Adenoma Detection Rates In Obese And Smoking Patients

At left, stained adenoma under the microscope.

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8273894

Here is a study showing higher detection rates for adenomas and serrated adenomas in obese and smoking patients undergoing colonoscopy. Adenomas are benign tumors that - if left in the colon - have a probability of turning into full-fledged cancer (e.g., for a given polyp, could be a 10% chance in 10 years). Therefore, when detected in endoscopic screening, adenomas are typically removed.  The more adenomas, the greater the chance for cancer, so it is not surprising that obese and smoking individuals tend to have higher rates of colorectal cancer, since they are developing more of the pre-cancerous adenomas.

This again underscores the fundamental importance of maintaining a healthy bodyweight and to refrain from smoking.  If you are already at a normal weight and do not smoke, great, keep it up; if not, lose weight and make every attempt to quit smoking.  In general people associate obesity with diabetes and smoking with lung cancer, and those associations are indeed correct; however, there are many, many diseases associated with both obesity and smoking - including colorectal cancer - so the health ramifications of weight control and no smoking are enormous.

Colonary Concepts Update

I previously wrote about the company Colonary Concepts and their development of a more palatable colonoscopy prep, something which from personal experience I can say is sorely needed. I found some updated information from their website that I reproduce below. The good news: they’ve gotten to the stage of a Phase 3 clinical trial, and their product may be ready for launch by early 2019. That would be a welcome (and long overdue!) development.

Where are you in the development process?

Our colon prep candidate is currently entering our Phase 3 clinical trial, following a successful Phase 1 at the Dartmouth-Hitchcock Medical Center, and a successful Phase 2 at the Indiana University Health and Dartmouth-Hitchcock Medical Centers.

Our constipation technology is currently in a Phase 1 clinical trial, targeting completion in 1H’17.

What makes your technology so different?

Instead of fasting, and needing to consume a large volume of white, viscous, unpalatable fluid, our approach features simple, tasty bars and beverages that you consume during the 24 hours before the procedure.

When will your products reach the market?

The FDA regulates colon prep products, and we’re entering our Phase 3 trial. Forecasting is tricky, but our target is to secure approvals and launch by early 2019.

Where will I be able to purchase the colon prep kits?

When our products are FDA-approved, we expect that your physician will prescribe them, just as conventional prep kits are prescribed today.

New Colonoscopy Prep In Testing

Here is a possibly good news: better-tasting colonoscopy preps are under development and are in the testing stage.  My own personal experience has been that the prep I used ranks among the most foul-tasting things I have ever consumed, and I honestly couldn't finish every bit of it toward the end.  Luckily, taking 95% of it was sufficient for a good preparation, but I really struggled to keep it down and was always on the verge of throwing up.  If these new preps under development solve that problem, that's great, and perhaps the competition will stimulate existing brands to attempt some much-needed improvement.  And if this raises adherence to CRC screening, so much the better.

Another Possible Non-Invasive CRC Screen?

Under study:

Background - Colorectal cancer is one of the main cause of cancer in the world. Colonoscopy is the best screen method, however the compliance is less than 50%. Quantification of human DNA (hDNA) in the feces may be a possible screen non-invasive method that is a consequence of the high proliferation and exfoliation of cancer cells.

Objective - To quantify the human DNA in the stools of patients with colorectal cancer or polyps.

Methods - Fifty patients with CRC, 26 polyps and 53 with normal colonoscopy were included. Total and human DNA were analyzed from the frozen stools.

Results - An increased concentration of hDNA in the stools was observed in colorectal cancer patients compared to controls and polyps. Tumors localized in the left side of the colon had higher concentrations of hDNA. There were no differences between polyps and controls. A cut off of 0.87 ng/mL of human DNA was determined for colorectal cancer patients by the ROC curve, with a sensitivity of 66% and a specificity of 86.8%. For polyps the cut off was 0.41, the sensitivity was 41% and the specificity 77.4%.

Conclusion - A higher concentration of hDNA had been found in colorectal cancer patients. The quantification of hDNA from the stools can be a trial method for the diagnosis of colorectal cancer.

Gut Microbiota As A Colorectal Cancer Screening Tool

A proposed method for non-invasive colorectal cancer screening is to test the gut microbiota from stool samples; this is interesting, but obviously requires more development.  One possibility is that a combination of different non-invasive screening tools - fecal occult blood, gene testing from fecal matter, microbiota together with risk factors, etc. - can together provide sufficient accuracy and precision to be an effective screening combination.  Or else, "bite the bullet" and get the colonoscopy.  The abstract of this paper is reproduced below.

