Operative Management of Radiation Injuries of the Intestinal Tract John C. Russell, MD, Hartford, Connecticut John P. Welch, MD, Hartford, Connecticut
Radiation therapy is an established method in the treatment of many intraabdominal malignancies. Almost 50 per cent of patients with all types of cancer receive radiation therapy at some time [I]. With the usual therapeutic doses of 4,000 to 6,000 rad, severe gastrointestinal symptoms develop in 2 to 5 per cent of patients [2,3]. Most patients with mild symptoms respond to antispasmodics, low residue diets, antiemetics, and antidiarrheal medications [4,5]. Agents such as corticosteroids, acetylsalicylate, salicylazosulfapyridine, and cholestyramine have also been used in the management of chronic radiation enteritis [6,7]. One to 2 per cent of patients require operation because of excessive bleeding, perforation, obstruction, fistulization, or intractability [3,8-121. The morbidity associated with operations on irradiated bowel is high, and the inflammatory process is progressive, often necessitating multiple operative procedures. Because of the complexity of management of radiation injuries of the bowel, a retrospective review was undertaken, directed at several questions: (1) What, if any, factors predispose the patient undergoing radiation therapy to future bowel complications? (2) Is there a difference in the morbidity and mortality associated with large bowel versus small bowel injuries? (3) When operation is required, is there a definitive advantage of resection over bypass procedures? (4) What operations are favored for specific complications such as obstruction, perforation, or fistula formation? From the Department of Surgery, Hartford Hospital, Hartford, Connecticut, and the University of Connecticut School of Medicine, Farmington, Connecticut. Repint requests should be addressed to John P. Welch, MD, 85 Jefferson Street, Hartford, Connecticut 06106. Presented at the Fifty-Ninth Annual Meeting of the New England Surgical Society, Dixville Notch, New Hampshire, September 29-October 1, 1978.
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Material and Methods
During the decade between 1968 and 1977, forty patients underwent one operation or more at the Hartford Hospital for radiation injuries to the large or small bowel. Thirty patients were female and ten were male. The median age at the time of radiation treatment was fifty-one years (range 23 to 79 years). The primary diseases included carcinoma of the cervix (24 per cent), carcinoma of the bladder (19 per cent), carcinoma of the ovary (17 per cent), carcinoma of the endometrium (12 per cent), other forms of cancer (24 per cent), and unknown diseases (4 per cent). The type of radiation treatment was classified as external beam only (68 per cent), intracavitary radium (5 per cent), a combination of these (22 per cent), and unknown (5 per cent). The range of dosage was 4,000to 6,000 rad over a four to five week interval. Between 1950 and 1970, an average of twenty-four patients with cervical cancer were treated with radiation therapy annually; the ten patients with carcinoma of the cervix in this series represent an incidence of 4 per cent. The major site of initial radiation injury was the small bowel (40 per cent), the rectum (30 per cent), the colon (15 per cent), and the combination of large and small bowel (15 per cent). In many patients a second area of injury later became manifest, requiring additional operative procedures. In all, 32 per cent of patients had injuries restricted to the colon and rectum, 40 per cent had injuries of small bowel alone, and 28 per cent required operations for injuries involving both large and small bowel. Rectal injuries were especially frequent in patients having intracavitary radium therapy (6 of 11,55 per cent) when compared with patients undergoing only external beam therapy (6 of 27, 22 per cent). The interval between radiation therapy and the first operation for radiation bowel injury ranged from two months to thirty years, with a median interval of eighteen months. Within one year of radiation therapy, 22 per cent underwent operation, compared to 57 per cent at two years and 74 per cent at four years. There was no predictable time interval between radiation therapy and large or small bowel injuries. The type of radiation injury was related to the area of bowel involved. (Table I.) Nearly 50 per cent (15 of 31) of
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TABLE I
Complications of Radiation Injury by Anatomic Location Small Bowel
Rectum
Colon
Total
Obstruction Bleeding, intractable diarrhea Perforation Fistula
15 5
2 6
5 2
22 13
3 8
3 4
5
6 17
Total
31
15
12
58
small bowel injuries caused obstruction. Bleeding was the most common indication for operation for colon injuries (6 of 15, 40 per cent), whereas obstruction or fistula formation characterized rectal injury (10 of 12,83 per cent). In the entire series the indications for operation were obstruction (39 per cent), fistula formation (29 per cent), bleeding or intractable diarrhea (22 per cent), and perforation (10 per cent). Results
Types of Operation. The operations performed are outlined in Table II. The choice of anastomotic technic varied with individual surgeons. Two layer open anastomosis using chromic catgut and silk was most often done. The group of ninety-six operative procedures included fifty-one intestinal anastomoses:
TABLE II
Summary of Operative Procedures Small Bowel
Resection and anastomosis with diversion Resection and anastomosis Resection only Bypass Combined resection and bypass Lysis of adhesions only Other operations Total l
Large Bowel
Combined
5
13
5
4 10 13
12 1
4
21
4 2
10 29 3
5
5 23”
31 Includes drainage of abdominal
Total
32 abscesses,
10 colostomy
96 clo-
sure.
TABLE III
Resection Resection Bypass Combined Colostomy Total
434
twenty-six enteroenterostomies, nine enterocolostomies, and sixteen colocolostomies. Small bowel resection and anastomosis (13) and diverting enteroenterostomy (12) were done with nearly equal frequency. In nineteen colon resections, primary anastomosis without proximal diversion was performed in only four instances. After nearly 50 per cent of colon resections, the colon ends were exteriorized or a Hartmann procedure was done. Artastomotic Leak. The incidence of anastomotic leak resulting in abscess or fistula was 31 per cent. (Table III.) Resection with or without proximal diversion led to anastomotic leakage in 31 per cent, whereas bypass procedures had a 29 per cent incidence of leakage. The lowest incidence of anastomotic breakdown (11 per cent) followed enterocolostomies. The anastomotic dehiscence rates following end-to-end or side-to-side anastomosis of small bowel were almost identical (5 of 13,38 per cent versus 4 of 10, 40 per cent) in this series. Because stapling technics or one layer anastomoses were done infrequently, a comparison of these methods with more traditional ones was not possible. Morbidity. In this series, the overall morbidity was 65 per cent (including the 31 per cent incidence of anastomotic dehiscence), encompassing major complications such as renal failure, intraabdominal and pelvic abscesses, cardiac arrhythmias, septic shock, stoma1 necrosis, hepatic failure, gastrointestinal bleeding, and wound dehiscence. Obstruction. Two cases of colon obstruction and five of rectal obstruction necessitated operation. (Table I.) Both colonic obstructions involved the distal sigmoid and were successfully managed by proximal colostomy and cecostomy, respectively. Two of five rectal strictures were also managed by loop colostomy without progression of radiation injury. Two colon resections were performed. An anastomotic leak followed anterior resection for a stricture 12 cm from the anal verge, requiring later abdominoperineal resection. (Table IV, case 1.) A pelvic abscess and enteroperineal fistula followed a sigmoid resection and Hartmann procedure. The fifth patient underwent multiple successful dilata-
Incidence of Anastomotic Leakage
and anastomosis with diversion and anastomosis procedures closure
Enteroenterostomy
Enterocolostomy
5113 (38%) 4110 (40%) l/3 (33%)
l/4 (25%) 013 (0) o/2 (0)
10126 (38%)
l/9 (11%)
Colocolostomy 2/5 (40 %) o/4 (0) O/l (0)
Total
3/6 (50%)
215 (40%) 6121 (29%) 4114 (29%) l/5 (20%) 316 (50%)
5/16 (31%)
16/51 (31%)
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Radiation-Induced
tions of a rectal stricture, but iatrogenic sigmoid perforation occurred with sigmoidoscopy, requiring emergency laparotomy. A persistent vesicovaginal fistula developed in this patient, forcing construction of an ileal conduit. Fifteen operations were necessary because of small bowel obstruction. Seven bypass procedures were done, with anastomotic leakage in three patients and one death. In six patients having small bowel resections with anastomosis, no leaks occurred, but later anastomotic strictures in two patients led to multiple operations and eventual death. (Table IV, cases 7 and 11.) Two patients undergoing lysis of adhesions only had obstruction caused by solitary bands or vo1vulus, and their subsequent course was uneventful. Proctocolitis and Enteritis. Intractable symptoms of proctocolitis and enteritis led to operation in thirteen patients. Two loop colostomies were done. Because of persistent bleeding and rectal stricture formation, the first patient required an anterior resection and finally abdominoperineal resection. (Table IV, case 1.) In the second case a fecal fistula developed at the site of the loop colostomy eight years later. Colon resection as primary therapy was done in five patients, including one total colectomy for toxic megacolon and one abdominoperineal resection for massive bleeding. (Table IV, case 9.) One of two low anterior resections with proximal colostomy leaked, requiring drainage. Although a sigmoid resection done for colitis healed primarily, recurrent symptoms led to two additional colon resections and eventual death. (Table IV, case 5.) A final patient with presumed rectosigmoid carcinoma proved to have radiation colitis via a colotomy and survived colotomy closure without complications. The five patients with radiation enteritis had symptoms of recurrent partial small bowel obstruction and intractable diarrhea. Two had lysis of adhesions and both eventually died. (Table IV, cases 6 and 7.) Another patient with malabsorption caused by ileal dysfunction survived small bowel resection uneventfully. An ileocecectomy and ileoascending colostomy in the fourth patient was the first of multiple procedures leading to death. (Table IV, case 5.) A final patient underwent jejunotransverse colostomy (side-to-side) witbout incident. Perforation. Three patients had colonic perforations. One died of fecal peritonitis eight days after sigmoid resection with Hartmann turn-in. (Table IV, case 8.) Plication only of an iatrogenic sigmoid perforation following sigmoidoscopy resulted in a large pelvic abscess. The third patient with sigmoid perforation survived resection and anastomosis, but later
