- Email: [email protected]
The Incidence of Colon Carcinoma Complicating Ulcerative Colitis
Gastrointestinal and Hepatobiliary Malignancies
0039-6109/86 $0.00
+
.20
The Incidence of Colon Carcinoma Complicating Ulcerative Colitis Robert Matheny, M.D., * and Richard E. Symrrwnds, Jr., M.D., F.A.C.S. t
There is now a well-recognized pathologic association between adenocarcinoma of the colon and ulcerative colitis. This association was first alluded to in 1925 by Crohn and Rosenberg in a case report of a colon cancer occurring in a patient with a 14-year history of ulcerative colitis. 5 Bargen, in 1928, was the first to report the distinct association of a malignant change in the mucosa with ulcerative colitis in 17 patients. 2 The dysplastic mucosal changes in the colon that may occur with ulcerative colitis were first described by Warren and Sommers in 1949. 22 Morson and Pang referred to the dysplastic change as "precancer."17 In an extensive review of the pathology of colons resected for ulcerative colitis, they demonstrated the occurrence of the dysplastic change in those colons found to contain cancer and in a number with a history of extensive colitis. The advocation of rectal biopsy as a means of following these patients was made on the basis that some "precancerous" lesions are often not polypoid but within the flat mucosa and, therefore, not identified by radiographic means. With present-day colonoscopy, the entire large bowel can be sampled for the dysplastic change; this along with historical and clinical findings is aiding in the quest for earlier detection of malignant change in patients with longstanding colitis.
RISK FACTORS Multiple factors contribute to the risk that a patient with ulcerative colitis will subsequently develop cancer. These factors may include extent of disease, age, and severity of disease. The prognosis of cancer with ulcerative colitis is the same, stage for stage, as that of any carcinoma of *Resident, General Surgery, Scott and White Memorial Hospital and Clinic, Temple, Texas tConsultant, General Surgery, Scott and White Clinic; and Assistant Professor of General Surgery, Texas A&M University College of Medicine, Temple, Texas
Surgical Clinics of North A11II!rica-Vol. 66, No.4, August 1986
801
802
ROBERT MATHENY AND RICHARD
E.
SYMMONDS, JR.
equal grade. The overlapping disease, however, causes a delay in the diagnosis of cancer, usually resulting in higher initial staging. The poorer course of cancer associated with colitis, therefore, makes it desirable to identify those patients at risk who would benefit from prophylactic colectomy or proctocolectomy. Patients with pancolitis have a higher incidence of developing carcinoma than those with partial or left-sided colonic involvement. 7, 9, 12, 15 Although earlier reports of patients with colonic malignancy involved those with extensive colitis, a certain percentage of cancers developed in patients with left-sided and rectal colitis only. Cook reports a 21 per cent occurrence of the cancer distal to the splenic flexure, and others report a range from 19 to 24 per cent. 4 , 9, 11 However, perhaps many of these patients were in an age group more likely to have left-sided cancer even without a history of ulcerative colitis as a predisposing factor, Therefore, some argue that those individuals with distal rectal and sigmoid disease may not be at a higher risk than the general population, 10, 18, 19 It seems unlikely that the mucosal changes that occur in colitis would predispose one area of the colon to cancer and not another. A probable explanation is that there is simply less total mucosal involvement with more containment of disease and that a somewhat longer period is needed until the dysplastic changes appear. Whether the difference in occurrence is a reflection of the amount of mucosal damage or of the aggressiveness of the colitis remains to be seen. Patients with pancolitis or limited disease should be followed by strict surveillance programs. The age of onset of symptoms has been reported as having a bearing on development of cancer, with those of a younger age group being more likely to develop colon cancer after a shorter duration of disease. 8 This has not been confirmed by other groups, and it is probable that this is only a reflection of a longer follow-up period. 7 No definitive statement can be made relating severity of disease to risk, because these factors would be difficult to standarize and follow. However, remission does not exclude a patient from risk. Colectomy reduces the risk (Fig. 1), but there have been reported cases occurring in the rectum after surgical treatment. 13 Although the majority of the offending mucosal surface has been removed, the remaining portion is still capable of dysplasia and probable malignant change. The risk becomes nil when the rectum is included in the resection.
