Distal Neoplasia Research Articles

Colon capsule endoscopy in clinical practice: lessons from a national 5-year observational prospective cohort.

Background and study aims Colon capsule endoscopy (CCE) has been proposed as an alternative to colonoscopy for screening patients at average risk of colorectal cancer (CRC). A prospective national cohort was developed to assess relevance of CCE in real-life practice and its short- and long-term impacts on clinical management. Patients and methods All patients who underwent a CCE in France were prospectively enrolled from January 2011 to May 2016 and reached annually by phone until May 2017. All CCE and colonoscopy reports were systematically collected. Results During the study period, 689 CCEs were analyzed from 14 medical centers. Median follow-up time was 35 months [IQR: 12–50]. Indication for CCE was mainly for elderly patients (median age: 70 years, IQR: [61–79]) due to anesthetic or colonoscopy contraindication (n = 307; 44.6 %). Only 337 CCEs (48.9 %) were both complete and with adequate bowel preparation. Advanced neoplasia (adenoma with high-grade dysplasia or CRC) was diagnosed following 32 CCEs (4.6 %). Among patients who underwent colonoscopy or therapeutic surgery following CCE, 18.8 % of all advanced neoplasias (6/32) had not been diagnosed by CCE mainly due to technical issues. Performing a colonoscopy in the case of significant polyps or insufficient bowel cleansing or after an incomplete CCE allowed the diagnosis of 96.9 % of all identified advanced neoplasias (31/32). Conclusions Outside the scope of academic trials, improvement is needed to increase the reliability of CCE as less than half were considered optimal i. e. complete with adequate bowel cleansing. Most of missed colonic advanced neoplasia were due to incomplete CCE with distal neoplasia location.

Continuing Medical Education Questions: August 2017: The Association between Distal Findings and Proximal Colorectal Neoplasia: A Systematic Review and Meta-Analysis.

Continuing Medical Education Questions: August 2017: The Association between Distal Findings and Proximal Colorectal Neoplasia: A Systematic Review and Meta-Analysis

Continuing Medical Education: August 2017: The Association between Distal Findings and Proximal Colorectal Neoplasia: A Systematic Review and Meta-Analysis

The American College of Gastroenterology is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American College of Gastroenterology designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Factors related to advanced colorectal neoplasm at the Policlínico Peruano Japonés.

Identifying persons at high risk for advanced colorectal neoplasia can aid in the prevention of colon cancer. Previous studies have shown that some patients can present with proximal advanced neoplasia with no distal findings. To determine the factors related to advanced neoplasia and advanced proximal colorectal neoplasia in a Latin American population. A prospective, cross-sectional, observational, analytic study was conducted. It included patients that underwent colonoscopy at the Policlínico Peruano Japonés within the time frame of January and July 2012. Advanced neoplasia was defined as the presence of lesions ≥ 10mm with a villous component, high-grade dysplasia, or carcinoma. The splenic flexure was the limit between the proximal and distal colon. A total of 846 patients were included in the study. Advanced neoplasia was detected in 108 patients (12.8%) and advanced proximal neoplasia in 55 patients (6.7%), 42 (76.4%) of whom had no neoplasia in the distal colon. Factors related to advanced neoplasia found in the multivariate analysis were age, at the intervals of 50-59 (p=0.019), 60-69 (p=0.016), and ≥ 70 years (0.002) and male sex (p=0.003). In the evaluation of advanced proximal neoplasia, the multivariate analysis identified the 60-69 year age interval (p=0.039) and advanced distal neoplasia (p=0.028) as factors related to advanced proximal disease. The ROC curve established the age cut-off point at 60 years for initially performing colonoscopy, rather than sigmoidoscopy. Age and sex are related to advanced neoplasia, whereas age and advanced distal neoplasia are related to advanced proximal neoplasia.

