Prior Colon Cancer Research Articles

Risk of colon cancer-related death in people who had cancer in the past.

The rate of second primary malignancies (SPM) is gradually increasing. Yet, the risk of death from primary cancer vs. SPM is still not well understood. In this study, we investigated the survival of patients with colorectal cancer (as SPM) who had cancer in the past (prior cancer) and the risk factors of SPM death in this population. Based on the Surveillance, Epidemiology, and End Results (SEER) database, we identified 1866 colon cancer patients with prior cancer in our main cohort and 43,959 colon cancer patients, including 37,440 patients with colon cancer as only malignancy and 6519 patients with colon cancer as subsequent colon cancer (SCC), in a second cohort and 3429 colon cancer patients, including 2371 patients with prior colon cancer (PCC) and 1058 patients with colon cancer as SPM, in a third cohort. After propensity score matching, 6519 pairs of subjects were identified in second cohort. Patients with prior prostate and breast cancer had a higher risk of developing colon cancer compared to those with gastrointestinal cancer. Also, colon cancer patients with different prior cancer had different survival rates. Furthermore, except for prior lung cancer (52.78 vs. 25.93%), most subjects died due to colon cancer complications. The ratio of colon cancer deaths to prior cancer deaths in patients with a low stage and high stage was 1.51 and 6.64, respectively. In addition, colon cancer-specific survival (CSS) and OS rates were significantly lower in subjects with colon cancer as the SPM than in those with PCC. Also, compared with PCC, SPM was associated with OS and CSS with HR 1.59 (95 CI 1.43-1.78) and HR 2.00 (95% CI 1.70-2.36). Furthermore, compared with only colon cancer, SCC was associated with OS and CSS with HR 1.23 (95 CI 1.17-1.29) and HR 1.13 (95% CI 1.06-1.21). Prior cancer was found to have an adverse impact on OS in patients with colon cancer (secondary cancer), most of whom died due to colon cancer as secondary cancer itself rather than prior cancer. Early detection and treatment strategies should be investigated in this population.

Transvaginal natural orifice transluminal endoscopic surgery (VNOTES) total retroperitoneal sentinel lymph node biopsy for an endometrial cancer patient with prior colon cancer surgery

Endometrial cancer (EC) is the most common gynecological malignancy. Although EC is surgically staged, sentinel lymph node biopsy has become more widely used and has been featured in recently published...

Immunohistochemical screening for mismatch repair protein deficiency in paediatric high-grade gliomas - institutional experience and review of literature.

Immunohistochemical (IHC) testing for mismatch repair (MMR) deficiency (MMRD) is used as a screening tool to identify microsatellite instability in various cancers (especially colon). This not only identifies hereditary cancer syndromes like Lynch and constitutional mismatch repair deficiency (CMMRD) but also aids in prognostication and prediction of sensitivity to checkpoint inhibitor drugs. There are very few reported studies on MMRD status of pediatric high-grade gliomas (pHGG) and none from the Indian subcontinent. The aim of this study is to evaluate the frequency of MMRD in pHGG and to assess if there is a need for universal screening with immunohistochemistry. Paraffin blocks of consecutive cases of pHGG (< 18years) were retrieved from 2 centres, and IHC with four MMR antibodies - MLH1, PMS2, MSH2 and MSH6 - was performed using tissue microarray-based technique. Three out of nine cases (33%) studied showed loss of staining. One case had loss of MSH2 and MSH6 confirmed by gene sequencing. Eight of the cases were glioblastoma. One case of IDH1-mutated anaplastic astrocytoma showed loss of MLH1 and PMS2 staining. Isolated PMS2 loss was noted in 1 case, where the non-tumour cells also showed loss of staining, indicative CMMRD syndrome. This patient had prior colon cancer with isolated PMS2 loss and responded to check-point inhibitor therapy with nivolumab. Our study shows that the frequency of MMRD to be about one-third of pHGG. Universal IHC screening for MMRD in all pHGGs may benefit early diagnosis and play a role in therapeutic decisions. A larger multi-institutional study will help better assess the prevalence and treatment implications in MMRD tumours.

How to identify patients who are less likely to have metachronous neoplasms after a colon cancer: a predictive model.

