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The Surgical Treatment of Ulcerative Colitis in the Pubertal Years
The Surgical Treatment of Ulcerative Colitis in the Pubertal Years ALBERTS. LYONS, M.D., F.A.C.S. Asnstant Attending Surgeon and Chief, Intestinal Rehabilitation Clinic, The Mount Sinai Hospital; Attending Surgeon, Italian Hospital, New York, N. Y.
IVAN D. BARONOFSKY, M.D., F.A.C.S. Surgeon-in-Chief, The Mount Sinai Hospital; Clinical Professor of Surgery, College of Physicians and Surgeons, Columbia University, New York, N.Y.
THE decision to perform ileostomy and colectomy in childhood is difficult at best. The marked reluctance to leaving a permanent ileostomy in a child is understandable, and the deferment of surgery may well be wise, provided the danger to life is minimal and the general condition of the patient remains good. However, too often, before surgical therapy is accepted, the patient is permitted to decline to a hopeless state from which restoration is virtually impossible without operation and survival with operation is problematic. 7 In a general way, both in children and in adults, we have placed more reliance on the patient's reaction to the disease than on the state of the bowel-as the guidepost to surgery. Danger to life (e.g., acute fulminating toxemia, massive hemorrhage, perforation) and invalidism (e.g., debility, rectovaginal fistula, resistant pyoderma and ulceration, arthritis) are, therefore, our two main indications for colectomy. 9 But what of the child either with persistent, prolonged ulcerative colitis or with frequent recrudescences who maintains general nutrition and strength between bouts and who manages to carry on despite the limitations of cramps, diarrhea and anemia? Recently we have come to realize more forcefully that an added reason for surgery in children is retardation of growth and development. The child who remains stunted and immature until into puberty may never reach full growth after recovery from the illness or indeed even
999
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after surgical extirpation of the colon if long delayed. On the other hand, in those whose height and development increase normally despite the presence of ulcerative colitis, the indications for surgery appear to be the same as in adults. The purpose of this study is to advance the proposition that retardation of growth and development during the course of ulcerative colitis in the prepubertal years is a separate and clear indication for performing colectomy before puberty has been reached. MATERIAL
Seven patients were treated surgically whose onset of ulcerative colitis was at eight to 12 years of age. In five, stunting and retardation of development (infantilism) had occurred preoperatively. In two, growth before operation had been normal. Operation (colectomy) was performed at the ages of ten to 16. CASE ABSTRACTS
No Recovery of Growth or Development CASE I (Fig. 1). R.B. Female. The gradual onset of ulcerative colitis occurred at the age of 8 years, with cramps, bloody diarrhea, and low grade fever. During the following 9 years, the disease was progressive and resistant to all forms of medical therapy-including corticoids, antibiotics and azulfidine. The complications which developed were: pyoderma gangrenosum with large ulcerations of the thighs, colocolonic fistula, rectovaginal fistula, arthritis of the ankles. She had 4 hospital admissions to The Mount Sinai Hospital, the last of which wa.S in February 1959. She was exceptionally stunted in height and development. At the age of almost 17 years, she had the appearance of a child of 11, except for the presence of pubic hair. She had menstruated occasionally and scantily for a year. There was mild dorsal kyphosis. On March 24, 1959, ileostomy and total proctocolectomy were performed. The pathologic specimen showed chronic nonspecific ulcerative colitis with multiple inflammatory polyps. The postoperative course was stormy and prolonged. She developed staphylococcal pneumonia and extensive infection of the legs at the sites of the cut-down infusions. Her convalescence has also been slow. The large thigh ulcerations have healed but the ankle ulcerations have not yet closed. A chronic bronchitis is still present. There has been no improvement yet in either height or development. CASE II (Fig. 2). J.T. Female. The onset of ulcerative colitis was at the age of 9 years. During the following 6 years, she had several hospital admissions for severe exacerbations of bloody diarrhea requiring transfusions. Temporary improvement occurred each time. The colon, however, showed progressive disease. During the last admission the symptoms did not abate despite corticoids, transfusions, and psychotherapy for 3 months on the psychiatric service. The patient's development was retarded and the growth stunted. At the age
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Fig. 1 (Case I). A, Patient at the age of 1772. Height 4 feet 8 inches. Onset at age of 8. Operation at age of 17. B, Roentgen film before operation, showing marked shortening of the colon, loss of haustrations, serrations of the luminal contours, and segmental narrowing of the left side of the colon. of 15}.1 years (when ileostomy and total proctocolectomy were performed) her height was 4 feet 7 inches. The epiphyseal age was much younger; the breasts, pubic hair and menses had failed to develop. Following total proctocolectomy and ileostomy on June 30, 1959, the anemia disappeared, the patient became active, gained weight, and felt well. However, height and sexual development have not yet progressed in any way. The pathologic specimen showed marked acute and chronic ulcerative colitis with fibrosis. CASE III. S.R. Female. The onset was at the age of 10 years. Repeated transfusions were necessary because of hemorrhage. Roentgen examinations established the presence of universal ulcerative colitis. Rectovaginal and perianal fistulas developed. Intermittent use of antibiotics and continuous administration of corticoids for 3 years were to no avail. She was markedly retarded in growth and development. A moderate kyphosis was present. On November 20, 1957, when the patient was 13}.1 years old, ileostomy and subtotal colectomy were performed at The Mount Sinai Hospital. The colon
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Fig. 2 (Case II). A, Patient at the age of 16, shortly after operation, wearing temporary appliance. Height 4 feet 7 inches. B, Roentgen film before operation, showing marked shortening of the colon, loss of haustrations, serrations of the luminal contours. There is narrowing at the ileocecal valve with dilatation of the ileum proximally.