INCIDENCE To direct appropriate treatment, it is necessary to have an impression of the overall risk of developing colon cancer for each patient. As noted, many factors enter into any formulation of risk and have contributed to some confusion in analysis. Age of onset, severity and extent of disease, treatment, and long-term follow-up are all variables and these have not been fully dealt with in some past reports. However, it is apparent that the risk of cancer is increased after the first decade of disease and continues to increase with time. 6 , 7, 11, 12 The overall incidence of occurrence for those with ulcerative colitis appears to be approximately 5 per cent. 1, 2, 14, 21 The
THE INCIDENCE OF COLON CARCINOMA COMPLICATING ULCERATIVE COLITIS
De Dombal Devroede Kewenter Greenstein
75
803
1966 1971 1978 1979
II: W
U Z
C3 u.. o
50
w u zw Cl
1:5 ~
~
25
~
::;)
::;; ::;)
U
10
20
30
40 Years of disease
Figure 1. The progressive risk of cancer from colitis over time. (From Devroede, C.: Cancer risk in extensive colitis. In Winawer, S. J., et aI., (eds.): Colorectal Cancer: Prevention, Epidemiology and Screening. New York, Raven Press, 1980, page 327, with permission.)
appearance of cancer in the first 5 years after onset of disease is very rare. As pointed out by Devroede, many previous studies have expressed the incidence as a percentage of a group.7 These studies are affected by the loss of patients to follow-up, short-term follow-up, and various factors such as intervening proctocolectomy; prospective studies were seldom performed until recent decades. Recent studies, however, have applied actuarial statistical analysis and have resulted in more general agreement (Fig. 2). The risk of developing colon cancer in patients with extensive disease is approximately 2 per cent per year after the first decade (and beginning at 20 years for left-sided disease). Those with disease limited to the rectum have a relatively lower risk.
SURVEILLANCE Patients with documented ulcerative colitis should be followed with serial endoscopic examinations, with biopsy of the mucosa and examination of the specimens for cellular dysplasia. Dysplasia is followed in other forms of cancer, most notably carcinoma of the cervix, to evaluate patients and prescribe treatment. The exact histologic and cytologic criteria in the case of ulcerative colitis are much more difficult to ascertain, because there is considerable variability in interpretation among individual observers. Dysplasia can be considered mild, moderate, or severe, with the severe case being taken as carcinoma in situ. 16 It is, however, difficult to classify, even for purposes of a prospective study, owing to the inflammation or regen-
804
ROBERT MATHENY AND RICHARD
E.
SYMMONDS, JR.
CANCER RISK IN EXTENSIVE COLITIS RESUL TS OF SURGICAL POLICY
*c:
70
UJ
<{
U
u. 0
60
>-
50
..J a:l <{ a:l
40
Bonnevle
1974
Lennard Jones
1977
Baker
1978
Devroede
No Policy
Kewenter
. Prophylactic Proctocolectomy
u Z
Greenstein
1966 1971 1978 1979
De Dombal
80
0
•
Selective Proctocolectomy Total Colectomy with Ileorectal anastomosis
l-
0
c: c..