Recent studies have suggested that the gut microbiome may be an important factor in the development of colorectal cancer. Abnormalities in the gut microbiome have been reported in patients with colorectal cancer; however, this microbial community has not been explored as a potential screen for early-stage disease. We characterized the gut microbiome in patients from three clinical groups representing the stages of colorectal cancer development: healthy, adenoma, and carcinoma. Analysis of the gut microbiome from stool samples revealed both an enrichment and depletion of several bacterial populations associated with adenomas and carcinomas. Combined with known clinical risk factors of colorectal cancer (e.g., BMI, age, race), data from the gut microbiome significantly improved the ability to differentiate between healthy, adenoma, and carcinoma clinical groups relative to risk factors alone. Using Bayesian methods, we determined that using gut microbiome data as a screening tool improved the pretest to posttest probability of adenoma more than 50-fold. For example, the pretest probability in a 65-year-old was 0.17% and, after using the microbiome data, this increased to 10.67% (1 in 9 chance of having an adenoma). Taken together, the results of our study demonstrate the feasibility of using the composition of the gut microbiome to detect the presence of precancerous and cancerous lesions. Furthermore, these results support the need for more cross-sectional studies with diverse populations and linkage to other stool markers, dietary data, and personal health information. Cancer Prev Res; 1–10. ©2014 AACR.

Possible Advances For Non-Invasive Colorectal Cancer Screening

For those who avoid the colonoscopy because of its invasive nature, here is a sample of some research in the field of detection.

BACKGROUND: 

Colorectal cancer (CRC) is one of the most common causes of cancer-related death around the world. MicroRNAs (miRNAs) are small non-coding RNAs that often are abnormally expressed in tumors. Detection and quantitation of miRNAs may provide information for the screening and early diagnosis of CRC.

OBJECTIVES:

The objective of our study was to determine whether fecal microRNAs (miR-29a, miR-145, miR-223, miR-224) could be used as biomarkers for the screening and early diagnosis of colorectal cancer.

METHODS: 

We carried out a retrospective analysis of the miRNAs in fecal samples from 80 CRC patients and 51 normal controls. The levels of 4 miRNAs (miR-29a, miR-145, miR-223, and miR-224) were quantitated using the SYBR Green miScript PCR system and 2 - Δ Δ Ct method.

RESULTS:

Our data indicated that the expression levels of miR-29a (p< 0.001), miR-223 (p< 0.001) and miR-224 (p< 0.001) are significantly lower in feces from CRC patients than these from normal volunteers, whereas their miR-145 levels are not significantly different (p= 0.59). Interestingly, the level of miR-29a (p< 0.001) in feces from individuals with rectum cancer is also significantly higher than that from patients with colon cancer.

CONCLUSION: 

The reduced expression of miR-29a, miR-223, and miR-224 in the feces from CRC patients could be an informative biomarker for screening and early diagnosis of CRC.

As recent posts have made clear, I have had my colonoscopy done, but I understand that many people want to avoid it. Any type of detection, even the blood stool tests, is better than nothing, and non-invasive testing continues to become more sophisticated.

Electronic Cleansing For Virtual Colonoscopy

A study says:

Electronic cleansing is an image post processing technique in which the tagged colonic content is subtracted from colon using CTC images. There are post processing artefacts, like: 1) soft tissue degradation; 2) incomplete cleansing; 3) misclassification of polyp due to pseudo enhanced voxels; and 4) pseudo soft tissue structures. The objective of the study was to subtract the tagged coloniccontent without losing the soft tissue structures. This paper proposes a novel adaptive method to solve the first three problems using a multi-step algorithm. It uses a new edge model-based method which involves colon segmentation, priori information of Hounsfield units (HU) of different colonic contents at specific tube voltages, subtracting the tagging materials, restoring the soft tissue structures based on selective HU, removing boundary between air-contrast, and applying a filter to clean minute particles due to improperly tagged endoluminal fluids which appear as noise. The main finding of the study was submerged soft tissue structures were absolutely preserved and the pseudo enhanced intensities were corrected without any artifact. The method was implemented with multithreading for parallel processing in a high performance computer. The technique was applied on a fecal tagged dataset (30 patients) where the tagging agent was not completely removed from colon. The results were then qualitatively validated by radiologists for any image processing artifacts.

This would seem to eliminate the need for extensive bowel cleansing; instead a dye would be consumed that would stain fecal matter, which could then be electronically subtracted from the image. Imaging ("virtual") colonoscopy is an alternative to the “real-life” version. Advantages being that it is less invasive and eliminates most of the potential side effects; negatives are that you would need regular colonoscopy if the imaging found something, and it is not offered at many locations. Then there is the radiation exposure, and whether or not you are comfortable with imaging accuracy vs. direct visualization (although some studies put accuracy as high, but those were with bowel cleansing).