showed advanced, diffuse ulcerative colitis. Two polyps were present. Although the postoperative course was prolonged, she recovered well and returned to physical activities which had been denied by the disease. Her nutrition and tissue turgor improved markedly. However, there was slight or virtually no improvement in height or development. Breast size did increase slightly and scant pubic hair appeared, but no other changes could be noted. At the age of almost 15 years, she was still stunted and appeared to be no older than 11 years. Early in 1959, at the age of 15 years, abdominoperineal resection of the rectum was performed. The lower sigmoid was found to be the site of an adenocarcinoma with lymph node metastases. Since the last operation, she has developed inguinal lymph node enlargement which responded to radiotherapy. Her growth and development have remained unchanged.
Recovery of Growth and Development CASE IV. D.F. Female. Ulcerative colitis began at the age of 8 years with bloody diarrhea. She had 9 hospital admissions in the following 2 years. Therapy
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included full doses of corticoids. She was extremely thin and considerably smaller than her contemporaries at the age of 10, when subtotal colectomy was performed in 1953. In the ensuing 2 years she had several readmissions for ileostomy dysfunction. Revision of ileostomy was finally performed, at the same time as abdominoperineal resection of the rectum in 1955. The colon and rectum showed advanced, diffuse ulcerative colitis with fibrosis. Increase in height and weight has been gradual but steady. At the age of 12, she began to menstruate, breasts developed, and her height had reached above 5 feet. Thus, this patient was operated upon at the age of 10, two years after the onset of ulcerative colitis during which her size and development were less than normal. Following operation-well before puberty-her development and growth have proceeded normally.
Partial Recovery of Growth and Development CASE V. L.M. Female. Diffuse ulcerative colitis began at the age of 11 years. Bloody diarrhea, arthralgias, rectal abscesses and rectovaginal fistula developed. Corticoids, at first moderately effective, later failed. On the children's psychiatric service she showed no improvement. At the age of 15 years, when she was admitted to The Mount Sinai Hospital, on February 8, 1958, she was bedridden, exceptionally emaciated, listless, and had the appearance of a child of 11 years. Because of her poor general condition, an ileostomy alone-as the first stage-was performed. The postoperative course was smooth. In the following months the change in her appearance and behavior was striking. She became more mature looking, attractive and well nourished. In August 1959 a total proctocolectomy was performed with an uneventful recovery. Since the first operation, two years ago, her breasts have not developed but pubic hair has appeared. Her height has increased an inch. Now at the age of 17, she is still immature in appearance and her height is still under 5 feet, but she is taller and older looking than she was before operation. No Retardation of Growth and Development CAsE VI (Fig. 3). D.S. Male. The onset of ulcerative colitis was at the age of 12 years, with severe abdominal cramps and bloody diarrhea lasting several months. Remission occurred on corticoid therapy. Six months later, an episode of toxemia with marked distention, fever and watery diarrhea responded to nasogastric intestinal intubation and antibiotics. The corticoids were continued in increased dosage. After recovery the patient continued to have recurrences of bloody diarrhea and fever. His nutrition was extremely poor, and he was unable to attend school. However, he continued to grow rapidly and to develop sexually at a normal rate. He was finally admitted to The Mount Sinai Hospital at the age of 15 for rlefinitive surgery. After admission, hemorrhage occurred requiring emergency ileostomy and total proctocolectomy, in February 1959. The colon and rectum showed advanced ulcerative colitis with denudation of the mucosa, pseudopolyps and marked fibrosis. He has now reached 6 feet 2 inches in height, has matured, and continues to gain weight. CAsE VII. J.G. Female. With onset of the menarche at the age of 12, ulcerative colitis began. Bloody diarrhea and anemia were the principal symptoms. During the next 2 years, repeated admissions were necessary for transfusions.