30
UJ
> I<{ ..J
20
::> ~
::>
u
10
10
20
30
40
YEARS OF DISEASE Figure 2. The decreased risk of cancer after surgery. (From Devroede, C.: Cancer risk in extensive colitis. In Winawer, S. J., et aI., (eds.): Colorectal Cancer: Prevention, Epidemiology and Screening. New York, Raven Press, 1980, page 330, with permission.)
eration that often accompanies the disease and the fact that the cellular changes are a continuum. Finally, these changes are known to regress in some patients. 2o In any event, documented mucosal dysplastic changes indicate that the potential for malignant transformation exists. Patients with such changes should be closely followed with repeat biopsy specimens from different areas of the colon. Patients should be informed of their condition and of the risk they run in developing a malignancy. Periodic proctoscopy, barium enemas with air contrast, and colonoscopy with biopsies will be needed at intervals of 2 to 3 years or after an exacerbation of disease. Patients with left-sided colitis may be followed at slightly longer intervals, as long as documentation of containment of their disease is made. SUMMARY The tendency for development of cancer in patients with ulcerative colitis is well documented. Each physician must take into account the
THE INCIDENCE OF COLON CARCINOMA COMPLICATING ULCERATIVE COLITIS
805
clinical presentation of the patient and the known risk factors and must adapt follow-up and consultation to the patient and family accordingly. Presently, after a 5- to 7-year history of ulcerative colitis, it is reasonable to document mucosal changes with air-contrast barium enema examination and laboratory assessment with carcinoembryonic antigen levels being obtained. If the extent of disease is more limited to the distal colon, then the surveillance should be modified accordingly because the relative risk is reduced. In the future, the addition of histochemical and immunohistologic analysis of mucosal biopsies will result in better criteria for patient selection for surgical intervention. Because of the delay in recognition of a cancerous lesion in patients with ulcerative colitis, a total proctocolectomy is recommended by some after the first decade of disease. Most prefer, however, to continue surveillance of some type. During surveillance, if moderate or severe dysplasia is found, a proctocolectomy should be performed. This mode of surveillance and treatment of patients at risk for developing colonic carcinoma subsequent to ulcerative colitis remains an evolving process. There will be further changes in management following better classification of the neoplastic changes and the discovery of the etiology of the disease process itself.
REFERENCES 1. Banks, B., Korelitz, B., and Zetzel, L.: The course of non-specific ulcerative colitis: Review of twenty years experience and late results. Gastroenterology, 32:983-1012, 1957. 2. Bargen, J.: Chronic ulcerative colitis associated with malignant disease. Arch. Surg., 17:561-576, 1928. 3. Bayless, T.: Commentary: Colon cancer and precancer in ulcerative colitis. In Winawer, S. J., et aI., (eds.): Colorectal Cancer: Prevention, Epidemiology And Screening. New York, Raven Press, 1980, pp. 397-401. 4. Cook, M., Path, M., and Goligher, J.: Carcinoma and epithelial dysplasia complicating ulcerative colitis. Gastroenterology, 68:1127, 1975. 5. Crohn, B., and Rosenberg, H.: The sigmoidoscopic picture of chronic ulcerative colitis (non-specific). Am. J. Med. Sci., 170:220-228, 1925. 6. de Dombal, F., Watts, J., Watkinson, G., et al.: Local complications of ulcerative colitis: Stricture, pseudo-polyposis and carcinoma of colon and rectum. Br. Med. J., 1:1442-1447, 1966. 7. Devroede, G., Taylor, W., and Sauer, W.: Cancer risk and life expectancy of children with ulcerative colitis. N. Engl. J. Med., 285:17, 1971. 8. Diamond, M., Yardley, J., and Bayless, T.: Colon carcinoma and severe epithelial dysplasia in patients with ulcerative colitis. Gastroenterology, 74:1120, 1978. 9. Edwards, F., and Truelove, S.: The course and prognosis of ulcerative colitis. IV. Carcinoma of the colon. Gut, 5:15, 1964. 10. Farmer, R., and Brown, C.: Ulcerative proctitis: Course and prognosis. Gastroenterology, 51:219-223, 1966. 11. Greenstein, A.: Cancer in universal and left sided ulcerative colitis: Factors determining risk. Gastroenterology, 77:290-294, 1979. 12. Kewenter, J., Ahlanan, H., and Hulten, L.: Cancer risk in extensive ulcerative colitis. Ann. Surg., 188:824-828, 1978. 13. MacDougall, I.: The risk of cancer in ulcerative colitis. Lancet, 2:655-658, 1964.
