Prognosis after Treatment of Villous Adenomas

Prognosis after Treatment of Villous Adenomas of the Colon and Rectum JOHN CHRISTIANSEN, M.D., PREBEN KIRKEGAARD, M.D., JYTTE IBSEN, M.D. With the existing evidence of neoplastic polyps of the colon and rectum as precursors of most or all colonic cancer, information of the short- and long-term course after treatment is a prerequisite of using the knowledge of the polyp-cancer sequence in an effective cancer prophylaxis. One hundred seventy-four patients treated for villous adenomas of the colon and rectum during the years 1960-1975 were re-examined. Survival and cure rates were estimated by actuarial analysis. The death rate of colonic cancer among patients treated for a benign villous adenoma was significantly higher than in an age and sex matched normal population, resulting in a significantly reduced crude survival rate among these patients. Almost all recurrences after treatment of benign villous adenomas occurred within the first four to five years resulting in a cumulated five years recurrence rate of roughly 30%, indicating that five years seem to be an adequate total control period following treatment. N EOPLASTIC polyps of the colon and rectum, particularly villous adenomas (v.a.), have gained increasing interest since their role as a precursor of most or all colonic cancers has been rendered probable.'13 With the development of modem endoscopic equipment, which permits not only a reliable diagnosis16 but also a satisfactory non-operative treatment8 this knowledge of the polyp-cancer sequence may be used as an effective cancer prophylaxis. How such a prophylaxis should be conducted regarding type of treatment and control examination, interval between control examinations and duration of the entire control period, implies knowledge of a variety of clinical and pathological features, and especially of the long-term clinical course following treatment. The present study was undertaken to provide further information on this subject. Materials and Methods Records of all patients with rectal and colonic polyps coded as villous adenomas between 1960 and 1975 were Reprint requests: John Christiansen, M.D., Department of Surgery D, Glostrup Hospital, DK-2600 Glostrup, Copenhagen, Denmark. Submitted for publication: October 31, 1978. From the Departments of Surgery D and Pathology, Glostrup Hospital, Copenhagen, Denmark reviewed. Criterion for inclusion in the study were as follows. 1) The first treatment of the lesion was undertaken in the period under review. 2) A diagnosis of v.a., according to the criteria described by Morson and Dawson"1 without demonstrable invasion of the muscularis mucosae, at the first histological examination whether performed on a biopsy or on a totally excised polyp. 3) No previous colonic surgery for cancer or polyps. One hundred seventy-four patients filled these requirements. The median age was 62 years (range: 28-85, Table 1). Presenting symptoms are shown in Table 2. The median duration of symptoms before treatment was eight months (range: 1-24). Forty-six patients died during the follow-up period. The cause of death was obtained in every case from hospital records or death certificates. In the calculation of cumulative recurrence rates the final year of "exposure to risk" of these patients was that of the last control examination as listed in the hospital records, irrespective of the time ofdeath. One patient was lost to follow-up. Five patients, all of whom were treated for a benign v.a., had had no control examinations after the primary treatment, and refused a control examination as described below. They did, however, answer a questionaire according to which they had no colonic symptoms, and were recorded as nonrecurrences. The remaining patients were reexamined with a double-contrast x-ray examination of the colon and, providing rectal excision had not been performed, a proctosigmoideoscopy. When the doublecontrast x-ray examination indicated the presence of polyps or other abnormalities, colonoscopy was performed. Cure rates and survival rates were estimated by the actuarial method6 with 95% confidence limits for the cumulated rates according to Greenwood's estimate.2 Expected mortality of colonic can- 0003-4932/79/0400/0404 $00.75 C J. B. Lippincott Company 404