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Fig. 3 (Case VI). A, Patient at the age of 16. Height 6 feet 2 inches. Onset at age of 12. Operation at age of 15. B, Roentgen film before operation, showing marked shortening of the colon, loss of haustrations, serrations of the luminal contours, and small irregular defects representing pseudopolyps.
Sigmoidoscopy and roentgen examinations showed that universal ulcerative colitis with pseudopolyps was present. Prolonged courses of corticoids and intensive psychotherapy had no effect on the progressive character and the disabling results of the disease. Her last admission was for hemorrhage requiring several transfusions. Her growth and development had proceeded normally throughout the illness. On February 28, 1958, at the age of 14~ years, ileostomy and total proctocolectomy were performed at The Mount Sinai Hospital. The colon and rectum were involved by advanced ulcerative colitis with numerous pseudopolyps. Her growth and development have continued in the 2 years since. She is taller than average and normally mature. SUMMARY OF FINDINGS
Of the five patients with infantilism, only one has shown evidence of proceeding to relatively normal growth and maturity (Case I, the
Surgical Treatment of Ulcerative Colitis in Pubertal Years
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patient whose disease began at eight years and was operated upon at the age of ten). A second patient has grown slightly but has not yet matured at the age of 17 (Case V, the patient whose disease began at the age of 11, with operation at the age of 15). The remaining three with retardation have continued to be stunted and immature, despite colectomy. One developed carcinoma in the rectal stump. This is apparently the second reported instance of the association of ulcerative colitis, infantilism and carcinoma of the colon.l' The two patients in whom growth and development advanced normally during illness have continued to progress postoperatively (in both, onset of the colitis was at the age of 12 years and operation at 1472 years). All the patients in this series were highly intelligent, well above average for their chronologie age. DISCUSSION
Retardation in growth and development has been reported in many chronic debilitating disease states (such as renal disease, congenital and rheumatic heart disease, congenital hemolytic icterus, celiac disease, diabetes mellitus, Still's disease, leprosy, malaria, tuberculosis). 3 Ileitis and infantilism have also occurred concomitantly. 8 • 16 • 17 Infantilism associated with ulcerative colitis was first discussed by Davidson in 1939. 4 Benson and Bargen, 3 in reporting 14 cases, stated that the term "chetivism" (puniness) had been coined earlier by Bauer1 to describe this retarded state. An examination of the details of their cases indicates that only one patient later achieved normal height and maturity; a few others added some growth and reached sexual development but remained distinctly below average. The great majority remained stunted and did poorly. Ricketts and Palmer 12 found that three of 23 children with ulcerative colitis had infantilism. Various causes have been suggested. The possible nutritional basis for infantilism has been particularly emphasized. The child severely ill with ulcerative colitis is universally low in caloric intake, high in nitrogen loss, and deficient in vitamins, minerals and fluids. The need for these in the growing organism is great and, therefore, marked retardation is apt to occur in patients who have severe colitis during the period of physical and sexual development. Malnutrition clinically 6 and experimentally 18 has been shown to have marked effects on growth and development. The lack of essential amino-acids can also produce extreme interference with growth. 14 Vitamin deficiencies have been found to affect adversely the endocrine control of growth 10 and maturity.l 6 Calcium loss or restriction has been