806
ROBERT MATHENY AND RICHARD
E.
SYMMONDS, JR.
14. McMillan, W., Jr., Garbutt, J., and Ruffin, J.: Problem of cancer in ulcerative colitis. South. Med. J., 61:526-528, 1968. 15. Morson, B.: Crohn's disease: Precancerous changes in colitis. Dis. Colon Rectum, 18:207, 1975. 16. Morson, B.: Use of dysplasia as an indicator of risk for malignancy in patients with ulcerative colitis. In Winawer, S. J., et aI., (eds.): Colorectal Cancer: Prevention, Epidemiology and Screening. New York, Raven Press, 1980, pp. 347-353. 1-7. Morson, B., and Pang, L.: Rectal biopsy as an aid to cancer control in ulcerative colitis. Gut, 8:423-434, 1967. 18. Nugent, W.: Surveillance of patients with ulcerative colitis: Lahey Clinic results. In Winawer, S. J., et aI., (eds.): New York, Raven Press, 1980, pp. 275-380. 19. Nugent, W., Veidenheimer, M., Zuberi, S., et aI.: Clinical course of ulcerative proctosigmoiditis. Am. J. Diagn. Dis., 15:321-326, 1970. 20. Sheahan, D.: In Winawer, S. J., ~t aI., (eds.): Colorectal Cancer: Prevention, Epidemiology and Screening. New York, Raven Press, 1980, pp. 355-373. 21. Sloan, W., Jr., Bargen, J., and Gage, R.: Life histories of patients with chronic ulcerative colitis: A review of 2000 cases. Gastroenterology, 16:25-38, 1950. 22. Warren, S., and Sommers, S.: Pathogenesis of ulcerative ~olitis. Am. J. Pathol., 25:657-679, 1949. Scott and White Memorial Hospital and Clinic 2401 South 31st Street Temple, Texas 76508 (Dr. Symmonds)
0039-6109/86 $0.00
+
.20
The Incidence of Colon Carcinoma Complicating Ulcerative Colitis Robert Matheny, M.D., * and Richard E. Symrrwnds, Jr., M.D., F.A.C.S. t
There is now a well-recognized pathologic association between adenocarcinoma of the colon and ulcerative colitis. This association was first alluded to in 1925 by Crohn and Rosenberg in a case report of a colon cancer occurring in a patient with a 14-year history of ulcerative colitis. 5 Bargen, in 1928, was the first to report the distinct association of a malignant change in the mucosa with ulcerative colitis in 17 patients. 2 The dysplastic mucosal changes in the colon that may occur with ulcerative colitis were first described by Warren and Sommers in 1949. 22 Morson and Pang referred to the dysplastic change as "precancer."17 In an extensive review of the pathology of colons resected for ulcerative colitis, they demonstrated the occurrence of the dysplastic change in those colons found to contain cancer and in a number with a history of extensive colitis. The advocation of rectal biopsy as a means of following these patients was made on the basis that some "precancerous" lesions are often not polypoid but within the flat mucosa and, therefore, not identified by radiographic means. With present-day colonoscopy, the entire large bowel can be sampled for the dysplastic change; this along with historical and clinical findings is aiding in the quest for earlier detection of malignant change in patients with longstanding colitis.
RISK FACTORS Multiple factors contribute to the risk that a patient with ulcerative colitis will subsequently develop cancer. These factors may include extent of disease, age, and severity of disease. The prognosis of cancer with ulcerative colitis is the same, stage for stage, as that of any carcinoma of *Resident, General Surgery, Scott and White Memorial Hospital and Clinic, Temple, Texas tConsultant, General Surgery, Scott and White Clinic; and Assistant Professor of General Surgery, Texas A&M University College of Medicine, Temple, Texas
Surgical Clinics of North A11II!rica-Vol. 66, No.4, August 1986
801
802
ROBERT MATHENY AND RICHARD
E.
