Medicine For People!

September 2010

This is the second in a series about colon cancer. Last month I explained that colon cancer develops in two different ways. It either arises directly from the colon wall or from starts out as a polyp. Polyps may disappear on their own, remain unchanged and benign, or advance to cancer. I also suggested that we maintain our perspective and place the threat of colon cancer in its proper place, ahead of all other cancers and behind heart disease.

As of this moment, colonoscopy holds the media's eye as the test to prevent colon cancer. In this newsletter series, I hope to overturn that view.

Colonoscopy: Screening or Diagnostic

Let me be clear that I do not argue against colonoscopy as a diagnostic tool. Alongside other tools, not least the mind of the doctor, it helps us determine why people have certain abdominal symptoms.

Besides diagnostic colonoscopy, however, we have screening colonoscopy, the same procedure used in people with no symptoms. From now on, that's our subject.

Screening colonoscopy

Screening by colonoscopy has been widely promoted. On the Internet you can even see a video of news anchor Katie Couric laughing and joking her way through her first colonoscopy. The procedure can find unsuspected cancer before symptoms occur, often at a stage in which the cancer can be easily removed. It may uncover previously unknown conditions such as diverticulosis.

Many cancers arise from polyps, which can be removed during colonoscopy. Most will be benign, but some will have the capacity to become cancer. Colonoscopy, unique among screening tests, not only identifies otherwise hidden early cancer but, by removing the polyps or early tumors, also treats or prevents it.

These are the reasons many physicians recommend this test. How can one argue against it?

Strangely enough, some very knowledgeable people do. Columbia University Medical Center doctors went on record this summer, "raising questions about the effectiveness of colonoscopies, which may be no better at preventing deaths from colon cancer than other, less arduous screening methods."

The US Preventive Services Task Force does not find screening colonoscopy superior to the two-stage iFOBT-colonoscopy program 1 endorsed in this series of newsletters.

Not quite so public, but still available for your inspection in a 2005 medical journal, Gastroenterology, gasteroentologist David Ransohoff, professor at the University of North Carolina and authority on colonoscopy screening, argued that we were overselling the value of screening colonoscopy. He pointed out that no randomized trials have evaluated the direct benefit of screening colonoscopy on colon cancer incidence or mortality.2 3 He presented evidence that the prevention rate failed to reach the 90 percent claimed, but was probably closer to 60 or 70 percent4

As an example, in a recent study, patients 50 years of age or older due for a screening colonoscopy were scoped with either the traditional colonoscopy or a newer scope designed to look behind the folds of the colon more readily. In total, 172 polyps found were removed and analyzed. The same day the patients were scoped again, using whichever type of scope was not used the first time. No extra time was allowed for the second procedure, yet repeat inspection of the colon on the same day found another 66 polyps. That means that about 28 percent of all the polyps found were missed the first time around. Though no cancer was missed, the miss rate for the polyps of most concern, those over nine millimeters in size, was 14 percent.

Would there have been other cancers found with a third colonoscopy, or an entirely different test? Possibly, but no one knows whether there would be enough to make further investigation worthwhile. More details here.

Certainly, other studies show that colonoscopy may miss between 6 - 12 percent of cancers, while it picks up about 90 percent.5 How does that 90% square with estimates that colonoscopy prevents much less than 90 percent of colon cancer? First, there no standard way of doing such studies and calculating the results, and second, any screening test looks at just one point in time. A colonoscopy every ten years may pick up most of the cancers present at that time, but won't detect cancer arising between screenings. And if the colonoscopy is missing some 28 percent of polyps, some of those polyps are going to misbehave before the ten years runs out.

Read more in the Appendix

Before we go further, do I think that colonoscopy is that poor a test? No, I do not, as you'll see further along. While colonoscopy may miss some cancers, it picks up many others. The take-home message is, you can't take your laxatives, plunk down your money, and think you've dodged the bullet.

