- Email: [email protected]
Surgical results in patients with ulcerative colitis treated with and without corticosteroids
The American Journal of Surgery VOLUME
113
FEBRUARY
1967
NUMBER
2
Surgical Results in Patients with Ulcerative Colitis Treated with and without Corticosteroids* FREDRICKW. MARX, JR., M.D. AND WILEY
From the Department of Surgery, Medicine, Los Angeles, California.
F. BARKER, M.D., Los Angeles, California
operatively must be protected with heavy doses of these same drugs during and after operation if an adrenal crisis is to be avoided, surgeons are now faced with an additional consideration. Not only are they operating upon patients critically ill from ulcerative colitis, but also on patients whose physiologic responses have been altered by abnormal dosages of these potent hormones. The use of steroids pre- and postoperatively has been welcomed by some gastroenterologists and surgeons. Hayes and Kushlan [3] and Colcock and Mathieson [a], for example, have advocated preoperative corticosteroid therapy, for they believed that the drugs improved the patients’ condition to the extent that they better tolerated the surgical procedure. Prohaska, Dragstedt, and Thompson [;I reported some increased difficulty with wound healing, and Brooks and Veith [6] expressed concern about sepsis in patients treated with corticosteroids, but both groups concluded that the drugs were not particularly detrimental to their patients with ulcerative colitis. In the reports of others, surgical experiences with steroid-treated patients with ulcerative colitis were by no means innocuous. In a selected series of patients treated at our hospital [7] a large number of severe complications was found among twenty-one steroid-treated patients; these complications, except for two cases of postoperative hypotension, did not occur at all among eighteen patients not treated with steroids.
1T.C.L.A. School of
study of Truelove and T Wittsdouble-blind [I ] in 1955 established without quesHE
tion the beneficial effects of steroids on the clinical course of ulcerative colitis. The improvement was shown subsequently by serial rectal biopsies to be truly anatomic [Z] and not merely due to the sense of well being, increased appetite, and reduction of fever which occur as a by-product of steroid therapy. Enthusiasm for the use of systemic corticosteroids, however, has always been tempered by the realization that untoward effects commonly occur. If use is prolonged and dosage is high, a true Cushing’s syndrome or a variant of it with hypertension, electrolyte imbalance, hypokalemia, muscle weakness, diabetes, osteoporosis, acute psychosis, and an increased susceptibility to infection may develop. The incidence of peptic ulceration is increased with prolonged therapy, and in children retardation of growth may occur. Primarily because of these problems, corticotrophin and the corticosteroids have been for the most part reserved for those patients in whom ulcerative colitis has proved refractory. Colectomy with ileostomy has come to be employed as the final therapeutic step and is suggested only for those patients whose cases represent medical failures. Since any patient who has received a substantial amount of systemic corticosteroids pre-
* Presented at the Seventh Annual Meeting of the Society for Surgery of the Alimentary Chicago, Illinois, June 25 and 26, 1966. 157
Tract,
Marx
158
and Barker
Because of such unfavorable results, physicians in the Departments of Gastroenterology and Surgery at the U.C.L.A. Center for the Health Sciences have tended to use corticosteroids sparingly, if at all, on patients who appear likely candidates for colectomy. On the other hand, many of our patients have been referred to our hospital having been treated already with systemic corticosteroids, and their continued use during and after surgery has been mandatory. It is the purpose of this retrospective study to compare the two groups of patients with ulcerative colitis, those treated with and without corticosteroids, with respect to surgical morbidity and mortality to determine what effect these hormones have had on their hospital course. MATERIAL
AND METHODS
The records of all patients with ulcerative colitis or granulomatous colitis (ileocolitis) operated upon at the U.C.L.A. Center for the Health Sciences were reviewed for the ten year period 1955 to 1965. The series was composed of 127 patients operated on for symptomatic ulcerative colitis; four underwent two procedures, primarily because their disease was confined initially to one portion of the large bowel (or was thought to be). At a later date the remainder of the colon or rectum still in continuity with the fecal stream became so involved with disease that it had to be resected as well. The patients’ ages ranged from four months to seventy-one years, but as in other series, the large majority were young adults. Seventy of the patients were women and fifty-seven were men. Specifically excluded from the series are those operations performed as a second procedure completely electively, such as an abdominoperineal resection of the involved part of the rectum in patients who had initially had a subtotal colectomy and ileostomy. Also excluded are those who have had a revision of their ileostomy or an operation for intestinal obstruction many months or years after leaving the hospital On the other hand, if patients had reoperation for ileostomy revision or intestinal obstruction in the immediate postoperative period, their procedures were considered complications of the primary procedure. Any serious intra-abdominal infections which occurred months or in some cases two or three years after the primary operation and which were clearly related to it, however, were considered complications of the operation. Minor stitch abscesses or seromas which did not delay the patient’s discharge from the hospital have been excluded. The patients were subdivided into two groups, those receiving corticosteroids during operation and in the postoperative course and those who did not,
Because corticotrophin (ACTH) and the eorticosteroids were frequently used on the same patient at different times, no attempt has been made to subdivide the series further on the basis of the type of hormone used. Some of those patients not treated with steroids had received systemic cortisone in the past and because of our prejudice against the drugs, it was our practice generally to avoid using them during and after the operative procedure. In some instances plasma cortisol levels were used to help determine whether supplementary corticosteroids would be necessary, while in other cases, the hormones were simply held in readiness if unexplained hypotension or other evidence of adrenal insufficiency should manifest itself during the operation or the postoperative period. If it did, and the number of times this occurred was rare, the patients were considered to be in the steroid-treated group. If there was no history of previous treatment with hormones, but because of unexplained hypotension (as in one case) the patient received heavy therapy with cortisones throughout the immediate postoperative period, he was placed in the steroid-treated group. On the other hand, a patient receiving one or two intravenous doses of cortisone during or after operation was not counted as a steroid-treated patient. It has been our practice to taper steroids rapidly postoperatively, a ten day to two week period usually being allowed after the wound is healed and the patient is doing well However, several patients were discharged from the hospital on maintenance doses of corticosteroids either arbitrarily or because an attempt to discontinue the hormones was unsuccessful earlier. RESULTS
The operations performed by both attending and senior resident surgeons on the 127 patients are listed in Table I and are subdivided into those treated with and without corticosteroids. The most common procedure performed was subtotal colectomy with ileostomy. The rectum and lower sigmoid colon were left in place and the upper end brought out as a mucous fistula through the lower part of the left paramedian incision. Although generally we consider ileostomy, total colectomy, and abdominoperineal removal of the rectum as more definitive procedures, subtotal colectomy with ileostomy was chosen initially because either the patient’s operation was an emergency and was made as short as possible, the patient refused the more extensive operation, the rectum looked salvageable for later ileorectal anastomosis, or the patient was a young man in whom the disease of the rectum seemed less of a problem than the possibility of rendering him impotent as a result American
Journal
of Surgery
Ulcerative
Colitis
T’.4HLE OPERATIONS
PERFORMED
IN PATIENTS
I ULCERATIVE
COLITIS
FROM
1955 TO 1965
Subtotal Colectomy with Ileostomy
Partial Colcctomy with Ileorcctal Anastomosis
Partial Colectomy with Colostomy
Ileostomy
16
31
0
2
0
1
37
37
3
2
1
0
Total l’roctocolcctomy with Ikostomy
Group
n’ITH
159
Transverse Colostomy
Corticosteroidtreated (50 patients) Noncorticosteroidtreated (80 patients*)
* One patient is not included because of death in the operating
of pelvic dissection. The single patient with ileostomy was one in whom an ileorectal anastomosis had been performed five and a half years before but such an exacerbation of disease occurred in the retained rectal segment that an ileostomy was reconstructed. The patient died in the postoperative period from sepsis. Included also is a single patient whose heart stopped in the operating room and upon whom no definitive operation was performed. Of the 131 operations performed, 23 were emergency procedures. (Table II.) Hemorrhage had become massive, a perforation had occurred, or the patient’s condition had rapidly deteriorated in the presence of acute fulminating disease or toxic megacolon with or without imminent perforation. Fourteen of the twenty-three operations were performed on patients treated with corticosteroid. In Table III is listed the total number of corticosteroid and nonsteroid-treated patients; the over-all mortality was between 14 and 15 per cent for both groups. Because the corticosteroid-treated group is weighted so heavily with emergency cases (28 per cent), the four columns on the right of the table have been added to subdivide
