Hazard function analysis for development of second primary colorectal cancer after surgery for primary colorectal cancer.

BACKGROUND AND AIM: Although history of colorectal cancer (CRC) is a known risk factor for developing second CRC, the optimal surveillance protocol has not been established. Using hazard function analysis to evaluate changes in the hazard rate for the development of second primary CRCs or high-grade adenomas (HGAs), we aimed to clarify when and on whom to focus in order to effectively identify second primary colorectal neoplasms after initial surgery for CRC. METHODS: We retrospectively enrolled 1823 consecutive patients with stage 0-III CRCs who underwent radical surgery between 2004 and 2015, and subsequent colonoscopic surveillance after surgery. The time-course changes in the risk rates for developing metachronous CRC and HGA after surgery were assessed. RESULTS: A peak was observed at 1.22 years after surgery in the hazard function curve for secondary colorectal neoplasms, which decreased until 4 years, then plateaued. Older patients were at higher risk than younger patients, both showing a peak at 1 year. Another peak at 6 to 8 years was observed in younger patients. Male patients showed a higher risk than female patients, and patients with synchronous lesions showed a markedly higher hazard rate than those without, with two distinct peaks around 1 and 9 years after surgery. CONCLUSIONS: Intensive colonoscopic surveillance is recommended after surgery for CRC during the first 2 to 3 years, and if the patient is under 60 years old and has concomitant CRC or HGA, surveillance is also recommended at 6 to 8 years after surgery.

Metachronous Neoplasia and Local Recurrence after Colorectal Endoscopic Submucosal Dissection.

Several reports discussed colonoscopic surveillance after polypectomy and endoscopic mucosal resection (EMR) for colorectal polyps, but only a few reports focused on prognostic analyses, and none involved metachronous neoplasia after colorectal endoscopic submucosal dissection (ESD). We conducted the present study to assess the risk of adenoma recurrence requiring endoscopic treatment, and to establish appropriate post-ESD colonoscopic surveillance. We enrolled 116 patients who had undergone colorectal ESD at Okayama University Hospital between February 2008 and July 2014 and had been followed-up >12 months. We retrospectively analyzed clinicopathological features of 101 lesions from 101 patients. Metachronous adenomas were detected in 21 cases (20.8%). We divided the patients into 2 groups according to the occurrence of metachronous adenomas. Our comparison of clinicopathological characteristics between these groups showed that in the metachronous adenomas group the number of synchronous adenomas at index colonoscopy was high and the rate of laterally spreading tumor-nongranular (LST-NG) was higher. A multivariate analysis indicated that the number of synchronous adenomas was significantly associated with metachronous adenomas (HR: 2.54, 95%CI: 1.04-6.52, p<0.05). The colonoscopic surveillance planning after colorectal ESD should be more meticulous for patients with more synchronous adenomas.

A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer.

Surveillance guidelines for the management of familial colorectal cancer (FCC), a dominant family history of colorectal cancer in which the polyposis syndromes and Lynch syndrome have been excluded, are not firmly established. The outcome of colonoscopic surveillance is studied using data from six centers. DNA mismatch repair deficiency was excluded by genetic testing. Families were classified as FCC type X if they fulfilled the original Amsterdam criteria (AC) and late onset (LOFCC) if they fulfilled the AC apart from not having a cancer aged under 50. The most advanced findings on colonoscopy were analyzed. One thousand five hundred eighty-five individuals (median age 47.3, 44% male) from 530 FCC families (349 FCC type X) underwent a total of 4,992 colonoscopies with 7,904 patient-years of follow-up. Results for FCC type X and LOFCC were very similar. At baseline, 22 prevalent asymptomatic colorectal cancers were diagnosed, 120 (7.6%) individuals had high-risk adenomas and 225 (14.2%) simple adenomas. One thousand eighty-eight individuals had a further colonoscopy (median follow-up of 6.2 years). Of nine individuals diagnosed with cancer, eight had a previous history of at least one polyp/adenoma. High-risk adenomas were detected in 92 (8.7%) and multiple adenomas were detected in 20 (1.9%) individuals. Both FCC type X and LOFCC have a high prevalence of colorectal cancers and on follow-up develop high-risk adenomas (including multiple adenomas), but infrequent interval cancers. They should be managed similarly with five-yearly colonoscopies undertaken from between 30 and 40 with more intensive surveillance in individuals developing multiple or high-risk adenomas.

Update and latest advances in mechanisms and management of colitis-associated colorectal cancer.

Colitis-associated colorectal cancer (CAC) is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease (IBD). Patients with IBD, including ulcerative colitis and Crohn's disease, are known to have an increased risk of developing CAC. Although the incidence of CAC has significantly decreased over the past few decades, individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer, and the incidence of CAC increases with duration. Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC. CAC has been shown to progress from colitis to dysplasia and finally to carcinoma. Accumulating evidence suggests that multiple immune-mediated pathways, DNA damage pathways, and pathogens are involved in the pathogenesis of CAC. Over the past decade, there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients. Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers. It is generally recommended that CAC patients undergo endoscopic removal or colectomy. This review summarizes the current understanding of CAC, particularly its epidemiology, mechanisms, and management. It focuses on the mechanisms that contribute to the development of CAC, covering advances in genomics, immunology, and the microbiome; presents evidence for management strategies, including endoscopy and colectomy; and discusses new strategies to interfere with the process and development of CAC. These scientific findings will pave the way for the management of CAC in the near future.