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Bowel Injury
stricture formation at the anastomosis required proximal diversion. There were three small bowel perforations. Resection and anastomosis of an ileal perforation led to enterocutaneous fistula formation and death. (Table IV, case 3.) A jejunal perforation was managed by jejunal plication, ileal resection, and ileocolostomy with a mucous fistula of the distal ileum. Four days later, the mucous fistula sloughed, and emergency ileocecectomy was done. The third case, an ileal perforation, was successfully treated with ileal plication and side-to-side ileoascending colostomy. Fistula. Fistulas ied to particularly vexing management problems. The four colonic fistulas were all successfully managed by diverting colostomy. One of the five rectal fistulas was controlled by diverting colostomy. In the remaining cases multiple surgical procedures were necessary. In one instance, two unsuccessful attempts (including gracilis flap) were made at closure of a rectovaginal fistula. An endsigmoid colostomy finally controlled the fistula output. A rectovesicovaginal fistula failed to close after combined ileal conduit and transverse loop colostomy and subsequent anterior resection. Construction of a double-barreled colostomy finally closed the fistula. However, closure of the colostomy led to prompt recurrence requiring a second double-barreled colostomy, and the patient died soon thereafter. A rectoperineal fistula with pelvic abscess recurred after attempted extraperitoneal closure. An ileal resection together with sigmoid loop colostomy controlled but did not close the fistula. The fourth patient (Table IV, case 1) with a rectoperineal sinus and pelvic abscess following anterior resection failed to respond to two drainage procedures and even abdominoperineal resection and died from complications of an uncontrollable enteroperineal fistula. Eight patients had small bowel fistulas that contributed directly to the death of three of them. Fistula recurrence followed small bowel resection and fistula excision in 60 per cent (3 of 5). In a fourth case an enterorectal fistula was treated with small bowel resection and plication of the rectal defect. Tumor was present at both ends of the fistula tract. An enterorectovesicovaginal fistula appearing one year later was controlled after small bowel resection, end-to-side ileocolostomy, mucous fistula of the distal ileum, and creation of an ileal conduit. An ileovesical fistula in another patient was controlled with small bowel resection, bladder closure, and drainage. Small bowel obstruction later occurred at the anastomosis, requiring side-to-side ileotransverse colostomy. Bypass operations were used in three additional cases. A side-to-side jejunocecostomy
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TABLE IV
Deaths from Radiation Bowel Injuries
Sex/ Case 1
Age (yr)
Underlying Condition
F/79
Ca endometrium
Radiation Injuries
Operations
Radiation proctitis, stricture, and abscess
Transverse colostomy. Anterior resection. I & D X 4, AP resection. Coccygectomy
Enteroperineal
Jejunocecostomy (bypass). Small bowel resection X 2. Ligation jejunum and ileum, cecostomy
fistula
RadiationDeath Interval 13yr
OperationDeath Interval
Cause of Death
2mo
Recurrent enteroperineal fistula, multiple system failure
2
MI66
Ca bladder
Small bowel obstruction
Side-to-side ileoileostomy
8mo
2mo
Enterocutaneous fistula, perforated gastric ulcer, pneumonia
3
F/52
Ca cervix
Small and large bowel obstruction
lleoascending colostomy, sigmoid colostomy and mucous fistula
2 yr
1 mo
Enterocutaneous fistula, ASCVD, bilateral femoral artery occlusion
Enterocutaneous fistula, erosion right external iliac artery
Ileoileostomy, ligation right external iliac artery and right ureter
Small bowel perforation
Closures sb perforation, sb resection, ileocolostomy, transverse colostomy, ileostomy
5 yr
7 days
Small bowel necrosis
Right colectomy, mucous fistula right colon
Sigmoidocutaneous fistula
Sigmoid colostomy, closure of mucous fistula
Small bowel
Enteroenterostomy
Enteritis, small bowel obstruction
lleoascending colostomy, resection ileum and cecum and anastomosis
Rectal bleeding
Sigmoid resection (partial)
Colitis
Segmental resections sigmoid and transverse colon
Enteritis
End ileostomy
4
5
MI57
F/73
Lymphosarcoma left groin
Ca ovary
6
F/75
Ca ovary (carcinoid)
Enteritis, small bowel obstruction
Lysis of adhesions
7
F/63
Ca cervix
Enteritis
Laparotomy, biopsy, lysis of adhesions
Small bowel obstruction (partial), ileovesical fistula
Resection terminal ileum, ileal resection, ileoascending colostomy, drainage of fistula
Small bowel obstruction. Undifferentiated carcinoma 34 yr
4mo
High output ileostomy 13 mo
4mo
3 yr
2mo
Malnutrition, enteritis
radiation
Malnutrition, failure
renal
lleotransverse colostomy (bypass) Right colectomy, ileotransverse colostomy 8
436
F/65
Ca endometrium
Sigmoid perforation, fecal peritonitis
Sigmoid resection, endsigmoid colostomy, Hartmann procedure
11 yr
8 days
Retraction colostomy, multiple system failure
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TABLE IV
(continued) OperaRadiationtionDeath Death Interval Interval
Sex/ Case
Age (yr)
Bowel Injury
Underlying Condition
Radiation Injuries
Operations
9
F/73
NA
Proctitis/colitis
Abdominoperineal resection
10
F/81
Ca bladder
Jejunovaginal fistula
11
F/49
Ca rectum
Cause of Death
30 yr
8 days
Multiple system failure
Small bowel resection, ileoileostomy (bypass), drainage pelvic abscess
2 yr
23 days
CVA, recurrent fistula
Small bowel obstruction
Small bowel resection X 2, lysis adhesions
4 yr
1 mo
Duodenal obstruction
Small bowel resection, gastrostomy, lysis adhesions
Small bowel obstruction, colon obstruction, duodenal obstruction
Gastrojejunostomy, colocolostomy (bypass)
Cachexia: radiation enteritis
Note: AP = abdominoperineal; ASCVD = atherosclerotic cardiovascular disease; Ca = carcinoma; CVA = cerebrovascular accident; NA = not known: sb = small bowel.
failed to control a high output ileoperineal fistula. (Table IV, case 1.) Small bowel resection also failed. Complete exclusion, including ligation of the jejunum just distal to the jejunocecostomy and ligation of the ileocecal valve, failed, and the patient died with a high output fistula. Bypass with partial exclusion (end-to-side jejunoileostomy) markedly decreased output from a distal jejunal fistula, while an enteroperineal fistula in the last patient was controlled with complete exclusion using a double-ended mucous fistula and small bowel anastomosis. Radiation Deaths. Of our forty patients, eighteen died during a one to ten year follow-up period. Eleven deaths (28 per cent) followed radiation bowel injury or operative complications. (Table IV.) Of the remaining deaths, five were caused by recurrent carcinema, one by renal failure, and one by leakage from an infected vascular graft. The patients dying of radiation injury could not be distinguished from the remaining twenty-nine patients by age, sex, frequency of abdominal operations prior to radiation therapy, or more severe acute radiation reactions during therapy. The patients described in Table IV did undergo on the average more operative procedures than the other patients (3.5 versus 2.0), and one patient had eleven operations. The most important determinant of the morbidity and mortality of the patients with radiation bowel injury was the location of the injury itself. Patients with small bowel injuries only had a 38 per cent mortality (6 of 16) due to irradiation, compared with a 15 per cent mortality (2 of 13) for colon and rectal injuries and a 27 per cent mortality (3 of 11) for
Volume 137, Aprtl 1979
combined small and large bowel injuries. Small bowel injuries were associated overall with more than four times the mortality of colon or rectal injuries (29 per cent versus ‘7per cent). (Table V.) Small bowel fistulas and severe enteritis were associated with a mortality rate of nearly 40 per cent. All four patients who died with rectal obstruction or rectovaginal fistulas did so from carcinomatosis rather than from radiation-induced injuries or postoperative complications. In nine patients, small bowel injuries were preterminal events, including three patients with recurrent small bowel fistulas. Two patients with colon injuries (Table IV, cases 8 and 9) died postoperatively with multisystem failure and septic or hypovolemic shock. TABLE
V
Mortality and Location of Intestinal injury*
Small Bowel7 Obstruction Enteritis Perforation Fistula Total Colon and Rectum* Obstruction Proctitis/Colitis Perforation Fistula Total
Deaths
Total
Mortality
4 2 3
15 5 3 8
27% 40% 0 38%
9
31
29%
1 1
7 8 3 9
0 12% 33% 0
2
27
7%
* Patients who died of causes directly attributable to radiation. + Includes some patients with colorectal injuries. f Includes some patients with small bowel injuries.