Factors related to advanced colorectal neoplasm at the Policlínico Peruano Japonés

BackgroundIdentifying persons at high risk for advanced colorectal neoplasia can aid in the prevention of colon cancer. Previous studies have shown that some patients can present with proximal advanced neoplasia with no distal findings. AimsTo determine the factors related to advanced neoplasia and advanced proximal colorectal neoplasia in a Latin American population. Material and methodsA prospective, cross-sectional, observational, analytic study was conducted. It included patients that underwent colonoscopy at the Policlínico Peruano Japonés within the time frame of January and July 2012. Advanced neoplasia was defined as the presence of lesions ≥ 10mm with a villous component, high-grade dysplasia, or carcinoma. The splenic flexure was the limit between the proximal and distal colon. ResultsA total of 846 patients were included in the study. Advanced neoplasia was detected in 108 patients (12.8%) and advanced proximal neoplasia in 55 patients (6.7%), 42 (76.4%) of whom had no neoplasia in the distal colon. Factors related to advanced neoplasia found in the multivariate analysis were age, at the intervals of 50-59 (p=0.019), 60-69 (p=0.016), and ≥ 70 years (0.002) and male sex (p=0.003). In the evaluation of advanced proximal neoplasia, the multivariate analysis identified the 60-69 year age interval (p=0.039) and advanced distal neoplasia (p=0.028) as factors related to advanced proximal disease. The ROC curve established the age cut-off point at 60 years for initially performing colonoscopy, rather than sigmoidoscopy. ConclusionsAge and sex are related to advanced neoplasia, whereas age and advanced distal neoplasia are related to advanced proximal neoplasia.

Association of distal hyperplastic polyps and proximal neoplastic lesions: a prospective study of 5613 subjects

Current evidence of whether distal hyperplastic polyps (HPs) are markers of proximal neoplasia (PN) is mixed. We evaluated the association between distal neoplasia and synchronous PN in asymptomatic subjects. We recruited 5819 Chinese asymptomatic screening participants 50 to 70 years of age who underwent colonoscopy in Hong Kong from 2008 to 2014, of whom 206 subjects with distal advanced neoplasia or cancer were excluded. The association between distal pathology (tubular adenomas [TAs], HPs, no polyps) and proximal pathology (PN, proximal advanced neoplasia [PAN]) was assessed by multivariate regression models, overall and stratified by the Asia Pacific Colorectal Screening scoring system (scores of 4-7, high risk; scores of 0-3, lower risk). The prevalence of PN in the no distal polyps group, distal HPs group, and distal TAs group was 14.8%, 19.3%, and 29.4%, respectively. The corresponding prevalence of PAN was 1.8%, 3.2%, and 3.5%. Participants with distal HPs did not have significantly higher odds of PN (adjusted odds ratio [AOR] 1.24; 95% confidence interval [CI], 0.97-1.59; P = .089), and their association with PAN was marginally significant (AOR 1.77; 95% CI, 1.00-3.13; P = .052), except in lower risk subjects for whom the odds of PAN were marginally higher in the distal HPs group than the no distal polyps group (AOR 1.97; 95% CI, 1.01-3.85; P = .048). Overall, the distal polyps group had significantly lower odds of PN than the distal TAs group (AOR 0.55; 95% CI, 0.40-0.76; P < .001). The increased risk of PN and PAN among those with distal HPs was modest. A direct association between distal HPs and PN is lacking, and this implies a need for a multivariate assessment of the risk of PAN. Recommending colonoscopy for every patient with distal HPs detected by screening sigmoidoscopy is not supported by this study.

Association Between Distal Hyperplastic Polyps and Proximal Neoplastic Lesions: A Prospective Study Among 5,613 Subjects