Vol. 189. No. 4 TABLE 1. Age and Sex Distribution in 174 Patients Age 30-40- 50-60- 70- Sex <30 39 49 59 69 79 80+ Total Men Women 2 2 1 3 9 6 25 14 34 16 26 22 7 7 104 70 Total 4 4 15 39 50 48 14 174 RECTAL VILLOUS ADENOMAS TABLE 3. Synchronous Tumors Which were Later Found to be Malignant in 75 Patients 405 Synchronous Synchronous Primary Malignant Benign v.a. v.a. v.a. Total Benign Malignant 27 10 34 4 61 14 Total 37 38 75 cer among patients with v.a. was estimated from a Danish normal population with the same age and sex distribution based on the mortality of colonic cancer in Denmark from 1971 to 1975. Differences were estimated according to the Poisson distribution using exact confidence limits.5 Differences between groups were estimated by the chi-square test. When a percentage statement is used, 95% confidence limits are given in brackets. Results Primary Histological Diagnosis In 98 patients the polyp was totally excised primarily while 76 patients only had a biopsy of the polyp performed. These 76 patients, in whom biopsy showed a benign v.a., subsequently had a total excision of the polyp. Histological examination with serial section of the entire polyp showed malignancy in 27 patients (36%, 25-47). (Patients in whom the excised polyp or the primary biopsy showed invasion of the muscularis mucosae were classified as having a cancer and were not included in the study according to the criteria). Synchronous Tumors Seventy-five patients (43%, 36-50) had a synchronous tumor, which in half the cases were found to TABLE 2. Presenting Symptoms in 174 Patients with No Previous Colonic Surgery Symptom Number of Patients Rectal bleeding 67 Diarrhea 40 Constipation 25 Mucous discharge 19 Abdominal pain 19 Prolapsing tumor 2 Rectal tenesmus 1 Anal pruritus I Total 174 be malignant (Table 3). Among the patients with a primary benign v.a., 18% (12-24) had a synchronous malignant tumor. In the following patients with benign and malignant v.a. will be treated separately, i.e. 120 and 54 patients respectively. Localization Localization of the v.a. is shown in Table 4. Eightytwo per cent (76-88) were localized in the rectum. Size Table 5 shows the size of the v.a. No difference between benign and malignant v.a. was found (p > 0.10). Fifty-nine per cent (46-72) of the malignant and 55% (46-64) of the benign v.a. were more than 2cm in diameter. Treatment The different types of treatment are shown in Table 6. Four patients with a malignant v.a. who had a local excision all died from metastatic disease within two years. Twelve patients with a benign v.a. had an abdominoperineal rectal excision because of a diagnosis of malignancy at the time of the operation based solely on epithelial dysplasia. Subsequent histological examination of the specimen did not demonstrate invasion through the muscularis mucosae. Cure Rate In 36 of 120 patients treated for a benign v.a., a recurrent benign v.a. was found. Figure 1 shows the cure rate TABLE 4. Localization of Villous Adenoma in 174 Patients Benign Malignant Total Rectum 99 44 143 Sigmoid colon 20 8 28 Descending colon 0 1 1 Transverse colon 1 1 2

406 CHRISTIANSEN, KIRKEGAARD AND IBSEN TABLE 5. Size of Villous Adenoma in 174 Patients with No cure rate Previous Colonic Surgery Benign Malignant v.a. v.a. Total 0- lcm 17 3 20 1-2cm 37 19 56 >2cm 66 32 98 Ann. Surg. * April 1979 estimated by an actuarial analysis. After five years the cure rate was roughly 70% (60-80) and remained almost constant hereafter. The right part of the curve should be considered with some caution since the number of patients in the last years of observation was small resulting in a large sample variation. Development of Colonic Cancer Four of the patients with a benign v.a. developed cancer of the colon and died of the disease. The expected number of deaths of colonic cancer during the follow-up period was estimated from the mortality of colonic cancer in the Danish population and was found to 0.49. This difference is significant (p < 0.01). Crude Survival Rates Figure 2 shows the cumulated survival rate among patients treated for a benign v.a. compared to a Danish normal population of equal age and sex distribution. The five year survival rate was 70% compared to 85% for the normal population (p < 0.05). The corresponding figures at 10 years were 57 and 66% (p 0.05). - Figure 3 shows the corresponding data for patients treated for malignant v.a. The five year survival rate was 47 versus 84% for the normal population (p < 0.01), and at 10 years 38 and 58% (p < 0.01). 2 4 6 8 10 12 14 yeors FIG. 1. Cumulated cure rate with 95% confidence limits in patients treated for a benign villous adenoma. found to be carcinomas when serial sections were examined of the totally excised polyp. Biopsy diagnosis failure of up to 50% has been reported.3'7'8'15 The frequency of synchronous tumors, benign as well as malignant in this series is of the same magnitude survival rote Discussion The present study emphasizes the importance of primary total excision of colonic polyps as a diagnostic measure, since 36% of v.a. diagnosed on a biopsy were TABLE 6. Various Types of Treatment in 174 Patients Benign Malignant v.a. v.a. Total Endoscopic excision 84 3 87 Local surgical excision 13 1 14 Resection 23 50 73 1I years ofter treotment FIG. 2. Cumulated crude survival rates in patients treated for a benign villous adenoma (O 0) and in an age and sex matched normal population (E - 0).