TABLE SURGICAL
Total No. of Operations
Group
__
____ __
IX
PATIENTS
-----Deaths-------Total Percentage
TABLE INDICATIONS
II
FOR EMERGENCY
CorticosteroidTreated
Indication
Massive hemorrhage Spontaneous perforation of the colon Severe fulminating disease or toxic megacolon Total
COLECTUMY
Non-
Patients
steroid Treated Patients
3
0
3
3
x
6 9
14
the groups further into emergency and elective cases. Table IV is a compilation of the morbidity statistics for both groups of patients operated upon. The complication listed was a major one for the patient and either was the cause of his death, required a corrective operation, or significantly prolonged the hospital course. The hemorrhage category, for example, includes only patients who had significant gastrointestinal or ink-abdominal bleeding postopera-
III WITH
ULCERATIVE
Emergency Total
COLITIS
Procedures Deaths
Nonemergency ~Procedures-Y Total Deaths
.-
Corticosteroidtreated patients Nonsteroid-treated patients
Vol. 113. Febvuary
MORTALITY
rooin
1967
50
7
81
12
14 14.8
14
5
36
2
9
5
72
7
160
Marx and Barker TABLE
POSTOPERATIVE
IV
COMPLICATIONS ULCERATIVE
Severe sepsis, intra-abdominal abscess, or septicemia Total number Number excluding emergencies Percentage excluding emergencies
emergencies
Severe wound infection Total number Number excluding emergencies Percentage excluding emergencies Wound dehiscence Total number Number excluding
WITH
CorticosteroidTreated Patients
NOtIsteroidTreated Patients
12 5 13.9
12 8 11.1
3 1
3 2
14 8 22.2
8 6 8.3 0 0
4 3 9.7
1 1 2.8
bowel Total number Total excluding emergencies Percentage excluding emergencies
4 3 8.3
2 1 1.4
Severe electrolyte imbalance with prolonged ileus Total number Number excluding emergencies Percentage excluding emergencies
5 3 8.3
3 3 4.2
Mechanical intestinal obstruction Total number Number excluding emergencies Percentage excluding emergencies
3 3 8.3
0 0
Psychosis Total number Number excluding emergencies Percentage excluding emergencies
6 3 8.3
2 0 . .
Convulsions Total number
1
1
4 2
1 0
Necrosis of stoma, severe dysfunction, or severe skin problems Total number
1
4
Bladder Total
0
2
emergencies
Retraction or perforation of mucous listula Total number Total excluding emergencies Percentage excluding emergencies or infarction
HeUKXrhage Total number Number excluding
dysfunction number
of small
emergencies
POSTOPERATIVE WITH
3 0
Perforation
UNCOMPLICATED
COLITIS
Complication
Pneumonia Total number Number excluding
TABLE IN PATIENTS
or urinary fistula
tively and excludes those who may, for example, have had a pint of blood ooze from their perineal wound the night after surgery. When the total number of patients in each category of complications appeared to be weighted against the corticosteroid-treated group, the patients whose cases were treated as emergencies were separated, and the percentage of complications computed from the group whose cases were not considered emergencies.
Group
ULCERATIVE
Tot al No. of Patients*
Total Percentage*
v COURSE
Iii
PATIENTS
COLITIS
Tutal Excluding Emergencies
Percentage Excluding Emergencies
Corticosteroidtreated (50 patients)
23
46
21
58.3
Nonsteroid-treated (81 patients)
53
65.5
51
70.8
*Statistically
significant
to chi square of 4.13,
p =
0.044.
Excluding ileostomy or mechanical urinary tract complications, it is apparent that the corticosteroid-treated patients account for an inordinate proportion of the morbidity statistics, even after allowances are made for the emergency procedures. To view the problem from another light, Table v has been constructed in which patients from each group who left the hospital after a completely uneventful postoperative course are compared. Excluding emergencies, there is an obvious trend in the figures favoring the nonsteroidtreated patient, although only in the total number and total percentages are the figures clearly significant in a statistical comparison. COMMENTS
In reviewing the mortality and morbidity figures in this series we are impressed by the seriousness of the clinical problem facing the surgeon who operates on a patient with ulcerative colitis. If medical therapy were ineffective in all instances, there would be no alternative but early surgery. Conservative therapy, however, including the corticosteroids, is frequently quite efficacious and when weighed against the alternative of an ileostomy for life, usually in a young adult, it is naturally chosen as the initial treatment. Current medical treatment for the disease often consists of an initial phase of diet control, vitamins, sedatives, antispasmodits, antibacterials, and psychotherapy, and in most centers, a second phase in which ‘the corticosteroids are added for those patients who fail to respond to the initial regimen. Colectomy and ileostomy are reserved for those whose disease continues to progress despite all medical efforts. By the time the patient is referred to the surgeon, he has usually lost a considerable amount of weight, is in a state of negative Amevican
Joumal
of Surgery
Ulcerative nitrogen balance, is losing large quantities of electrolytes and often blood through the rectum, and may have one or many of the other complications besides the debilitating diarrhea such as arthritis, pyoderma gangrenosum, uveitis, perirectal abscesses or fistulas, hepatitis, or acute psychosis which frequently accompany the disease. The present surgical treatment of ulcerative colitis, concomitant ileostomy and colectomy, first began to be practiced to any extent at about the same time that corticosteroids were being introduced clinically. Without question, many of the accusations made against the corticosteroids as the surgeon viewed his mortality and morbidity statistics were misdirected. During the past decade it has been fairly well established that the number of perforations of the colon or instances of massive colonic bleeding is no greater now than in the presteroid era, and that certain systemic complications of the disease, such as arthritis, improve as much if not more than the colitis with corticosteroid therapy. Furthermore, even if the patient with typical ulcerative colitis who is referred for colectomy had had no drug or hormonal therapy at all, a lengthy operation of this sort on a debilitated patient would be expected to be hazardous. Estimates of the loss of electrolytes from diarrhea are often difficult to assess preoperatively, and losses after ileostomy are often excessive in the postoperative period. Spillage of contents of the colon from a thin, friable bowel during operation may result in postoperative peritonitis with considerable loss of fluid to extracellular space and sometimes the formation of intra-abdominal abscesses. Resistance to infection of any sort is notoriously low in the chronically depleted patient and the number of wound abscesses or pneumonia would be expected to be high. Because of protein and vitamin depletion, wound healing is commonly delayed and an unusual number of dehiscences or retraction of mucous fistulas could be predicted. Since it is generally accepted that many patients with ulcerative colitis are suffering from deep emotional problems, a fair number of frank postoperative psychoses would be expected to develop during and immediately after the period of stress after colectomy and ileostomy. On the other hand, statistics on morbidity in this study would indicate that steroidtreated patients have more complications postVol. 113. February
1967
Colitis
161
operatively than those in whom the hormones have been withheld. Admittedly, 26 per cent of the steroid-treated patients were operated upon on an emergency basis whereas only 11 per cent of the nonsteroid-treated patients were considered emergency cases, but this bias appears to be built into the corticosteroid-treated group because of current medical practice. For the most part, corticosteroids are reserved for those patients who do not have remission while under other modes of conservative treatment, and if only the majority of such patients respond favorably to steroids, the minority presumably continue to do poorly for the next few weeks or until the gastroenterologist decides that there is no recourse but an operation. During that interval or delay, the conditions of some patients will undoubtedly become emergencies which otherwise would not if a course of corticosteroids had not been instituted. Among the complications listed, several appear to be completely unconnected with whether the patient had or had not received corticosteroids during and after his operative procedure. The fact that in three steroidtreated and in no nonsteroid-treated patients did mechanical intestinal obstruction develop appears completely fortuitous, for at ldparotomy it was necessary only to lyse a few fibrinous adhesions to correct the problem. Urinary tract difficulties were confined to two of the thirtyseven nonsteroid-treated patients who had undergone total proctocolectomy with ileostomy. Stoma1 necrosis or severe ileostomy dysfunction is most certainly a reflection of some technical difficulty during the operation rather than on whether steroids were administered or not. The number of perforations or infarctions of the small bowel was higher in the steroid-treated than in the nonsteroidtreated group, and this finding was stressed as a significant and unique one for steroid-treated patients in a previous report by one of us (W.F.B.) [7]. In this larger series, however, two cases of perforation of the small bowel have occurred among our nonsteroid-treated patients, and more recently a third case occurred in a patient whose final operation is the only one which took place during the ten year period but whose case was not included in either series. This case defied classification into either category besides illustrating an interesting clinical problem.