We evaluated the association between distal neoplasia and synchronous proximal neoplasia among asymptomatic subjects in a colorectal cancer screening programme, as current evidence on this association is inconclusive. We recruited Chinese asymptomatic screening participants aged 50-70 years who underwent colonoscopy in Hong Kong from 2008-2014. 206 subjects with distal advanced neoplasia or cancer were excluded. The association between distal pathology (tubular adenoma [TA]; hyperplastic polyps [HPs]; no polyps) and proximal pathology (proximal neoplasia [PN]; proximal advanced neoplasia [PAN]) was assessed by multivariate regression models – overall and stratified by the Asia Pacific Colorectal Screening (APCS) scoring system (score 4-7: high-risk; 0-3: lower-risk). A total of 5,842 screening participants underwent colonoscopy. We excluded 206 subjects who were found to have distal advanced neoplasia or distal cancer, and 23 subjects who were intolerant to the laxative regimen or whose bowel preparation was poor. Their average age was 57.6 years (SD 4.87). The prevalence of PN in the “no distal polyp” group, “distal HP” group and “distal TA” group was 14.8%, 19.3% and 29.4%, respectively. The corresponding prevalence of PAN was 1.8%, 3.2% and 3.5%. Participants with distal HPs did not have significantly higher odds of PN (adjusted odds ratio [AOR]=1.24, 95% C.I. 0.97-1.59, P = .089) or PAN (AOR=1.77, 95% C.I. 1.00-3.13, P = .052), except in lower-risk subjects where the odds of PAN was marginally higher in the “distal HP” group than the “no distal polyp” group (AOR=1.97, 95% C.I. 1.01-3.85, P = .048). Overall, the “distal polyp” group had significantly lower odds of PN than the distal TA group (AOR=0.55, 95% C.I. 0.40-0.76, P < .001). The increased risk of PN and PAN among those with distal HPs was modest. Recommending colonoscopy for every patient with distal HPs detected by screening sigmoidoscopy is not supported by the present findings.

Occurrence of Distal Colorectal Neoplasia Among Whites and Blacks Following Negative Flexible Sigmoidoscopy: An Analysis of PLCO Trial.

It is unclear whether the higher rate of colorectal cancer (CRC) among non-Hispanic blacks (blacks) is due to lower rates of CRC screening or greater biologic risk. We aimed to evaluate whether blacks are more likely than non-Hispanic whites (whites) to develop distal colon neoplasia (adenoma and/or cancer) after negative flexible sigmoidoscopy (FSG). We analyzed data of participants with negative FSGs at baseline in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial who underwent repeat FSGs 3 or 5 years later. Subjects with polyps or masses were referred to their physicians for diagnostic colonoscopy. We collected and reviewed the records of diagnostic evaluations. Our analytic cohort consisted of 21,550 whites and 975 blacks. We did a comparison by race (whites vs. blacks) in the findings of polyps or masses at repeat FSG, the follow-up of abnormal test results and the detection of colorectal neoplasia at diagnostic colonoscopy. At the follow-up FSG examination, 304 blacks (31.2 %) and 4183 whites (19.4 %) had abnormal FSG, [adjusted relative risk (RR) = 1.00; 95 % confidence interval (CI), 0.90-1.10]. However, blacks were less likely to undergo diagnostic colonoscopy (76.6 % vs. 83.1 %; RR = 0.90; 95 % CI, 0.84-0.96). Among all included patients, blacks had similar risk of any distal adenoma (RR = 0.86; 95 % CI, 0.65-1.14) and distal advanced adenoma (RR = 1.01; 95 % CI, 0.60-1.68). Similar results were obtained when we restricted our analysis to compliant subjects who underwent diagnostic colonoscopy (RR = 1.01; 95 % CI, 0.80-1.29) for any distal adenoma and (RR = 1.18; 95 % CI, 0.73-1.92) for distal advanced adenoma. We did not find any differences between blacks and whites in the risk of distal colorectal adenoma 3-5 years after negative FSG. However, follow-up evaluations were lower among blacks.

Diagnostic Accuracy of a Qualitative Fecal Immunochemical Test Varies With Location of Neoplasia But Not Number of Specimens