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demonstrated to halve the rate of growth in animals.l 3 Other prolonged mineral losses can alter spermatogenesis and ovarian development. 6 • 19 Chronic infection, producing endocrine malfunction, has also been offered as a contributing factor to retardation. 1 • 3 Although the evidence is meager, it may be of interest that the anterior pituitary gland of one of the patients with ulcerative colitis and infantilism described by Davidson4 showed basophilic hyperplasia. However, the only conclusion possible on the basis of present knowledge is that the mechanism of retardation in ulcerative colitis is not known. Moreover, totally unexplained is the fact that some children become stunted while others with equally severe symptoms, nutritional deficiencies and pathologic changes in the colon continue to grow normally and mature sexually. Furthermore, it is not understood why some individuals fail to resume growth and maturation even after cure of the disease by surgical or medical means. What is certain is that, once the retardation occurs and the patient enters the pubertal years with the underlying disease process still present, he has a high chance of never recovering growth or even full maturity-even after extirpation of the diseased colon. Thus, the years immediately before puberty are vital in deciding on operative treatment of ulcerative colitis. If the child is permitted to reach puberty chronologically while still stunted, the retardation may continue beyond recall, as in Cases I, II and III. Even the patient in Case V has had only partial restoration. It is to be noted that the only child with retardation who recovered growth and development completely was operated upon at the age of ten, well before puberty. However, as long as the child continues to grow normally (as in Cases VI and VII), the indications for col~ctomy can depend on other factors. The pathologic state of the bowel evidently bears no relationship to the degree of growth or development, for the patients with normal development had as advanced disease as those with marked stunting. Comparison of the roentgen films (Figs. 1, B, 2, B, 3, B) confirms this observation. The reaction of the patient to the disease is, therefore, the determining factor in choosing surgery. Consequently, the presence of manifest retardation of growth and maturity requires extirpation of the diseased colon before the time of puberty, no matter what the pathologic state of the bowel. SUMMARY
The case studies of seven children, with the onset of ulcerative colitis between the ages of eight and 12 and later operated upon, are used to illustrate the propositions:
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1. Retardation of growth and development (infantilism) in the prepubertal years is a clear reason for performing colectomy before puberty has been reached. 2. The retardation has no apparent relationship to the degree of pathologic change in the colon. REFERENCES
1. Apert, E.: Infantilism. London, Martin Hopkinson, Ltd., 1933. 2. Bacon, H. E.: Ulcerative Colitis. Philadelphia and Montreal, J. B. Lippincott
Co., 1958. 3. Benson, R. E. and Bargen, J. A.: Chronic Ulcerative Colitis as a Cause of Retarded Sexual and Somatic Development. Gastroenterology 1: 147, 1943. 4. Davidson, S.: Infantilism in Ulcerative Colitis. Arch. Int. Med. 64: 1187, 1939. 5. Hirabayshi, N.: Experimentelle Untersuchungen under den Einfluss der Salze. Virchow's Arch. f. Path. Anat. 250: 661, 1924. 6. Jackson, C. M.: Recent Work on Effects of Inanition and Malnutrition on Growth and Structure. Arch. Path. 7: 1042, 1929. 7. King, R. C., Lindner, A. E. and Pollard, H. M.: Chronic Ulcerative Colitis in Childhood. Arch. Dis. Childhood 31,: 257, 1959. 8. Logan, A. H. and Brown, P. W.: Infantilism and Ileitis. Proc. Staff Meet. Mayo Olin. 13: 335, 1938. 9. Lyons, A. S.: Ulcerative Colitis in Children. Pediat. Olin. North America 3: 153,1956. 10. McCollum, E. V. and Simmonds, N.: Newer Knowledge of Nutrition. New York, Macmillan Co., 1929. 11. Ricketts, W. E., Benditt, E. and Palmer, W. L.: Chronic Ulcerative Colitis with Infantilism and Carcinoma of Colon. Gastroenterology 5: 272, 1945. 12. Ricketts, W. E. and Palmer, W. L.: Complications of Ulcerative Colitis. Gastroenterology 7: 55, 1946. 13. Simmonds, N.: Observations on Rearing of Young. Am. J. Hyg. 4: 1, 1924. 14. Smith, A. H.: Phenomena of Retarded Growth. J. Nutrition 4:427, 1931. 15. Snapper, I., Groen, J. and Foyer, A.: Infantilism and Ileitis. Proc. Soc. Internat. Congress of Gastroenterology, 1937, p. 935. 16. Sutton, T. S. and Brief, B. J.: Cellular Changes in Hypophyses of Vitamin A Deficient Rats. Endocrinology 23: 211, 1938. 17. Tanner, N. C.: Terminal Ileitis and Infantilism. Proc. Royal Soc. Med. 32: 444, 1939. 18. Waters, H. S.: Capacity of Animals to Grow Under Adverse Conditions. Agricultural Science 29: 71, 1908. 7 East 80th Street New York 21, N.Y. (Dr. Lyons)
IVAN D. BARONOFSKY, M.D., F.A.C.S. Surgeon-in-Chief, The Mount Sinai Hospital; Clinical Professor of Surgery, College of Physicians and Surgeons, Columbia University, New York, N.Y.