Marx and Barker The patient was a fourteen year old Dutch girl who had had an emergency subtotal colectomy and ileostomy performed in May 1961, while on heavy steroid therapy. After wound infection and pneumonia, the dose of corticosteroids was tapered off and the patient did well for five months. About that
time the insidious onset of fever, weight loss, and rectal bleeding developed and she returned to the hospital. While she was being studied on the medical service, marked abdominal pain developed. A laparotomy was performed at which two spontaneous perforations of the small bowel were found. Corticosteroids were begun again only just before the second operation, and although the perforations were closed, the patient subsequently died from intra-abdominal abscesses and septicemia. The corticosteroids, however, are not so readily absolved from the increased incidence of the remaining complications among the patients treated with these drugs. It is of considerable interest that except for patients who experienced wound dehiscence, the nonsteroid-treated group also had the same complications as those treated with steroids, but in proportionateIy fewer numbers. As mentioned previously, debilitated patients undergoing a total colectomy with ileostomy would be expected to have certain postoperative difficulties. The corticosteroids, however, are notorious for causing or enhancing the problems from which these patients suffered. Resistance to infection is diminished with the corticosteroids, partly due to an inhibition of a local inflammatory response and possibly due to some generalized effect. If the wound or abdomen should be contaminated during operation or if a respiratory infection should occur, the complication might be expected to grow to major proportions if abetted by cortisone. Severe sepsis, severe wound infections, and pneumonia did occur among twentynine of fifty steroid-treated patients compared with twenty-three of eighty-one who were not treated with steroids. Healing is delayed in animals and in patients receiving large doses of cortisone. A deficiency in the normal fibrous reaction did result in an increased number of wound dehiscences and retraction of mucous fistulas into the abdominal cavity. Without question, the excessive loss of potassium from the preoperative occurrence of coIonic diarrhea or excessive ileostomy drainage postoperatively is enhanced by the effect of the corticosteroids. Generally, in the disease the control of water and electrolytes in the body
presents a formidable problem to the attending physician or surgeon, and this series would indicate that these problems are compounded when corticosteroids are added. The most frequent and troublesome side effect was a severe paralytic ileus which responded only to unusually farge quantities of electrolytes. Serious “hemorrhage” mentioned in Table v does not refer to colonic bleeding in a retained rectal stump, but mainly to upper gastrointestinal bleeding, which is frequently the final occurrence in a series of postoperative complications after colectomy. The so-called “stress” ulcer may occur without the addition of exogenous corticosteroids, but the fact that peptic ulceration is increased with their use is well documented in the literature. In those patients who died from hemorrhage and were autopsied, superficial peptic ulceration was found. Thorn and associates IS] have implicated the corticosteroids as a cause of convulsions in patients with disorders of the central nervous system ; they may also have played a role in the seizures of one of our patients. The cause and effect relationship between the other central nervous system complication, acute psychosis, and the corticosteroids is much better known, and the high number of steroid-treated patients in whom this problem developed postoperatively undoubtedly reflects their use. Considering the greater morbidity among steroid-treated patients with ulcerative colitis who underwent surgical procedures for their disease, it might appear at first paradoxical that the mortality was not greater. We believe that the main reason for this is that corticosteroids in themselves added no completely new complications. Diabetes, osteoporosis, and hypertension, all recognized complications of prolonged steroid therapy not usually associated with ulcerative colitis, either did not occur in our series of patients, or if they did, apparently had no deleterious effect on the immediate postoperative course. With the possibility of sepsis, wound or electrolyte complications, or postoperative psychosis, the attending surgeons treated complications as expeditiously as possible in both groups of patients, and although their incidence was higher in the steroid-treated group, the mortality fortunately was not. We believe that it has been largely because of the similarity of complications in the two Anzerican Journal of Surgery
Ulcerative groups that there have been so many contradictory reports as to whether the steroids are harmful or not in operative treatment of ulcerative colitis. We can only conclude that for patients with ulcerative colitis, just as in patients suffering from arthritis, dermatologic disorders, or blood dyscrasias, the use of cortisone may be quite helpful in alleviating the disease, but the drugs have definite detrimental side effects. If the steroid-treated patient with ulcerative colitis is subjected to an operation, any of these detrimental side effects can be expected to increase the possibility of the development of a serious postoperative complication. SUMMARY
The postoperative course of fifty corticosteroid-treated and eighty-one nonsteroidtreated patients with ulcerative colitis is analyzed in terms of mortality and morbidity. Although the mortality for the two groups is essentially the same, the morbidity is significantly greater for the steroid-treated patients. Although some of the complications were clearly unconnected with administration of the drugs and the complications were not unique to one or the other group, severe wound infections, intra-abdominal abscess, septicemia, wound dehiscence, retraction of mucous fistulas, severe electrolyte imbalance, hemorrhage, convulsions, and psychosis were all increased with corticosteroid administration. REFERENCES 1. TRUELOVE, S. C. and WITTS, L. J. Cortisone in ulcerative colitis: final report on therapeutic trial. &it. M. J., 2: 1041, 1955. 2. TRUELOVE. S. C. Treatment of ulcerative colitis with local hydrocortisone hemisuccinate sodium. &it. A[. /., 2: 1072, 1958. 3. HAYES, M. ;2. and KUSHLA~;, S. D. Influence of hormonal therapy for ulcerative colitis. Gastroenterozogy, 30: 75, 1956. 4. COLCOCK, B. P. and MATHIESON, W. L. Complications of the surgical treatment of chronic ulcerative colitis. .4uch. Surg., i2: 399, 1956. 5. PROHASKA, J. V., DRAGSTEDT, L. R., II, and THOMPSON, R. G. Ulcerative colitis: surgical problems in corticosteroid treated patients. Ann. Surg., 154: 408, 1961. 6. BROOKS, J. R. and I’EITH, F. J. The timing and choice of surgery for ulcerative colitis. J.A.M.A., 194: 115, 1965. 7. KELLNER, H., HERSCH, R. A., and BARKER! W. F. The effect of adrenocortical steroids on the postoperative course of patients with ulcerative colitis. Gnstroenterology, 45: 27, 1963. 8. THORN, G. W., JENKINS, D., LAIDLOW, J. C., GOETZ, Vol. 113.Februavy
1967
Colitis
163
F. C., UINGMAN, J. F., ARONS, W. L., SWEETEN, D. H. P., and MCCRACKEN, B. H. Medical Uses of Cortisone, chapt. 2, p. 96. New York, 1954. Edited by F. D. W. Lukens. McGraw-Hill Book Co., Inc. DISCUSSION CLAUDE 13. WELCH (Boston, Mass.): Dr. Mars. was amazed to learn that your gastroenterologist
I