We compared the accuracy of a qualitative fecal immunochemical test (FIT) in identifying patients with proximal vs distal advanced neoplasia and evaluated whether analysis of 2 specimens performed better than analysis of 1 specimen. Distal advanced neoplasia was defined as colorectal cancer (CRC), any colorectal adenoma ≥10 mm in diameter, high-grade dysplasia, or a lesion with villous or tubulovillous histologic characteristics in a location distal to the splenic flexure, including the descending colon, the rectosigmoid, and the rectum. We collected data from 5343 subjects (50-70 years old) who received 2 FITs (Hemosure; cutoff value, 10 μg hemoglobin/g feces) before colonoscopy in an invitational CRC screening program in Hong Kong from 2008 through 2012. We calculated the FIT's sensitivity, specificity, positive predictive value (PPV), and negative predictive value in detecting colorectal neoplasia. Of the participants, 13.6%, 12.2%, and 6.0% had distal, proximal, and synchronous distal or proximal neoplasia, respectively. Advanced neoplasia was detected in 291 subjects (5.4%); 22 (0.4%) had CRC. FIT detected distal advanced adenoma with 39.7% sensitivity (95% confidence interval [CI], 32.0%-48.0%) vs proximal advanced adenoma with 25.0% sensitivity (95% CI, 17.3%-34.6%; P = .014), distal advanced neoplasia with 40.0% sensitivity (95% CI, 32.5%-47.9%) vs proximal advanced neoplasia with 27.9% sensitivity (95% CI, 20.0%-37.4%; P = .039), and any distal adenoma ≥10 mm, irrespective of other lesion characteristics, with 39.5% sensitivity (95% CI, 31.0%-48.7%) vs. proximal adenoma with 25.3% sensitivity (95% CI, 16.5%-36.6%; P = .038). The specificity of FIT in detecting CRC was similar between the proximal and distal colon. FIT detected distal lesions with higher PPV than proximal lesions. One FIT detected advanced neoplasia with 31.8% sensitivity (95% CI, 25.9%-38.4%) and 92.4% specificity (95% CI, 91.6%-93.2%), whereas 2 FITs detected advanced neoplasia with 34.1% sensitivity (95% CI, 28.0%-40.8%; P = .617) and 91.9% specificity (95% CI, 91.0%-92.7%; P = .327). FIT detected distal advanced neoplasia with greater sensitivity and higher PPV than proximal advanced neoplasia. In an analysis of data from subjects who underwent CRC screening in Hong Kong, FIT detected distal advanced neoplasia with higher sensitivity than proximal advanced neoplasia. Analysis of 1 vs 2 specimens by FIT identified advanced neoplasia with similar test characteristics.

Abstract IA18: Pathogenesis of gastric cancer: Lessons and therapeutic targets from mouse models

Abstract Many if not most gastrointestinal cancers arise in the setting of chronic inflammation, and a prime example is H. pylori-associated gastric cancer. We have utilized murine models of both proximal and distal gastric neoplasia to investigate the role of chronic inflammation in the development of malignancy. The development of gastric cancer in the mouse is dependent upon commensal flora and activation of both immature myeloid cells and cancer-associated fibroblasts. Gastric cancer arises in highly innervated portions of the stomach, and can be suppressed by surgical or chemical denervation of the stomach. Neurons and neurotransmitters promote the growth of gastric stem cells in organoid culture in vitro. Carcinogenesis of the stomach is associated with activation and early activation and amplification of epithelial stem or progenitor cells appears to be a requirement for the development of neoplasia. Further, conditional loss in gastric stem cells of tumor suppressor genes in vivo may not be sufficient for tumorigenesis but instead may require inflammatory signals in order to maintain self-renewal. In summary, the early stages of tumor development are often niche-dependent, and targeting the cancer niche represents an attractive strategy for cancer prevention and cancer therapy. Citation Format: Timothy C. Wang. Pathogenesis of gastric cancer: Lessons and therapeutic targets from mouse models. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr IA18.

NOTES total mesorectal excision (TME) for patients with rectal neoplasia: a preliminary experience.