Patients with prior colon cancer have increased risk of metachronous colorectal neoplasms; therefore, endoscopic surveillance is indicated. Current recommendations are not risk-stratified. We investigated predictive factors for colorectal neoplasms to build a model to spare colonoscopies for low-risk patients. This was a multicenter, retrospective study including patients who underwent surgery for colon cancer in 2001 - 2008 (derivation cohort) and 2009 - 2013 (validation cohort). A predictive model for neoplasm occurrence at second surveillance colonoscopy was developed and validated. 421 and 203 patients were included in derivation and validation cohort, respectively. At second surveillance colonoscopy, 112 (26.6 %) and 55 (27.1 %) patients had metachronous neoplasms in derivation and validation groups; three cancers were detected in the latter. History of left-sided colon cancer (OR 1.64, 95 %CI 1.02 - 2.64), ≥ 1 advanced adenoma at index colonoscopy (OR 1.90, 95 %CI 1.05 - 3.43), and ≥ 1 adenoma at first surveillance colonoscopy (OR 2.06, 95 %CI 1.29 - 3.27) were independently predictive of metachronous colorectal neoplasms at second surveillance colonoscopy. For patients without such risk factors, diagnostic accuracy parameters were: 89.3 % (95 %CI 82.0 %-94.3 %) and 78.2 % (95 %CI 65.0 %-88.2 %) sensitivity, and 28.5 % (95 %CI 23.5 %-33.9 %) and 33.8 % (95 %CI 26.2 %-42.0 %) specificity in derivation and validation group, respectively. No cancer would be missed. Patients with prior left-sided colon cancer or ≥ 1 advanced adenoma at index colonoscopy or ≥ 1 adenoma at first surveillance colonoscopy had a significantly higher risk of neoplasms at second surveillance colonoscopy; patients without such factors had much lower risk and could safely skip the second surveillance colonoscopy. A prospective, multicenter validation study is needed.

Time to surgery in colon cancer: Predictors and association with survival—An analysis of the National Cancer Database (NCDB).

599 Background: Time-to-surgery (TTS) refers to the wait time from the diagnosis of cancer to surgical resection of the primary tumor. In breast and bladder cancers, longer TTS has been shown to be associated with lower long-term survival. Prior evidence in colon cancer, has shown that older age, urban residence, and comorbidity are independent predictors of TTS. However, evaluation of TTS with survival in colon cancer has been limited to mostly single-center studies. Using the NCDB, this study aimed to both evaluate patient and clinical factors associated with TTS, and determine if TTS was associated with overall survival in colon cancer. Methods: Patients with colon cancer who underwent partial or subtotal colectomy/hemicolectomy were included, excluding those receiving neoadjuvant therapy. With prior colon cancer studies showing a median TTS of 15-20 days, we dichotomized the number of days from diagnosis to definitive surgery (TTS) as ≤ 21 days or &gt; 21 days. A modified Poisson regression model was utilized to evaluate relative risk of TTS &gt; 21 days. Overall survival in association with TTS was estimated using both the Kaplan-Meier method and multivariable Cox regression model, adjusting for patient-, disease- and facility-level characteristics. All analyses were conducted with SAS version 9.4, p-values &lt; 0.05 were considered significant. Results: We identified 26,999 colon cancer patients from 2006-2012 from the NCDB. Approximately 25.7% of patients had a TTS &gt; 21 days. Patients with comorbidities, who were older, were African American, with lower disease stage, and treated in academic facilities located in the Northeast, had a significantly increased relative risk of a TTS &gt; 21 days. Considering survival, a TTS &gt; 21 days was associated with a 24.5% decreased adjusted risk of death (95% CI: 21.6% to 27.2%). Conclusions: A longer TTS with colon cancer is understandably associated with older age, greater comorbidity, and lower stage, but questionably so in African American patients. However, given that TTS &gt; 21 days was associated with a lower adjusted risk of death, it may indicate that a reasonable delay could be pursued for more accurate preoperative evaluation and staging in colon cancer.

Colorectal cancer prevention.