would consider that no patient about to undergo surgery ought to have steroids. As a matter of fact. in nearly every place in the country, I believe no patient ever comes to surgery without having had a course of steroids; perhaps that accounts for some of our feelings about it. I was also quite interested to note in some of the medical literature the implication that toxic megacolon should be treated by large doses of steroids, and I hope that you will comment upon the complication of megacolon when you close the discussion. JOHN VAN PROHASKA (Chicago, Ill.) : I agree with Dr. Marx in most of the observations he has so well recorded. The most important among these are some of the differences between the corticosteroid-treated patients and those patients not receiving the hormone. As he so well stated, the major difference is a prolonged morbidity. Morbidity is an inclusive term and in the corticosteroid-treated patient it map be broken into several components. Among the factors which contribute to postoperative morbidity, one may include delayed wound healing, disturbance in electrolyte balance, low plasma proteins, and perhaps a vulnerabilitv to wound infection. One must remember that corticosteroids cannot be suddenly discontinued in the immediate postoperative state. Therefore, the postoperative patients linger on in a slowly- decreasing hypersteroid condition. There are permanent complications caused by prolonged use of corticosteroids. Notable among these is the retardation of body growth, producing a real psychological effect on the young patient. Osteoporosis may result in permanent deformity due to compression fractures of the vertebrae. Nevertheless, many of these complications and sequelae which may be attributed to prolonged use of corticosteroids are preventable. We have operated on 260 patients with inflammatory diseases of the bowel who have received corticosteroids for a long time. We find that the incidence of serious complications is no greater than in patients not treated with the hormone. The morbidity of the steroid-treated patients, nevertheless, is markedly prolonged. I am glad to know that somebody else has observed that corticosteroid-treated patients do get along after major surgery provided proper care is given to them. ALBERT S. LYONS (New York, N. Y.): Dr. Barker expressed concern with his 14 per cent mortality as compared with 4 per cent and 2 per cent that is sometimes reported in other quarters. I am not sure
164
Marx and Barker
what that 14 per cent and 4 per cent and 2 per cent mean. I think it is very difficult to compare 100 or 200 patients from one clinic with 100 or 200 in another clinic. So much depends on the state of the disease, the state of the patients who are subjected to surgery, and what proportion in the series they occupy. It is very difficult to classify these for comparison. If these were a few thousand of one series compared with a few thousand of another, the difficulty would be minimized. We have tried to lower the mortality in one small segment of this group, those with toxic dilatation of the colon, by employing cecostomy as a preliminary procedure. We reported this a few years ago and in the intervening years this procedure has been so startling in its efficacy that we have continued it. We must make it clear that it is not for all patients, nor is it a definitive procedure, but merely one to prepare the patient for more definitive surgery. I also believe that in all the clinics throughout the country, the lower mortality is due less to the changes in operative technic than to improvement in the total management of the patient. One of these improvements in total management refers to the use of corticoids. All of us as surgeons undoubtedly deplore the extended and injudicious use of the corticoids. It is certainly dismaying to see a patient who has a disease produced by the corticoids in addition to his ulcerative colitis, but I think we must also recognize that there are patients who are restored from a nearly moribund state, .in great debility and with acute toxemia, to one which permits a more extensive procedure under safer conditions just by the use of the corticoids. I think the danger does exist that once these patients are restored, they will be kept going beyond the point of optimal improvement and will be either subjected to surgery too late or will be carried along while hovering just above disability until a medical disaster occurs. I think it is this mistake that Drs. Barker and Marx are counseling against. B. MARDEN BLACK (Rochester, Minn.): In our institution steroids have always been used rather reluctantly in the treatment of this disease. We are faced with the problem of operating on patients who have been taking large doses of steroids, often for several years, and of course we must learn to adjust to it. With proper preparation of the patient, our experience has been much the same as that recounted and we can operate without too much morbidity. I have been most impressed with impaired healing of wounds and with dehiscences rather than with stoma1 problems. W. H. NICKEL (New York, N. Y.): As a small subgroup of a much larger group of patients we have treated at the Cornell Medical Center there have been seven or eight patients with toxic megacolon. One or more perforations of the colon have developed in three
of these patients, all of whom were taking steroids. The important point that I would like to make is not that the perforation occurred, because perforation has always been one of the leading causes of death in ulcerative colitis both before and after the advent of steroids, but rather the suppression of signs and symptoms by the steroids which one would normally expect to be present when a perforation of the intestinal tract occurs; so much so that we have come to rely more on the daily flat plate of the abdomen, sometimes even taken twice a day, rather than on our diagnostic acumen in patients with this severely critical condition. We have adopted a policy of attempting withdrawal of all steroids after operation with or without the use of ACTH. We find that there is a small group of patients who become addicted to this drug and who are never completely weaned away from it. WILEY F. BARKER (closing): I particularly want to reinforce Dr. Nickel’s observation that you just can’t believe anything that you palpate in the abdomen of a patient who is taking large doses of corticosteroids. Concerning toxic megacolon, I believe that Dr. Truelove has made the statement that the problems of potassium balance that accompany steroids may make the toxic megacolon even worse, and whereas it is undoubtedly true that our surgical management of toxic megacolon has not been good, neither has any other management been good except for that reported by Dr. Lyons. We do not have any experience with that treatment yet, but I anticipate that we will. This has been a rather painful reappraisal of our results in an unusual situation, one in which we have gasteroenterologists who fear the steroids perhaps as much or more than surgeons do. This has resulted in approximately equal experience in treated and nontreated patients. Our gastroenterologists have been wise in refraining from placing critically ill patients who seem destined for the operating room on steroids at the last moment. Neither we nor they believe that there has really been any improvement in the general status of such patients on steroids, and indeed, and I think I am also speaking for the gastroenterologists in this, systemic steroids are apt to be used only in those patients in whom a prompt remission might otherwise be expected and who might not be destined for operation. We would have liked to have discussed the difference in effects of corticosteroids as opposed to ACTH, but there is so much overlap that it is impossible. Thus, we believe steroids have a role in the treatment of ulcerative colitis, but to rephrase Dr. Marx’s last words, when they are used in the patient coming to operation, an increased hazard associated with their use must be recognized. This is not anything specific and is a quantitative rather than a qualitative difference. American Journal of Suvgery
113
FEBRUARY
1967
NUMBER
2
Surgical Results in Patients with Ulcerative Colitis Treated with and without Corticosteroids* FREDRICKW. MARX, JR., M.D. AND WILEY
From the Department of Surgery, Medicine, Los Angeles, California.