THE decision to perform ileostomy and colectomy in childhood is difficult at best. The marked reluctance to leaving a permanent ileostomy in a child is understandable, and the deferment of surgery may well be wise, provided the danger to life is minimal and the general condition of the patient remains good. However, too often, before surgical therapy is accepted, the patient is permitted to decline to a hopeless state from which restoration is virtually impossible without operation and survival with operation is problematic. 7 In a general way, both in children and in adults, we have placed more reliance on the patient's reaction to the disease than on the state of the bowel-as the guidepost to surgery. Danger to life (e.g., acute fulminating toxemia, massive hemorrhage, perforation) and invalidism (e.g., debility, rectovaginal fistula, resistant pyoderma and ulceration, arthritis) are, therefore, our two main indications for colectomy. 9 But what of the child either with persistent, prolonged ulcerative colitis or with frequent recrudescences who maintains general nutrition and strength between bouts and who manages to carry on despite the limitations of cramps, diarrhea and anemia? Recently we have come to realize more forcefully that an added reason for surgery in children is retardation of growth and development. The child who remains stunted and immature until into puberty may never reach full growth after recovery from the illness or indeed even
999
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ALBERTS. LYONS1 IVAN
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BARONOFSKY
after surgical extirpation of the colon if long delayed. On the other hand, in those whose height and development increase normally despite the presence of ulcerative colitis, the indications for surgery appear to be the same as in adults. The purpose of this study is to advance the proposition that retardation of growth and development during the course of ulcerative colitis in the prepubertal years is a separate and clear indication for performing colectomy before puberty has been reached. MATERIAL
Seven patients were treated surgically whose onset of ulcerative colitis was at eight to 12 years of age. In five, stunting and retardation of development (infantilism) had occurred preoperatively. In two, growth before operation had been normal. Operation (colectomy) was performed at the ages of ten to 16. CASE ABSTRACTS
No Recovery of Growth or Development CASE I (Fig. 1). R.B. Female. The gradual onset of ulcerative colitis occurred at the age of 8 years, with cramps, bloody diarrhea, and low grade fever. During the following 9 years, the disease was progressive and resistant to all forms of medical therapy-including corticoids, antibiotics and azulfidine. The complications which developed were: pyoderma gangrenosum with large ulcerations of the thighs, colocolonic fistula, rectovaginal fistula, arthritis of the ankles. She had 4 hospital admissions to The Mount Sinai Hospital, the last of which wa.S in February 1959. She was exceptionally stunted in height and development. At the age of almost 17 years, she had the appearance of a child of 11, except for the presence of pubic hair. She had menstruated occasionally and scantily for a year. There was mild dorsal kyphosis. On March 24, 1959, ileostomy and total proctocolectomy were performed. The pathologic specimen showed chronic nonspecific ulcerative colitis with multiple inflammatory polyps. The postoperative course was stormy and prolonged. She developed staphylococcal pneumonia and extensive infection of the legs at the sites of the cut-down infusions. Her convalescence has also been slow. The large thigh ulcerations have healed but the ankle ulcerations have not yet closed. A chronic bronchitis is still present. There has been no improvement yet in either height or development. CASE II (Fig. 2). J.T. Female. The onset of ulcerative colitis was at the age of 9 years. During the following 6 years, she had several hospital admissions for severe exacerbations of bloody diarrhea requiring transfusions. Temporary improvement occurred each time. The colon, however, showed progressive disease. During the last admission the symptoms did not abate despite corticoids, transfusions, and psychotherapy for 3 months on the psychiatric service. The patient's development was retarded and the growth stunted. At the age
Surgical Treatment of Ulcerative Colitis in Pubertal Years
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Fig. 1 (Case I). A, Patient at the age of 1772. Height 4 feet 8 inches. Onset at age of 8. Operation at age of 17. B, Roentgen film before operation, showing marked shortening of the colon, loss of haustrations, serrations of the luminal contours, and segmental narrowing of the left side of the colon. of 15}.1 years (when ileostomy and total proctocolectomy were performed) her height was 4 feet 7 inches. The epiphyseal age was much younger; the breasts, pubic hair and menses had failed to develop. Following total proctocolectomy and ileostomy on June 30, 1959, the anemia disappeared, the patient became active, gained weight, and felt well. However, height and sexual development have not yet progressed in any way. The pathologic specimen showed marked acute and chronic ulcerative colitis with fibrosis. CASE III. S.R. Female. The onset was at the age of 10 years. Repeated transfusions were necessary because of hemorrhage. Roentgen examinations established the presence of universal ulcerative colitis. Rectovaginal and perianal fistulas developed. Intermittent use of antibiotics and continuous administration of corticoids for 3 years were to no avail. She was markedly retarded in growth and development. A moderate kyphosis was present. On November 20, 1957, when the patient was 13}.1 years old, ileostomy and subtotal colectomy were performed at The Mount Sinai Hospital. The colon
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Fig. 2 (Case II). A, Patient at the age of 16, shortly after operation, wearing temporary appliance. Height 4 feet 7 inches. B, Roentgen film before operation, showing marked shortening of the colon, loss of haustrations, serrations of the luminal contours. There is narrowing at the ileocecal valve with dilatation of the ileum proximally.
