients, demonstrating high accuracy of the search criteria (kappa = 0.96). SEC patients were more likely to have clinical risk factors for CRN. They were older and had longer disease duration. PSC was also more common in SEC patients (28%, n = 12/43) compared to 6% (3/50) controls (P = 0.005). A history of prior CRN, the development of subsequent CRN and rate of colectomy were not significantly different between the SEC group and controls.
The full SEC cohort was then stratified into two groups: those with either prior or synchronous adenomatous dysplasia at index (n = 27) or none (n = 52). Further chart review excluded 26 patients from analysis of 'to time of subsequent CRN'; 19 were for lack of subsequent endoscopy (3 with prior or synchronous CRN and 16 with none) and 7 developed subsequent CRN within 3 months of index diagnosis (7 with prior or synchronous CRN and 0 with none), leaving a total of 53 SEC patients for analysis of incident CRN (Figure 1d). Control patients with at least one follow-up colonoscopy were matched and stratified by colorectal neoplasia history. CUC was the predominant IBD type. There were no significant differences in median age, sex distribution, IBD subtype, IBD extent, the duration of IBD, or the presence of PSC. Rates of past and current smoking were also similar with the majority of patients in each group being never smokers. Median follow-up to last colonoscopy or colectomy was 24 months (IQR, 16–47) among SEC patients and 31 months (IQR, 19–58) among controls (P = 0.7); there were no significant differences when patients were stratified by prior or synchronous CRN history ( Table 3 ).
Fifteen of 53 (28%) SEC patients and 11 of 100 (11%) control patients developed subsequent CRN ( Table 4 ). Among SEC patients, subsequent neoplasia arose in the form of unifocal LGD (n = 8), multifocal LGD (n = 4), SSA (n = 1), traditional serrated adenoma (n = 1) and HGD (n = 1). No cancers arose in patients with SEC. Ten subsequent lesions were endoscopically visible (91%). Among SEC patients, subsequent CRN occurred on the same side of the colon (proximal or distal to splenic flexure) as the index SEC lesion in only 5 of 11 (45%) cases. Among controls, the subsequent neoplastic lesions included unifocal LGD (n = 6), multifocal LGD (n = 2), SSA (n = 1), HGD (n = 1) and CRC (n = 1). The single control patient who developed cancer had no history of prior or synchronous CRN.
The cumulative incidence of subsequent CRN at 1 and 3 years was 12% (95% CI, 0–30%) and 30% (3–57%), respectively, in SEC patients was 4% (0–12%) and 9% (0–23%), respectively, in controls (P = 0.047, log-rank). However, this difference was not statistically significant following stratification for prior/synchronous CRN history. Thereafter, the cumulative incidence of subsequent CRN at 1 and 3 years was 25% (0–68%) and 60% (5–100%), respectively, in SEC patients with prior/synchronous CRN, and 17% (0–47%) and 31% (0–74%) respectively in controls with prior/synchronous CRN (P = 0.09). For those without prior/synchronous CRN, the 1 and 3 year incidence of subsequent CRN was 6% (0–21%) and 17% (0–44%), respectively, in SEC patients compared to 0% (0–0%) and 2% (0–8%), respectively in controls (P = 0.1) (Figure 2).
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Figure 2.
Cumulative incidence of subsequent colorectal neoplasia (CRN) for: (a) All serrated epithelial change patients (—SEC all) compared to IBD controls (- - Ctrl all); (b) serrated epithelial change patients with a history of prior or synchronous CRN (— SEC with prior CRN) compared to IBD controls with prior CRN (- - Ctrl with prior CRN); and (c) serrated epithelial change patients without history of prior or synchronous CRN (— SEC without prior CRN) compared to IBD controls without prior colorectal neoplasia (- - Ctrl without prior CRN).
Results
Detection Rate and Baseline Characteristics
Figure 1 diagrams the flow of patients identified, excluded, re-classified and diagnosed. A total of 79 patients with SEC and 10 with SSP were identified and the number of cases was reported by year (Figure S1). A total of 4208 unique IBD patients underwent colonoscopy between 2010 and 2012. During the same time period, a total of 43 cases of SEC and 9 cases of SSP were found, for an estimated detection rate of 10 per 1000 (95% CI, 8–14) for SEC and 2 per 1000 (1–4) for SSP, respectively.
(Enlarge Image)
Figure 1.
Flow diagram of patient selection: (a) Characteristics of chronic colitis patients with serrated epithelial changes (SEC) or sessile serrated polyp (SSP), 2006–12 (Table 1); (b) patients included in detection rate calculation; (c) characteristics of serrated epithelial change (SEC) patients and randomly selected control IBD patients undergoing colonoscopy between 2010–12 (Table 2); (d) patients included in time to event analysis (Table 3, Table 4 and Figure 2); SNO-Med, systematised nomenclature of medicine; CPT, current procedural terminology (American Medical Association); ICD-9, international classification of diseases (9th Edition); SEC, serrated epithelial change; SSP, sessile serrated polyp; IBD, inflammatory bowel disease; TSA, traditional serrated adenoma. * Non-dysplastic indications; †Immediately after index - Lymphoma; ¥ Ovarian cancer metastatic to the colon.
(Enlarge Image)
Figure S1.
Serrated epithelial change (SEC) and sessile serrated polyp (SSP) diagnoses by year, 2006–2012.