Natural orifice transluminal endoscopic surgery (NOTES) and single-incision laparoscopy are emerging, minimally invasive techniques. Total mesorectal excision (TME), the gold standard treatment for patients with resectable distal rectal tumors, is usually performed in an "up-to-down" approach, either laparoscopically or via open techniques. A transanal, "down-to-up" TME has already been reported. Our NOTES variant of TME (NOTESTME) is based on a transperineal approach without any form of abdominal assistance. The aim was to reduce further the invasiveness of the procedure while optimizing the anatomical definition of the distal mesorectum. This approach may lead to reduced postoperative pain, decreased hernia formation and improved cosmesis when compared to standard laparoscopy. NOTESTME was attempted in 16 patients with distal rectal neoplasia (i.e., distal edge of the tumor lower than the pouch of Douglas, between 0 and 12 cm from the dentate line). Additional inclusion criteria consisted of an ASA status ≤III and the absence of previous abdominal surgery. NOTESTME was completed in all patients. Additional abdominal, single-incision laparoscopic assistance was required in 6 (38 %) patients. Mean operative time was 265 min (range 155-440 min). The morbidity rate was 18.8 % (two small bowel obstructions and one pelvic abscess), requiring re-operation in each case. No leaks occurred, and the mortality rate at 30 and 90 days was 0 %. Resection margins were negative in all patients. A median of 17 nodes (range 12-81) was retrieved per specimen. Mean length of hospital stay was 10 days (range 4-29 days). Patients were followed for an average of 7 months (range 3-23 months). NOTESTME was feasible and safe in this series of patients with mid- or low rectal tumors. The short-term mortality and morbidity rates are acceptable, with no apparent compromise in the oncological quality of the resection. Larger, randomized controlled trials with long-term follow-up are warranted.

Rate of Detection of Advanced Neoplasms in Proximal Colon by Simulated Sigmoidoscopy vs Fecal Immunochemical Tests

We compared the ability of biennial fecal immunochemical testing (FIT) and one-time sigmoidoscopy to detect colon side-specific advanced neoplasms in a population-based, multicenter, nationwide, randomized controlled trial. We identified asymptomatic men and women, 50-69 years old, through community health registries and randomly assigned them to groups that received a single colonoscopy examination or biennial FIT. Sigmoidoscopy yield was simulated from results obtained from the colonoscopy group, according to the criteria proposed in the UK Flexible Sigmoidoscopy Trial for colonoscopy referral. Patients who underwent FIT and were found to have ≥75 ng hemoglobin/mL were referred for colonoscopy. Data were analyzed from 5059 subjects in the colonoscopy group and 10,507 in the FIT group. The main outcome was rate of detection of any advanced neoplasm proximal to the splenic flexure. Advanced neoplasms were detected in 317 subjects (6.3%) in the sigmoidoscopy simulation group compared with 288 (2.7%) in the FIT group (odds ratio for sigmoidoscopy, 2.29; 95% confidence interval, 1.93-2.70; P = .0001). Sigmoidoscopy also detected advanced distal neoplasia in a higher percentage of patients than FIT (odds ratio, 2.61; 95% confidence interval, 2.20-3.10; P = .0001). The methods did not differ significantly in identifying patients with advanced proximal neoplasms (odds ratio, 1.17; 95% confidence interval, 0.78-1.76; P = .44). This was probably due to the lower performance of both strategies in detecting patients with proximal lesions (sigmoidoscopy detected these in 19.1% of patients and FIT in 14.9% of patients) vs distal ones (sigmoidoscopy detected these in 86.8% of patients and FIT in 33.5% of patients). Sigmoidoscopy, but not FIT, detected proximal lesions in lower percentages of women (especially those 50-59 years old) than men. Sigmoidoscopy and FIT have similar limitations in detecting advanced proximal neoplasms, which depend on patients' characteristics; sigmoidoscopy underperforms for women 50-59 years old. Screening strategies should be designed on the basis of target population to increase effectiveness and cost-effectiveness. ClinicalTrials.gov number: NCT00906997.

Predictive factors of proximal advanced neoplasia in the large bowel.