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Comments
Radiation injury to the bowel can be divided into three stages: acute, subacute, and chronic. The acute radiation syndrome of nausea, vomiting, diarrhea, and crampy abdominal pain experienced during radiation therapy is caused by direct toxic effects on the rapidly dividing cells of the gut mucosa and is usually self-limited [13]. Within six to eighteen months of treatment a subacute syndrome sometimes appears, with symptoms of bowel obstruction or gastrointestinal bleeding. Histologically, a progressive obliterative endarteritis progressing to fibrosis of multiple layers of the bowel wall is seen. The chronic symptoms of radiation bowel damage appear one to two years after therapy or later [2,9]. At operation in the chronic stages of injury, the involved bowel serosa appears thickened, dull, and gray, with decreased peristalsis. Normal tissue planes are obliterated; the intestine is friable and easily injured with surgical manipulation. Fibrosis may become so extensive in the pelvis that a “frozen pelvis” develops. Classic findings of recurrent cancer such as sciatica, leg edema, or a pelvic mass [14] may lead to inappropriate therapy of such patients. The presence of radiation injuries should be suspected and contrast studies, sigmoidoscopy, and biopsy carried out with a high index of suspicion. In the subacute and chronic forms, radiation bowel injury is a progressive disease [15]. In this series the radiation-to-operation interval was as great as thirty years, but was usually only a few years as in other reports [13]. At repeat laparotomy, previously normal-appearing bowel may have become strictured and fibrotic. The final result of radiation damage in a particular patient (normal bowel, perforation, or stricture) depends on the tissue sensitivity to radiation, its blood supply and degree of mobility, and the degree of hypertrophic scarring following acute tissue necrosis. Some authors believe that the gross pathologic findings are directly related to the latent period, with ulcerative lesions occurring earlier than fibrotic ones [16]. The present series fails to confirm such a temporal relationship. The etiology of radiation injuries to the bowel is complex. With the use of supervoltage radiation and wide treatment fields, there is risk of bowel injury, especially since cancericidal doses approach doses toxic to the normal bowel. Rubin [17] has defined the minimum and maximum injurious doses acceptable to the clinician as 4,500 to 6,500 rad for the small bowel and colon and 5,500 to 8,000 rad for the rectum. The risk of small bowel injury (obstruction, perforation, or ulceration) increases from 1 to 5 per
43%
cent at doses of 4,500 rad to 25 to 50 per cent at 6,500 rad [18]. Clearly the dose, time, fractionation, degree of shielding, and type of radiation therapy are related to the type of injury seen. Rectal injuries usually follow intracavitary irradiation, although small bowel lying in the pelvis may also be injured [19]. Whereas the small bowel appears to be more sensitive to radiation than the colorectum [20], rectal injuries have predominated in most series, perhaps due to the mobility of the small intestine. Multiple risk factors may predispose patients to bowel injuries as well. Vasculitis induced by pelvic inflammatory disease has been incriminated [12]. There is probably a cumulative toxicity of radiation therapy and chemotherapy as well [21,22]; Phillips and Fu [23] believe that the radiation dosage should be decreased by 10 to 80 per cent for the same degree of bowel injury when radiotherapy is combined with chemotherapy. A controlled retrospective trial has shown a statistically significant increase of radiation injuries in patients who have had previous abdominal surgery [24]. Twenty-five patients in this series underwent abdominal operations at some interval prior to radiation therapy. Two thirds of the group underwent a combination of radiotherapy and operation as primary treatment of their malignancies. Adhesions from previous operations may restrict the normal movement of the small bowel in and out of radiation portals. Other risk factors implicated by some include hypertension, generalized atherosclerosis [25], diabetes mellitus, and previous supracervital hysterectomy [4]. Endomorphs, female patients, and the elderly appear to be at increased risk for small bowel injury because of a deeper cul-de-sac, a higher incidence of immobile small bowel, and the presence of larger amounts of small intestine in the pelvis [26]. Controlled trials are needed to confirm or disprove these hypotheses. Patients with a history of abdominal surgery should undergo small bowel series and barium enema prior to radiation therapy to identify adherent bowel in the pelvis. The treatment fields can then be varied to avoid excessive radiation to a particular segment of the bowel. Emptying of the rectum with a rectal tube helps to protect it from a radium source, while placing patients in the prone position displaces the small bowel out of the pelvic treatment fields. Green, Iba, and Smith [26] d iscussed exclusion of the small bowel from the pelvic floor by imbrication of the cul-de-sac before radiation. The narrow vagina and retroflexion or retroversion of the uterus may also predispose the normal pelvic organs to higher radiation doses [13,27]. In laboratory animals, pitressin infusion decreases the severity of radiation injury of
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the small bowel [28]. Neutralization of proteases in animals has also modified the mucosal slough accompanying radiation therapy [22]. According to Buchler et al [29], patients experiencing severe acute radiation syndromes have an increased incidence of chr,onic injuries, although chronic injuries have developed in some patients without acute symptoms. In this series 78 per cent of patients with chronic injuries reported significant symptoms during the course of therapy that were easily controlled by medication. Only 6 per cent of our patients had severe acute symptoms requiring termination of therapy. If circumstances allow, assessment should include complete contrast studies, including small bowel series, fistulography, barium enema, cystography, and intravenous pyelography. Sin%e these patients are often anemic or hypoalbuminemic, nutritional evaluation and support are vital. The increased morbidity and mortality associated with anergy is well known. Despite the use of intravenous hyperalimentation [30,31], operative intervention is usually needed for closure of radiation-induced enterocutaneous fistulas [32]. The small bowel should be decompressed prior to operation with long tube suction, and systemic antibiotics are given as prophylaxis against septic complications. The possibility of a colonic malignancy at the site of a previous radiation proctocolitis [33] or radiation stricture [15] should be considered. When forced to operate on irradiated small bowel, the surgeon must frequently choose between resection and bypass procedures. Theoretical objections to resection and end-to-end anastomosis include (1) division of mesenteric vessels to bowel that may already be ischemic and (2) considerable dissection of bowel from surrounding adhesions. Bypasses are limited by the potential for development of blind loop syndromes and the retention of diseased bowel in vivo. Swan, Fowler, and Baronow [34] reviewed a series of 199 patients with small bowel injury from the literature, concluding that bypass procedures had a lower dehiscence rate (6 versus 36 per cent) and mortality (10 versus 21 per cent) than did resection and anastomosis. We have not demonstrated a decreased anastomotic dehiscence rate with bypass procedures, and we share the belief of others [22,32] that bypass procedures also have limitations. Many authors recommend wide resection when feasible to ensure anastomosis of healthy bowel [9,25,25,35]. Small bowel anastomoses can also be protected by temporary loop ileostomy [25] or tube jejunostomy [36]. Most [35] would agree that localized areas of radiation-injured small bowel with stricture can be
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137, April 1979
Bowel Injury
resected with a reasonable mortality, and that bypass procedures are preferred when extensive mobilization of bowel in the pelvis is necessary for adequate resection [4,37]. If a patient with a small bowel suture line leak is reoperated on, the bowel ends should be exteriorized [38]. Simple lysis of adhesions may be inadequate and dangerous [3,4], although obstruction in these patients may be caused by an isolated band. The approach to anastomosis in irradiated small intestine should be cautious [39]. “Healthy-appearing” bowel must be used, and frozen section control may assist in selection of proper areas [3,4,9] However, macroscopically normal bowel that bleeds freely has frequently leaked at the site of anastomosis [25]. Intraoperative decompression with enterotomy can be performed through a segment of bowel that is to be resected [40]. Methylene blue has been instilled into the bowel to check the integrity of the denuded wall at sites of dissection [22]. The small intestine should be decompressed using a long tube in the postoperative period. The management of small bowel fistulas is especially difficult. Decompression or single bypass usually will not allow such fistulas to heal spontaneously, even with optimal nutritional support. In this series there was a high failure rate associated with resection of the fistula with anastomosis, but partial or total exclusion of the fistula with bypass was generally successful. Sugg et al 1361 propose temporary double-barreled ileostomy if any damaged bowel is left within the abdomen; they performed proximal enterostomy even if normal-appearing bowel remained within the abdomen. Piver and Lele [42] found that total isolation of enterocutaneous and enterovaginal fistulas (12 of 43 caused by radiation) was associated with a 21 per cent morbidity and zero mortality, compared to a 50 per cent morbidity and 28 per cent mortality with bypass and partial isolation of the area with a mucous fistula. There is some disagreement about management of colon injuries, depending on the exact site of injury. In most cases of active proctocolitis, colostomy should be performed initially to allow edema and infection to subside [11,42]. Sometimes permanent colostomy is wise [2,11,43]. Colon disease can progress even in the presence of a colostomy. In the case of stenosis of the colorectum, resection may be possible. Palmer and Bush [32] described twenty-nine cases of rectosigmoid stenosis treated by low anterior resection and anastomosis wrapped with omentum, with only two deaths. They recommend the Hartmann procedure for necrosis or fistula of the rectosigmoid. Other authors [16] claim that it is rarely
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possible to perform an anastomosis
in the low colon
or rectum since these portions of the bowel are usually damaged together. Dean and Taylor [43] have
reported several cases of pull-through operations with preservation of the distal rectum. The presacral space should be drained in such operations 1361.Six of eight cases of combined abdominotranssacral proctocolectomy and coloproctostomy reported by Marks [44] were successful, using as little as 1 cm of distal rectal stump. Rectovaginal fistulas are usually best managed by diverting colostomy alone. Attempts at repair without diversion or colostomy closure after apparent fistula closure leads to fistula recurrence because of the intrinsically poor healing properties of this tissue. Certain rectovaginal fistulas may be closed at a later time if well vascularized tissue is available [32]. In the presence of multiple perineal fistulas or concurrent genitourinary injuries, pelvic exenteration may be necessary [36]. Operation for radiation-induced bowel injuries prolongs some lives and in some studies has been associated with a very low mortality [15]. However, with a morbidity of 62 per cent [9] and a mortality as high as 37 per cent as a sequel to radiation injury [3,9,16,38,40], operation for minor complaints in these patients should be avoided at all costs. Successful operative treatment is one of the greater challenges for the gastrointestinal surgeon today.