Median ages at index were 57 years [interquartile range, (IQR) 48–65] and 48 years (IQR 42–57) for the SEC and SSP groups respectively ( Table 1 ). CUC was the predominant form of IBD in SEC (84%) but was less common among SSP cases (40%) (P = 0.005). Median disease duration was longer in the SEC group compared to the SSP group at 18 (IQR 10.5–29) and 9.5 (IQR 1.5–22.5) years, respectively. Overall, the median age at IBD diagnosis was 34 years (IQR 25.5–46.5) in SEC and 34.5 years (31–44.75) in SSP. Proportions of patients with extensive disease were similar, 77% in SEC and 70% in SSP. PSC was found in 23 of SEC patients (29%), but was not seen in the SSP cohort. CRN was diagnosed prior to (n = 19) or synchronous with (n = 8) index lesions in 27 of SEC patients (34%). Six of 27 (22%) had both prior and synchronous dysplasia at index. SEC occurred in the same side of the colon (proximal or distal to splenic flexure) as prior dysplasia in 8 of 19 (42%), and in 11 of 14 (79%) of those with synchronous lesions. In SSP patients, CRN was diagnosed prior to (n = 2) or synchronous with (n = 4) in 6 of the 10 patients (60%). All SSP lesions were visible and therefore targeted at index colonoscopy; however, only 38% of SEC patients were diagnosed with targeted biopsies, despite similar use of chromoendoscopy (20%) at index in each group. Because only 10 SSP patients were found during the entire study period, outcome analyses were not performed on this group.
The sub-set of IBD patients diagnosed with SEC between 2010 and 2012 was compared to a random sample of IBD patients who had colonoscopy during the same time period (Figure 1c, Table 2 ). A total of 52 records were reviewed to obtain 50 control patients, demonstrating high accuracy of the search criteria (kappa = 0.96). SEC patients were more likely to have clinical risk factors for CRN. They were older and had longer disease duration. PSC was also more common in SEC patients (28%, n = 12/43) compared to 6% (3/50) controls (P = 0.005). A history of prior CRN, the development of subsequent CRN and rate of colectomy were not significantly different between the SEC group and controls.
Incidence of Subsequent CRN
The full SEC cohort was then stratified into two groups: those with either prior or synchronous adenomatous dysplasia at index (n = 27) or none (n = 52). Further chart review excluded 26 patients from analysis of 'to time of subsequent CRN'; 19 were for lack of subsequent endoscopy (3 with prior or synchronous CRN and 16 with none) and 7 developed subsequent CRN within 3 months of index diagnosis (7 with prior or synchronous CRN and 0 with none), leaving a total of 53 SEC patients for analysis of incident CRN (Figure 1d). Control patients with at least one follow-up colonoscopy were matched and stratified by colorectal neoplasia history. CUC was the predominant IBD type. There were no significant differences in median age, sex distribution, IBD subtype, IBD extent, the duration of IBD, or the presence of PSC. Rates of past and current smoking were also similar with the majority of patients in each group being never smokers. Median follow-up to last colonoscopy or colectomy was 24 months (IQR, 16–47) among SEC patients and 31 months (IQR, 19–58) among controls (P = 0.7); there were no significant differences when patients were stratified by prior or synchronous CRN history ( Table 3 ).
Fifteen of 53 (28%) SEC patients and 11 of 100 (11%) control patients developed subsequent CRN ( Table 4 ). Among SEC patients, subsequent neoplasia arose in the form of unifocal LGD (n = 8), multifocal LGD (n = 4), SSA (n = 1), traditional serrated adenoma (n = 1) and HGD (n = 1). No cancers arose in patients with SEC. Ten subsequent lesions were endoscopically visible (91%). Among SEC patients, subsequent CRN occurred on the same side of the colon (proximal or distal to splenic flexure) as the index SEC lesion in only 5 of 11 (45%) cases. Among controls, the subsequent neoplastic lesions included unifocal LGD (n = 6), multifocal LGD (n = 2), SSA (n = 1), HGD (n = 1) and CRC (n = 1). The single control patient who developed cancer had no history of prior or synchronous CRN.
The cumulative incidence of subsequent CRN at 1 and 3 years was 12% (95% CI, 0–30%) and 30% (3–57%), respectively, in SEC patients was 4% (0–12%) and 9% (0–23%), respectively, in controls (P = 0.047, log-rank). However, this difference was not statistically significant following stratification for prior/synchronous CRN history. Thereafter, the cumulative incidence of subsequent CRN at 1 and 3 years was 25% (0–68%) and 60% (5–100%), respectively, in SEC patients with prior/synchronous CRN, and 17% (0–47%) and 31% (0–74%) respectively in controls with prior/synchronous CRN (P = 0.09). For those without prior/synchronous CRN, the 1 and 3 year incidence of subsequent CRN was 6% (0–21%) and 17% (0–44%), respectively, in SEC patients compared to 0% (0–0%) and 2% (0–8%), respectively in controls (P = 0.1) (Figure 2).
(Enlarge Image)
Figure 2.
Cumulative incidence of subsequent colorectal neoplasia (CRN) for: (a) All serrated epithelial change patients (—SEC all) compared to IBD controls (- - Ctrl all); (b) serrated epithelial change patients with a history of prior or synchronous CRN (— SEC with prior CRN) compared to IBD controls with prior CRN (- - Ctrl with prior CRN); and (c) serrated epithelial change patients without history of prior or synchronous CRN (— SEC without prior CRN) compared to IBD controls without prior colorectal neoplasia (- - Ctrl without prior CRN).
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