Screening Colonoscopy in its second decade

In the 1980s the screening test of choice for colon cancer was the flexible sigmoidoscopy, in which a flexible tube, much like a colonoscope but shorter, was advanced through the rectum and sigmoid colon into the descending, or left, colon. Most colon cancer arose in that section of the colon. As time passed, though, surgeons noted an increase in colon cancer in the ascending or right colon, beyond the reach of the sigmoidoscope. Voices were raised as to the advisability of colonoscopy, so without proof this would actually reduce death rate at an acceptable cost (in both time, money, and complications), doctors switched from the short sigmoidoscope to the longer colonoscope. The dreaded pre-procedure prep was instituted, the anesthesia requirements escalated, insurance companies increased their reimbursements, and off we went.

Complications

While we like to say that colonoscopy is a safe procedure with a minimal complication rate, those complications do add up when everyone over the age of 50 gets several colonoscopies over the years. One every ten years isn't too bad, but since most people harbor a polyp or two, they may wind up on an every three to five year schedule.

What are the chances something will go wrong?

The authoritative estimates6 are that only about two people per thousand experience serious complications.7 I said estimate, because rigorous safety evaluations just do not exist.8

Please forgive the detail that follows. As I write this I think of a scene in Duke Hospital in 1968, where as a medical student I watched as a five year old child died in the catheterization laboratory. The child had a life-threatening heart valve defect that the pediatric team hoped to be able to repair but needed the images from this test if they were to succeed. Before the procedure they had told the mother how safe this procedure was, how rarely something went wrong, but now something had. The mother didn't take it well, crying loudly in the hallway of the pediatric ward. The resident physician's requests not to disturb the other parents fell on distressed and deaf ears.

So, similarly, things rarely go wrong with colonoscopy. When they do, the most common problem is perforation of the colon, which can cause G.I. bleeding and even death. Another complication we call "ileus," a painful and dangerous condition where the bowel stops moving food and gas through. Ileus is treated by withholding fluids and suctioning the GI tract through a tube through the nose or mouth. Another complication is irregular heartbeat and heart failure. A recently published estimate from an analysis9 of Medicare claims data for a group of 118,000 people from 2001 to 2005, aged 66 to 95, turned up numbers for these complications.

Events per 1000 people within 30 days of outpatient colonoscopy


Control group

Screening colonoscopy, no polyp removal

Colonoscopy with polyp removal

Perforation, GI bleeding, transfusion

about 2 or 3 in each group

10

Paralytic ileus, severe pain, nausea, vomiting, dehydration

about 6 in each group

13

Irregular heartbeat, heart failure

about 14 in each group

23

To get into the above table, people had to have the above problems severely enough to end up in the hospital or emergency department. Most of those excess complications, about 20 per 1000 or 2%, occurred following polyp removal. Read more here.

Adverse events, especially following polypectomy, occurred much more frequently in people with diabetes, chronic lung disease, heart failure, atrial fibrillation, or stroke. Adverse events were over twice as frequent in people over age 85 as they were in those under 70. They are higher for women. Read more here, and on rarer complications in the endnotes10 11 12 13 14.

Shortcomings of Colonoscopy as screening test

In a moment, I'll tell you several ways in which physicians are working to improve this test, but let me just summarize here the problems we know we need to solve.

  • You have to do a lot of colonoscopies to find one cancer. If you take a population of healthy people over the age of fifty, you have to do 77 colonoscopies to find one cancer.15
  • Generally well people are reluctant to undergo the procedure. Colonoscopies are pricey and no fun16. The current program corrals just 40 or 50 percent of Americans over the age of 50.17
  • Doctors vary in competence at this procedure. Quality control18 is difficult19.
  • Twenty to twenty-five percent of the time, once the $1500 procedure is underway, the doctor finds that the laxatives did not clean20 out the bowel properly21 22, decreasing the ability to find early cancer. In very rare cases the bowel prep has led to deaths23 and lesser complications.24
  • When a polyp is found on a screening colonoscopy, patients sometimes undergo excessive further surveillance. As one researcher in this field concluded25

"Some surveillance colonoscopy seems to be inappropriately performed and in excess of guidelines, particularly for hyperplastic polyps and low-risk lesions such as a small adenoma."