Summary
A review of forty cases of radiation-induced gastrointestinal injuries is presented. Based on this experience and reports in the literature, preoperative management and operative technics are discussed. The increased risk of radiation bowel injury is recognized in patients who have had previous operations. Preradiation contrast studies are advised to identify trapped loops of intestine in the pelvis. Small bowel resection is recommended with localized segments of disease. Bypass operations are preferable to avoid any extensive dissections. Bypass operations have anastomotic dehiscence rates similar to those of resections. Proctocolitis is usually managed by diverting colostomy, with resection in a few favorable cases or with treatment failures. Most rectovaginal fistulas are managed by permanent colostomy. Small bowel fistulas are best treated by bypass with partial or total exclusion rather than by primary resection. Vigorous preoperative and postoperative nutritional support and evaluation are vital because of the poor healing qualities of irradiated bowel. Multiple op-
440
erative procedures should be anticipated because the natural history of radiation bowel injury is slowly progressive. Acknowledgment: We would like to thank Dr. Spinks H. Marsh of the Department of Radiotherapy for his help in retrieving medical data. References 1. Bloomer WD, Hellman S: Normal tissue responses to radiation therapy. N Engl J Med 293: 80, 1975. 2. Ashbaugh DG, Owens JC: Intestinal complications following irradiation for gynecologic cancer. Arch Surg 87: 116, 1963. 3. Cram AE, Pearlman NW, Jochimsen PR: Surgical management of complications of radiation-injured gut. Am J Surg 133: 551, 1977. 4. DeCosse JJ, Rhodes RS, Wentz WB, et al: The natural history and management of radiation induced injury of the gastrointestinal tract. Ann Surg 170: 369, 1969. 5. Donaldson SS: Nutritional consequences of radiotherapy. Cancer Res 37: 2407, 1977. 6. Mennie AT, Dalley VM, Dinneen LC: Treatment of radiationinduced gastrointestinal distress with acetylsalicylate. Lancet 2: 942, 1975. 7. Goldstein F, Khoury J, Thornton J: Treatment of chronic radiation enteritis and colitis with salicylazosulfapyridine and systemic corticosteroids. Am J Gastroenferol65: 201, 1976. 8. Dencker H, Johnsson JE, Liedberg G, et al: Surgical aspects of radiation injury to the small and large intestines. Acfa Chir Stand 137: 692, 1971. 9. Dirksen PK, Matolo NM, Trelford JD: Complications following operation in the previously irradiated abdominopelvic cavity. Am Surg 43: 234, 1977. 10. Requarth W, Roberts S: Intestinal injuries following irradiation of pelvic viscera for malignancy. Arch Surg 73: 682, 1956. 11. Smith AN, Douglas M, McLean N. et al: Intestinal complications of pelvic irradiation for gynecologic cancer. Surg Gynecol Obstet 127: 721, 1968. 12. VanNagell JR Jr, Parker JC Jr, Maruyama Y: The effect of pelvic inflammatory disease on enteric complications following radiation therapy for cervical cancer. Am J Obstet Gynecol 128: 767, 1977. 13. Rubin P, Casarett GW: Clinical Radiation Pathology. Philadelphia, WB Saunders, 1968. 14. Kaplan AL, Hudgins PT, Wall JA: Postradiation pelvic fibrosis simulating recurrent carcinoma. Am J Obstet Gynecol92: 117, 1965. 15. Localio SA, Stone A, Friedman M: Surgical aspects of radiation enteritis. Surg Gynecol Obstef 129: 1163, 1969. 16. Deveney CW, Lewis FR Jr, Schrock TR: Surgical management of radiation injury of the small and large intestine. Dis Co/on Rectum 19: 25, 1976. 17. Rubin P: The radiographic expression of radiotherapeutic injury. Sem in Roentgen01 9: 5, 1974. 18. Roswit B, Malsky SJ, Reid CB: Severe radiation injuries of the stomach, small intestine, colon and rectum. Am JRoentgenol 114, 460, 1972. 19. Johnsson JE; Bladder and intestinal injuries following radiation therapy of carcinoma of the uterine cervix. Acfa Rad Ther fhys Biol 15: 541, 1976. 20. Friedman M: Calculated risks of radiation injury of normal tissue in treatment of cancer of testis, p 390. Proceedings of the Second National Conference of the American Cancer Society, 1952. 2 1. Donaldson SS, Jundt S, Ricour C: Radiation enteritis in children. A retrospective review, clinicopathologic correlation, and
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dietary management. Cancer 35: 1167, 1975. 22. Morgenstern L, Thompson R, Friedman NB: Tha modern enigma of radiation enteropathy: sequelae and solutions. Am J Surg 134: 166, 1977. 23. Phillips TL, Fu KK: Quantification of combined radiation therapy and chemotherapy effects on critical normal tissues. Cancer 37: 1166, 1976. 24. Loludice T. Baxter D, Balint J: Effects of abdominal surgery on the development of radiation enteropathy. Gastmenterology 73: 1093,1977. 25. Jackson BT: Bowel damage from radiation. Proc Roy Sot Med 69: 683, 1976. 26. Green N, Iba G, Smith WR: Measures to minimize small intestine injury in the irradiated pelvis. Cancer 35: 1633, 1975. 27. Kagan AR, DiSaia PJ, Wollin M, et al: The narrow vagina, the antecedent for irradiation injury. Gynecol Oncol 4: 291, 1976. 28. Steckel KJ, Snow HD, Collins JD, et al: Successful radiation protection of the normal intestinal tract in the dog. Radiology 111: 451, 1974. 29. Buchler DA, Kline JC, Peckham BM, et al: Radiation reactions in cervical cancer therapy. Am J Obstet Gynecol111: 745, 1971. 30. Aguirre A, Fischer JE, Welch CE: The role of surgery in hyperalimentation in therapy of gastrointestinal-cutaneous fistulae. Ann Surg 180: 393, 1974. 31. MacFadyen BV Jr, Dudrick SJ, Ruberg RL: Management of gastrointestinal fistulas with parenteral hyperalimentation. Surgery 74: 100, 1973. 32. Palmer JA, Bush RS: Radiation injuries to the bowel associated with the treatment of carcinoma of the cervix. Surgery 80: 458, 1976. 33. Castro EB, Rosen PP, Quan SHQ: Carcinoma of large intestine in patients irradiated for carcinoma of cervix and uterus. Cancer 31: 45, 1973. 34. Swan RW, Fowler WC Jr, Boronow RC: Surgical management of radiation injury to the small intestine. Surg Gynecol O&Met 142: 325, 1976. 35. Joelsson I, Raf L: Late injuries of the small intestine following radiotherapy for uterine carcinoma. Acfa Chir Stand 139: 194, 1973. 36. Sugg WL, Lawler WH, Ackerman LV, et al: Operative therapy for severe irradiational injury in the enteral and urinary tracts. Ann Surg 157: 62, 1963. 37. Wiley HM, Sugarbaker ED: Roentgenotherapeutic changes in the small intestine. Cancer 3: 629, 1950. 38. Wellwood JM, Jackson BT: The intestinal complications of radiotherapy. Br J Surg 60: 814, 1973. 39. Schrock TR, Deveney CW, Dunphy JE: Factors contributing to leakage of colonic anastomoses. Ann Surg 177: 513, 1973. 40. Deitel M, Degani C, Alexander MA; Major gastrointestinal problems after radiotherapy. Management and nutritional considerations. lnt Surg 62: 334, 1977. 41. Piver MS, Lele F, Lele S: Enterovaginal and enterocutaneous fistulae in women with gynecologic malignancies. Obstet Gynecol48: 560, 1976. 42. Perkins DE, Spjut HJ: Intestinal stenosis following radiation therapy. A roentgenologic-pathologic study. Am JRoentgenol 88: 953, 1962. 43. Dean RE, Taylor ES: Surgical treatment of complications resulting from irradiation therapy of cervical cancer. Am J Obstet Gyneco/ 79: 34, 1960. 44. Marks G: Combined abdominotranssacral reconstruction of the radiation-injured rectum. Am J Surg 131: 54, 1976.
Discussion J. Englebert Dunphy (San Francisco, CA): I agree with the authors’ views in every respect. In fact, their experience
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Injury
is very similar to ours at the University of California, San Francisco reported quite a few years ago by my colleague, Ted Schrock. I can only emphasize a few points. The risk of anastomosis after repair of a fistula, as was pointed out herein, is exceedingly high, and that makes it an unacceptable operation. The reason that it is so high is that irradiation alone is the major factor leading to breakdown of the fistula if the bowel has been damaged even slightly. However, when you add the risk of contamination, so that you have infection and irradiation, the failure rate is bound to be extremely high. I suspect that if every patient had undergone resection and anastomosis, the anastomotic leakage rate would have been even higher. Even though the authors chose selected, less favorable cases in which to perform the bypass, they had the same rate of anastomotic leakage. I think if they had not done a bypass operation and had gone ahead and carried out extensive resection, the leakage rate would have been even higher. You can see throughout the paper that they emphasize great caution and conservatism. I would like to emphasize that the bowel, which has not even been touched, may break down, and there are one or two examples in the authors’ series in which they operated in one area and a spontaneous leak developed elsewhere. This relates to collagen turnover in the intestinal tract. There is growing evidence that any operation on the bowel, and especially on the colon, leads to an increased turnover of collagen and a weakening of the walls of the bowel throughout the colon. There is a particularly good study coming out from Sweden on this same topic, emphasizing that the entire bowel is to some extent jeopardized whenever you do an operation involving mobilization and handling of the bowel, especially if an anastomosis is performed. Radiation therapists are not fully aware of the fact that high voltage X-rays sufficient to produce a regression of cancer are sufficient to damage the intestinal tract. I am concerned about screening operations, prior to irradiation, to decide how extensive the X-ray treatment should be. I hope we can find a simpler way of doing it, because patients who have been screened and then have to have X-ray therapy are even more vulnerable to injury because they have had that added factor of possible adhesions and fixation of bowel. W. Bradford Patterson (Boston, MA): I support Dr. Dunphy’s favorable comments on this excellent and courageous paper. I will not comment on the technical aspects of management, but make some observations about radiation and its effects on tissues. Radiation enteritis is not a good term. It implies an inflammatory change, while really it is a problem of ischemia. The telangiectasia in the submucosa appear as soon as three months after radiation. These are fragile, thin-walled vessels which can lead to the severe hemorrhagic complications that were reported. Later on, proliferation of the subintimal tissues leads to occlusion and diminished
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muscular blood flow. This is followed by fibrosis and contracture. Was this sequence in fact seen, of hemorrhage first, followed later by the complications related to contracture? We have investigated in the dog the problem of radiation damage to small intestine and ways of reducing this damage. A Thiry fistula, or isolated segment of small bowel, was transplanted to the subcutaneous tissue of the abdomen. One end of the segment was a mucous fistula. A nylon snare was placed around the vascular pedical and exteriorized below the xiphoid so that it could be occluded prior to irradiating this isolated segment of bowel. Both tumor cells and normal cells when they are anoxic are more resistant to radiation. By making the small bowel temporarily ischemic and therefore anoxic, we hoped to protect it. The vascular pedicle was occluded during the radiation therapy. The mucosa of the bowel, which was temporarily anoxic, was less damaged by irradiation than the unprotected bowel. Even up to 3,000 rad we found considerable protection in the acute stages of damage. We have not done the experiments to see whether this could afford protection from late damage. With this kind of “biologic trick” and new radiotherapy technics such as “dynamic shaping” of the fields during therapy to reduce the exposure of viscera, these complications may eventually be just a bad memory.