F. BARKER, M.D., Los Angeles, California
operatively must be protected with heavy doses of these same drugs during and after operation if an adrenal crisis is to be avoided, surgeons are now faced with an additional consideration. Not only are they operating upon patients critically ill from ulcerative colitis, but also on patients whose physiologic responses have been altered by abnormal dosages of these potent hormones. The use of steroids pre- and postoperatively has been welcomed by some gastroenterologists and surgeons. Hayes and Kushlan [3] and Colcock and Mathieson [a], for example, have advocated preoperative corticosteroid therapy, for they believed that the drugs improved the patients’ condition to the extent that they better tolerated the surgical procedure. Prohaska, Dragstedt, and Thompson [;I reported some increased difficulty with wound healing, and Brooks and Veith [6] expressed concern about sepsis in patients treated with corticosteroids, but both groups concluded that the drugs were not particularly detrimental to their patients with ulcerative colitis. In the reports of others, surgical experiences with steroid-treated patients with ulcerative colitis were by no means innocuous. In a selected series of patients treated at our hospital [7] a large number of severe complications was found among twenty-one steroid-treated patients; these complications, except for two cases of postoperative hypotension, did not occur at all among eighteen patients not treated with steroids.
1T.C.L.A. School of
study of Truelove and T Wittsdouble-blind [I ] in 1955 established without quesHE
tion the beneficial effects of steroids on the clinical course of ulcerative colitis. The improvement was shown subsequently by serial rectal biopsies to be truly anatomic [Z] and not merely due to the sense of well being, increased appetite, and reduction of fever which occur as a by-product of steroid therapy. Enthusiasm for the use of systemic corticosteroids, however, has always been tempered by the realization that untoward effects commonly occur. If use is prolonged and dosage is high, a true Cushing’s syndrome or a variant of it with hypertension, electrolyte imbalance, hypokalemia, muscle weakness, diabetes, osteoporosis, acute psychosis, and an increased susceptibility to infection may develop. The incidence of peptic ulceration is increased with prolonged therapy, and in children retardation of growth may occur. Primarily because of these problems, corticotrophin and the corticosteroids have been for the most part reserved for those patients in whom ulcerative colitis has proved refractory. Colectomy with ileostomy has come to be employed as the final therapeutic step and is suggested only for those patients whose cases represent medical failures. Since any patient who has received a substantial amount of systemic corticosteroids pre-
* Presented at the Seventh Annual Meeting of the Society for Surgery of the Alimentary Chicago, Illinois, June 25 and 26, 1966. 157
Tract,
Marx
158
and Barker
Because of such unfavorable results, physicians in the Departments of Gastroenterology and Surgery at the U.C.L.A. Center for the Health Sciences have tended to use corticosteroids sparingly, if at all, on patients who appear likely candidates for colectomy. On the other hand, many of our patients have been referred to our hospital having been treated already with systemic corticosteroids, and their continued use during and after surgery has been mandatory. It is the purpose of this retrospective study to compare the two groups of patients with ulcerative colitis, those treated with and without corticosteroids, with respect to surgical morbidity and mortality to determine what effect these hormones have had on their hospital course. MATERIAL
AND METHODS
The records of all patients with ulcerative colitis or granulomatous colitis (ileocolitis) operated upon at the U.C.L.A. Center for the Health Sciences were reviewed for the ten year period 1955 to 1965. The series was composed of 127 patients operated on for symptomatic ulcerative colitis; four underwent two procedures, primarily because their disease was confined initially to one portion of the large bowel (or was thought to be). At a later date the remainder of the colon or rectum still in continuity with the fecal stream became so involved with disease that it had to be resected as well. The patients’ ages ranged from four months to seventy-one years, but as in other series, the large majority were young adults. Seventy of the patients were women and fifty-seven were men. Specifically excluded from the series are those operations performed as a second procedure completely electively, such as an abdominoperineal resection of the involved part of the rectum in patients who had initially had a subtotal colectomy and ileostomy. Also excluded are those who have had a revision of their ileostomy or an operation for intestinal obstruction many months or years after leaving the hospital On the other hand, if patients had reoperation for ileostomy revision or intestinal obstruction in the immediate postoperative period, their procedures were considered complications of the primary procedure. Any serious intra-abdominal infections which occurred months or in some cases two or three years after the primary operation and which were clearly related to it, however, were considered complications of the operation. Minor stitch abscesses or seromas which did not delay the patient’s discharge from the hospital have been excluded. The patients were subdivided into two groups, those receiving corticosteroids during operation and in the postoperative course and those who did not,
Because corticotrophin (ACTH) and the eorticosteroids were frequently used on the same patient at different times, no attempt has been made to subdivide the series further on the basis of the type of hormone used. Some of those patients not treated with steroids had received systemic cortisone in the past and because of our prejudice against the drugs, it was our practice generally to avoid using them during and after the operative procedure. In some instances plasma cortisol levels were used to help determine whether supplementary corticosteroids would be necessary, while in other cases, the hormones were simply held in readiness if unexplained hypotension or other evidence of adrenal insufficiency should manifest itself during the operation or the postoperative period. If it did, and the number of times this occurred was rare, the patients were considered to be in the steroid-treated group. If there was no history of previous treatment with hormones, but because of unexplained hypotension (as in one case) the patient received heavy therapy with cortisones throughout the immediate postoperative period, he was placed in the steroid-treated group. On the other hand, a patient receiving one or two intravenous doses of cortisone during or after operation was not counted as a steroid-treated patient. It has been our practice to taper steroids rapidly postoperatively, a ten day to two week period usually being allowed after the wound is healed and the patient is doing well However, several patients were discharged from the hospital on maintenance doses of corticosteroids either arbitrarily or because an attempt to discontinue the hormones was unsuccessful earlier. RESULTS
The operations performed by both attending and senior resident surgeons on the 127 patients are listed in Table I and are subdivided into those treated with and without corticosteroids. The most common procedure performed was subtotal colectomy with ileostomy. The rectum and lower sigmoid colon were left in place and the upper end brought out as a mucous fistula through the lower part of the left paramedian incision. Although generally we consider ileostomy, total colectomy, and abdominoperineal removal of the rectum as more definitive procedures, subtotal colectomy with ileostomy was chosen initially because either the patient’s operation was an emergency and was made as short as possible, the patient refused the more extensive operation, the rectum looked salvageable for later ileorectal anastomosis, or the patient was a young man in whom the disease of the rectum seemed less of a problem than the possibility of rendering him impotent as a result American
Journal
of Surgery
Ulcerative
Colitis
T’.4HLE OPERATIONS
PERFORMED
IN PATIENTS
I ULCERATIVE
COLITIS
FROM
1955 TO 1965
Subtotal Colectomy with Ileostomy
Partial Colcctomy with Ileorcctal Anastomosis
Partial Colectomy with Colostomy
Ileostomy
16
31
0
2
0
1
37
37
3
2
1
0
Total l’roctocolcctomy with Ikostomy
Group
n’ITH
159
Transverse Colostomy
Corticosteroidtreated (50 patients) Noncorticosteroidtreated (80 patients*)
* One patient is not included because of death in the operating
of pelvic dissection. The single patient with ileostomy was one in whom an ileorectal anastomosis had been performed five and a half years before but such an exacerbation of disease occurred in the retained rectal segment that an ileostomy was reconstructed. The patient died in the postoperative period from sepsis. Included also is a single patient whose heart stopped in the operating room and upon whom no definitive operation was performed. Of the 131 operations performed, 23 were emergency procedures. (Table II.) Hemorrhage had become massive, a perforation had occurred, or the patient’s condition had rapidly deteriorated in the presence of acute fulminating disease or toxic megacolon with or without imminent perforation. Fourteen of the twenty-three operations were performed on patients treated with corticosteroid. In Table III is listed the total number of corticosteroid and nonsteroid-treated patients; the over-all mortality was between 14 and 15 per cent for both groups. Because the corticosteroid-treated group is weighted so heavily with emergency cases (28 per cent), the four columns on the right of the table have been added to subdivide