showed advanced, diffuse ulcerative colitis. Two polyps were present. Although the postoperative course was prolonged, she recovered well and returned to physical activities which had been denied by the disease. Her nutrition and tissue turgor improved markedly. However, there was slight or virtually no improvement in height or development. Breast size did increase slightly and scant pubic hair appeared, but no other changes could be noted. At the age of almost 15 years, she was still stunted and appeared to be no older than 11 years. Early in 1959, at the age of 15 years, abdominoperineal resection of the rectum was performed. The lower sigmoid was found to be the site of an adenocarcinoma with lymph node metastases. Since the last operation, she has developed inguinal lymph node enlargement which responded to radiotherapy. Her growth and development have remained unchanged.
Recovery of Growth and Development CASE IV. D.F. Female. Ulcerative colitis began at the age of 8 years with bloody diarrhea. She had 9 hospital admissions in the following 2 years. Therapy
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included full doses of corticoids. She was extremely thin and considerably smaller than her contemporaries at the age of 10, when subtotal colectomy was performed in 1953. In the ensuing 2 years she had several readmissions for ileostomy dysfunction. Revision of ileostomy was finally performed, at the same time as abdominoperineal resection of the rectum in 1955. The colon and rectum showed advanced, diffuse ulcerative colitis with fibrosis. Increase in height and weight has been gradual but steady. At the age of 12, she began to menstruate, breasts developed, and her height had reached above 5 feet. Thus, this patient was operated upon at the age of 10, two years after the onset of ulcerative colitis during which her size and development were less than normal. Following operation-well before puberty-her development and growth have proceeded normally.
Partial Recovery of Growth and Development CASE V. L.M. Female. Diffuse ulcerative colitis began at the age of 11 years. Bloody diarrhea, arthralgias, rectal abscesses and rectovaginal fistula developed. Corticoids, at first moderately effective, later failed. On the children's psychiatric service she showed no improvement. At the age of 15 years, when she was admitted to The Mount Sinai Hospital, on February 8, 1958, she was bedridden, exceptionally emaciated, listless, and had the appearance of a child of 11 years. Because of her poor general condition, an ileostomy alone-as the first stage-was performed. The postoperative course was smooth. In the following months the change in her appearance and behavior was striking. She became more mature looking, attractive and well nourished. In August 1959 a total proctocolectomy was performed with an uneventful recovery. Since the first operation, two years ago, her breasts have not developed but pubic hair has appeared. Her height has increased an inch. Now at the age of 17, she is still immature in appearance and her height is still under 5 feet, but she is taller and older looking than she was before operation. No Retardation of Growth and Development CAsE VI (Fig. 3). D.S. Male. The onset of ulcerative colitis was at the age of 12 years, with severe abdominal cramps and bloody diarrhea lasting several months. Remission occurred on corticoid therapy. Six months later, an episode of toxemia with marked distention, fever and watery diarrhea responded to nasogastric intestinal intubation and antibiotics. The corticoids were continued in increased dosage. After recovery the patient continued to have recurrences of bloody diarrhea and fever. His nutrition was extremely poor, and he was unable to attend school. However, he continued to grow rapidly and to develop sexually at a normal rate. He was finally admitted to The Mount Sinai Hospital at the age of 15 for rlefinitive surgery. After admission, hemorrhage occurred requiring emergency ileostomy and total proctocolectomy, in February 1959. The colon and rectum showed advanced ulcerative colitis with denudation of the mucosa, pseudopolyps and marked fibrosis. He has now reached 6 feet 2 inches in height, has matured, and continues to gain weight. CAsE VII. J.G. Female. With onset of the menarche at the age of 12, ulcerative colitis began. Bloody diarrhea and anemia were the principal symptoms. During the next 2 years, repeated admissions were necessary for transfusions.