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John C. Russell (closing): We share with Dr. Dunphy his concern about the possible effect of “pretreatment laparotomy” in enhancing subsequent radiation bowel injury. In a retrospective study, LoIudice and co-workers [24] showed that previous abdominal surgery is a statistically significant factor predisposing to radiation bowel injury. However, to our knowledge there are no randomized, prospective studies looking specifically at the effects of pretreatment laparotomy. We hope that such data will soon become available, as more patients undergo exploration prior to radiotherapy. Dr. Patterson very nicely stressed the ischemic nature of radiation bowel injury. Other authors have found a sequence of acute hemorrhagic injuries followed by the development of fibrosis. In reviewing our data we could not confirm this sequence. As also noted by Dr. Patterson, anoxia provides relative protection against radiation damage. Pitressin infusion into the superior mesenteric artery decreases the severity of radiation injury of the small bowel in laboratory animals. Experimental work with beta-aminopropionitrile and certain phosphorothioates as radioprotectors of normal, oxygenated cells and limited clinical trials with metronidazole as a radiosensitizer of anoxic tumor cells, suggest that in the future pharmacologic manipulations during radiotherapy may lessen the incidence of radiation-induced gastrointestinal injuries.
The American Journal of Surgery
Radiation therapy is an established method in the treatment of many intraabdominal malignancies. Almost 50 per cent of patients with all types of cancer receive radiation therapy at some time [I]. With the usual therapeutic doses of 4,000 to 6,000 rad, severe gastrointestinal symptoms develop in 2 to 5 per cent of patients [2,3]. Most patients with mild symptoms respond to antispasmodics, low residue diets, antiemetics, and antidiarrheal medications [4,5]. Agents such as corticosteroids, acetylsalicylate, salicylazosulfapyridine, and cholestyramine have also been used in the management of chronic radiation enteritis [6,7]. One to 2 per cent of patients require operation because of excessive bleeding, perforation, obstruction, fistulization, or intractability [3,8-121. The morbidity associated with operations on irradiated bowel is high, and the inflammatory process is progressive, often necessitating multiple operative procedures. Because of the complexity of management of radiation injuries of the bowel, a retrospective review was undertaken, directed at several questions: (1) What, if any, factors predispose the patient undergoing radiation therapy to future bowel complications? (2) Is there a difference in the morbidity and mortality associated with large bowel versus small bowel injuries? (3) When operation is required, is there a definitive advantage of resection over bypass procedures? (4) What operations are favored for specific complications such as obstruction, perforation, or fistula formation? From the Department of Surgery, Hartford Hospital, Hartford, Connecticut, and the University of Connecticut School of Medicine, Farmington, Connecticut. Repint requests should be addressed to John P. Welch, MD, 85 Jefferson Street, Hartford, Connecticut 06106. Presented at the Fifty-Ninth Annual Meeting of the New England Surgical Society, Dixville Notch, New Hampshire, September 29-October 1, 1978.
Volume 137, April 1979
Material and Methods
During the decade between 1968 and 1977, forty patients underwent one operation or more at the Hartford Hospital for radiation injuries to the large or small bowel. Thirty patients were female and ten were male. The median age at the time of radiation treatment was fifty-one years (range 23 to 79 years). The primary diseases included carcinoma of the cervix (24 per cent), carcinoma of the bladder (19 per cent), carcinoma of the ovary (17 per cent), carcinoma of the endometrium (12 per cent), other forms of cancer (24 per cent), and unknown diseases (4 per cent). The type of radiation treatment was classified as external beam only (68 per cent), intracavitary radium (5 per cent), a combination of these (22 per cent), and unknown (5 per cent). The range of dosage was 4,000to 6,000 rad over a four to five week interval. Between 1950 and 1970, an average of twenty-four patients with cervical cancer were treated with radiation therapy annually; the ten patients with carcinoma of the cervix in this series represent an incidence of 4 per cent. The major site of initial radiation injury was the small bowel (40 per cent), the rectum (30 per cent), the colon (15 per cent), and the combination of large and small bowel (15 per cent). In many patients a second area of injury later became manifest, requiring additional operative procedures. In all, 32 per cent of patients had injuries restricted to the colon and rectum, 40 per cent had injuries of small bowel alone, and 28 per cent required operations for injuries involving both large and small bowel. Rectal injuries were especially frequent in patients having intracavitary radium therapy (6 of 11,55 per cent) when compared with patients undergoing only external beam therapy (6 of 27, 22 per cent). The interval between radiation therapy and the first operation for radiation bowel injury ranged from two months to thirty years, with a median interval of eighteen months. Within one year of radiation therapy, 22 per cent underwent operation, compared to 57 per cent at two years and 74 per cent at four years. There was no predictable time interval between radiation therapy and large or small bowel injuries. The type of radiation injury was related to the area of bowel involved. (Table I.) Nearly 50 per cent (15 of 31) of
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TABLE I
Complications of Radiation Injury by Anatomic Location Small Bowel
Rectum
Colon
Total
Obstruction Bleeding, intractable diarrhea Perforation Fistula
15 5
2 6
5 2
22 13
3 8
3 4
5
6 17
Total
31
15
12
58
small bowel injuries caused obstruction. Bleeding was the most common indication for operation for colon injuries (6 of 15, 40 per cent), whereas obstruction or fistula formation characterized rectal injury (10 of 12,83 per cent). In the entire series the indications for operation were obstruction (39 per cent), fistula formation (29 per cent), bleeding or intractable diarrhea (22 per cent), and perforation (10 per cent). Results
Types of Operation. The operations performed are outlined in Table II. The choice of anastomotic technic varied with individual surgeons. Two layer open anastomosis using chromic catgut and silk was most often done. The group of ninety-six operative procedures included fifty-one intestinal anastomoses:
TABLE II
Summary of Operative Procedures Small Bowel
Resection and anastomosis with diversion Resection and anastomosis Resection only Bypass Combined resection and bypass Lysis of adhesions only Other operations Total l
Large Bowel
Combined
5
13
5
4 10 13
12 1
4
21
4 2
10 29 3
5
5 23”
31 Includes drainage of abdominal
Total
32 abscesses,
10 colostomy
96 clo-
sure.
TABLE III
Resection Resection Bypass Combined Colostomy Total
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twenty-six enteroenterostomies, nine enterocolostomies, and sixteen colocolostomies. Small bowel resection and anastomosis (13) and diverting enteroenterostomy (12) were done with nearly equal frequency. In nineteen colon resections, primary anastomosis without proximal diversion was performed in only four instances. After nearly 50 per cent of colon resections, the colon ends were exteriorized or a Hartmann procedure was done. Artastomotic Leak. The incidence of anastomotic leak resulting in abscess or fistula was 31 per cent. (Table III.) Resection with or without proximal diversion led to anastomotic leakage in 31 per cent, whereas bypass procedures had a 29 per cent incidence of leakage. The lowest incidence of anastomotic breakdown (11 per cent) followed enterocolostomies. The anastomotic dehiscence rates following end-to-end or side-to-side anastomosis of small bowel were almost identical (5 of 13,38 per cent versus 4 of 10, 40 per cent) in this series. Because stapling technics or one layer anastomoses were done infrequently, a comparison of these methods with more traditional ones was not possible. Morbidity. In this series, the overall morbidity was 65 per cent (including the 31 per cent incidence of anastomotic dehiscence), encompassing major complications such as renal failure, intraabdominal and pelvic abscesses, cardiac arrhythmias, septic shock, stoma1 necrosis, hepatic failure, gastrointestinal bleeding, and wound dehiscence. Obstruction. Two cases of colon obstruction and five of rectal obstruction necessitated operation. (Table I.) Both colonic obstructions involved the distal sigmoid and were successfully managed by proximal colostomy and cecostomy, respectively. Two of five rectal strictures were also managed by loop colostomy without progression of radiation injury. Two colon resections were performed. An anastomotic leak followed anterior resection for a stricture 12 cm from the anal verge, requiring later abdominoperineal resection. (Table IV, case 1.) A pelvic abscess and enteroperineal fistula followed a sigmoid resection and Hartmann procedure. The fifth patient underwent multiple successful dilata-
Incidence of Anastomotic Leakage
and anastomosis with diversion and anastomosis procedures closure
Enteroenterostomy
Enterocolostomy
5113 (38%) 4110 (40%) l/3 (33%)
l/4 (25%) 013 (0) o/2 (0)
10126 (38%)
l/9 (11%)
Colocolostomy 2/5 (40 %) o/4 (0) O/l (0)
Total
3/6 (50%)
215 (40%) 6121 (29%) 4114 (29%) l/5 (20%) 316 (50%)
5/16 (31%)
16/51 (31%)
The American Journal et Surgery
Radiation-Induced
