Differences between men and women with respect to colorectal cancer mortality despite screening colonoscopy.

BACKGROUND AND AIMS: Women aged 55 to 59 years have a similar prevalence rate and number needed to screen for colorectal adenomas as men at a 10-year younger age. The aim of this study was to determine sex-specific differences in colorectal cancer mortality and estimate the association with adenomas at screening colonoscopy. METHODS: This retrospective study analyzed 323,139 individuals who underwent colonoscopy within a national colorectal cancer screening program in Austria between January 2007 and December 2020. RESULTS: Median patient age was 60 years (interquartile range, 54-67), and the sex distribution in all age groups was nearly identical. Men had significantly higher odds of having an adenoma or serrated polyp, low-risk polyp, high-risk polyp, or colorectal cancer detected at colonoscopy than women (odds ratio [OR] 1.83; 95% confidence interval [CI], 1.80-1.86; OR, 1.46; 95% CI, 1.44-1.49; OR, 1.74; 95% CI, 1.69-1.80; and OR, 1.87; 95% CI, 1.70-2.05, respectively). Strikingly, male sex, when compared with female sex, was associated with an almost 2-fold (hazard ratio, 1.67; 95% CI, 1.05-2.67) increased risk to die from colorectal cancer when an adenoma or serrated polyp was found at the screening colonoscopy and a 4-fold (hazard ratio, 4.14; 95% CI, 2.72-6.3) increased risk when a high-risk polyp was found at the screening colonoscopy. The cumulative incidence for death of colorectal cancer for 60-year-old individuals was 8.5-fold higher in men as compared with women. Markedly, this sex gap narrowed with increasing age, whereas the difference in deaths of other causes remained similar in all age groups. CONCLUSIONS: Our findings strengthen the necessity of sex-specific screening recommendations. Importantly, further prospective studies should focus on sex differences in tumor biology to propose personalized surveillance guidelines.

Role of Endoscopic Resection Versus Surgical Resection in Management of Malignant Colon Polyps: a National Cancer Database Analysis.

BACKGROUND: Endoscopic resection (polypectomy) or surgery, are the main approaches in management of malignant colon polyps. There are very few large population-based studies comparing outcomes between the two. METHODS: Using the National Cancer Database, we identified patients ≥ 18 years with the first diagnosis of T1N0M0 malignant polyp from 2004 to 2015. Patients with a positive resection margin were excluded. Outcomes were compared between those who had surgery versus those who had polypectomy. Overall survival was compared using Kaplan-Meier curves. Multivariate Cox proportional hazards analysis was performed to generate hazard ratios, adjusted for patient, demographic, and tumor factors. RESULTS: A total of 31,062 patients met the inclusion criteria, out of which 2593 (8.3%) underwent polypectomy alone and 28,469 (91.7%) had surgery. Overall survival was significantly better in the surgical group compared with the polypectomy group. One-year and 5-year survival for surgery were 95.8% and 86.1% respectively compared with 94.2% and 80.6% for polypectomy (p < .0001). Hazard ratio for surgery after adjusting for various clinical-, demographic-, and tumor-level factors was 0.53 (p < .0001). CONCLUSION: Our study is the largest population-based analysis of patients with T1N0M0 malignant colon polyps. Overall survival was higher in patients who underwent surgery compared with polypectomy. This remained consistent even after adjusting for multiple patient and tumor factors between the two groups.

Malignant colorectal polyps: endoscopic polypectomy and watchful waiting is not inferior to subsequent bowel resection. A nationwide propensity score-based analysis.