SYMMONDS, JR.
equal grade. The overlapping disease, however, causes a delay in the diagnosis of cancer, usually resulting in higher initial staging. The poorer course of cancer associated with colitis, therefore, makes it desirable to identify those patients at risk who would benefit from prophylactic colectomy or proctocolectomy. Patients with pancolitis have a higher incidence of developing carcinoma than those with partial or left-sided colonic involvement. 7, 9, 12, 15 Although earlier reports of patients with colonic malignancy involved those with extensive colitis, a certain percentage of cancers developed in patients with left-sided and rectal colitis only. Cook reports a 21 per cent occurrence of the cancer distal to the splenic flexure, and others report a range from 19 to 24 per cent. 4 , 9, 11 However, perhaps many of these patients were in an age group more likely to have left-sided cancer even without a history of ulcerative colitis as a predisposing factor, Therefore, some argue that those individuals with distal rectal and sigmoid disease may not be at a higher risk than the general population, 10, 18, 19 It seems unlikely that the mucosal changes that occur in colitis would predispose one area of the colon to cancer and not another. A probable explanation is that there is simply less total mucosal involvement with more containment of disease and that a somewhat longer period is needed until the dysplastic changes appear. Whether the difference in occurrence is a reflection of the amount of mucosal damage or of the aggressiveness of the colitis remains to be seen. Patients with pancolitis or limited disease should be followed by strict surveillance programs. The age of onset of symptoms has been reported as having a bearing on development of cancer, with those of a younger age group being more likely to develop colon cancer after a shorter duration of disease. 8 This has not been confirmed by other groups, and it is probable that this is only a reflection of a longer follow-up period. 7 No definitive statement can be made relating severity of disease to risk, because these factors would be difficult to standarize and follow. However, remission does not exclude a patient from risk. Colectomy reduces the risk (Fig. 1), but there have been reported cases occurring in the rectum after surgical treatment. 13 Although the majority of the offending mucosal surface has been removed, the remaining portion is still capable of dysplasia and probable malignant change. The risk becomes nil when the rectum is included in the resection.
INCIDENCE To direct appropriate treatment, it is necessary to have an impression of the overall risk of developing colon cancer for each patient. As noted, many factors enter into any formulation of risk and have contributed to some confusion in analysis. Age of onset, severity and extent of disease, treatment, and long-term follow-up are all variables and these have not been fully dealt with in some past reports. However, it is apparent that the risk of cancer is increased after the first decade of disease and continues to increase with time. 6 , 7, 11, 12 The overall incidence of occurrence for those with ulcerative colitis appears to be approximately 5 per cent. 1, 2, 14, 21 The
THE INCIDENCE OF COLON CARCINOMA COMPLICATING ULCERATIVE COLITIS
De Dombal Devroede Kewenter Greenstein
75
803
1966 1971 1978 1979
II: W
U Z
C3 u.. o
50
w u zw Cl
1:5 ~
~
25
~
::;)
::;; ::;)
U
10
20
30
40 Years of disease
Figure 1. The progressive risk of cancer from colitis over time. (From Devroede, C.: Cancer risk in extensive colitis. In Winawer, S. J., et aI., (eds.): Colorectal Cancer: Prevention, Epidemiology and Screening. New York, Raven Press, 1980, page 327, with permission.)
appearance of cancer in the first 5 years after onset of disease is very rare. As pointed out by Devroede, many previous studies have expressed the incidence as a percentage of a group.7 These studies are affected by the loss of patients to follow-up, short-term follow-up, and various factors such as intervening proctocolectomy; prospective studies were seldom performed until recent decades. Recent studies, however, have applied actuarial statistical analysis and have resulted in more general agreement (Fig. 2). The risk of developing colon cancer in patients with extensive disease is approximately 2 per cent per year after the first decade (and beginning at 20 years for left-sided disease). Those with disease limited to the rectum have a relatively lower risk.