You can read more about what to expect following a polyp here.

  • We do not have the money or the medical workers to provide colonoscopy to everyone we advise it for. With so many worthwhile medical interventions available, with the considerable prices we can't always afford, we need to budget carefully.

The Future of Colonoscopy

Shortcomings can always be overcome. Colonoscopy technology advances. Newer scopes will become more flexible and more easily guided through all the bends of the large intestine, with less force on the surrounding organs and tissues, with advanced image processing26 to allow safer, more comfortable and more accurate examination.27

Some people require screening colonoscopy

Some families carry a genetic predisposition to very high rates of colon cancer, and other people face such a high risk of colon cancer that colonoscopy screening seems our best bet, here in 2010. For those families and those people, the benefits of colonoscopy outweigh the risks.

Summary

Authorities in this field are beginning to question the wisdom of colonoscopy for all healthy people over the age of 50.

The strongest argument for screening colonoscopy compares it to no screening at all. In such a scenario, under the more optimistic assumptions, if you look 1000 people 60 years old, of whom five were slated to die of colon cancer in the next ten years, something in the range of three lives will be saved with screening colonoscopy as currently done. About 2 percent of those people will require an emergency department visit, or less often hospitalization, as a result.

I advocate a two-stage screening program. Most people qualify for a stool test to eliminate most of those 1000 colonoscopies. Such a program should save at least as many lives as currently we do. That less-expensive, less-invasive test will tell you whether you actually need a screening colonoscopy. That test goes by the alien-seeming name of iFOBT.

More next month!

Appendix

Endnotes

1 USPFTF recs 627.full.pdf

Screening for Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement

Description: Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for colorectal cancer. Methods: To update its recommendation, the USPSTF commissioned 2 studies: 1) a targeted systematic evidence review on 4 selected questions relating to test characteristics and benefits and harms of screening technologies, and 2) a decision analytic modeling analysis using population modeling techniques to compare the expected health outcomes and resource requirements of available screening modalities when used in a programmatic way over time. Recommendations: The USPSTF recommends screening for colorectal cancer using fecal occult blood testing, sigmoidoscopy, or colonoscopy in adults, beginning at age 50 years and continuing until age 75 years. The risks and benefits of these screening methods vary. (A recommendation) The USPSTF recommends against routine screening for colorectal cancer in adults 76 to 85 years of age. There may be considerations that support colorectal cancer screening in an individual patient. (C recommendation) The USPSTF recommends against screening for colorectal cancer in adults older than age 85 years. (D recommendation) The USPSTF concludes that the evidence is insufficient to assess the benefits and harms of computed tomographic colonography and fecal DNA testing as screening modalities for colorectal cancer. (I statement)

Ann Intern Med. 2008;149:627-637.

Evidence is adequate to estimate the harms of colonoscopy. In the United States, perforation of the colon occurs in an estimated 3.8 per 10 000 procedures (4). Serious complications—defined as deaths attributable to colonoscopy or adverse events requiring hospital admission, including perforation, major bleeding, diverticulitis, severe abdominal pain, and cardiovascular events—are significantly more common, occurring in an estimated 25 per 10 000 procedures

Value declines p age 75 "lead time between the detection and treatment of colorectal neoplasia and a mortality benefit is substantial, and competing causes of mortality make it progressively less likely that this benefit will be realized with advancing age."

2 Current Gastroenterology Reports 2009, 11:406–412

3 Colonoscopy editorial 1.pdf

GASTROENTEROLOGY 2005;129:1815

Have we oversold colonoscopy?