BACKGROUND AND AIMS: The optimal treatment of patients with malignant colorectal polyps is unsettled. The surgical dilemma following polypectomy is selecting between watchful waiting (WW) and subsequent bowel resection (SBR), but the long-term survival outcomes have not been established yet. This nationwide study compared survival of patients after WW or SBR. METHODS: Danish nationwide study with 100% follow-up of all patients with malignant colorectal polyps (the Danish Colorectal Cancer Group database) in a 10-year period from 2001 to 2011. All patients' charts and histological reports were individually reviewed. Survival rates were calculated with Cox proportional hazard model after propensity score matching. RESULTS: A total of 692 patients were included (WW, 424 (61.3%), SBR, 268 (38.7%)) with a mean follow-up of 7.5 years (3-188 months). Following propensity score matching, there was no significant difference in overall or disease-free survival (p = 0.344 and p = 0.184) or rate of local recurrence (WW, 7.2%, SBR, 2%, p = 0.052) or distant metastases (WW, 3.3%, SBR, 4.6%, p = 0.77). In the SBR group, there was no residual tumor or lymph node metastases in the resected specimen in 82.5% of the patients. CONCLUSION: Subsequent bowel resection may not be superior to endoscopic polypectomy and watchful waiting with regard to overall and disease-free survival in patients with malignant colorectal polyps.

Transanal endoscopic surgery is effective and safe after endoscopic polypectomy of potentially malignant rectal polyps with questionable margins.

AIM: To determine the percentage of residual lesion observed in the pathology study of transanal endoscopic surgery (TEM) specimens after endoscopic polypectomy of malignant rectal polyps with questionable margins, and the need for further surgery. Secondary aims: to determine the morbidity and mortality associated with this procedure and to identify the percentage of recurrence after excision by TEM. METHODS: Observational study with prospective data collection of all patients undergoing TEM after endoscopic polypectomy for malignant rectal polyps or non-invasive high-grade neoplasia, from January 2004 to December 2016. An en bloc full-thickness wall excision of the scar was performed. Variables recorded: histology of TEM specimen, 30-day morbidity and mortality according to the Clavien-Dindo classification, need for salvage surgery and recurrence. RESULTS: Fifty out of 690 patients undergoing TEM during the study period (36 adenocarcinomas, five non-invasive high-grade neoplasias and 9 neuroendocrine tumors) were included. Post-surgery histology showed residual lesion in 21 (42%) patients: 7 neuroendocrine tumors, 10 adenomas and 4 adenocarcinomas (two pT1, one pT2 and one pT3). The pT2 and pT3 patients (4%) underwent salvage surgery. No recurrence was observed, and mean follow-up was 29.1Â ± 21.6 months. The 30-day morbidity rate was 14%, but 4/7 with Clavien-Dindo grade I. CONCLUSIONS: After endoscopic polypectomy of malignant rectal polyps with questionable margins, the presence of residual lesion in the pathology study of transanal resection specimens is high. TEM with full-thickness resection of these lesions is an appropriate treatment, allowing disease control and achieving minimal morbidity.

DCLK1 Expression in Colorectal Polyps Increases with the Severity of Dysplasia.

BACKGROUND: The expression of doublecortin-like kinase 1 (DCLK1) has been investigated in cancer; however not in precancerous adenomatous polyps. MATERIALS AND METHODS: Immunohistological expression of DCLK1 was evaluated in various grades of adenomas, cancerous polyps, and hyperplastic polyps in resected human tissue specimens. RESULTS: Ninety-two specimens were positive for DCLK1 and 134 were negative. Cancerous polyps showed a high DCLK1 positivity rate compared to adenomas (68.4% vs. 36.8%; p<0.01). The rate of DCLK1 positivity was not significantly different among the three grades of adenomas (mild, moderate, and severe). DCLK1 was highly positive in advanced adenomas than low risk adenomas (49.6% vs. 29.3%; p<0.01). CONCLUSION: The expression of DCLK1 was found in low-grade adenomas and increased with worsening severity of dysplasia. DCLK1 expression was highly observed in advanced adenomas, which had a clinically higher malignant potential.

Squamoid morules in the pseudoinvasive foci of colonic polyp morphologically mimic invasive carcinoma.