IntroductionThe aim of the study was to evaluate the impact of sex, age, family history and distal findings on the risk of proximal advanced neoplasia (cancer or advanced adenoma) in the large bowel.Material and methodsRecords for 10 111 asymptomatic participants of the Colonoscopy Screening Program (CSP), recruited from the Warsaw region between 2000 and 2004, were analyzed. A multivariate logistic regression model was used to estimate the impact of sex, age, family history and most advanced distal lesions on the occurrence of proximal advanced neoplasia. To enhance comparability of the study two definitions of the proximal colon were applied – either the splenic flexure (1st) or the bend between the descending and sigmoid colon (2nd definition) represented the boundary.ResultsOne hundred and thirty-three (1st) and 167 patients (2nd definition) were found to have at least one advanced neoplastic lesion in the proximal part, respectively. Eleven and 14 patients were found to have carcinoma, while in 130 and 163 patients at least one proximal advanced adenoma appeared. Men were at twice as high risk of having advanced neoplasia in the proximal colon than women (OR = 1.94, 95% CI: 1.31–2.87, p = 0.001 or OR = 1.69, 95% CI: 1.20–2.40, p = 0.003, respectively). The presence of distal advanced neoplastic lesions was associated with 3.5 times higher risk of proximal advanced neoplasia (OR = 3.58, 95% CI: 2.00–6.43, p < 0.0001 or OR = 3.41, 95% CI: 1.95–5.96, p < 0.0001), respectively.ConclusionsThe results may confirm some limitation of flexible sigmoidoscopy in the screening settings in comparison with colonoscopy, at least in men and people with distal advanced neoplasia.

A single FIT (≥ 50 ng Hb/mL) detected 38% of screen-detected advanced colorectal neoplasia

Source Citation de Wijkerslooth TR, Stoop EM, Bossuyt PM, et al. Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia. Am J Gastroenterol. 2012;...

Tailoring Colorectal Cancer Screening by Considering Risk of Advanced Proximal Neoplasia

BackgroundQuantifying the risk of advanced proximal colorectal neoplasia might allow tailoring of colorectal cancer screening, with colonoscopy for those at high risk and less invasive screening for very low-risk persons. MethodsWe analyzed findings from 10,124 consecutive adults aged≥50 years who underwent screening colonoscopy to the cecum. We quantified the risk of advanced neoplasia (tubular adenoma≥1 cm, a polyp with villous histology or high-grade dysplasia, or adenocarcinoma) both proximally (cecum to splenic flexure) and distally (descending colon to anus). The prevalence of advanced proximal neoplasia was quantified by age, gender, and distal findings. ResultsThe mean (standard deviation) age was 57.5 (6.0) years; 44% were women; 7835 (77%) had no neoplasia, and 1856 (18%) had 1 or more nonadvanced adenomas. Overall, 433 subjects (4.3%) had advanced neoplasia (267 distally, 196 proximally, 30 both), 33 (0.33%) of which were adenocarcinoma (18 distal, 15 proximal). The risk of advanced proximal neoplasia increased with age decade (1.13%, 2.00%, and 5.26%, respectively; P=.001) and was higher in men (relative risk [RR], 1.91; confidence interval [CI], 1.32-2.77). In women aged less than 70 years, the risk was 1.1% overall (vs 2.2% in men; RR, 1.98; CI, 1.42-2.76) and 0.86% in those with no distal neoplasia (vs 1.54% in men; RR, 1.81; CI, 1.20-2.74). ConclusionsRisk of advanced proximal neoplasia is a function of age and gender. Women aged less than 60 to 70 years have a very low risk, particularly those with no distal adenoma. Sigmoidoscopy with or without occult blood testing may be sufficient and even preferable for screening these subgroups.

Immunochemical Fecal Occult Blood Testing Is Equally Sensitive for Proximal and Distal Advanced Neoplasia

