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Annals of Surgical Oncology 9:439-443 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

Colonoscopy in Asymptomatic Individuals With a Family History of Colorectal Cancer

K.N. Syrigos, MD, PhD, A. Charalampopoulos, MD, J.L. Ho, MD, A. Zbar, MD, FRCS, V.A. Murday, MD and R.J. Leicester, FRCS

From the Department of Clinical Oncology (KNS, AZ), Imperial College of Science Technology and Medicine, Hammersmith Hospital Campus, London, United Kingdom; and Colorectal Unit (AC, JLH, ZA), Department of Surgery, St. George’s Hospital, London, United Kingdom.

Correspondence: Address correspondence and reprint requests to: Konstantinos N. Syrigos, MD, PhD, Oncology Unit, 3rd Department of Medicine, Building Z, Sotiria General Hospital, Mesogion 152, 115 26 Athens, Greece; Fax: 3010-77-19-981; E-mail: knsyrigos{at}usa.net


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: This study was performed to evaluate the use of total colonoscopy as the optimal screening test in asymptomatic individuals with a family history of colorectal cancer (CRC).

Methods: Colonoscopy was performed in 249 asymptomatic individuals who had one or two first-degree relatives (FDRs) with CRC; individuals with three or more FDRs with CRC were excluded.

Results: Eighty-six colonic lesions were found in 51 individuals (51 of 249; 20.5%). Among these 51 subjects, 27 had neoplastic polyps (n = 38) and 29 had metaplastic polyps (n = 44). Although no invasive cancer was detected, in 14 individuals the lesions had a high malignancy potential because of their size and histopathology. We did not confirm a statistically significant difference in the incidence of neoplastic polyps according to the number of affected FDRs. Finally, the presence of metaplastic polyps was a very strong indication for the concomitant presence of metaplastic polyps (P < .0001).

Conclusions: Total colonoscopy is the optimal screening procedure for the examination of asymptomatic individuals with a family history of CRC.

Key Words: Total colonoscopy • Familial colon cancer • First-degree relative • Neoplastic polyps


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Colorectal cancer (CRC), together with breast and lung cancer, is one of the most frequent malignancies in the Western world and is the second leading cause of death due to cancer. Because there is strong evidence that the majority of CRCs arise from malignant transformation of adenomatous polyps, secondary prevention designed to detect cancers at an earlier stage seems justified. Moreover, the detection of asymptomatic polyps by colonoscopy with attendant polypectomy has been shown to prevent the development of CRC in screened cohorts.1 Aside from familial polyposis syndromes and families with a specific inherited susceptibility to CRC, as defined by the hereditary nonpolypotic syndromes, a simple history of CRC in one or more first-degree relatives (FDR) is generally accepted as conferring an increased risk for the development of CRC2,3; the risk is increased with multiple affected relatives and with decreasing age of the affected relatives.

Several groups have reported the yield for screening total colonoscopy (TC) in asymptomatic people with a family history of CRC,4–8 and they have shown an incidence of adenomatous polyps that does not in general exceed that found by screening colonoscopy in average-risk people.9 Because of the therapeutic value of TC, it is expected that factors predicting for significant polyps in asymptomatic average-risk individuals—most notably, the presence of male sex and increasing age10,11—should also be predictive for polyp disease in those patients with a family history of either polyps or CRC.12

This study evaluated the incidence of polyps discovered by TC in a cohort of completely asymptomatic individuals with one or two FDRs with a history of CRC. Our objective was to determine whether TC could contribute to the early detection of premalignant (and malignant) colonic lesions in this group and to define the location and type of neoplastic disease identified.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
A retrospective chart review was performed of consecutive TCs performed for completely asymptomatic patients with a history of CRC in one or two first-FDRs (parent, sibling, or child). Patients were excluded if they had undergone a barium enema or TC within 5 years, had a history of colonoscopic polypectomy, had a genetic disorder such as familial polyposis (or variants) or hereditary nonpolyposis CRC, or had a personal history of ulcerative colitis. Patients who had more than two FDRs with CRC were also excluded from analysis. The study was approved by the regional ethics committee with assessment of data designed to confirm subject risk status and asymptomatic status. Asymptomatic subjects did not report diarrhea, constipation, lower-abdominal pain, or rectal bleeding within 3 months before their TC.

The study included 249 asymptomatic individuals with a family history of CRC who were colonoscopically examined in the Colorectal Surgery Unit of St. George’s Hospital, London, United Kingdom, from 1992 to 1997. Patients included 107 men and 142 women (range, 22–75 years; mean, 44 ± 11.7 years), and all participants had either 1 (n = 212; 85%) or 2 (n = 37; 15%) FDRs diagnosed with CRC.