tions of a rectal stricture, but iatrogenic sigmoid perforation occurred with sigmoidoscopy, requiring emergency laparotomy. A persistent vesicovaginal fistula developed in this patient, forcing construction of an ileal conduit. Fifteen operations were necessary because of small bowel obstruction. Seven bypass procedures were done, with anastomotic leakage in three patients and one death. In six patients having small bowel resections with anastomosis, no leaks occurred, but later anastomotic strictures in two patients led to multiple operations and eventual death. (Table IV, cases 7 and 11.) Two patients undergoing lysis of adhesions only had obstruction caused by solitary bands or vo1vulus, and their subsequent course was uneventful. Proctocolitis and Enteritis. Intractable symptoms of proctocolitis and enteritis led to operation in thirteen patients. Two loop colostomies were done. Because of persistent bleeding and rectal stricture formation, the first patient required an anterior resection and finally abdominoperineal resection. (Table IV, case 1.) In the second case a fecal fistula developed at the site of the loop colostomy eight years later. Colon resection as primary therapy was done in five patients, including one total colectomy for toxic megacolon and one abdominoperineal resection for massive bleeding. (Table IV, case 9.) One of two low anterior resections with proximal colostomy leaked, requiring drainage. Although a sigmoid resection done for colitis healed primarily, recurrent symptoms led to two additional colon resections and eventual death. (Table IV, case 5.) A final patient with presumed rectosigmoid carcinoma proved to have radiation colitis via a colotomy and survived colotomy closure without complications. The five patients with radiation enteritis had symptoms of recurrent partial small bowel obstruction and intractable diarrhea. Two had lysis of adhesions and both eventually died. (Table IV, cases 6 and 7.) Another patient with malabsorption caused by ileal dysfunction survived small bowel resection uneventfully. An ileocecectomy and ileoascending colostomy in the fourth patient was the first of multiple procedures leading to death. (Table IV, case 5.) A final patient underwent jejunotransverse colostomy (side-to-side) witbout incident. Perforation. Three patients had colonic perforations. One died of fecal peritonitis eight days after sigmoid resection with Hartmann turn-in. (Table IV, case 8.) Plication only of an iatrogenic sigmoid perforation following sigmoidoscopy resulted in a large pelvic abscess. The third patient with sigmoid perforation survived resection and anastomosis, but later
Volume 137, April 1979
Bowel Injury
stricture formation at the anastomosis required proximal diversion. There were three small bowel perforations. Resection and anastomosis of an ileal perforation led to enterocutaneous fistula formation and death. (Table IV, case 3.) A jejunal perforation was managed by jejunal plication, ileal resection, and ileocolostomy with a mucous fistula of the distal ileum. Four days later, the mucous fistula sloughed, and emergency ileocecectomy was done. The third case, an ileal perforation, was successfully treated with ileal plication and side-to-side ileoascending colostomy. Fistula. Fistulas ied to particularly vexing management problems. The four colonic fistulas were all successfully managed by diverting colostomy. One of the five rectal fistulas was controlled by diverting colostomy. In the remaining cases multiple surgical procedures were necessary. In one instance, two unsuccessful attempts (including gracilis flap) were made at closure of a rectovaginal fistula. An endsigmoid colostomy finally controlled the fistula output. A rectovesicovaginal fistula failed to close after combined ileal conduit and transverse loop colostomy and subsequent anterior resection. Construction of a double-barreled colostomy finally closed the fistula. However, closure of the colostomy led to prompt recurrence requiring a second double-barreled colostomy, and the patient died soon thereafter. A rectoperineal fistula with pelvic abscess recurred after attempted extraperitoneal closure. An ileal resection together with sigmoid loop colostomy controlled but did not close the fistula. The fourth patient (Table IV, case 1) with a rectoperineal sinus and pelvic abscess following anterior resection failed to respond to two drainage procedures and even abdominoperineal resection and died from complications of an uncontrollable enteroperineal fistula. Eight patients had small bowel fistulas that contributed directly to the death of three of them. Fistula recurrence followed small bowel resection and fistula excision in 60 per cent (3 of 5). In a fourth case an enterorectal fistula was treated with small bowel resection and plication of the rectal defect. Tumor was present at both ends of the fistula tract. An enterorectovesicovaginal fistula appearing one year later was controlled after small bowel resection, end-to-side ileocolostomy, mucous fistula of the distal ileum, and creation of an ileal conduit. An ileovesical fistula in another patient was controlled with small bowel resection, bladder closure, and drainage. Small bowel obstruction later occurred at the anastomosis, requiring side-to-side ileotransverse colostomy. Bypass operations were used in three additional cases. A side-to-side jejunocecostomy
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and Welch
TABLE IV
Deaths from Radiation Bowel Injuries
Sex/ Case 1
Age (yr)
Underlying Condition
F/79
Ca endometrium
Radiation Injuries
Operations
Radiation proctitis, stricture, and abscess
Transverse colostomy. Anterior resection. I & D X 4, AP resection. Coccygectomy
Enteroperineal
Jejunocecostomy (bypass). Small bowel resection X 2. Ligation jejunum and ileum, cecostomy
fistula
RadiationDeath Interval 13yr
OperationDeath Interval
Cause of Death
2mo
Recurrent enteroperineal fistula, multiple system failure
2
MI66
Ca bladder
Small bowel obstruction
Side-to-side ileoileostomy
8mo
2mo
Enterocutaneous fistula, perforated gastric ulcer, pneumonia
3
F/52
Ca cervix
Small and large bowel obstruction
lleoascending colostomy, sigmoid colostomy and mucous fistula
2 yr
1 mo
Enterocutaneous fistula, ASCVD, bilateral femoral artery occlusion
Enterocutaneous fistula, erosion right external iliac artery
Ileoileostomy, ligation right external iliac artery and right ureter
Small bowel perforation
Closures sb perforation, sb resection, ileocolostomy, transverse colostomy, ileostomy
5 yr
7 days
Small bowel necrosis
Right colectomy, mucous fistula right colon
Sigmoidocutaneous fistula
Sigmoid colostomy, closure of mucous fistula
Small bowel
Enteroenterostomy
Enteritis, small bowel obstruction
lleoascending colostomy, resection ileum and cecum and anastomosis
Rectal bleeding
Sigmoid resection (partial)
Colitis
Segmental resections sigmoid and transverse colon
Enteritis
End ileostomy
4
5
MI57
F/73
Lymphosarcoma left groin
Ca ovary
6
F/75
Ca ovary (carcinoid)
Enteritis, small bowel obstruction
Lysis of adhesions
7
F/63
Ca cervix
Enteritis
Laparotomy, biopsy, lysis of adhesions
Small bowel obstruction (partial), ileovesical fistula
Resection terminal ileum, ileal resection, ileoascending colostomy, drainage of fistula
Small bowel obstruction. Undifferentiated carcinoma 34 yr
4mo
High output ileostomy 13 mo
4mo
3 yr
2mo
Malnutrition, enteritis
radiation
Malnutrition, failure
renal
lleotransverse colostomy (bypass) Right colectomy, ileotransverse colostomy 8
436
F/65
Ca endometrium
Sigmoid perforation, fecal peritonitis
Sigmoid resection, endsigmoid colostomy, Hartmann procedure
11 yr
8 days
Retraction colostomy, multiple system failure
The American Journel of Surgery
Radiation-Induced
TABLE IV
(continued) OperaRadiationtionDeath Death Interval Interval
Sex/ Case
Age (yr)
Bowel Injury
Underlying Condition
Radiation Injuries
Operations
9
F/73
NA
Proctitis/colitis
Abdominoperineal resection
10
F/81
Ca bladder
Jejunovaginal fistula
11
F/49
Ca rectum
Cause of Death
30 yr
8 days
Multiple system failure
Small bowel resection, ileoileostomy (bypass), drainage pelvic abscess
2 yr
23 days
CVA, recurrent fistula
Small bowel obstruction
Small bowel resection X 2, lysis adhesions
4 yr
1 mo
Duodenal obstruction
Small bowel resection, gastrostomy, lysis adhesions
Small bowel obstruction, colon obstruction, duodenal obstruction
Gastrojejunostomy, colocolostomy (bypass)
Cachexia: radiation enteritis
Note: AP = abdominoperineal; ASCVD = atherosclerotic cardiovascular disease; Ca = carcinoma; CVA = cerebrovascular accident; NA = not known: sb = small bowel.
failed to control a high output ileoperineal fistula. (Table IV, case 1.) Small bowel resection also failed. Complete exclusion, including ligation of the jejunum just distal to the jejunocecostomy and ligation of the ileocecal valve, failed, and the patient died with a high output fistula. Bypass with partial exclusion (end-to-side jejunoileostomy) markedly decreased output from a distal jejunal fistula, while an enteroperineal fistula in the last patient was controlled with complete exclusion using a double-ended mucous fistula and small bowel anastomosis. Radiation Deaths. Of our forty patients, eighteen died during a one to ten year follow-up period. Eleven deaths (28 per cent) followed radiation bowel injury or operative complications. (Table IV.) Of the remaining deaths, five were caused by recurrent carcinema, one by renal failure, and one by leakage from an infected vascular graft. The patients dying of radiation injury could not be distinguished from the remaining twenty-nine patients by age, sex, frequency of abdominal operations prior to radiation therapy, or more severe acute radiation reactions during therapy. The patients described in Table IV did undergo on the average more operative procedures than the other patients (3.5 versus 2.0), and one patient had eleven operations. The most important determinant of the morbidity and mortality of the patients with radiation bowel injury was the location of the injury itself. Patients with small bowel injuries only had a 38 per cent mortality (6 of 16) due to irradiation, compared with a 15 per cent mortality (2 of 13) for colon and rectal injuries and a 27 per cent mortality (3 of 11) for
Volume 137, Aprtl 1979
combined small and large bowel injuries. Small bowel injuries were associated overall with more than four times the mortality of colon or rectal injuries (29 per cent versus ‘7per cent). (Table V.) Small bowel fistulas and severe enteritis were associated with a mortality rate of nearly 40 per cent. All four patients who died with rectal obstruction or rectovaginal fistulas did so from carcinomatosis rather than from radiation-induced injuries or postoperative complications. In nine patients, small bowel injuries were preterminal events, including three patients with recurrent small bowel fistulas. Two patients with colon injuries (Table IV, cases 8 and 9) died postoperatively with multisystem failure and septic or hypovolemic shock. TABLE
V
Mortality and Location of Intestinal injury*
Small Bowel7 Obstruction Enteritis Perforation Fistula Total Colon and Rectum* Obstruction Proctitis/Colitis Perforation Fistula Total
Deaths
Total
Mortality
4 2 3
15 5 3 8
27% 40% 0 38%
9
31
29%
1 1
7 8 3 9
0 12% 33% 0
2
27
7%
* Patients who died of causes directly attributable to radiation. + Includes some patients with colorectal injuries. f Includes some patients with small bowel injuries.