TABLE SURGICAL
Total No. of Operations
Group
__
____ __
IX
PATIENTS
-----Deaths-------Total Percentage
TABLE INDICATIONS
II
FOR EMERGENCY
CorticosteroidTreated
Indication
Massive hemorrhage Spontaneous perforation of the colon Severe fulminating disease or toxic megacolon Total
COLECTUMY
Non-
Patients
steroid Treated Patients
3
0
3
3
x
6 9
14
the groups further into emergency and elective cases. Table IV is a compilation of the morbidity statistics for both groups of patients operated upon. The complication listed was a major one for the patient and either was the cause of his death, required a corrective operation, or significantly prolonged the hospital course. The hemorrhage category, for example, includes only patients who had significant gastrointestinal or ink-abdominal bleeding postopera-
III WITH
ULCERATIVE
Emergency Total
COLITIS
Procedures Deaths
Nonemergency ~Procedures-Y Total Deaths
.-
Corticosteroidtreated patients Nonsteroid-treated patients
Vol. 113. Febvuary
MORTALITY
rooin
1967
50
7
81
12
14 14.8
14
5
36
2
9
5
72
7
160
Marx and Barker TABLE
POSTOPERATIVE
IV
COMPLICATIONS ULCERATIVE
Severe sepsis, intra-abdominal abscess, or septicemia Total number Number excluding emergencies Percentage excluding emergencies
emergencies
Severe wound infection Total number Number excluding emergencies Percentage excluding emergencies Wound dehiscence Total number Number excluding
WITH
CorticosteroidTreated Patients
NOtIsteroidTreated Patients
12 5 13.9
12 8 11.1
3 1
3 2
14 8 22.2
8 6 8.3 0 0
4 3 9.7
1 1 2.8
bowel Total number Total excluding emergencies Percentage excluding emergencies
4 3 8.3
2 1 1.4
Severe electrolyte imbalance with prolonged ileus Total number Number excluding emergencies Percentage excluding emergencies
5 3 8.3
3 3 4.2
Mechanical intestinal obstruction Total number Number excluding emergencies Percentage excluding emergencies
3 3 8.3
0 0
Psychosis Total number Number excluding emergencies Percentage excluding emergencies
6 3 8.3
2 0 . .
Convulsions Total number
1
1
4 2
1 0
Necrosis of stoma, severe dysfunction, or severe skin problems Total number
1
4
Bladder Total
0
2
emergencies
Retraction or perforation of mucous listula Total number Total excluding emergencies Percentage excluding emergencies or infarction
HeUKXrhage Total number Number excluding
dysfunction number
of small
emergencies
POSTOPERATIVE WITH
3 0
Perforation
UNCOMPLICATED
COLITIS
Complication
Pneumonia Total number Number excluding
TABLE IN PATIENTS
or urinary fistula
tively and excludes those who may, for example, have had a pint of blood ooze from their perineal wound the night after surgery. When the total number of patients in each category of complications appeared to be weighted against the corticosteroid-treated group, the patients whose cases were treated as emergencies were separated, and the percentage of complications computed from the group whose cases were not considered emergencies.
Group
ULCERATIVE
Tot al No. of Patients*
Total Percentage*
v COURSE
Iii
PATIENTS
COLITIS
Tutal Excluding Emergencies
Percentage Excluding Emergencies
Corticosteroidtreated (50 patients)
23
46
21
58.3
Nonsteroid-treated (81 patients)
53
65.5
51
70.8
*Statistically
significant
to chi square of 4.13,
p =
0.044.
Excluding ileostomy or mechanical urinary tract complications, it is apparent that the corticosteroid-treated patients account for an inordinate proportion of the morbidity statistics, even after allowances are made for the emergency procedures. To view the problem from another light, Table v has been constructed in which patients from each group who left the hospital after a completely uneventful postoperative course are compared. Excluding emergencies, there is an obvious trend in the figures favoring the nonsteroidtreated patient, although only in the total number and total percentages are the figures clearly significant in a statistical comparison. COMMENTS
In reviewing the mortality and morbidity figures in this series we are impressed by the seriousness of the clinical problem facing the surgeon who operates on a patient with ulcerative colitis. If medical therapy were ineffective in all instances, there would be no alternative but early surgery. Conservative therapy, however, including the corticosteroids, is frequently quite efficacious and when weighed against the alternative of an ileostomy for life, usually in a young adult, it is naturally chosen as the initial treatment. Current medical treatment for the disease often consists of an initial phase of diet control, vitamins, sedatives, antispasmodits, antibacterials, and psychotherapy, and in most centers, a second phase in which ‘the corticosteroids are added for those patients who fail to respond to the initial regimen. Colectomy and ileostomy are reserved for those whose disease continues to progress despite all medical efforts. By the time the patient is referred to the surgeon, he has usually lost a considerable amount of weight, is in a state of negative Amevican
Joumal
of Surgery
Ulcerative nitrogen balance, is losing large quantities of electrolytes and often blood through the rectum, and may have one or many of the other complications besides the debilitating diarrhea such as arthritis, pyoderma gangrenosum, uveitis, perirectal abscesses or fistulas, hepatitis, or acute psychosis which frequently accompany the disease. The present surgical treatment of ulcerative colitis, concomitant ileostomy and colectomy, first began to be practiced to any extent at about the same time that corticosteroids were being introduced clinically. Without question, many of the accusations made against the corticosteroids as the surgeon viewed his mortality and morbidity statistics were misdirected. During the past decade it has been fairly well established that the number of perforations of the colon or instances of massive colonic bleeding is no greater now than in the presteroid era, and that certain systemic complications of the disease, such as arthritis, improve as much if not more than the colitis with corticosteroid therapy. Furthermore, even if the patient with typical ulcerative colitis who is referred for colectomy had had no drug or hormonal therapy at all, a lengthy operation of this sort on a debilitated patient would be expected to be hazardous. Estimates of the loss of electrolytes from diarrhea are often difficult to assess preoperatively, and losses after ileostomy are often excessive in the postoperative period. Spillage of contents of the colon from a thin, friable bowel during operation may result in postoperative peritonitis with considerable loss of fluid to extracellular space and sometimes the formation of intra-abdominal abscesses. Resistance to infection of any sort is notoriously low in the chronically depleted patient and the number of wound abscesses or pneumonia would be expected to be high. Because of protein and vitamin depletion, wound healing is commonly delayed and an unusual number of dehiscences or retraction of mucous fistulas could be predicted. Since it is generally accepted that many patients with ulcerative colitis are suffering from deep emotional problems, a fair number of frank postoperative psychoses would be expected to develop during and immediately after the period of stress after colectomy and ileostomy. On the other hand, statistics on morbidity in this study would indicate that steroidtreated patients have more complications postVol. 113. February
1967
Colitis
161
operatively than those in whom the hormones have been withheld. Admittedly, 26 per cent of the steroid-treated patients were operated upon on an emergency basis whereas only 11 per cent of the nonsteroid-treated patients were considered emergency cases, but this bias appears to be built into the corticosteroid-treated group because of current medical practice. For the most part, corticosteroids are reserved for those patients who do not have remission while under other modes of conservative treatment, and if only the majority of such patients respond favorably to steroids, the minority presumably continue to do poorly for the next few weeks or until the gastroenterologist decides that there is no recourse but an operation. During that interval or delay, the conditions of some patients will undoubtedly become emergencies which otherwise would not if a course of corticosteroids had not been instituted. Among the complications listed, several appear to be completely unconnected with whether the patient had or had not received corticosteroids during and after his operative procedure. The fact that in three steroidtreated and in no nonsteroid-treated patients did mechanical intestinal obstruction develop appears completely fortuitous, for at ldparotomy it was necessary only to lyse a few fibrinous adhesions to correct the problem. Urinary tract difficulties were confined to two of the thirtyseven nonsteroid-treated patients who had undergone total proctocolectomy with ileostomy. Stoma1 necrosis or severe ileostomy dysfunction is most certainly a reflection of some technical difficulty during the operation rather than on whether steroids were administered or not. The number of perforations or infarctions of the small bowel was higher in the steroid-treated than in the nonsteroidtreated group, and this finding was stressed as a significant and unique one for steroid-treated patients in a previous report by one of us (W.F.B.) [7]. In this larger series, however, two cases of perforation of the small bowel have occurred among our nonsteroid-treated patients, and more recently a third case occurred in a patient whose final operation is the only one which took place during the ten year period but whose case was not included in either series. This case defied classification into either category besides illustrating an interesting clinical problem.