VOl. 189.o NO. 4 RECTAL VILLOUS ADENOMAS 407 as reported by others3"15 but lower'8 as well as higher" frequencies have been found. In this and other studies7"15"17"19 the major part of v.a. was found in the rectum, a concept which still seems to be true even in series where routine colonoscopy has been used. A positive correlation between tumor size and the incidence of malignancy is well documented,4'18 but even small v.a. may harbor an invasive carcinoma.7'20 In the present study no significant difference in size was demonstrated between benign and malignant v.a. The practice of using the size of a colonic polyp as guideline for excision versus further radiological control3"10 seems to be a precarious policy. With the low risk encountered in colonoscopic excision this practice should be abandoned.20 The evidence for an etiological relationship between benign neoplastic polyps of the colon and carcinoma is strong. Firstly, about one-third of all operative specimens for cancer of the colon and rectum contains one or more benign neoplastic polyp in addition to the cancer.13 Secondly, it has been found that 3.5% of patients who have had a partial resection of the colon for carcinoma are at risk of developing a new carcinoma in the residual bowel, and that this will happen more than twice as often in those who also had benign neoplastic polyps in the resected specimen.13 Finally, patients treated for benign neoplastic polyps are at increased risk from the subsequent development of a carcinoma as demonstrated in the present study. It thus seems evident, that an effective cancer prophylaxis regarding colonic cancer implies control examinations at suitable intervals of patients treated for benign v.a. and other neoplastic polyps of the colon. A crucial point, however, is the duration of the control period. It has been estimated that a polyp-cancer sequence requires 10-15 years,'3 i.e. once the adenoma has been removed and synchronous lesions searched for and removed the first ten years should carry a low risk of cancer. This may be true but is so far only a hypothesis and implies ideal conditions, i.e. even the smallest synchronous polyp should be diagnosed and removed together with the adenoma. In this series almost all recurrent benign v.a. occurred within the first five years and so did the four carcinomas. Consequently we find a control period of five years without recurrences to be a well founded and practicable policy. How the control examination should be conducted must partly be a question of resources and expertise. We perform a proctosigmoideoscopy and a double contrast barium enema once a year. If the radiological examination suggests the presence of a polyp, colonoscopy is performed and the polyp is excised. survival rate 2 4 6 8 10 12yeors ofter treotment FIG. 3. Cumulated crude survival rates in patients treated for a malignant villous adenoma (O 0) and in an age and sex matched normal population (C1 Ol). If the histological examination reveals invasion of the muscularis mucosae, radical cancer surgery is performed, an approach which is supported by the course of the four patients with a malignant v.a. treated with local excision in this series. Recent studies, however, seem to show that in carefully selected cases with special emphasis on the histological evaluation of the thoroughness of surgical excision-a policy of local excision of malignant v.a. may be adopted.9"14 Treatment and control along the lines described above of patients with neoplastic polyps of the colon and rectum represent in our opinion one of the fields in gastroenterology where rational cancer prophylaxis may be achieved. References 1. Brahme, F., Ekelund, G. R., Norden, J. G., et al.: Metachronous Colorectal Polyps: Comparison of Development of Colorectal Polyps and Carcinomas in Persons with and without Histories of Polyps. Dis. Colon Rectum, 17:166, 1974. 2. Cutler, S. H. and Ederer, F. J.: Maximum Utilization of the Life Table Method in Analyzing Survival. J. Chron. Dis., 8:699, 1958. 3. Enterline, H. T.: Pathology of Colonic Polyps as it Relates to Surgical Management. Ann. Clin. Lab. Sci., 4:145, 1974.

408 CHRISTIANSEN, KIFRKIEGAARD AND IBSEN Ann. Surg. * April 1979 4. Evans, J. T., Imakori, S. and Lin, K.: Villous Adenomas of the Colon and Rectum. J. Surg. Oncol., 4:117, 1972. 5. Geigy Documenta: Scientific Tables. 6th edition, J. R. Geigy, S. A., Basle, 1962. 6. Hill, B.: Principles of Medical Statistics. Seventh edition, London, Lancet Ltd. 1961. pp. 220-236. 7. Jahadi, M. R. and Bailey, W.: Papillary Adenomas of the Colon and Rectum: A Twelve-year Review. Dis. Colon Rectum, 18:249, 1975. 8. Livistone, G. M., Troncale, F. J. and Sheahan, D. G.: Value of a Single Forceps Biopsy of Colonic Polyps. Gastroenterology, 73:1296, 1977. 9. Lock, M. R., Ritchie, J. K. and Lockhart-Mummery, H. E.: Results of Local Excision for "Early" Colorectal Cancer. Gut, 18:A 959, 1977. 10. Marshak, R. H., Lindner, A. E. and Maklansky, D.: Adenomatous Polyps of the Colon. A Rational Approach. JAMA, 235:2856, 1976. 11. McCabe, J. C., McSherry, C. K., Sussman, E. B., et al.: Villous Tumors of the Large Bowel. Am. J. Surg. 126:336, 1973. 12. Morson, B. C. and Dawson, I. M. P.: Gastrointestinal Pathology. Oxford, Blackwell. 1972. pp. 522-548. 13. Morson, B. C.: Genesis of Colorectal Cancer. Clin. Gastroenterol., 5:505, 1976. 14. Morson, B. C., Bussey, H. J. R. and Samoorian, S.: Policy of Local Excision for Early Cancer of the Colorectum. Gut, 18:1045, 1977. 15. Quan, S. H. Q. and Castro, E. B.: Papillary Adenomas (Villous Tumors): A Review of 215 Cases. Dis. Colon Rectum, 14:267, 1971. 16. Smith, L. E. and Nivatvongs, S.: Complications in Colonoscopy. Dis. Colon Rectum, 18:214, 1975. 17. Southwood, W. F. W.: Villous Tumours of the Large Intestine: Their Pathogenesis, Symptomathology, Diagnosis and Management. Ann. R. Coll. Surg., 30:23, 1962. 18. Takolander, R. J.: Villous Papilloma of the Colon and Rectum. Acta Chir. Scand. Suppl., 473, 1977. 19. Wheat, Jr., M. W. and Ackerman, L. V.: Villous Adenomas of the Large Intestine. Ann. Surg., 147:476, 1958. 20. Winawer, S. J.: Comment, Gastroenterology, 71:1101, 1976.