Colorectal adenomas can show focal squamous differentiation or squamoid morules. We describe histologic findings of squamoid morules in the pseudoinvasive foci of colorectal polyps mimicking invasive carcinoma. Five colonic polyps with squamoid morules in the pseudoinvasive foci were collected. Histologic review and immunostains for cytokeratin 5/6, p63, synaptophysin, and chromogranin were performed on cases with squamoid morules. Forty-seven consecutive colorectal polyps with pseudoinvasion, none of which showed squamoid morules by histology review, and their clinicopathologic features were compared with the cases containing squamoid morules. Cases with squamoid morules more frequently occurred in younger patients (P=.047) and were located in right colon (P=.027) than those without squamoid morules. Diagnosis of the polyps included tubular/tubulovillous adenoma with low-grade (with squamoid morules, n=3; versus without squamoid morules, n=29) or high-grade dysplasia (n=2 versus n=15) and sessile serrated adenoma (none versus n=3). Squamoid morules formed nodules protruding into the lumen of glandular structures or partially replaced adenomatous glands without forming a discrete nodule. They also presented as solid nests showing a well-formed morular structure around the bottom of adenomatous glands or myxoinflammatory stroma. Importantly, squamoid morules often formed a pseudocribriform or solid nest sitting in the stroma of pseudoinvasive foci. All cases (n=4) showed cytokeratin 5/6 positivity and p63 negativity in squamoid morules. Three and 1 of 4 cases showed focal positivity for synaptophysin and chromogranin, respectively, in squamoid morules. Squamoid morules in colonic adenomatous polyps can mimic invasive carcinoma when present in the pseudoinvasive foci. Pathologists should be aware of their presence.

Differences in Effectiveness and Use of Robotic Surgery in Patients Undergoing Minimally Invasive Colectomy.

BACKGROUND: We compared patient outcomes of robot-assisted surgery (RAS) and laparoscopic colectomy without robotic assistance for colon cancer or nonmalignant polyps, comparing all patients, obese versus nonobese patients, and male versus female patients. METHODS: We used the 2013-2015 American College of Surgeons National Surgical Quality Improvement Program data to examine a composite outcome score comprised of mortality, readmission, reoperation, wound infection, bleeding transfusion, and prolonged postoperative ileus. We used propensity scores to assess potential heterogeneous treatment effects of RAS by patient obesity and sex. RESULTS: In all, 17.1% of the 10,844 of patients received RAS. Males were slightly more likely to receive RAS. Obese patients were equally likely to receive RAS as nonobese patients. In comparison to nonRAS, RAS was associated with a 3.1% higher adverse composite outcome score. Mortality, reoperations, wound infections, sepsis, pulmonary embolisms, deep vein thrombosis, myocardial infarction, blood transfusions, and average length of hospitalization were similar in both groups. Conversion to open surgery was 10.1% lower in RAS versus nonRAS patients, but RAS patients were in the operating room an average of 52.4 min longer. We found no statistically significant differences (p > 0.05) by obesity status and gender. CONCLUSIONS: Worse patient outcomes and no differential improvement by sex or obesity suggest more cautious adoption of RAS.

Prognostic significance of stromal GREM1 expression in colorectal cancer.

Cancer-associated fibroblasts are the dominant cell population in the cancer stroma. Gremlin 1 (GREM1), an antagonist of the bone morphogenetic protein pathway, is expressed by cancer-associated fibroblasts in a variety of human cancers. However, its biological significance for cancer patients is largely unknown. We applied RNA in situ hybridization to evaluate the prognostic value of stromal GREM1 expression in a large cohort of 670 colorectal cancers (CRCs). Overall, GREM1 expression in CRCs was lower than that of the matched normal mucosa, and GREM1 expression had a strong positive correlation with BMI1 and inverse correlations with EPHB2 and OLFM4. RNA in situ hybridization localized the GREM expression to smooth muscle cells of the muscularis mucosa and fibroblasts around crypt bases and in the submucosal space of a normal colon. In various colon polyps, epithelial GREM1 expression was exclusively observed in traditional serrated adenomas. In total, 44% of CRCs were positive for stromal GREM1, which was associated with decreased lymphovascular invasion, a lower cancer stage, and nuclear ß-catenin staining. Stromal GREM1 was significantly associated with improved recurrence-free and overall survival, although it was not found to be an independent prognostic marker in multivariate analyses. In addition, for locally advanced stage II and III CRC, it was associated with better, stage-independent clinical outcomes. In summary, CRCs are frequently accompanied by GERM1-expressing fibroblasts, which are closely associated with low lymphovascular invasion and a better prognosis, suggesting stromal GREM1 as a potential biomarker and possible candidate for targeted therapy in the treatment of CRCs.