Introduction: To develop a regression model that can reliably predict the recommended time interval for surveillance colonoscopy, possibly eliminating the need for pathology. Methods: We retrospectively analyzed 625 patients who had colonoscopy with polyps in the year 2013 at a university hospital. Exclusion criteria included patients with prior colon cancer or colorectal surgery, IBD, colon cancer syndrome, polyps not retrieved, or a lesion only biopsied. Binary logistic regression was performed using Statistical Package for the Social Sciences v.21. The binary dependent variable was the surveillance interval recommendation of 3 years or other than 3 years. The reference value was the 2012 AGA guidelines. In this study, we treated screening and surveillance together and hyperplastic polyps beyond the splenic flexure as adenomas, as there is evidence that pathologist may misclassify SSA as hyperplastic. Independent variables were defined as follows: number of polyps (1, 2, 3, or > 4), size of the polyps (any polyp >10mm or not), and location of the polyps (0, 1, 2, or >3 polyps proximally). Results: Two thousand two hundred three colonoscopies were reviewed. Six hundred twenty-five exams met the study criteria. Of those, 429 were for screening and 196 for surveillance. Polyp size, number, and location were all significant factors in determining the interval. The nagelkerke R square is 0.803, and the omnibus tests of the coefficients were all <0.000 (Table 1). Sensitivity and specificity for the model is 92.2% and 94.9%, respectively. Area under the ROC curve was 0.93. For the 3-year interval, 3.5% of patients got a false positive result, and 2.4% got a false negative result. Two patients with pathology of rectal carcinoid and a rectal leiomyoma were assigned “not 3 years.” False positives occurred mainly in patients with multiple hyperplastic polyps (15 patients) or large benign polyps (5 patients). False negatives occurred in 3 patients with tubulovillous adenoma less than 10 mm and in 15 patients with between 3-5 small polyps.Table 1: Coefficients of RegressionConclusion: This regression model may allow gastroenterologists to reliably determine surveillance interval at the time of procedure, saving time, cost, and possibly improving adherence and decreasing anxiety. Furthermore, the consistency of pathology has been challenged for diagnosis of sessile serrated adenomas in the proximal colon, thus putting the utility of pathology in question. Though validation is needed, this model may be used to discard resected polyps without pathology evaluation when the results are unlikely to change clinical behavior.

In Vivo Diagnosis of Colorectal Polyps by GI Endoscopists Using HD Narrow-Band Imaging

Introduction: To determine if ASGE thresholds for changing the management of diminutive colorectal polyps can be met by systematically training gastroenterology fellows and faculty in the application of the NICE classification during routine colonoscopy. Methods: Two gastroenterology fellows and 2 attending physicians, all without prior NBI training were given a pretest and a post-test involving typing of polypoid lesions in accordance with the NICE classification. In between tests was an interactive practice session with active feedback including slides with questions and answers. Custom NICE classification reference cards were posted in the endoscopy rooms for optional rapid review. Commercially available Olympus colonoscopes CF-H180 were used with the xenon light source. The Evis Exera II video processor was used with a 26-inch LCD monitor positioned within 2-3 arm lengths. Excluded from predictions were cases of prior colon cancer, colectomy, IBD, or polyposis syndrome. Polyps were detected under white-light, narrow-band illumination was activated, and stills of the polyp to be assessed were captured. For each detected polyp the location, Paris classification of morphology, NICE classification, prediction of colorectal polyp histology, and level of confidence in the prediction were documented. Polyps were resected by snare or biopsy forceps and placed in individual transport jars for pathology. Polyp size and histology was measured and assessed by a pathologist blinded to the histology prediction. Results: Eight hundred fifty-three colonoscopies were performed by 4 gastroenterology endoscopists. Three hundred patients with median age of 62 years underwent polypectomy, yielding 583 polyps. Compared to the histopathology diagnosis, the trained endoscopist predicted the correct colonoscopy surveillance interval in 81-99% of patients depending upon the surveillance interval recommended for those with 1-2 low-risk adenomas. Post-NBI training test results were mostly concordant (±4.6%) with confident prediction-histology agreement rates. The negative predictive value for NBI-assisted adenomatous polyp screening ranged from 86-90%. Conclusion: Routine use of the NICE classification in assessing colorectal polyps can increase early diagnostic yield and support both “remove and discard” or “leave in place” strategies. We focused on the training of endoscopists using previously published methods and materials including computer-based and didactic training that lasted no more than 20 minutes. Eliminating the time spent estimating polyp size and relying on actual measurement of polyp size expedites NBI training and ensures the endoscopist’s surveillance interval recommendations are based solely on the ability to distinguish polyps.