Fecal immunochemical testing (FIT) is increasingly used for colorectal cancer (CRC) screening. We aimed to estimate its diagnostic accuracy in invitational population screening measured against colonoscopy. Participants (50-75 years) in an invitational primary colonoscopy screening program were asked to complete one sample FIT before colonoscopy. We estimated FIT sensitivity, specificity, and predictive values in detecting CRC and advanced neoplasia (carcinomas and advanced adenomas) for cutoff levels of 50 (FIT50), 75 (FIT75), and 100 (FIT100) ng hemoglobin (Hb)/ml, corresponding with, respectively, 10, 15 and 20 μg Hb/g feces. A total of 1,256 participants underwent a FIT and screening colonoscopy. Advanced neoplasia was detected by colonoscopy in 119 (9%), 8 (0.6%) of them had CRC. At FIT50, 121 (10%) had a positive test result; 45 (37%) had advanced neoplasia and 7 (6%) had CRC. A total of 74 of 1,135 FIT50 negatives (7%) had advanced neoplasia including 1 (0.1%) CRC. FIT50 had a sensitivity of 38% (95% confidence interval (CI): 29-47) for advanced neoplasia and 88% (95% CI: 37-99) for CRC at a specificity of 93% (95% CI: 92-95) and 91% (95% CI: 89-92), respectively. The positive and negative predictive values for FIT50 were 6% (95% CI: 3-12) and almost 100% (95% CI: 99-100) for CRC, and 37% (95% CI: 29-46) and 93% (95% CI: 92-95) for advanced neoplasia. The sensitivity and specificity of FIT75 for advanced neoplasia were 33% (95% CI: 25-42) and 96% (95% CI: 94-97). At FIT100, 71 screenees (6%) had a positive test result. The sensitivity and specificity of FIT100 were for advanced neoplasia 31% (95% CI: 23-40) and 97% (95% CI: 96-98), and for CRC 75% (95% CI: 36-96) and 95% (95% CI: 93-96). The area under curve for detecting advanced neoplasia was 0.70 (95% CI: 0.64-0.76). FIT had a similar sensitivity for proximal and distal advanced neoplasia at cutoffs of 50 (38% vs. 37%; P=0.99), 75 (33% vs. 31%; P=0.85) and 100 (33% vs. 29%; P=0.68) ng Hb/ml. Nine out of ten screening participants with CRC and four out of ten with advanced neoplasia will be detected using one single FIT at low cutoff. Sensitivity in detecting proximal and distal advanced neoplasia is comparable.

Relationship Between Distal and Proximal Neoplasia

To the Editor:— In their recent article, Dodou and de Winter underlined that all types of distal lesions are predictive of proximal neoplasia (PN).1 This conclusion is especially important for colorectal cancer screening. If so, colonoscopy should be performed instead of flexible rectosigmoidoscopy. Risk of advanced proximal colon neoplasm progressing to fatal cancer is relatively low (1 % per year).2,3 On the other hand we must remember that lesions can be missed even in colonoscopy especially flat ones that may progress more rapidly to cancer. Cost of colonoscopy is another issue of concern for patients with distal lesions.

Relationship Between Distal and Proximal Neoplasia

Authors Reply:--- In a recent meta-analysis, we found that all types of distal lesions are predictive of proximal neoplasia (PN) and that on average 60 % of PN are isolated, that is, not accompanied by distal lesions.1 A commentary by Dr. Filik concluded that if all types of distal lesions are predictive of PN, colonoscopy should be performed instead of flexible sigmoidoscopy (FS). We thank Dr. Filik for his comment. In this reply we highlight why FS should not be abandoned in favor of colonoscopy. Deciding which colon inspection method is most suitable for screening depends on many parameters, including discomfort, complication rates, logistics, and costs.2 FS is performed without sedation, leading to more pain than colonoscopy. Colonoscopy has a complication rate that, although low, is 10 times higher than that of FS. Colonoscopy is further accompanied by a loss of three working days for preparing for, undergoing, and recovering from the procedure, compared to half a day in FS. Colonoscopy has the theoretical advantage over FS that it allows inspection of the proximal colon. Recent population-based studies have reported that, compared to no screening, colonoscopy led to significant reductions of cancer incidence in the distal colon and associated mortality, but its efficacy in the proximal colon was similar to that of FS.3 It remains unclear whether these studies failed to show a protective effect of colonoscopy against proximal colon cancer incidence because of poor design or practical limitations (e.g., by including cases in which colonoscopy was performed by non-gastroenterologists), inherent visualization problems of colonoscopy (e.g., miss of flat and pale proximal adenomas), or inherent properties of the proximal colon (e.g., the aggressive nature of proximal tumors). Randomized controlled trials of screening colonoscopy are underway, but their results will not be available before 2021. In an effort to improve the predictive value of FS, Imperiale et al.4 introduced a clinical index including distal findings, gender, and age. The index was applied to a cohort of asymptomatic individuals 50 years or older undergoing screening colonoscopy for the first time and detected 92 % of individuals with advanced proximal neoplasia. Using the index could reduce the number of screening colonoscopies by 40 % as compared to sending everyone to colonoscopy. In our meta-analysis, health characteristics were an important moderator of the association between distal and proximal lesions, with proximal advanced neoplasia being better predicted in asymptomatic populations, young populations, and populations with a low prevalence for proximal advanced neoplasia. Combining the FS outcome with demographics, health characteristics, genetic predisposition, and environmental risks can improve the prediction of PN and strengthen the role of FS as a screening modality. Technological advances in imaging and visualization as well as emerging techniques such as virtual colonoscopy will also contribute to future lesion detection.