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Fig. 3 (Case VI). A, Patient at the age of 16. Height 6 feet 2 inches. Onset at age of 12. Operation at age of 15. B, Roentgen film before operation, showing marked shortening of the colon, loss of haustrations, serrations of the luminal contours, and small irregular defects representing pseudopolyps.
Sigmoidoscopy and roentgen examinations showed that universal ulcerative colitis with pseudopolyps was present. Prolonged courses of corticoids and intensive psychotherapy had no effect on the progressive character and the disabling results of the disease. Her last admission was for hemorrhage requiring several transfusions. Her growth and development had proceeded normally throughout the illness. On February 28, 1958, at the age of 14~ years, ileostomy and total proctocolectomy were performed at The Mount Sinai Hospital. The colon and rectum were involved by advanced ulcerative colitis with numerous pseudopolyps. Her growth and development have continued in the 2 years since. She is taller than average and normally mature. SUMMARY OF FINDINGS
Of the five patients with infantilism, only one has shown evidence of proceeding to relatively normal growth and maturity (Case I, the
Surgical Treatment of Ulcerative Colitis in Pubertal Years
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patient whose disease began at eight years and was operated upon at the age of ten). A second patient has grown slightly but has not yet matured at the age of 17 (Case V, the patient whose disease began at the age of 11, with operation at the age of 15). The remaining three with retardation have continued to be stunted and immature, despite colectomy. One developed carcinoma in the rectal stump. This is apparently the second reported instance of the association of ulcerative colitis, infantilism and carcinoma of the colon.l' The two patients in whom growth and development advanced normally during illness have continued to progress postoperatively (in both, onset of the colitis was at the age of 12 years and operation at 1472 years). All the patients in this series were highly intelligent, well above average for their chronologie age. DISCUSSION
Retardation in growth and development has been reported in many chronic debilitating disease states (such as renal disease, congenital and rheumatic heart disease, congenital hemolytic icterus, celiac disease, diabetes mellitus, Still's disease, leprosy, malaria, tuberculosis). 3 Ileitis and infantilism have also occurred concomitantly. 8 • 16 • 17 Infantilism associated with ulcerative colitis was first discussed by Davidson in 1939. 4 Benson and Bargen, 3 in reporting 14 cases, stated that the term "chetivism" (puniness) had been coined earlier by Bauer1 to describe this retarded state. An examination of the details of their cases indicates that only one patient later achieved normal height and maturity; a few others added some growth and reached sexual development but remained distinctly below average. The great majority remained stunted and did poorly. Ricketts and Palmer 12 found that three of 23 children with ulcerative colitis had infantilism. Various causes have been suggested. The possible nutritional basis for infantilism has been particularly emphasized. The child severely ill with ulcerative colitis is universally low in caloric intake, high in nitrogen loss, and deficient in vitamins, minerals and fluids. The need for these in the growing organism is great and, therefore, marked retardation is apt to occur in patients who have severe colitis during the period of physical and sexual development. Malnutrition clinically 6 and experimentally 18 has been shown to have marked effects on growth and development. The lack of essential amino-acids can also produce extreme interference with growth. 14 Vitamin deficiencies have been found to affect adversely the endocrine control of growth 10 and maturity.l 6 Calcium loss or restriction has been
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D.