All participants underwent TC under sedation. Before TC, each patient underwent clinical examination, including digital rectal examination, proctoscopy, and rigid sigmoidoscopy. Diagnoses of all lesions detected by TC were confirmed by histology. The {chi}2 test was used to evaluate the differences among the groups studied, and the Wilcoxon rank test was used to compare the distribution of the ages of individuals studied.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Of the individuals examined, 198 (79.5%) had negative colonoscopies, whereas in 51(20.5%) asymptomatic individuals, 86 colonic polyps were found and rejected (Table 1). Polyps were multiple in 21 (41%) cases. Of the 51 patients with polyps, 12 (23.5%) had right-sided colonic lesions, and 7 (13.7%) had combined right- and left-sided colonic lesions. According to their macroscopic appearance, polyps were labeled as sessile (78 of 86; 90.7%) or pedunculated (8 of 86; 9.3%). With regard to their size, 75 polyps (87.2%) were of small size (2–5 mm in maximal diameter), 6 polyps (6.9%) were of medium size (5–10 mm), and 5 polyps (5.8%) were of large size (>1 cm). Histology classified the polyps as either neoplastic (n = 38; 44.2%) or metaplastic (n = 44; 51.1%) (Table 2).


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  		TABLE 1. Number of polyps per individual detected by total colonoscopy in asymptomatic patients with a family history of colorectal cancer
 

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  		TABLE 2. The location of the 86 polypoid lesions found; 14 (36.8%) of 38 neoplastic lesions were located proximal to the splenic flexure and would have been missed on flexible sigmoidoscopy
 
Overall, 24 (28%) lesions were located proximal to the splenic flexure and were beyond the reach of the flexible sigmoidoscope, with 14 of the adenomatous polyps (36.8%) detected proximal to the splenic flexure. The distribution of the polyps found throughout the various anatomical segments of the colon is listed in Table 2.

All participants with positive colonoscopic findings were classified into two main categories on the basis of the main histological type of the polyp rejected.

Individuals With Neoplastic (Adenomatous) Polyps
Thirty-eight adenomatous polyps were found in 27 (11%) of 249 subjects (14 women; mean age of all subjects, 48.6 years). Of these patients, 11 (41%) had multiple adenomas; adenomatous polyps were located proximal to the splenic flexure in 10 patients and were right- and left-sided in colonic location in 2 patients. With regard to the size of the neoplastic polyps, 27 adenomas were <5 mm, 6 adenomas were 6 to 10 mm, and 5 adenomas were >1 cm. In 14 (51.8%) of 27 individuals, the adenomas discovered were villous and had a high degree of dysplasia. Table 3 lists the age distribution of the 27 individuals with adenomatous polyps. It is shown that the incidence of colonic adenomas was stratified according to age, reaching its peak in the sixth decade of life, whereas 12 (44.4%) of 27 individuals were <50 years old.


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  		TABLE 3. Age stratification of individuals with positive colonoscopic findings
 
With regard to the number of FDRs with CRC, we found that 22 (81.4%) of 27 individuals had 1 such relative. Although the incidence of adenomatous polyps in asymptomatic individuals with two FDRs with CRC (5 of 37; 13.5%) was not statistically higher when compared with those individuals with 1 FDR with CRC (22 of 212; 10.3%), the numbers are too small to draw valid conclusions (Table 4).


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  		TABLE 4. No statistically significant difference was found in the incidence of neoplastic polyps with strength of positive family history
 
Individuals With Metaplastic Polyps
Forty-four metaplastic polyps were found in 29 individuals (29 of 249; 11.6%) aged 32 to 75 years (mean age, 48.25 years). Of the metaplastic polyps found, 36 (81.8%) were located in the colon distal to the splenic flexure and within reach of the flexible sigmoidoscope.

Synchronous adenomatous polyps were found in 7 (24%) of 29 individuals who also had metaplastic polyps, compared with 20 (9%) of 225 individuals without metaplastic polyps. This difference was statistically very significant (P < .0001).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In this study, polyps were found in 20.5% of asymptomatic individuals with a family history of CRC. They were multiple in more than 40% of cases and were adenomatous in a similar percentage, and more than one third of the adenomatous polyps were located proximal to the splenic flexure. More than 70% of these adenomas were diminutive polyps (i.e., <5 mm in maximal diameter), but half of all adenomas found had villous histology and a relatively high grade of dysplasia. Nearly half of the adenomas detected were discovered in asymptomatic individuals who were <50 years old. Most metaplastic polyps found were detected distal to the splenic flexure, with synchronous proximal adenomas in nearly one quarter of cases.