4 Ann Intern Med. 2009;150:1-8.

Association of Colonoscopy and Death From Colorectal Cancer

Background: Colonoscopy is advocated for screening and prevention of colorectal cancer (CRC), but randomized trials supporting the benefit of this practice are not available. Objective: To evaluate the association between colonoscopy and CRC deaths. Design: Population-based, case–control study. Setting: Ontario, Canada. Patients: Persons age 52 to 90 years who received a CRC diagnosis from January 1996 to December 2001 and died of CRC by December 2003. Five controls matched by age, sex, geographic location, and socioeconomic status were randomly selected for each case patient. Measurements: Administrative claims data were used to detect exposure to any colonoscopy and complete colonoscopy (to the cecum) from January 1992 to an index date 6 months before diagnosis in each case patient and the same assigned date in matched controls. Exposures in case patients and controls were compared by using conditional logistic regression to control for comorbid conditions. Secondary analyses were done to see whether associations differed by site of primary CRC, age, or sex. Results: 10 292 case patients and 51 460 controls were identified; 719 case patients (7.0%) and 5031 controls (9.8%) had undergone colonoscopy. Compared with controls, case patients were less likely to have undergone any attempted colonoscopy (adjusted conditional odds ratio [OR], 0.69 [95% CI, 0.63 to 0.74; P 0.001]) or complete colonoscopy (adjusted conditional OR, 0.63 [CI, 0.57 to 0.69; P 0.001]). Complete colonoscopy was strongly associated with fewer deaths from left-sided CRC (adjusted conditional OR, 0.33 [CI, 0.28 to 0.39]) but not from right-sided CRC (adjusted conditional OR, 0.99 [CI, 0.86 to 1.14]). Limitation: Screening could not be differentiated from diagnostic procedures. Conclusion: In usual practice, colonoscopy is associated with fewer deaths from CRC. This association is primarily limited to deaths from cancer developing in the left side of the colon.

Colonoscopy results .pdf

5 "pooled adenoma miss rate fluctuates around 22% (19–26%) [23] . With regard to CRC, miss rates range from 2 to 6% [24] . Digestion 2007;76:20–25 Colonoscopy screen.pdf

6 The incidence of bleeding, perforation, and cardiorespiratory complications was 0.22%, 0.03%, and 0.06%, respectively. Dtsch Arztebl Int 2008; 105(24): 434–40

7 "colonoscopy is generally safe, it is still an invasive procedure with a 0.2% rate of serious complications (13, 19)—10 times higher than for any other commonly used cancer screening test. Repeated examinations over time may incur a substantial cumulative rate of complications" Ann Intern Med. 2009;150:50-52.

8 Ann Intern Med. 2009;150:849-857.

9 Ann Intern Med. 2009;150:849-857.

10 Surg Endosc (1997) 11: 71–73

11 Acute pancreatitis and ileus post colonoscopy.

Ko HH, Jamieson T, Bressler B.

Can J Gastroenterol. 2009 Aug;23(8):551-3. 

Department of Medicine, University of British Columbia, Vancouver, Canada.

Postpolypectomy bleeding and perforation are the most common complications of colonoscopy. A case of acute pancreatitis and ileus after colonoscopy is described. A 60-year-old woman underwent a gastroscopy and colonoscopy for investigation of iron deficiency anemia. Gastroscopy was normal; however, the colonoscope could not be advanced beyond the splenic flexure due to a tight angulation. Two polypectomies were performed in the descending colon. After the procedure, the patient developed a distended, tender abdomen. Bloodwork was remarkable for an elevated amylase level. An abdominal x-ray and computed tomography scan showed pancreatitis (particularly of the tail), a dilated cecum and a few air-fluid levels. The patient improved within 24 h of a repeat colonoscopy and decompression tube placement. The patient had no risk factors for pancreatitis. The causal mechanism of pancreatitis was uncertain but likely involved trauma to the tail of the pancreas during the procedure. Our patient developed ileus, likely secondary to pancreatitis. The present case is the first report of clinical pancreatitis and ileus associated with colonoscopy.

12 Vertebral venous air embolism: an unusual complication following colonoscopy: report of a case.

Chorost MI, Wu JT, Webb H, Ghosh BC.

Dis Colon Rectum. 2003 Aug;46(8):1138-40. 

Department of Surgery, State University Health Science Center at Brooklyn, Brooklyn, New York 11209, USA.