Marx and Barker The patient was a fourteen year old Dutch girl who had had an emergency subtotal colectomy and ileostomy performed in May 1961, while on heavy steroid therapy. After wound infection and pneumonia, the dose of corticosteroids was tapered off and the patient did well for five months. About that
time the insidious onset of fever, weight loss, and rectal bleeding developed and she returned to the hospital. While she was being studied on the medical service, marked abdominal pain developed. A laparotomy was performed at which two spontaneous perforations of the small bowel were found. Corticosteroids were begun again only just before the second operation, and although the perforations were closed, the patient subsequently died from intra-abdominal abscesses and septicemia. The corticosteroids, however, are not so readily absolved from the increased incidence of the remaining complications among the patients treated with these drugs. It is of considerable interest that except for patients who experienced wound dehiscence, the nonsteroid-treated group also had the same complications as those treated with steroids, but in proportionateIy fewer numbers. As mentioned previously, debilitated patients undergoing a total colectomy with ileostomy would be expected to have certain postoperative difficulties. The corticosteroids, however, are notorious for causing or enhancing the problems from which these patients suffered. Resistance to infection is diminished with the corticosteroids, partly due to an inhibition of a local inflammatory response and possibly due to some generalized effect. If the wound or abdomen should be contaminated during operation or if a respiratory infection should occur, the complication might be expected to grow to major proportions if abetted by cortisone. Severe sepsis, severe wound infections, and pneumonia did occur among twentynine of fifty steroid-treated patients compared with twenty-three of eighty-one who were not treated with steroids. Healing is delayed in animals and in patients receiving large doses of cortisone. A deficiency in the normal fibrous reaction did result in an increased number of wound dehiscences and retraction of mucous fistulas into the abdominal cavity. Without question, the excessive loss of potassium from the preoperative occurrence of coIonic diarrhea or excessive ileostomy drainage postoperatively is enhanced by the effect of the corticosteroids. Generally, in the disease the control of water and electrolytes in the body
presents a formidable problem to the attending physician or surgeon, and this series would indicate that these problems are compounded when corticosteroids are added. The most frequent and troublesome side effect was a severe paralytic ileus which responded only to unusually farge quantities of electrolytes. Serious “hemorrhage” mentioned in Table v does not refer to colonic bleeding in a retained rectal stump, but mainly to upper gastrointestinal bleeding, which is frequently the final occurrence in a series of postoperative complications after colectomy. The so-called “stress” ulcer may occur without the addition of exogenous corticosteroids, but the fact that peptic ulceration is increased with their use is well documented in the literature. In those patients who died from hemorrhage and were autopsied, superficial peptic ulceration was found. Thorn and associates IS] have implicated the corticosteroids as a cause of convulsions in patients with disorders of the central nervous system ; they may also have played a role in the seizures of one of our patients. The cause and effect relationship between the other central nervous system complication, acute psychosis, and the corticosteroids is much better known, and the high number of steroid-treated patients in whom this problem developed postoperatively undoubtedly reflects their use. Considering the greater morbidity among steroid-treated patients with ulcerative colitis who underwent surgical procedures for their disease, it might appear at first paradoxical that the mortality was not greater. We believe that the main reason for this is that corticosteroids in themselves added no completely new complications. Diabetes, osteoporosis, and hypertension, all recognized complications of prolonged steroid therapy not usually associated with ulcerative colitis, either did not occur in our series of patients, or if they did, apparently had no deleterious effect on the immediate postoperative course. With the possibility of sepsis, wound or electrolyte complications, or postoperative psychosis, the attending surgeons treated complications as expeditiously as possible in both groups of patients, and although their incidence was higher in the steroid-treated group, the mortality fortunately was not. We believe that it has been largely because of the similarity of complications in the two Anzerican Journal of Surgery
Ulcerative groups that there have been so many contradictory reports as to whether the steroids are harmful or not in operative treatment of ulcerative colitis. We can only conclude that for patients with ulcerative colitis, just as in patients suffering from arthritis, dermatologic disorders, or blood dyscrasias, the use of cortisone may be quite helpful in alleviating the disease, but the drugs have definite detrimental side effects. If the steroid-treated patient with ulcerative colitis is subjected to an operation, any of these detrimental side effects can be expected to increase the possibility of the development of a serious postoperative complication. SUMMARY
The postoperative course of fifty corticosteroid-treated and eighty-one nonsteroidtreated patients with ulcerative colitis is analyzed in terms of mortality and morbidity. Although the mortality for the two groups is essentially the same, the morbidity is significantly greater for the steroid-treated patients. Although some of the complications were clearly unconnected with administration of the drugs and the complications were not unique to one or the other group, severe wound infections, intra-abdominal abscess, septicemia, wound dehiscence, retraction of mucous fistulas, severe electrolyte imbalance, hemorrhage, convulsions, and psychosis were all increased with corticosteroid administration. REFERENCES 1. TRUELOVE, S. C. and WITTS, L. J. Cortisone in ulcerative colitis: final report on therapeutic trial. &it. M. J., 2: 1041, 1955. 2. TRUELOVE. S. C. Treatment of ulcerative colitis with local hydrocortisone hemisuccinate sodium. &it. A[. /., 2: 1072, 1958. 3. HAYES, M. ;2. and KUSHLA~;, S. D. Influence of hormonal therapy for ulcerative colitis. Gastroenterozogy, 30: 75, 1956. 4. COLCOCK, B. P. and MATHIESON, W. L. Complications of the surgical treatment of chronic ulcerative colitis. .4uch. Surg., i2: 399, 1956. 5. PROHASKA, J. V., DRAGSTEDT, L. R., II, and THOMPSON, R. G. Ulcerative colitis: surgical problems in corticosteroid treated patients. Ann. Surg., 154: 408, 1961. 6. BROOKS, J. R. and I’EITH, F. J. The timing and choice of surgery for ulcerative colitis. J.A.M.A., 194: 115, 1965. 7. KELLNER, H., HERSCH, R. A., and BARKER! W. F. The effect of adrenocortical steroids on the postoperative course of patients with ulcerative colitis. Gnstroenterology, 45: 27, 1963. 8. THORN, G. W., JENKINS, D., LAIDLOW, J. C., GOETZ, Vol. 113.Februavy
1967
Colitis
163
F. C., UINGMAN, J. F., ARONS, W. L., SWEETEN, D. H. P., and MCCRACKEN, B. H. Medical Uses of Cortisone, chapt. 2, p. 96. New York, 1954. Edited by F. D. W. Lukens. McGraw-Hill Book Co., Inc. DISCUSSION CLAUDE 13. WELCH (Boston, Mass.): Dr. Mars. was amazed to learn that your gastroenterologist
I