With regard to the incidence of asymptomatic adenomas in patients with a family history of CRC, our findings are in agreement with those of other investigators4,6,12,13 and are more than7–9 and less than5 some other reports. The retrospective nature of our study may affect results, and differences in these studies may be accounted for by delineation of patients who were truly asymptomatic and by the accuracy of recording of a family history of CRC.14 These findings may also be compared with the reported prevalence of colonic polyps in autopsy series, which ranges from 2.3% to 69% and represents differences in adenoma definition and divergent risk and age distribution.15,16

Our finding that one third of adenomas in asymptomatic individuals were located beyond the reach of the flexible sigmoidoscope is virtually identical to the findings of Gryska and Cohen5 and Baker et al.6 This highlights the need for total colonic examination in these patients, and because the majority of these polyps were smaller than 5 mm in maximal diameter in our study, we would recommend that TC be the current method of choice because of its superiority over double-contrast barium enema in the detection of diminutive lesions.17 With regard to virtual colonoscopy, it introduction might lessen, in the near future, the need for TC, which is an invasive approach, but it is unlikely that it would be used as a screening procedure, because of its expense. Besides, the conventional colonoscopy should also be performed if lesions needing biopsy are found.

Our findings mirror those previously reported, which showed that from 37% to 61% of diminutive polyps were adenomas.18,19 These are likely to be underreported in the assessment of asymptomatic individuals undergoing TC because of a positive family history; in some studies, smaller lesions were not biopsied and were not subjected to histology.5 Moreover, the potential proximalization of adenomatous lesions detected where the primary indication for TC was a positive family history is in agreement with a preliminary report from the National Polyp Study Group, which showed that a right-sided adenoma location was associated with an increased familial risk of CRC.20

Although traditionally, the size of adenomas directly correlates with their malignant potential, in our study 6 of the 27 diminutive adenomas were severely dysplastic, with a villous growth pattern. This finding is in agreement with a greater severity of dysplasia in adenomas obtained from patients with a positive family history, as reported by Bazzoli et al.21 The significance of hyperplastic or metaplastic polyps discovered during the conduct of TC in both the average-risk and higher-risk case is controversial. In this study, most of these lesions were distally located and were associated with a significant incidence of proximally located adenomas. We found that asymptomatic individuals with a family history of CRC and metaplastic polyps had a 3-fold increased risk for the existence of synchronous adenomas when compared with asymptomatic individuals with a family history of CRC without metaplastic polyps. This difference was statistically significant (P < .0001) and is in agreement with other reports assessing the clinical significance of metaplastic polyps.22–24

In our study, the incidence of colonic adenomas was stratified according to age, reaching its peak in the sixth decade of life. A significant percentage, however, of the neoplastic polyps (16%) were detected in individuals aged 30 to 49 years. Therefore, our data suggest that asymptomatic individuals with a family history of CRC should undergo colonoscopy at a younger age.

In general, it is expected that the overall incidence of adenomas detected by TC will not strictly reflect the indication for investigation, but rather the background incidence of adenomas in the population, because these smaller lesions are asymptomatic.25 Whether or not there is a family history of CRC or adenomas, the predictive power for an adenoma in patients selected for screening TC shows that increasing patient age and male sex are important.11,26 Where excellent-quality endoscopy and radiology are both available in an institution, the selective use of TC in a cost-effective manner may be defined by demographic factors that predict for the probability that an individual patient has an adenoma. In those cases in which there is a family history of CRC, however, the lack of difference in the prevalence of adenomas between screened patients with and without a positive family history might either suggest an error in the previous assessments of lifetime CRC risk in those with a family history or suggest that the increased risk for CRC in this group is operating through different mechanisms than those implicated in the adenoma-carcinoma sequence of sporadic cases. Evidence for the latter suggestion is the finding of a greater degree of high-grade dysplasia in smaller adenomas in those asymptomatic patients with a family history of CRC. More studies are required in these patients to assess whether there are differences in the molecular biology of sporadic and familial adenomas.

We cannot determine from this study whether the number of FDRs affects the likelihood of detection of adenomas in the screened relative. The literature on this point is conflicting, with some reports showing no difference between one or two affected FDRs13,27 and others suggesting that two FDRs with CRC increases the risk of neoplastic disease over one FDR.6,28

The current recommendations of the American Cancer Society,29 which state that people with one or more FDRs who were diagnosed with CRC at <55 years of age should undergo a screening colonoscopy every 3 to 5 years beginning at the age of 35 to 40 years, may need modification, because it is likely that the risk of adenomas is higher in those with a family history of colonic adenomas, rather than CRC.12 Moreover, the characteristics of the index cancer patients significantly affect screening TC in relatives, where the probability of detecting adenomas increases when the index patient is young (i.e., <50 years of age) or male.30

Received for publication August 30, 2001. Accepted for publication February 9, 2002.


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TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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