The yield and cost of colonoscopy in patients with metastatic cancer of unknown primary

Although gastroenterologists are asked to perform colonoscopy in patients with metastatic cancer of unknown primary (MCUP), studies evaluating this practice are lacking. To determine the yield and cost of colonoscopy in patients referred for colonoscopy with an indication of MCUP. We prospectively and retrospectively assessed colonoscopies performed from 2000 to 2011 at a county, a university, and a Veterans Administration medical centre to identify patients referred for colonoscopy for the indication of MCUP. Exclusion criteria included overt or occult bleeding, iron-deficiency anaemia, familial-colon-cancer syndrome, prior colon cancer, imaging suggesting colorectal lesion, and palpable rectal mass. Outcomes were the number of primary colon cancers and costs based on 2012 Medicare reimbursements. Two (1%) of the 160 patients meeting enrollment criteria had a primary colon cancer identified, and both died within 1month after diagnosis without receiving therapy targeted at colon cancer. One patient without colon cancer had a perforation because of colonoscopy, which required surgery and colostomy. The cost of a strategy of routinely performing colonoscopy in patients referred with MCUP was $84736 per colon primary identified. Primary colon cancer was rarely identified at colonoscopy in patients with MCUP and no standard indications for diagnostic colonoscopy. Furthermore, the cost to diagnose one additional colon primary was very high. Those with colon cancer had advanced disease and were unable to benefit from targeted therapy. Routine colonoscopy for MCUP cannot be recommended at present.

Diagnostic Yield of Endoscopy for Weight Loss: Results of a Comparative Cohort Study vs. Non-Weight Loss Controls

Background: Gastroenterologists are commonly asked to perform pan-endoscopy in patients with weight loss. This request is based on historical series revealing a high prevalence of GI causes of involuntary weight loss (Lankisch J Int Med 2001). However, in the absence of specific GI symptoms or signs, such as bleeding, dysphagia, diarrhea, constipation, or anemia, the yield of endoscopy may be low and its appropriateness unclear. We studied patients referred for endoscopy because of weight loss, and evaluated the yield of endoscopy vs. non-weight loss controls. Methods: We performed a retrospective analysis of patients referred to the endoscopy unit of a University-based VA medical center from 2000-2010 with a primary indication of weight loss. We excluded patients who would otherwise qualify for endoscopy regardless of weight loss, such as those with positive fecal occult blood, iron deficiency, previous imaging study with a colonic abnormality, familial GI cancer syndrome, GI bleeding, or prior colon cancer. Although we allowed for diarrhea and constipation, we performed a sensitivity analysis in which this sub-group was also excluded. We gathered data on patient characteristics, duration and amount of weight loss, body mass index (BMI), and endoscopy findings. We calculated the proportion of cases in which an explanatory luminal diagnosis was identified by endoscopy, and compared this to the yield in 2 age and sex-matched control groups: 1) group undergoing screening colonoscopy; and 2) group undergoing diagnostic colonoscopy for a non-weight loss indication. We conducted separate analyses for colonoscopy and upper endoscopy (EGD). We employed chi-squared for pairwise comparisons. Results: There were 95 colons and 61 EGDs identified (mean age=65; 93% male; BMI=23). Patients lost a mean of 22 lbs over a 9 month average period. The Figure reveals the diagnostic yield of the study groups. Two of the 95 colonoscopy patients (2.1%) had primary colon cancer and 3 had colitis as the explanation for weight loss. The screening colonoscopy control group resulted in no colon cancers, and the diagnostic colonoscopy control group revealed 4 cancers (4.2%) and 1 case of colitis (1.1%). After excluding diarrhea and constipation, there was 1 case of colitis (1.8%) and no cancer. There were no significant differences among any pair-wise comparisons. Of the EGD cases, there was 1 gastric cancer (1.6%); the non-weight loss control EGDs revealed 2 gastric cancers (3.3%) (p=NS). Conclusion: In the absence of other GI “red flag” features, patients with weight loss rarely harbor an underlying luminal disease; there is no difference in diagnostic yield of endoscopy vs. age and sex-matched controls. These data suggest that pan-endoscopy for weight loss is unlikely to be cost-effective in the absence of other concurrent indications for a GI procedure.