Postgastrectomy gastric cancer patients are at high risk for colorectal neoplasia: a case control study.

BACKGROUND/AIMS: Several studies have shown that colorectal neoplasms (CRN) including colorectal cancer (CRC) may be prevalent in patients with gastric cancer. However, in most of these studies, colonoscopy to investigate the prevalence of CRN was performed prior to surgery. We aimed to investigate whether CRN was more prevalent in postgastrectomy gastric cancer patients than in healthy individuals. METHODS: We reviewed the medical records of those patients within a cohort of gastric cancer patients with gastrectomy who underwent colonoscopy between 2016 and 2017. Controls age- and sex-matched with gastric cancer patients at a 2:1 ratio were identified among those who underwent colonoscopy at a health-promotion center. The frequencies of CRN, advanced CRN (ACRN), and CRC among patients with gastrectomy were compared with those in the control subjects. A total of 744 individuals (gastric cancer, 248; control, 496) were included. RESULTS: The rates of CRN and ACRN in the gastric cancer group were higher than those in the healthy individuals (CRN, 47.6% vs. 34.7%, P< 0.001; ACRN, 16.9% vs. 10.9%, P= 0.020). The rate of CRC was comparable between the 2 groups (2.0% vs. 0.6%, P= 0.125). Multivariate analysis identified previous gastrectomy for gastric cancer and male sex as significant risk factors for (A)CRN. CONCLUSIONS: CRN and ACRN were more prevalent in patients who underwent surgery for gastric cancer than in the control group. Regular surveillance colonoscopy at appropriate intervals is indicated after gastrectomy.

Features of incident colorectal cancer in Lynch syndrome.

BACKGROUND AND OBJECTIVE: Despite intensive colonoscopic surveillance, a substantial proportion of Lynch syndrome (LS) patients develop colorectal cancer (CRC). The aim of this study was to characterize incident CRC in LS patients. METHODS: All patients diagnosed with incident CRC after start of colonoscopic surveillance were identified in the Dutch LS Registry of 905 patients. A retrospective analysis of patient records was carried out for patient characteristics, survival, CRC characteristics and findings of previous colonoscopy. RESULTS: Seventy-one patients (7.8%) were diagnosed with incident CRC. Median interval between incident CRC diagnosis and previous colonoscopy was 23.8 (range 6.7-45.6) months. Median tumor diameter was 2.5 cm, and 17% of the tumors were sessile or flat. Most patients (83%) had no lymph node metastases. There was no association between tumor size and colonoscopy interval or lymph node status. Most patients (65%) had no adenomas during previous colonoscopy. Two patients (2.8%) eventually died from metastatic CRC. CONCLUSION: The high frequency of incident CRC in LS likely results from several factors. Our findings lend support to the hypothesis of fast conversion of adenomas to CRC, as 65% of patients had no report of polyps during previous colonoscopy. High-quality colonoscopies are essential, especially as tumors and adenomas are difficult to detect because of their frequent non-polypoid appearance. Early detection due to surveillance as well as the indolent growth of CRC, as demonstrated by the lack of lymph node metastases, contributes to the excellent survival observed.

Rural-urban differences in the long-term risk of colorectal cancer after adenoma removal: a population-based study.

BACKGROUND: We investigated the impact of municipality of residence on colonoscopic surveillance and colorectal cancer risk after adenoma resection in a French well-defined administrative area. METHODS: This registry-based study included all patients residing in Côte d'Or (n=5769) first diagnosed with colorectal adenomas between January 1, 1990, and December 31, 1999. Information about colonoscopic surveillance and colorectal cancer incidence was collected until December 31, 2003. RESULTS: A rural place of residence reduced the probability of colonoscopic surveillance in men [HR=0.89 (95%CI: 0.79-0.99), p=0.041] and in patients without family history of colorectal cancer [HR=0.91(0.82-0.99), p=0.044]. After a median follow-up of 7.7 years, 87 patients developed invasive colorectal cancer. After advanced adenoma removal, the standardized incidence ratio for colorectal cancer was 3.03 (95%CI: 1.92-4.54) for rural patients and 1.87 (95%CI: 1.26-2.66) for urban patients compared with the general population. The risk of colorectal cancer was higher in rural patients than in urban ones only after removal of the initial advanced adenoma [HR=1.73 (95%CI: 1.01-3.00, p=0.048)]. Further adjustment for surveillance colonoscopy, physician location, and other confounders had little impact on these results. CONCLUSION: The increased risk of subsequent colorectal cancer after advanced adenoma removal in French rural patients was not explained by a lower rate of colonoscopic surveillance. The role of socio-economic and environmental factors requires further exploration.