Although fiberoptic colonoscopy has gained wide popularity as a diagnostic and therapeutic tool, there remains an inherent complication rate following colonoscopic evaluation. Endoscopically induced bowel perforation and uncontrolled bleeding often necessitate immediate surgical intervention. Another often-unrecognized complication is the introduction of air into the vertebral venous system. A case of vertebral venous air embolism after routine diagnostic colonoscopy is reported with a review of current literature

13 GASTROINTESTINAL ENDOSCOPY Volume 63, No. 4 : 2006 pg 730

14 Mesenteric panniculitis following colonoscopy, polypectomy, and epinephrine injection.

Lee KJ, Ehrenpreis ED, Greenberg J, Yang GY, Horowitz J.

Endoscopy. 2010;42 Suppl 2:E44-5. Epub 2010 Feb 15. 

15 Of about 55,000 people screening in the German province of Bavaria in 2006, 1.3% were found to have cancer of the colon. Deutsches Ärzteblatt InternationalDtsch Arztebl Int 2008; 105(24): 434–40 colonoscopy rate quality.pdf

16 Deutsches Ärzteblatt InternationalDtsch Arztebl Int 2008; 105(24): 434–40 colonoscopy rate quality.pdf

17 Gilbert Welch, MD Should I be tested for cancer? pg 199 note 2

18 "continuous quality improvement (CQI) programs must be implemented to achieve desirable outcomes. Although professional societies have recommended such CQI programs [27] , few endoscopic centers have followed the guidelines" Digestion 2007;76:20–25 Colonoscopy screen.pdf

19 Colorectal Cancer Screening by Colonoscopy – Current Issues

Digestion 2007;76:20–25

Of all colorectal cancer screening methods, colonoscopy used as a primary screening tool is both the most promising and the most discussed in the current literature. Several countries have introduced colonoscopic screening on a national scale, but many issues still require further research. The practicality of using colonoscopic screening can be questionable given the huge target population, which requires a great increase in endoscopic resources. Limiting the target population by shifting the use of colonoscopy from low-risk to high-risk groups is a valid option. The quality of colonoscopy related to the individual colonoscopist's skill has become a surprisingly considerable problem, and it is obvious that continuous quality improvement programs need to be established. The accuracy of detecting important colorectal lesions is also still influenced by the old problem of cleansing the large bowel, and further research would be welcome. Technological improvements in current endoscopic equipment will hopefully increase the diagnostic yield of colonoscopy and eventually strengthen its use.

20 "certain patient characteristics, suitable for a screening population, are independently associated with poor colonic cleansing: male gender, increasing age, usage of tricyclic antidepressants, a history of stroke or liver cirrhosis, and late colonoscopy starting times" Digestion 2007;76:20–25 Colonoscopy screen.pdf

21 Digestion 2007;76:20–25 Colonoscopy screen.pdf

22 Cscope bowell prep.pdf

Impact of colonoscopy preparation quality on detection of suspected colonic neoplasia

Background: Suboptimal bowel preparation for colonoscopy can lead to missed colonic lesions. The aim of this study was to describe the impact of preparation quality on detection of suspected colonic neoplasia. Methods: Data from the Clinical Outcomes Research Initiative national endoscopic database for the period January 1, 2000 to December 31, 2001, were analyzed. Patient demographics, quality of preparation, and colonoscopy findings were abstracted from the database. Results: Overall, 93,004 colonoscopies with adequate documentation were reviewed. Preparation was adequate for 71,501 (76.9%) of these procedures. On multivariate analysis, preparation adequacy was associated with colonic lesion detection, odds ratio (OR) 1.21: 95% CI [1.16, 1.25]. Adequate preparation demonstrated a closer association with identification of nonsignificant lesions (polyps .9 mm), OR 1.23: 95% CI [1.19, 1.28], compared with significant lesion detection (mass lesion, polyps >9 mm), OR 1.05: 95% CI [0.98, 1.11]. Conclusions: Bowel preparation is inadequate for almost a quarter of patients undergoing colonoscopy. These results suggest that inadequate preparation quality only hinders detection of smaller lesions, while having negligible impact on detection of larger lesions.These results should be confirmed in prospective studies.