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Comments
Radiation injury to the bowel can be divided into three stages: acute, subacute, and chronic. The acute radiation syndrome of nausea, vomiting, diarrhea, and crampy abdominal pain experienced during radiation therapy is caused by direct toxic effects on the rapidly dividing cells of the gut mucosa and is usually self-limited [13]. Within six to eighteen months of treatment a subacute syndrome sometimes appears, with symptoms of bowel obstruction or gastrointestinal bleeding. Histologically, a progressive obliterative endarteritis progressing to fibrosis of multiple layers of the bowel wall is seen. The chronic symptoms of radiation bowel damage appear one to two years after therapy or later [2,9]. At operation in the chronic stages of injury, the involved bowel serosa appears thickened, dull, and gray, with decreased peristalsis. Normal tissue planes are obliterated; the intestine is friable and easily injured with surgical manipulation. Fibrosis may become so extensive in the pelvis that a “frozen pelvis” develops. Classic findings of recurrent cancer such as sciatica, leg edema, or a pelvic mass [14] may lead to inappropriate therapy of such patients. The presence of radiation injuries should be suspected and contrast studies, sigmoidoscopy, and biopsy carried out with a high index of suspicion. In the subacute and chronic forms, radiation bowel injury is a progressive disease [15]. In this series the radiation-to-operation interval was as great as thirty years, but was usually only a few years as in other reports [13]. At repeat laparotomy, previously normal-appearing bowel may have become strictured and fibrotic. The final result of radiation damage in a particular patient (normal bowel, perforation, or stricture) depends on the tissue sensitivity to radiation, its blood supply and degree of mobility, and the degree of hypertrophic scarring following acute tissue necrosis. Some authors believe that the gross pathologic findings are directly related to the latent period, with ulcerative lesions occurring earlier than fibrotic ones [16]. The present series fails to confirm such a temporal relationship. The etiology of radiation injuries to the bowel is complex. With the use of supervoltage radiation and wide treatment fields, there is risk of bowel injury, especially since cancericidal doses approach doses toxic to the normal bowel. Rubin [17] has defined the minimum and maximum injurious doses acceptable to the clinician as 4,500 to 6,500 rad for the small bowel and colon and 5,500 to 8,000 rad for the rectum. The risk of small bowel injury (obstruction, perforation, or ulceration) increases from 1 to 5 per
43%
cent at doses of 4,500 rad to 25 to 50 per cent at 6,500 rad [18]. Clearly the dose, time, fractionation, degree of shielding, and type of radiation therapy are related to the type of injury seen. Rectal injuries usually follow intracavitary irradiation, although small bowel lying in the pelvis may also be injured [19]. Whereas the small bowel appears to be more sensitive to radiation than the colorectum [20], rectal injuries have predominated in most series, perhaps due to the mobility of the small intestine. Multiple risk factors may predispose patients to bowel injuries as well. Vasculitis induced by pelvic inflammatory disease has been incriminated [12]. There is probably a cumulative toxicity of radiation therapy and chemotherapy as well [21,22]; Phillips and Fu [23] believe that the radiation dosage should be decreased by 10 to 80 per cent for the same degree of bowel injury when radiotherapy is combined with chemotherapy. A controlled retrospective trial has shown a statistically significant increase of radiation injuries in patients who have had previous abdominal surgery [24]. Twenty-five patients in this series underwent abdominal operations at some interval prior to radiation therapy. Two thirds of the group underwent a combination of radiotherapy and operation as primary treatment of their malignancies. Adhesions from previous operations may restrict the normal movement of the small bowel in and out of radiation portals. Other risk factors implicated by some include hypertension, generalized atherosclerosis [25], diabetes mellitus, and previous supracervital hysterectomy [4]. Endomorphs, female patients, and the elderly appear to be at increased risk for small bowel injury because of a deeper cul-de-sac, a higher incidence of immobile small bowel, and the presence of larger amounts of small intestine in the pelvis [26]. Controlled trials are needed to confirm or disprove these hypotheses. Patients with a history of abdominal surgery should undergo small bowel series and barium enema prior to radiation therapy to identify adherent bowel in the pelvis. The treatment fields can then be varied to avoid excessive radiation to a particular segment of the bowel. Emptying of the rectum with a rectal tube helps to protect it from a radium source, while placing patients in the prone position displaces the small bowel out of the pelvic treatment fields. Green, Iba, and Smith [26] d iscussed exclusion of the small bowel from the pelvic floor by imbrication of the cul-de-sac before radiation. The narrow vagina and retroflexion or retroversion of the uterus may also predispose the normal pelvic organs to higher radiation doses [13,27]. In laboratory animals, pitressin infusion decreases the severity of radiation injury of
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the small bowel [28]. Neutralization of proteases in animals has also modified the mucosal slough accompanying radiation therapy [22]. According to Buchler et al [29], patients experiencing severe acute radiation syndromes have an increased incidence of chr,onic injuries, although chronic injuries have developed in some patients without acute symptoms. In this series 78 per cent of patients with chronic injuries reported significant symptoms during the course of therapy that were easily controlled by medication. Only 6 per cent of our patients had severe acute symptoms requiring termination of therapy. If circumstances allow, assessment should include complete contrast studies, including small bowel series, fistulography, barium enema, cystography, and intravenous pyelography. Sin%e these patients are often anemic or hypoalbuminemic, nutritional evaluation and support are vital. The increased morbidity and mortality associated with anergy is well known. Despite the use of intravenous hyperalimentation [30,31], operative intervention is usually needed for closure of radiation-induced enterocutaneous fistulas [32]. The small bowel should be decompressed prior to operation with long tube suction, and systemic antibiotics are given as prophylaxis against septic complications. The possibility of a colonic malignancy at the site of a previous radiation proctocolitis [33] or radiation stricture [15] should be considered. When forced to operate on irradiated small bowel, the surgeon must frequently choose between resection and bypass procedures. Theoretical objections to resection and end-to-end anastomosis include (1) division of mesenteric vessels to bowel that may already be ischemic and (2) considerable dissection of bowel from surrounding adhesions. Bypasses are limited by the potential for development of blind loop syndromes and the retention of diseased bowel in vivo. Swan, Fowler, and Baronow [34] reviewed a series of 199 patients with small bowel injury from the literature, concluding that bypass procedures had a lower dehiscence rate (6 versus 36 per cent) and mortality (10 versus 21 per cent) than did resection and anastomosis. We have not demonstrated a decreased anastomotic dehiscence rate with bypass procedures, and we share the belief of others [22,32] that bypass procedures also have limitations. Many authors recommend wide resection when feasible to ensure anastomosis of healthy bowel [9,25,25,35]. Small bowel anastomoses can also be protected by temporary loop ileostomy [25] or tube jejunostomy [36]. Most [35] would agree that localized areas of radiation-injured small bowel with stricture can be
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resected with a reasonable mortality, and that bypass procedures are preferred when extensive mobilization of bowel in the pelvis is necessary for adequate resection [4,37]. If a patient with a small bowel suture line leak is reoperated on, the bowel ends should be exteriorized [38]. Simple lysis of adhesions may be inadequate and dangerous [3,4], although obstruction in these patients may be caused by an isolated band. The approach to anastomosis in irradiated small intestine should be cautious [39]. “Healthy-appearing” bowel must be used, and frozen section control may assist in selection of proper areas [3,4,9] However, macroscopically normal bowel that bleeds freely has frequently leaked at the site of anastomosis [25]. Intraoperative decompression with enterotomy can be performed through a segment of bowel that is to be resected [40]. Methylene blue has been instilled into the bowel to check the integrity of the denuded wall at sites of dissection [22]. The small intestine should be decompressed using a long tube in the postoperative period. The management of small bowel fistulas is especially difficult. Decompression or single bypass usually will not allow such fistulas to heal spontaneously, even with optimal nutritional support. In this series there was a high failure rate associated with resection of the fistula with anastomosis, but partial or total exclusion of the fistula with bypass was generally successful. Sugg et al 1361 propose temporary double-barreled ileostomy if any damaged bowel is left within the abdomen; they performed proximal enterostomy even if normal-appearing bowel remained within the abdomen. Piver and Lele [42] found that total isolation of enterocutaneous and enterovaginal fistulas (12 of 43 caused by radiation) was associated with a 21 per cent morbidity and zero mortality, compared to a 50 per cent morbidity and 28 per cent mortality with bypass and partial isolation of the area with a mucous fistula. There is some disagreement about management of colon injuries, depending on the exact site of injury. In most cases of active proctocolitis, colostomy should be performed initially to allow edema and infection to subside [11,42]. Sometimes permanent colostomy is wise [2,11,43]. Colon disease can progress even in the presence of a colostomy. In the case of stenosis of the colorectum, resection may be possible. Palmer and Bush [32] described twenty-nine cases of rectosigmoid stenosis treated by low anterior resection and anastomosis wrapped with omentum, with only two deaths. They recommend the Hartmann procedure for necrosis or fistula of the rectosigmoid. Other authors [16] claim that it is rarely
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possible to perform an anastomosis
in the low colon
or rectum since these portions of the bowel are usually damaged together. Dean and Taylor [43] have
reported several cases of pull-through operations with preservation of the distal rectum. The presacral space should be drained in such operations 1361.Six of eight cases of combined abdominotranssacral proctocolectomy and coloproctostomy reported by Marks [44] were successful, using as little as 1 cm of distal rectal stump. Rectovaginal fistulas are usually best managed by diverting colostomy alone. Attempts at repair without diversion or colostomy closure after apparent fistula closure leads to fistula recurrence because of the intrinsically poor healing properties of this tissue. Certain rectovaginal fistulas may be closed at a later time if well vascularized tissue is available [32]. In the presence of multiple perineal fistulas or concurrent genitourinary injuries, pelvic exenteration may be necessary [36]. Operation for radiation-induced bowel injuries prolongs some lives and in some studies has been associated with a very low mortality [15]. However, with a morbidity of 62 per cent [9] and a mortality as high as 37 per cent as a sequel to radiation injury [3,9,16,38,40], operation for minor complaints in these patients should be avoided at all costs. Successful operative treatment is one of the greater challenges for the gastrointestinal surgeon today.