would consider that no patient about to undergo surgery ought to have steroids. As a matter of fact. in nearly every place in the country, I believe no patient ever comes to surgery without having had a course of steroids; perhaps that accounts for some of our feelings about it. I was also quite interested to note in some of the medical literature the implication that toxic megacolon should be treated by large doses of steroids, and I hope that you will comment upon the complication of megacolon when you close the discussion. JOHN VAN PROHASKA (Chicago, Ill.) : I agree with Dr. Marx in most of the observations he has so well recorded. The most important among these are some of the differences between the corticosteroid-treated patients and those patients not receiving the hormone. As he so well stated, the major difference is a prolonged morbidity. Morbidity is an inclusive term and in the corticosteroid-treated patient it map be broken into several components. Among the factors which contribute to postoperative morbidity, one may include delayed wound healing, disturbance in electrolyte balance, low plasma proteins, and perhaps a vulnerabilitv to wound infection. One must remember that corticosteroids cannot be suddenly discontinued in the immediate postoperative state. Therefore, the postoperative patients linger on in a slowly- decreasing hypersteroid condition. There are permanent complications caused by prolonged use of corticosteroids. Notable among these is the retardation of body growth, producing a real psychological effect on the young patient. Osteoporosis may result in permanent deformity due to compression fractures of the vertebrae. Nevertheless, many of these complications and sequelae which may be attributed to prolonged use of corticosteroids are preventable. We have operated on 260 patients with inflammatory diseases of the bowel who have received corticosteroids for a long time. We find that the incidence of serious complications is no greater than in patients not treated with the hormone. The morbidity of the steroid-treated patients, nevertheless, is markedly prolonged. I am glad to know that somebody else has observed that corticosteroid-treated patients do get along after major surgery provided proper care is given to them. ALBERT S. LYONS (New York, N. Y.): Dr. Barker expressed concern with his 14 per cent mortality as compared with 4 per cent and 2 per cent that is sometimes reported in other quarters. I am not sure
164
Marx and Barker
what that 14 per cent and 4 per cent and 2 per cent mean. I think it is very difficult to compare 100 or 200 patients from one clinic with 100 or 200 in another clinic. So much depends on the state of the disease, the state of the patients who are subjected to surgery, and what proportion in the series they occupy. It is very difficult to classify these for comparison. If these were a few thousand of one series compared with a few thousand of another, the difficulty would be minimized. We have tried to lower the mortality in one small segment of this group, those with toxic dilatation of the colon, by employing cecostomy as a preliminary procedure. We reported this a few years ago and in the intervening years this procedure has been so startling in its efficacy that we have continued it. We must make it clear that it is not for all patients, nor is it a definitive procedure, but merely one to prepare the patient for more definitive surgery. I also believe that in all the clinics throughout the country, the lower mortality is due less to the changes in operative technic than to improvement in the total management of the patient. One of these improvements in total management refers to the use of corticoids. All of us as surgeons undoubtedly deplore the extended and injudicious use of the corticoids. It is certainly dismaying to see a patient who has a disease produced by the corticoids in addition to his ulcerative colitis, but I think we must also recognize that there are patients who are restored from a nearly moribund state, .in great debility and with acute toxemia, to one which permits a more extensive procedure under safer conditions just by the use of the corticoids. I think the danger does exist that once these patients are restored, they will be kept going beyond the point of optimal improvement and will be either subjected to surgery too late or will be carried along while hovering just above disability until a medical disaster occurs. I think it is this mistake that Drs. Barker and Marx are counseling against. B. MARDEN BLACK (Rochester, Minn.): In our institution steroids have always been used rather reluctantly in the treatment of this disease. We are faced with the problem of operating on patients who have been taking large doses of steroids, often for several years, and of course we must learn to adjust to it. With proper preparation of the patient, our experience has been much the same as that recounted and we can operate without too much morbidity. I have been most impressed with impaired healing of wounds and with dehiscences rather than with stoma1 problems. W. H. NICKEL (New York, N. Y.): As a small subgroup of a much larger group of patients we have treated at the Cornell Medical Center there have been seven or eight patients with toxic megacolon. One or more perforations of the colon have developed in three
of these patients, all of whom were taking steroids. The important point that I would like to make is not that the perforation occurred, because perforation has always been one of the leading causes of death in ulcerative colitis both before and after the advent of steroids, but rather the suppression of signs and symptoms by the steroids which one would normally expect to be present when a perforation of the intestinal tract occurs; so much so that we have come to rely more on the daily flat plate of the abdomen, sometimes even taken twice a day, rather than on our diagnostic acumen in patients with this severely critical condition. We have adopted a policy of attempting withdrawal of all steroids after operation with or without the use of ACTH. We find that there is a small group of patients who become addicted to this drug and who are never completely weaned away from it. WILEY F. BARKER (closing): I particularly want to reinforce Dr. Nickel’s observation that you just can’t believe anything that you palpate in the abdomen of a patient who is taking large doses of corticosteroids. Concerning toxic megacolon, I believe that Dr. Truelove has made the statement that the problems of potassium balance that accompany steroids may make the toxic megacolon even worse, and whereas it is undoubtedly true that our surgical management of toxic megacolon has not been good, neither has any other management been good except for that reported by Dr. Lyons. We do not have any experience with that treatment yet, but I anticipate that we will. This has been a rather painful reappraisal of our results in an unusual situation, one in which we have gasteroenterologists who fear the steroids perhaps as much or more than surgeons do. This has resulted in approximately equal experience in treated and nontreated patients. Our gastroenterologists have been wise in refraining from placing critically ill patients who seem destined for the operating room on steroids at the last moment. Neither we nor they believe that there has really been any improvement in the general status of such patients on steroids, and indeed, and I think I am also speaking for the gastroenterologists in this, systemic steroids are apt to be used only in those patients in whom a prompt remission might otherwise be expected and who might not be destined for operation. We would have liked to have discussed the difference in effects of corticosteroids as opposed to ACTH, but there is so much overlap that it is impossible. Thus, we believe steroids have a role in the treatment of ulcerative colitis, but to rephrase Dr. Marx’s last words, when they are used in the patient coming to operation, an increased hazard associated with their use must be recognized. This is not anything specific and is a quantitative rather than a qualitative difference. American Journal of Suvgery