Gastrointest Endosc 2003;58:76-9.

23 Adverse renal and metabolic effects associated with oral sodium phosphate bowel preparation.

AB - Colorectal cancer can be prevented by the removal of adenomatous polyps during screening colonoscopy, but adequate bowel preparation is required. Oral sodium phosphate (OSP), an effective bowel purgative, is available over the counter and requires a substantially lower volume than polyethylene glycol-based preparative agents. Accumulating reports implicate OSP in electrolyte disturbances as well as acute kidney injury (AKI) in a syndrome termed phosphate nephropathy (a form of nephrocalcinosis). Despite published case reports and case series, the actual incidence, risk factors, and natural history of phosphate nephropathy remain largely undefined. Several recent observational studies have provided new information on these important issues while supporting a link between OSP and acute phosphate nephropathy as well as the development of chronic kidney disease in elderly patients, many of whom had a normal serum creatinine at the time of OSP ingestion. This review summarizes current knowledge about the renal complications of OSP, risk factors for its development, and the pathophysiology of acute and chronic kidney damage in nephrocalcinosis.

Clin J Am Soc Nephrol 2008 Sep;3(5):1494-503

24 Ann Intern Med. 2009;150:849-857.

25 too much cscope 264.full.pdf

Colorectal Surveillance after Polypectomy

Pauline A. Mysliwiec, MD, MPH;

Background: Increasing use of colonoscopy for colorectal cancer screening and surveillance of colorectal adenomas after polypectomy has given rise to concerns about the availability of endoscopic resources in the United States. Guidelines recommend surveillance after polypectomy at 3 to 5 years for a small adenoma, and follow-up is not advised for hyperplastic polyps. The intensity of physicians' surveillance is largely unstudied. Objective: To survey practicing gastroenterologists and general surgeons about their perceived need for the frequency of surveillance after polypectomy, to compare survey responses to practice guidelines, and to identify factors influencing their recommendations for surveillance. Design: Survey study conducted by the National Cancer Institute. Setting: A nationally representative study of physicians in the United States. Participants: 349 gastroenterologists and 316 general surgeons. Measurements: Questionnaires mailed in 1999 and 2000 assessed physicians' recommendations for surveillance after polypectomy in asymptomatic, average-risk patients. Results: Response rates were 83%. Among gastroenterologists (317 of 349) and surgeons (125 of 316) who perform screening colonoscopy, 24% (95% CI, 19.3% to 28.7%) of gastroenterologists and 54% (CI, 44.9% to 62.5%) of surgeons recommend surveillance for a hyperplastic polyp. For a small adenoma, most physicians recommended surveillance colonoscopy and more than 50% recommended examinations every 3 years or more often. Physicians indicated that published evidence was very influential in their practice (83% [CI, 78.8% to 87.2%] of gastroenterologists and 78% [CI, 72.5% to 86.8%] of surgeons). By contrast, only half of respondents reported that guidelines were very influential. Limitations: The study was based on physicians' self-reported practice patterns. Results may overestimate or underestimate the performance of surveillance colonoscopy. Conclusions: Some surveillance colonoscopy seems to be inappropriately performed and in excess of guidelines, particularly for hyperplastic polyps and low-risk lesions such as a small adenoma. These results suggest unnecessary demand for endoscopic resources.

Ann Intern Med. 2004;141:264-271.

26 Currently available but in the development stage are narrow band imaging colonoscopy [http://www.wjgnet.com/1007-9327/full/v16/i3/WJG-16-392-g001.htm ] and dye techniques [http://www2.cochrane.org/reviews/en/ab006439.html ].

27 Understanding the risks of colonoscopy: looking forward

GASTROINTESTINAL ENDOSCOPY Volume 69, No. 3 : Part 2 of 2 : 2009 pg 672

story: 

Medicine for People! is published by Douwe Rienstra, MD at Port Townsend, Washington.