Management of malignant colorectal polyps in New Zealand.

BACKGROUND: The management of colorectal polyps containing a focus of malignancy is problematic, and the risks of under- and over-treatment must be balanced. The primary aim of this study was to describe the management and outcomes of patients with malignant polyps in the New Zealand population; the secondary aim was to investigate prognostic factors. METHODS: Retrospective review of relevant clinical records at five New Zealand District Health Boards. RESULTS: Out of the 414 patients identified, 51 patients were excluded because of the presence of other relevant colorectal pathology, leaving 363 patients for analysis. Of these, 182 had a polypectomy, and 181 had a bowel resection as definitive treatment. The overall 5-year survival was not altered with resection but was improved with re-excision of any form (repeat polypectomy or bowel resection). There were 110 rectal lesions and 253 colonic lesions. A total of 16% of patients who had resection after polypectomy were found to have residual cancer in the resected specimen. Ischaemic heart disease, chronic obstructive pulmonary disease and metastatic disease were found to negatively impact overall survival (P < 0.001). Resection was more likely to follow polypectomy if polypectomy margins were positive, fragmentation occurred for sessile lesions and for pedunculated lesions with a higher Haggitt level. CONCLUSION: Polypectomy is oncologically safe in selected patients. Re-excision improves overall survival and should be considered in patients with low comorbidity (American Society of Anesthesiologists score 1 and 2) and where there is concern about margins (sessile lesions and positive polypectomy margins). In the majority of patients, however, no residual disease is found.

Obesity and Colorectal Cancer.

There is strong evidence that modifiable lifestyle factors such as obesity play a key role in colorectal carcinogenesis. Epidemiologic data have consistently reported a positive association between obesity and colorectal cancer. The relative risk associated with general obesity (as assessed by BMI) is higher in men than in women and for cancer of the colon than for cancer of the rectum. Abdominal obesity (as assessed by waist circumference (WC) or waist-to-hip ratio) is associated with an increased risk of colorectal cancer in both sexes, with stronger associations for cancer of the colon than for cancer of the rectum. Plausible biological mechanisms include insulin resistance, hyperinsulinemia, chronic inflammation, altered levels of growth factors, adipocytokines and steroid hormones. In addition to its effect on colorectal cancer incidence, obesity may play a role in colorectal cancer recurrence, treatment outcomes and survival. Understanding the effects of childhood and adolescent obesity and weight change over the life course in relation to future risk of colorectal cancer is incomplete but essential for targeted preventive recommendations. This chapter summarizes the current evidence on the relationship between obesity and colorectal cancer and colorectal adenoma, a common precursor lesion.

Long-Term Impact of the Dutch Colorectal Cancer Screening Program on Cancer Incidence and Mortality-Model-Based Exploration of the Serrated Pathway.

BACKGROUND: We aimed to predict the long-term colorectal cancer incidence, mortality, and colonoscopy demand of the recently implemented Dutch colorectal cancer screening program. METHODS: The Adenoma and Serrated pathway to Colorectal Cancer model was set up to simulate the Dutch screening program consisting of biennial fecal immunochemical testing combined with the new Dutch surveillance guidelines, between 2014 and 2044. The impact of screening and surveillance was evaluated under three sets of natural history assumptions differing in the contribution of the serrated pathway to colorectal cancer incidence. In sensitivity analyses, other assumptions concerning the serrated pathway were varied. Model-predicted outcomes were yearly colorectal cancer incidence, mortality, and colonoscopy demand per year. RESULTS: Assuming an aging population, colorectal cancer incidence under 30 years of screening is predicted to decrease by 35% and 31% for a contribution of 0% and 30% of the serrated pathway to colorectal cancer, respectively. For colorectal cancer mortality, reductions are 47% and 45%. In 2044, 110,000 colonoscopies will be required annually assuming no contribution of the serrated pathway (27 per 1,000 individuals in the screening age range). Including the serrated pathway influences predicted screening effectiveness if serrated lesions are neither detected nor treated at colonoscopy, and/or if colorectal cancers arising from serrated lesions have substantially lower survival rates than those arising from adenomas. CONCLUSIONS: The Dutch screening program will markedly decrease colorectal cancer incidence and mortality but considerable colonoscopy resources will be required. IMPACT: Predictions of long-term screening effectiveness are preferably based on both pathways to colorectal cancer to transparently describe the impact of uncertainties regarding the serrated pathway on long-term predictions.