Prognostic significance of high‐grade dysplasia in colorectal adenomas

Colonoscopy to detect and remove polyps has contributed to a reduction in colorectal carcinoma. Three-year follow up is recommended for patients considered to be at high risk (at least three adenomas, adenoma ≥ 1 cm, villous or high-grade features). Our study focused on patients diagnosed with high-grade dysplasia with regard to initial management and follow up. A search of patients who had had endoscopic removal of a high-grade adenoma was carried out. Patients with the following were excluded: follow up of < 1 year, polyposis syndromes, prior colon cancer and a diagnosis of adenocarcinoma within 6 months following initial diagnosis. Eighty-three patients treated between 1999 and 2007 for high-grade dysplasia (HGD) in a colorectal adenoma were identified. Over a median follow-up period of 4 years, 53 (64%) developed further adenomatous polyps. Among these, 7% had an adenoma with HGD or an adenocarcinoma. In all these patients, the initial high-grade adenoma was > 1 cm in diameter. Initial follow-up colonoscopy was performed on average 7 months following the initial diagnosis. Ten per cent of patients underwent prophylactic segmental resection, and 6% received argon laser therapy. The study demonstrates that patients who have a colorectal adenoma > 1 cm with HGD may be at high risk of developing further adenomas with HGD or carcinoma. Close follow up is warranted.

Colon Cancer Miss Rates in Medicare Population

Purpose: Based on the national polyp study, colonoscopy is widely used for colon cancer screening. However, the sensitivity of colonoscopy for colon cancer screening has not been studied in a large population base outside academic centers in the United States. Aim: To study the miss rates and the factors influencing the sensitivity of colonoscopy in the diagnosis of colon cancer in the US. Methods: Inclusion criteria: National sample of 5% Medicare data in 2005-2006 was used to identify patients ≥69 years old who underwent inpatient surgery for colon cancer. Only patients who were enrolled in both Part A and B and were not members of HMO in 4 years before cancer surgery and had a colonoscopy in the 3 years before the surgery were included. This algorithm had sensitivity of 53.8% and PPV of 95%. Definition of missed cancer: Patients diagnosed with colon cancer between 6 and 36 months after the most recent colonoscopy. Exclusion criteria: Patients with prior colon cancer history, inflammatory bowel disease, familial colon cancer syndromes or who received a flexible sigmoidoscopy between the date of last colonoscopy and a month before cancer surgery were excludedResults: A total of 1567 patients were identified to have undergone inpatient surgery for colon cancer during 2005-2006. The rate of missed cancer was 5.7% (n=89). The risk factors for missed cancer were history of diverticular disease [OR 8.45 (95% CI 5.27-13.56)], colonoscopy done in office [OR 2.35 (p<0.035)] and not having previous polypectomy [OR 14.64 (p<0.0001)]. There was no difference found in sensitivity for right (proximal to splenic flexure) and left sided cancers nor any geographical variation was found. Age, sex, race and volume of procedures done by the endoscopist did not influence the sensitivity of colonoscopy for colon cancer.Limitation: Because of lack of access to endoscopy reports, it is unclear whether these were all missed cancers or new cancers that developed in the interim. Conclusion: Colonoscopy has around 95% sensitivity for colon cancer. Similar to the data from other countries, diverticular disease, office procedures and no prior polypectomy are risk factors for missed cancer in United States. However, there is no significant difference in diagnosis of right sided vs. left sided cancers.