BARONOFSKY
demonstrated to halve the rate of growth in animals.l 3 Other prolonged mineral losses can alter spermatogenesis and ovarian development. 6 • 19 Chronic infection, producing endocrine malfunction, has also been offered as a contributing factor to retardation. 1 • 3 Although the evidence is meager, it may be of interest that the anterior pituitary gland of one of the patients with ulcerative colitis and infantilism described by Davidson4 showed basophilic hyperplasia. However, the only conclusion possible on the basis of present knowledge is that the mechanism of retardation in ulcerative colitis is not known. Moreover, totally unexplained is the fact that some children become stunted while others with equally severe symptoms, nutritional deficiencies and pathologic changes in the colon continue to grow normally and mature sexually. Furthermore, it is not understood why some individuals fail to resume growth and maturation even after cure of the disease by surgical or medical means. What is certain is that, once the retardation occurs and the patient enters the pubertal years with the underlying disease process still present, he has a high chance of never recovering growth or even full maturity-even after extirpation of the diseased colon. Thus, the years immediately before puberty are vital in deciding on operative treatment of ulcerative colitis. If the child is permitted to reach puberty chronologically while still stunted, the retardation may continue beyond recall, as in Cases I, II and III. Even the patient in Case V has had only partial restoration. It is to be noted that the only child with retardation who recovered growth and development completely was operated upon at the age of ten, well before puberty. However, as long as the child continues to grow normally (as in Cases VI and VII), the indications for col~ctomy can depend on other factors. The pathologic state of the bowel evidently bears no relationship to the degree of growth or development, for the patients with normal development had as advanced disease as those with marked stunting. Comparison of the roentgen films (Figs. 1, B, 2, B, 3, B) confirms this observation. The reaction of the patient to the disease is, therefore, the determining factor in choosing surgery. Consequently, the presence of manifest retardation of growth and maturity requires extirpation of the diseased colon before the time of puberty, no matter what the pathologic state of the bowel. SUMMARY
The case studies of seven children, with the onset of ulcerative colitis between the ages of eight and 12 and later operated upon, are used to illustrate the propositions:
Surgical Treatment of Ulcerative Colitis in Pubertal Years
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1. Retardation of growth and development (infantilism) in the prepubertal years is a clear reason for performing colectomy before puberty has been reached. 2. The retardation has no apparent relationship to the degree of pathologic change in the colon. REFERENCES
1. Apert, E.: Infantilism. London, Martin Hopkinson, Ltd., 1933. 2. Bacon, H. E.: Ulcerative Colitis. Philadelphia and Montreal, J. B. Lippincott
Co., 1958. 3. Benson, R. E. and Bargen, J. A.: Chronic Ulcerative Colitis as a Cause of Retarded Sexual and Somatic Development. Gastroenterology 1: 147, 1943. 4. Davidson, S.: Infantilism in Ulcerative Colitis. Arch. Int. Med. 64: 1187, 1939. 5. Hirabayshi, N.: Experimentelle Untersuchungen under den Einfluss der Salze. Virchow's Arch. f. Path. Anat. 250: 661, 1924. 6. Jackson, C. M.: Recent Work on Effects of Inanition and Malnutrition on Growth and Structure. Arch. Path. 7: 1042, 1929. 7. King, R. C., Lindner, A. E. and Pollard, H. M.: Chronic Ulcerative Colitis in Childhood. Arch. Dis. Childhood 31,: 257, 1959. 8. Logan, A. H. and Brown, P. W.: Infantilism and Ileitis. Proc. Staff Meet. Mayo Olin. 13: 335, 1938. 9. Lyons, A. S.: Ulcerative Colitis in Children. Pediat. Olin. North America 3: 153,1956. 10. McCollum, E. V. and Simmonds, N.: Newer Knowledge of Nutrition. New York, Macmillan Co., 1929. 11. Ricketts, W. E., Benditt, E. and Palmer, W. L.: Chronic Ulcerative Colitis with Infantilism and Carcinoma of Colon. Gastroenterology 5: 272, 1945. 12. Ricketts, W. E. and Palmer, W. L.: Complications of Ulcerative Colitis. Gastroenterology 7: 55, 1946. 13. Simmonds, N.: Observations on Rearing of Young. Am. J. Hyg. 4: 1, 1924. 14. Smith, A. H.: Phenomena of Retarded Growth. J. Nutrition 4:427, 1931. 15. Snapper, I., Groen, J. and Foyer, A.: Infantilism and Ileitis. Proc. Soc. Internat. Congress of Gastroenterology, 1937, p. 935. 16. Sutton, T. S. and Brief, B. J.: Cellular Changes in Hypophyses of Vitamin A Deficient Rats. Endocrinology 23: 211, 1938. 17. Tanner, N. C.: Terminal Ileitis and Infantilism. Proc. Royal Soc. Med. 32: 444, 1939. 18. Waters, H. S.: Capacity of Animals to Grow Under Adverse Conditions. Agricultural Science 29: 71, 1908. 7 East 80th Street New York 21, N.Y. (Dr. Lyons)