Upregulation of nemo-like kinase is an independent prognostic factor in colorectal cancer.

AIM: To investigate the expression and oncogenic role of nemo-like kinase (NLK) in colorectal cancer. METHODS: Expression of NLK protein was assessed by immunohistochemistry in tissue specimens from 56 cases of normal colorectal mucosa, 51 cases of colorectal adenoma, and 712 cases of colorectal cancer. In addition, NLK expression was knocked down using a lentivirus carrying NLK small hairpin RNA in colorectal cancer cells. Cell viability methylthiazoletetrazolium assays, colony formation assays, flow cytometry cell cycle assays, Transwell migration assays, and gene expression assays were performed to explore its role on proliferation and migration of colorectal cancer. RESULTS: Expression of NLK protein progressively increased in tissues from the normal mucosa through adenoma to various stages of colorectal cancer. Overexpression of NLK protein was associated with advanced tumor-lymph node-metastasis stages, poor differentiation, lymph node and distant metastases, and a higher recurrence rate of colorectal cancer (P < 0.05). Multivariate analyses showed that NLK expression was an independent prognostic factor to predict overall survival (hazard ratio 2.57, 95% confidence interval: 1.66-3.98; P < 0.001) and disease-free survival (hazard ratio 1.96, 95% confidence interval: 1.40-2.74: P < 0.001) of colorectal cancer patients. Furthermore, knockdown of NLK expression in colorectal cancer cell lines reduced cell viability, colony formation, and migration, and arrested tumor cells at the G0/G1 phase of the cell cycle. At the gene level, knockdown of NLK expression inhibited matrix metalloproteinase-2 expression in colorectal cancer cells. CONCLUSION: NLK overexpression is an independent prognostic factor in colorectal cancer and knockdown of NLK expression inhibits colorectal cancer progression and metastasis.

Post-polypectomy Guideline Adherence: Importance of Belief in Guidelines, Not Guideline Knowledge or Fear of Missed Cancer.

BACKGROUND: Adherence to post-polypectomy surveillance guideline recommendations is suboptimal. Surveillance is frequently over- and under-recommend, resulting in strained colonoscopy capacity, potential risks without expected benefits, and missed opportunities for colorectal cancer risk reduction. AIMS: To identify factors associated with adherence to post-polypectomy surveillance guidelines. METHODS: We conducted a three-phase study with a retrospective review of usual care post-polypectomy surveillance recommendations through medical chart abstraction (Phase I), prospective online physician survey (Phase II), and analysis of survey-based and other physician-based predictors of usual care surveillance recommendations (Phase III). Subjects included patients who underwent usual care colonoscopy 2011-2012 (Phases I and III) and gastroenterology (GI) attendings and fellows (Phases II and III). We identified rates of recommendations consistent with guideline adherence, surveillance overuse, and surveillance underuse based on usual care medical chart documentation and physician survey, as well as predictors of physician adherence to guidelines. RESULTS: We reviewed 640 patient charts for 28 survey respondents. Rates of usual practice recommendations consistent with guideline adherence, surveillance overutilization, and underutilization were 84, 13, and 3%, respectively. At survey, 82% of physicians were concerned about missed cancer. Eleven percentage believed that guidelines were not aggressive enough. GI trainees were 2.5 times more likely to issue guideline-adherent recommendations [OR 2.5, 95% CI (1.5-4.2)]. Disagreement with guideline aggressiveness was independently associated with 40% lower likelihood of adherence [OR 0.6, 95% CI (0.4-0.8)]. CONCLUSIONS: Belief in the appropriate aggressiveness of guidelines and trainee position, but not fear of missed cancer or guideline knowledge, was associated with adherence to post-polypectomy surveillance guidelines.

Genetic characteristics of mitochondrial DNA was associated with colorectal carcinogenesis and its prognosis.