Patient Preferences for Colon Cancer Screening Tests

Intro: Recent data suggests that only about 60% of patients over age 50 have had colon cancer screening. Since colon cancer is the third leading cause of cancer-related deaths in the U.S. this is an important issue. Understanding patient preferences is necessary for patient-centered care and patient satisfaction. Taking into account patient preferences may improve colon cancer screening rates. We have designed a novel computerized educational tool and patient preference survey utilizing Maximum Differences Scaling (Max Diff, Sawtooth Software), an effective tool for evaluating consumer product preferences. Methods: This is a prospective, non-randomized pilot study. We collected self-reported demographic information from 92 patients age 50 and above recruited from primary care clinics at a VA Hospital and a University based clinic. Patients who had a history of colon cancer, lacked capacity to give verbal consent or could not read and write English were excluded. The investigators (DB, AI) helped participants navigate the computer educational tool and survey. The survey compared characteristics of the following tests: fecal occult blood testing (FOBT), sigmoidoscopy, colonoscopy, CT colonography and colon capsule. Results: We interviewed 92 subjects; mean age was 65.5 (SD 8.99); 88% male; 17.5% were Black; and 6.5% were Hispanic; 59% reported having greater than high school education; 73.4% reported good to excellent overall health. 88% had undergone prior colon cancer screening and 26% had refused colon cancer screening at some point in the past. Of the patients who had refused screening, 46% didn't like the test offered, 26% of patients didn't realize screening was important, 4% said the timing was bad, 4% couldn't get a ride, 21% had other reasons. After taking the preference survey, 96.7% reported they were willing to have screening if they could choose the test. The majority (63%) indicated that they preferred colonoscopy, however a significant proportion would prefer a different test; 23% chose colon capsule, 10% CT colonography, 4% FOBT and none chose sigmoidoscopy. Respondents felt the computer survey was easy to complete (94.6%) and that the program helped them understand the testing options (96.7%). Conclusions: Patients have different preferences for colon cancer screening tests. Offering multiple testing options and incorporating patient preferences into clinical practice using a Maximum Difference Scaling survey may improve screening rates.

Aspirin Should Not Be Promoted for Colon Cancer Prevention: Counterpoint

There is little question that aspirin can decrease the risk of large bowel cancer. A large number of observational studies in humans, both case-control and cohort, consistently show a strong protective effect of aspirin ([1][1]). Importantly, three randomized controlled trials show that aspirin

Colon cancer metastasis to small bowel detected by capsule endoscopy

A 78 year-old male with history of colorectal carcinoma, diagnosed in 1997, surgically removed with negative lymph nodes. Four years later the patient developed a local recurrence without any metastasis, with positive lymph nodes. The patient underwent radiation and chemotherapy. He remained asymptomatic with normal lab. work up until last year when he presented with intermittent bouts of crampy abdominal pain and constipation, experiencing relief with self induced vomiting. These episodes grew more frequent and the patient then presented a drop in his hgb from 13 to 11.8g/dl with melena. At this time an EGD and colonoscopy were normal. Abdomino-pelvic CT Scan was also non diagnostic as was an UGIS's. After intestinal obstruction was excluded, capsule endoscopy was performed. The study showed a clear area of active oozing of blood associated to an ulcerated mass at the jejunum. The patient was refered for surgery. The only finding was the lesion originally detected by the capsule at the jejunum. It was resected followed by an end to end anastomosis. The histologic analysis of the mass revealed it to be a metastatic lesion from prior colon cancer, with spread limited to the small bowel. This is to our knowledge the first case of a colonic metastatic solitary lesion to the small bowel detected by the M2A endoscopic capsule. This finding shows that wireless endoscopy is an invaluable tool in cases of obscure GI bleeding as well as in chronic abdominal pain. It is noteworthy that in this case that the patient had two prior abdominal surgeries, and the possibility of partial small bowel obstruction secondary to adhesions was entertained. There is still controversy regarding the use of endoscopic capsule in that setting, but we think that the only absolute contraindication would be a patient who refuses to have surgery or who has serious contrindications for surgery should it become necessary to remove a capsule retained in an obstructed bowel. In this case, the prompt diagnostic approach with the M2A made early intervention possible due to the finding of the ulcerated mass where all other modalities were non-diagnostic. Without the use of the capsule endoscope, this patient may have gone undiagnosed for a long time allowing for progression of the metastasis. In conclusion, if there is a clinical suspicion that small bowel pathology is causing the patient's problem, M2A endoscopic capsule technology should be used more frequently and liberally in the early phases of the work up.