SURVEILLANCE Patients with documented ulcerative colitis should be followed with serial endoscopic examinations, with biopsy of the mucosa and examination of the specimens for cellular dysplasia. Dysplasia is followed in other forms of cancer, most notably carcinoma of the cervix, to evaluate patients and prescribe treatment. The exact histologic and cytologic criteria in the case of ulcerative colitis are much more difficult to ascertain, because there is considerable variability in interpretation among individual observers. Dysplasia can be considered mild, moderate, or severe, with the severe case being taken as carcinoma in situ. 16 It is, however, difficult to classify, even for purposes of a prospective study, owing to the inflammation or regen-
804
ROBERT MATHENY AND RICHARD
E.
SYMMONDS, JR.
CANCER RISK IN EXTENSIVE COLITIS RESUL TS OF SURGICAL POLICY
*c:
70
UJ
<{
U
u. 0
60
>-
50
..J a:l <{ a:l
40
Bonnevle
1974
Lennard Jones
1977
Baker
1978
Devroede
No Policy
Kewenter
. Prophylactic Proctocolectomy
u Z
Greenstein
1966 1971 1978 1979
De Dombal
80
0
•
Selective Proctocolectomy Total Colectomy with Ileorectal anastomosis
l-
0
c: c..
30
UJ
> I<{ ..J
20
::> ~
::>
u
10
10
20
30
40
YEARS OF DISEASE Figure 2. The decreased risk of cancer after surgery. (From Devroede, C.: Cancer risk in extensive colitis. In Winawer, S. J., et aI., (eds.): Colorectal Cancer: Prevention, Epidemiology and Screening. New York, Raven Press, 1980, page 330, with permission.)
eration that often accompanies the disease and the fact that the cellular changes are a continuum. Finally, these changes are known to regress in some patients. 2o In any event, documented mucosal dysplastic changes indicate that the potential for malignant transformation exists. Patients with such changes should be closely followed with repeat biopsy specimens from different areas of the colon. Patients should be informed of their condition and of the risk they run in developing a malignancy. Periodic proctoscopy, barium enemas with air contrast, and colonoscopy with biopsies will be needed at intervals of 2 to 3 years or after an exacerbation of disease. Patients with left-sided colitis may be followed at slightly longer intervals, as long as documentation of containment of their disease is made. SUMMARY The tendency for development of cancer in patients with ulcerative colitis is well documented. Each physician must take into account the
THE INCIDENCE OF COLON CARCINOMA COMPLICATING ULCERATIVE COLITIS
805
clinical presentation of the patient and the known risk factors and must adapt follow-up and consultation to the patient and family accordingly. Presently, after a 5- to 7-year history of ulcerative colitis, it is reasonable to document mucosal changes with air-contrast barium enema examination and laboratory assessment with carcinoembryonic antigen levels being obtained. If the extent of disease is more limited to the distal colon, then the surveillance should be modified accordingly because the relative risk is reduced. In the future, the addition of histochemical and immunohistologic analysis of mucosal biopsies will result in better criteria for patient selection for surgical intervention. Because of the delay in recognition of a cancerous lesion in patients with ulcerative colitis, a total proctocolectomy is recommended by some after the first decade of disease. Most prefer, however, to continue surveillance of some type. During surveillance, if moderate or severe dysplasia is found, a proctocolectomy should be performed. This mode of surveillance and treatment of patients at risk for developing colonic carcinoma subsequent to ulcerative colitis remains an evolving process. There will be further changes in management following better classification of the neoplastic changes and the discovery of the etiology of the disease process itself.