Clinical value of mitochondrial DNA has been described in colorectal cancer (CRC). To clarify its role in colorectal carcinogenesis, mitochondrial microsatellite instability (mtMSI) and other markers were investigated in CRCs and their precancerous lesions, as a multitier genetic study. DNA was isolated from paired normal and tumoral tissues in 78 tubular adenomas (TAs), 34 serrated polyps (SPs), and 100 CRCs. mtMSI, nucleus microsatellite instability (nMSI), KRAS mutation, and BRAF mutation were investigated in these tumors and their statistical analysis was performed. mtMSI was found in 30% of CRCs and 21.4% of precancerous lesions. Mitochondrial copy number was higher in SPs than TAs and it was associated with mtMSI in low grade TAs. KRAS and BRAF mutations were mutually exclusive in TAs and SPs. CRCs with mtMSI showed shorter overall survival times than the patients without mtMSI. In CRCs without nMSI or BRAF mutation, mtMSI was a more accurate marker for predicting prognosis. The genetic change of mitochondrial DNA is an early and independent event in colorectal precancerous lesions and mtMSI and mitochondrial contents are associated with the tubular adenoma-carcinoma sequence, resulting in poor prognosis. This result suggested that the genetic change in mitochondrial DNA appears to be a possible prognosis marker in CRC.

Standard versus limited colon resection for high risk T1 colon cancer. A matched case-control study.

BACKGROUND AND AIMS: The National Comprehensive Cancer Network (NCCN) recommends a colectomy in presence of high risk T1 colon polyps considering the risk of incomplete lymph node dissection or presence of residual disease. We evaluated the outcomes of segmental versus standard colon resection for high risk T1 colon cancers, in order to demonstrate if segmental colectomy (SegCR) allows same short-term and oncological results compared to standard radical colectomy (StaCR). METHODS. A matched case-control study on patients who had undergone segmental versus standard colon resection was performed. One-hundred and two patients with high risk T1 colon cancer after endoscopic polypectomy, divided in 2 homogeneous groups of 51 cases, were analyzed and intra-operative, post-operative and oncological data were compared. RESULTS. Segmental colectomy allowed less operative time and intra-operative blood loss compared to StaCR (p < 0.001). Hospital stay after SegCR was shorter compared to StaCR (p < 0.001). No differences were found in terms of overall morbidity and mortality rates. Five-year actuarial overall, disease-free and disease-specific survival after StaCR were similar to SegCR (87%, 96% and 95% vs. 88%, 97% and 94%, respectively, p = 0.51, p=0.33, p=0.78). CONCLUSIONS. According to our findings, SegCR can be a valid alternative to StaCR for high risk T1 colon polyps. Segmental colectomy allows better peri-operative outcomes compared to StaCR ensuring the same oncological long-term outcomes.

Malignancy and mortality of colorectal polyps.

OBJECTIVES: To evaluate the rate of morbidity and mortality associated with colorectal polyps after the next 8-years period of endoscopic polypectomy, in a high risk managed care population. MATERIAL AND METHOD: Cohorts of 77 subjects with benign neoplasms were identified with a colonoscopy in 1999. Three groups of subjects: benign neoplasms with polypectomy, benign neoplasms without polypectomy, and no neoplasms were evaluated. Five years recurrence rates (1999-2004) of benign or new malignant colorectal neoplasms were identified: for the benign determined for the baseline benign neoplasms with polypectomy and no neoplasm groups neoplasm without polypectomy, only rates for malignancy were observed. Malignancy was evaluated with immunohistochemical p53 (tumor protein 53) and PCNA (Proliferating Cell Nuclear Antigen) staining pattern. Over the next 8 years 2004-2012 were evaluated the mortality and the recurrence rate of the benign polyps. RESULTS: 77 subjects were enrolled in our study; 71.4% were diagnosed with benign and 2.5% with malignant neoplasms. The 5-years cumulative incidence rates of malignant colorectal neoplasms in the no neoplasm (n = 20) and benign neoplasm groups (n = 55) were (n = 1) 5% and ( n = 10) 18.1%, respectively (p < 0.005). A lower 5-years malignancy rate was observed in benign neoplasms group with polypectomy (12%) compared to the benign neoplasm group without polypectomy (33.3%) (p < 0.05). The 8-years mortality rate was compared into benign recurrent polyps group and into malign group: the lower 8-years mortality rate was observed into benign polyp no neoplasm group (0%) and into benign recurrent polyps group (40%); the highest rate was observed into neoplasm group (100%). CONCLUSIONS: The high recurrence rate of benign colorectal neoplasms and a higher incidence of colorectal cancer in subjects at high risk-history of benign colorectal neoplasm-highlight a healthcare opportunity for surveillance and/or interventions to reduce the morbidity associated with colorectal neoplasms.