Colonoscopy In Old Age: What Best to Measure?

A paper looked at the utility of having patients 75+ years old have colonoscopies, which goes against current recommendations.

Among patients 76-85 years old in the United States, colonoscopy use was associated with decreased risks of both distal and proximal CRC, with a smaller risk reduction in distal colon. Due to inherent limitations associated with our retrospective design, future prospective studies are needed to validate these findings.

It is not surprising that a cohort of patients getting colonoscopies - the "gold standard" for colon cancer screening - will exhibit decreased risk for that disease.

But the better measurement would have been - did these patients end up living significantly longer? Did they have better morbidity and mortality? Were there tangible long-term benefits to compensate for the risk (old patients have a higher risk of side effects from colonoscopy that those in the 50-70 age range), cost, and inconvenience of the procedure at such an advanced age?

The recommendations against colonoscopy for age 75+ is not because folks think there is no disease risk at that age, it is because the thought is that these patients will most likely die of other causes and that the cost:benefit ratio for this class of patients is skewed in the direction of greater cost and less benefit.

Superiority of Colonoscopy

While colonoscopy is not perfect and has some risks, and although alternatives like iFOBT are certainly useful and better than nothing, studies such as this remind us why colonoscopy remains the "gold standard" for colorectal cancer screening. Note that a certain percentage of iFOBT-negative patients not only had colorectal cancer, but had advanced forms of that disease. Also keep in mind that actual (as compared to virtual) colonoscopy also allows the endoscopist to remove polyps during the procedure, eliminating the possibility that those can become cancer later on.

The immunochemical faecal occult blood test (iFOBT) is a simple, non-invasive colorectal cancer (CRC) screening method for reducing CRC-related mortality. However, the sensitivity of iFOBT is imperfect and certain colonic neoplasms that require removal may be missed. The aim of this study was to investigate the incidence and characteristics of CRC in asymptomatic, iFOBT-negative patients who underwent opportunistic screening. A total of 919 subclinical patients (276 iFOBT-positive and 643 iFOBT-negative) in the health screening program of our hospital underwent total colonoscopy (TCS) within 2 years after iFOBT. The patients were divided into an iFOBT-positive and an iFOBT-negative group and the TCS findings were compared between the two groups. Although the incidence of advanced neoplasia (CRC, high-grade dysplasia, adenoma sized ≥10 mm and tubulovillous adenoma) was significantly higher in the iFOBT-positive group, these lesions were also found in 6.3% of iFOBT-negative patients. The lesions tended to be proximally located and non-protruding. In conclusion, screening with iFOBT remains clinically significant. However, colonoscopy is indispensable for reducing the incidence and mortality of CRC.

Mike's Colonoscopy

Screening for colorectal cancer, a major cause of morbidity and mortality in developed counties is important. It was time for me to get my colonoscopy, and after some procrastination, I followed in the footsteps of Larry the Cable Guy and Mark Cuban and got it done.

The procedure itself was uneventful, and much of my anxiety and fear about the procedure was, in my case, unwarranted. I admit that the prep was not pleasant. I didn’t mind so much the day before, with the liquid diet. I also didn’t mind too much being up half the night going to the bathroom, all the endless toilet visits. I had a sigmoidoscopy done years before, so I expected that.

The worst part for me was the repulsive taste of the laxative solution (in my case, Moviprep). It was difficult getting down and difficult keeping down. Following the suggestions of the hospital gastroenterology unit, I added Crystal Light to the solution; in retrospect, that may have been a mistake. The sickeningly sweet taste may have been a combination of the prep itself (which tastes bad) and the concentrated added lemonade flavoring. It may be a good idea to make sure the additive is necessary before using it. If you think you can stomach the laxative alone (some people can and some cannot), then that might be the more prudent approach.

There are other prep solutions of course, and some people use the pill option. But I have read that, in some cases, the pill options and related prep types can cause kidney damage, so I went for the more standard prep options. Keep in mind that these preps, even with insurance, are somewhat expensive, but are necessary (in some cases, patients are told they can use a cheaper MiraLAX-Gatorade prep option).

So, based on my experience, I agree with Larry and Mark and advise to follow your physician’s recommendations about getting your screening done. There is a low risk of complications from the procedure, but in the hands of a capable and experienced endoscopist, these risks will be very low – certainly lower than the risk of cancer.

For those more interested in technical details and some recent advancements in technique, I would recommend to watch YouTube videos from a well-known MD Anderson gastroenterologist, Dr. Raju, who has helped to refine advanced endoscopic techniques that I hope will one day be the standard of care here in the USA (and elsewhere).

Actionable: Follow the advice of your physician, get screened for colorectal cancer when appropriate, utilizing whatever method you and your physician agree on.