REFERENCES 1. Banks, B., Korelitz, B., and Zetzel, L.: The course of non-specific ulcerative colitis: Review of twenty years experience and late results. Gastroenterology, 32:983-1012, 1957. 2. Bargen, J.: Chronic ulcerative colitis associated with malignant disease. Arch. Surg., 17:561-576, 1928. 3. Bayless, T.: Commentary: Colon cancer and precancer in ulcerative colitis. In Winawer, S. J., et aI., (eds.): Colorectal Cancer: Prevention, Epidemiology And Screening. New York, Raven Press, 1980, pp. 397-401. 4. Cook, M., Path, M., and Goligher, J.: Carcinoma and epithelial dysplasia complicating ulcerative colitis. Gastroenterology, 68:1127, 1975. 5. Crohn, B., and Rosenberg, H.: The sigmoidoscopic picture of chronic ulcerative colitis (non-specific). Am. J. Med. Sci., 170:220-228, 1925. 6. de Dombal, F., Watts, J., Watkinson, G., et al.: Local complications of ulcerative colitis: Stricture, pseudo-polyposis and carcinoma of colon and rectum. Br. Med. J., 1:1442-1447, 1966. 7. Devroede, G., Taylor, W., and Sauer, W.: Cancer risk and life expectancy of children with ulcerative colitis. N. Engl. J. Med., 285:17, 1971. 8. Diamond, M., Yardley, J., and Bayless, T.: Colon carcinoma and severe epithelial dysplasia in patients with ulcerative colitis. Gastroenterology, 74:1120, 1978. 9. Edwards, F., and Truelove, S.: The course and prognosis of ulcerative colitis. IV. Carcinoma of the colon. Gut, 5:15, 1964. 10. Farmer, R., and Brown, C.: Ulcerative proctitis: Course and prognosis. Gastroenterology, 51:219-223, 1966. 11. Greenstein, A.: Cancer in universal and left sided ulcerative colitis: Factors determining risk. Gastroenterology, 77:290-294, 1979. 12. Kewenter, J., Ahlanan, H., and Hulten, L.: Cancer risk in extensive ulcerative colitis. Ann. Surg., 188:824-828, 1978. 13. MacDougall, I.: The risk of cancer in ulcerative colitis. Lancet, 2:655-658, 1964.
806
ROBERT MATHENY AND RICHARD
E.
SYMMONDS, JR.
14. McMillan, W., Jr., Garbutt, J., and Ruffin, J.: Problem of cancer in ulcerative colitis. South. Med. J., 61:526-528, 1968. 15. Morson, B.: Crohn's disease: Precancerous changes in colitis. Dis. Colon Rectum, 18:207, 1975. 16. Morson, B.: Use of dysplasia as an indicator of risk for malignancy in patients with ulcerative colitis. In Winawer, S. J., et aI., (eds.): Colorectal Cancer: Prevention, Epidemiology and Screening. New York, Raven Press, 1980, pp. 347-353. 1-7. Morson, B., and Pang, L.: Rectal biopsy as an aid to cancer control in ulcerative colitis. Gut, 8:423-434, 1967. 18. Nugent, W.: Surveillance of patients with ulcerative colitis: Lahey Clinic results. In Winawer, S. J., et aI., (eds.): New York, Raven Press, 1980, pp. 275-380. 19. Nugent, W., Veidenheimer, M., Zuberi, S., et aI.: Clinical course of ulcerative proctosigmoiditis. Am. J. Diagn. Dis., 15:321-326, 1970. 20. Sheahan, D.: In Winawer, S. J., ~t aI., (eds.): Colorectal Cancer: Prevention, Epidemiology and Screening. New York, Raven Press, 1980, pp. 355-373. 21. Sloan, W., Jr., Bargen, J., and Gage, R.: Life histories of patients with chronic ulcerative colitis: A review of 2000 cases. Gastroenterology, 16:25-38, 1950. 22. Warren, S., and Sommers, S.: Pathogenesis of ulcerative ~olitis. Am. J. Pathol., 25:657-679, 1949. Scott and White Memorial Hospital and Clinic 2401 South 31st Street Temple, Texas 76508 (Dr. Symmonds)