Characteristics of missed or interval colorectal cancer and patient survival: a population-based study.

BACKGROUND & AIMS: Colorectal cancers (CRCs) diagnosed within a few years after an index colonoscopy can arise from missed lesions or the development of a new tumor. We investigated the proportion, characteristics, and factors that predict interval CRCs that develop within 6-60 months of colonoscopy. METHODS: We performed a population-based cohort study of Utah residents who underwent colonoscopy examinations from 1995 through 2009 at Intermountain Healthcare or the University of Utah Health System, which provide care to more than 85% of state residents. Colonoscopy results were linked with cancer histories from the Utah Population Database to identify patients who underwent colonoscopy 6-60 months before a diagnosis of CRC (interval cancer). Logistic regression was performed to identify risk factors associated with interval cancers. RESULTS: Of 126,851 patients who underwent colonoscopies, 2659 were diagnosed with CRC; 6% of these CRCs (159 of 2659) developed within 6 to 60 months of a colonoscopy. Sex and age were not associated with interval CRCs. A higher percentage of patients with interval CRC were found to have adenomas at their index colonoscopy (57.2%), compared with patients found to have CRC detected at colonoscopy (36%) or patients who did not develop cancer (26%) (P < .001). Interval CRCs tended to be earlier-stage tumors than those detected at index colonoscopy, and to be proximally located (odds ratio, 2.24; P < .001). Patients with interval CRC were more likely to have a family history of CRC (odds ratio, 2.27; P = .008) and had a lower risk of death than patients found to have CRC at their index colonoscopy (hazard ratio, 0.63; P < .001). CONCLUSIONS: In a population-based study in Utah, 6% of all patients with CRC had interval cancers (cancer that developed within 6 to 60 months of a colonoscopy). Interval CRCs were associated with the proximal colon, earlier-stage cancer, lower risk of death, higher rate of adenoma, and family history of CRC. These findings indicate that interval colorectal tumors may arise as the result of distinct biologic features and/or suboptimal management of polyps at colonoscopy.

Standardized long-term follow-up after endoscopic resection of large, nonpedunculated colorectal lesions: a prospective two-center study.

OBJECTIVES: Endoscopic removal of large, nonpedunculated colorectal lesions is challenging. Long-term outcome data based on standardized protocols, including detailed inspection of the resection site, are scarce. The aims of the present study were to evaluate the safety and efficacy of endoscopic resection (ER) of large, nonpedunculated lesions (LNLs; >20 mm) and to assess the long-term recurrence rate afterward. METHODS: A total of 243 consecutive patients (141 men, 102 women) with 252 adenomas (>20 mm) was followed up using a standardized protocol after complete ER. After endoscopic treatment, the patients received standardized follow-up examinations after 3-6 months and 12 months. The postpolypectomy scar was re-examined, assessed for residual neoplasia, and biopsied at each follow-up colonoscopy. RESULTS: Evident residual neoplasia was noted after 3-6 months in 58 of 183 lesions (31.69%). After 12 months, 126 LNLs were examined, with 19 late recurrences (16.37%). Twenty-one (6.5%) postpolypectomy scars were not detected during 321 surveillance examinations. Biopsy evidence of residual/recurrent lesions was found in 16 of 228 macroscopically inconspicuous polypectomy scars (7%). All residual adenomas were treated using ER and/or argon plasma coagulation. There were 43 complications with the 252 lesions (17%), including 20 major complications (7.9%), all managed conservatively. CONCLUSIONS: A detailed study design with systematic biopsies of inconspicuous scars reveals a significant number of residual adenomas after completed resection. However, these residual neoplasias can be effectively treated at follow-up colonoscopies.