The Relationship Between Distal and Proximal Colonic Neoplasia: A Meta-Analysis

OBJECTIVESTo investigate the association between proximal colonic neoplasia and distal lesions as a function of the lesion type. The extent to which health, demographic, and study characteristics moderate this association was also examined.DATA SOURCESGoogle Scholar, Web of Science, Scopus, and PubMed.STUDY ELIGIBILITY CRITERIAStudies allowing the calculation of OR of proximal neoplasia(PN) and proximal advanced neoplasia (PAN) for distal hyperplastic polyps (HP), nonadvanced adenomas (NAA), adenomas (AD), and advanced neoplasia (AN); also, studies for which the proportions of subjects with isolated (i.e., not accompanied by distal lesions) PN (IPN) and PAN (IPAN) over the total number of subjects with PN or PAN could be calculated.STUDY APPRAISAL AND SYNTHESIS METHODSThirty-two studies were included for calculating OR between proximal neoplasia and distal lesions and 40 studies for proportions of IPN and IPAN. Subgroup analyses were conducted for presence of symptoms, prevalence of PN and PAN, age, proportion of males, geographic region, study design, and demarcation point.RESULTSThe association between distal lesions and proximal neoplasia increased with the severity of the distal lesions. Odds of PN were higher in subjects with HP compared to subjects with a normal distal colon. Odds of PN and PAN were higher in subjects with NAA, AD, and AN than in subjects with a normal distal colon. PAN were more strongly associated with distal lesions in asymptomatic populations, in young populations, and in populations with a low prevalence of PAN. In approximately 60% of the subjects with PN and PAN, these neoplasia were isolated.LIMITATIONSThe present results may be affected by publication bias and dichotomization in the subgroup analyses. Limitations related to the individual studies include self-selection, lesion misclassification and misses, and technological advances leading to changes in the detection of lesions during the time span of the included studies.CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGSAll types of distal lesions are predictive of PN. All types of distal neoplasia are predictive of PAN. The association between distal lesions and proximal neoplasia increases with the severity of the distal lesion. The association between distal lesions and proximal advanced neoplasia is stronger in low-risk groups as compared to high-risk groups.

Simulation of colorectal cancer screening: What we do and do not know and does it matter

Simulation modelling is increasingly used to inform decision-making on screening, including colorectal cancer screening strategies. The strength of simulation is its ability to handle complexity and to identify the implications of uncertainty in a formal, documented, reproducible and consistent way. Important specific uncertainties concerning colorectal cancer screening are the dwell time of adenomas and the associated sensitivity of the various tests. Concerning these issues, for distal colorectal neoplasia, knowledge has been greatly increased by the recent availability of the once only sigmoidoscopy randomised trial results. Other uncertainties concern the quality of life effects of screening, diagnostic and surveillance colonoscopies, and the true total costs of the various screening modalities in a routine high throughput efficient setting. A limitation of simulation of screening is that complexity leads to lack of insight and understanding into the models used, and therefore a lack of sound criticism, acceptance and use amongst decision makers. Modellers are currently focussing on ways to make models and the implications of assumptions more transparent. Thus it is important to further develop the quality and acceptability of simulation, especially that for colorectal cancer screening.