Summary
A review of forty cases of radiation-induced gastrointestinal injuries is presented. Based on this experience and reports in the literature, preoperative management and operative technics are discussed. The increased risk of radiation bowel injury is recognized in patients who have had previous operations. Preradiation contrast studies are advised to identify trapped loops of intestine in the pelvis. Small bowel resection is recommended with localized segments of disease. Bypass operations are preferable to avoid any extensive dissections. Bypass operations have anastomotic dehiscence rates similar to those of resections. Proctocolitis is usually managed by diverting colostomy, with resection in a few favorable cases or with treatment failures. Most rectovaginal fistulas are managed by permanent colostomy. Small bowel fistulas are best treated by bypass with partial or total exclusion rather than by primary resection. Vigorous preoperative and postoperative nutritional support and evaluation are vital because of the poor healing qualities of irradiated bowel. Multiple op-
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erative procedures should be anticipated because the natural history of radiation bowel injury is slowly progressive. Acknowledgment: We would like to thank Dr. Spinks H. Marsh of the Department of Radiotherapy for his help in retrieving medical data. References 1. Bloomer WD, Hellman S: Normal tissue responses to radiation therapy. N Engl J Med 293: 80, 1975. 2. Ashbaugh DG, Owens JC: Intestinal complications following irradiation for gynecologic cancer. Arch Surg 87: 116, 1963. 3. Cram AE, Pearlman NW, Jochimsen PR: Surgical management of complications of radiation-injured gut. Am J Surg 133: 551, 1977. 4. DeCosse JJ, Rhodes RS, Wentz WB, et al: The natural history and management of radiation induced injury of the gastrointestinal tract. Ann Surg 170: 369, 1969. 5. Donaldson SS: Nutritional consequences of radiotherapy. Cancer Res 37: 2407, 1977. 6. Mennie AT, Dalley VM, Dinneen LC: Treatment of radiationinduced gastrointestinal distress with acetylsalicylate. Lancet 2: 942, 1975. 7. Goldstein F, Khoury J, Thornton J: Treatment of chronic radiation enteritis and colitis with salicylazosulfapyridine and systemic corticosteroids. Am J Gastroenferol65: 201, 1976. 8. Dencker H, Johnsson JE, Liedberg G, et al: Surgical aspects of radiation injury to the small and large intestines. Acfa Chir Stand 137: 692, 1971. 9. Dirksen PK, Matolo NM, Trelford JD: Complications following operation in the previously irradiated abdominopelvic cavity. Am Surg 43: 234, 1977. 10. Requarth W, Roberts S: Intestinal injuries following irradiation of pelvic viscera for malignancy. Arch Surg 73: 682, 1956. 11. Smith AN, Douglas M, McLean N. et al: Intestinal complications of pelvic irradiation for gynecologic cancer. Surg Gynecol Obstet 127: 721, 1968. 12. VanNagell JR Jr, Parker JC Jr, Maruyama Y: The effect of pelvic inflammatory disease on enteric complications following radiation therapy for cervical cancer. Am J Obstet Gynecol 128: 767, 1977. 13. Rubin P, Casarett GW: Clinical Radiation Pathology. Philadelphia, WB Saunders, 1968. 14. Kaplan AL, Hudgins PT, Wall JA: Postradiation pelvic fibrosis simulating recurrent carcinoma. Am J Obstet Gynecol92: 117, 1965. 15. Localio SA, Stone A, Friedman M: Surgical aspects of radiation enteritis. Surg Gynecol Obstef 129: 1163, 1969. 16. Deveney CW, Lewis FR Jr, Schrock TR: Surgical management of radiation injury of the small and large intestine. Dis Co/on Rectum 19: 25, 1976. 17. Rubin P: The radiographic expression of radiotherapeutic injury. Sem in Roentgen01 9: 5, 1974. 18. Roswit B, Malsky SJ, Reid CB: Severe radiation injuries of the stomach, small intestine, colon and rectum. Am JRoentgenol 114, 460, 1972. 19. Johnsson JE; Bladder and intestinal injuries following radiation therapy of carcinoma of the uterine cervix. Acfa Rad Ther fhys Biol 15: 541, 1976. 20. Friedman M: Calculated risks of radiation injury of normal tissue in treatment of cancer of testis, p 390. Proceedings of the Second National Conference of the American Cancer Society, 1952. 2 1. Donaldson SS, Jundt S, Ricour C: Radiation enteritis in children. A retrospective review, clinicopathologic correlation, and
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dietary management. Cancer 35: 1167, 1975. 22. Morgenstern L, Thompson R, Friedman NB: Tha modern enigma of radiation enteropathy: sequelae and solutions. Am J Surg 134: 166, 1977. 23. Phillips TL, Fu KK: Quantification of combined radiation therapy and chemotherapy effects on critical normal tissues. Cancer 37: 1166, 1976. 24. Loludice T. Baxter D, Balint J: Effects of abdominal surgery on the development of radiation enteropathy. Gastmenterology 73: 1093,1977. 25. Jackson BT: Bowel damage from radiation. Proc Roy Sot Med 69: 683, 1976. 26. Green N, Iba G, Smith WR: Measures to minimize small intestine injury in the irradiated pelvis. Cancer 35: 1633, 1975. 27. Kagan AR, DiSaia PJ, Wollin M, et al: The narrow vagina, the antecedent for irradiation injury. Gynecol Oncol 4: 291, 1976. 28. Steckel KJ, Snow HD, Collins JD, et al: Successful radiation protection of the normal intestinal tract in the dog. Radiology 111: 451, 1974. 29. Buchler DA, Kline JC, Peckham BM, et al: Radiation reactions in cervical cancer therapy. Am J Obstet Gynecol111: 745, 1971. 30. Aguirre A, Fischer JE, Welch CE: The role of surgery in hyperalimentation in therapy of gastrointestinal-cutaneous fistulae. Ann Surg 180: 393, 1974. 31. MacFadyen BV Jr, Dudrick SJ, Ruberg RL: Management of gastrointestinal fistulas with parenteral hyperalimentation. Surgery 74: 100, 1973. 32. Palmer JA, Bush RS: Radiation injuries to the bowel associated with the treatment of carcinoma of the cervix. Surgery 80: 458, 1976. 33. Castro EB, Rosen PP, Quan SHQ: Carcinoma of large intestine in patients irradiated for carcinoma of cervix and uterus. Cancer 31: 45, 1973. 34. Swan RW, Fowler WC Jr, Boronow RC: Surgical management of radiation injury to the small intestine. Surg Gynecol O&Met 142: 325, 1976. 35. Joelsson I, Raf L: Late injuries of the small intestine following radiotherapy for uterine carcinoma. Acfa Chir Stand 139: 194, 1973. 36. Sugg WL, Lawler WH, Ackerman LV, et al: Operative therapy for severe irradiational injury in the enteral and urinary tracts. Ann Surg 157: 62, 1963. 37. Wiley HM, Sugarbaker ED: Roentgenotherapeutic changes in the small intestine. Cancer 3: 629, 1950. 38. Wellwood JM, Jackson BT: The intestinal complications of radiotherapy. Br J Surg 60: 814, 1973. 39. Schrock TR, Deveney CW, Dunphy JE: Factors contributing to leakage of colonic anastomoses. Ann Surg 177: 513, 1973. 40. Deitel M, Degani C, Alexander MA; Major gastrointestinal problems after radiotherapy. Management and nutritional considerations. lnt Surg 62: 334, 1977. 41. Piver MS, Lele F, Lele S: Enterovaginal and enterocutaneous fistulae in women with gynecologic malignancies. Obstet Gynecol48: 560, 1976. 42. Perkins DE, Spjut HJ: Intestinal stenosis following radiation therapy. A roentgenologic-pathologic study. Am JRoentgenol 88: 953, 1962. 43. Dean RE, Taylor ES: Surgical treatment of complications resulting from irradiation therapy of cervical cancer. Am J Obstet Gyneco/ 79: 34, 1960. 44. Marks G: Combined abdominotranssacral reconstruction of the radiation-injured rectum. Am J Surg 131: 54, 1976.
Discussion J. Englebert Dunphy (San Francisco, CA): I agree with the authors’ views in every respect. In fact, their experience
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is very similar to ours at the University of California, San Francisco reported quite a few years ago by my colleague, Ted Schrock. I can only emphasize a few points. The risk of anastomosis after repair of a fistula, as was pointed out herein, is exceedingly high, and that makes it an unacceptable operation. The reason that it is so high is that irradiation alone is the major factor leading to breakdown of the fistula if the bowel has been damaged even slightly. However, when you add the risk of contamination, so that you have infection and irradiation, the failure rate is bound to be extremely high. I suspect that if every patient had undergone resection and anastomosis, the anastomotic leakage rate would have been even higher. Even though the authors chose selected, less favorable cases in which to perform the bypass, they had the same rate of anastomotic leakage. I think if they had not done a bypass operation and had gone ahead and carried out extensive resection, the leakage rate would have been even higher. You can see throughout the paper that they emphasize great caution and conservatism. I would like to emphasize that the bowel, which has not even been touched, may break down, and there are one or two examples in the authors’ series in which they operated in one area and a spontaneous leak developed elsewhere. This relates to collagen turnover in the intestinal tract. There is growing evidence that any operation on the bowel, and especially on the colon, leads to an increased turnover of collagen and a weakening of the walls of the bowel throughout the colon. There is a particularly good study coming out from Sweden on this same topic, emphasizing that the entire bowel is to some extent jeopardized whenever you do an operation involving mobilization and handling of the bowel, especially if an anastomosis is performed. Radiation therapists are not fully aware of the fact that high voltage X-rays sufficient to produce a regression of cancer are sufficient to damage the intestinal tract. I am concerned about screening operations, prior to irradiation, to decide how extensive the X-ray treatment should be. I hope we can find a simpler way of doing it, because patients who have been screened and then have to have X-ray therapy are even more vulnerable to injury because they have had that added factor of possible adhesions and fixation of bowel. W. Bradford Patterson (Boston, MA): I support Dr. Dunphy’s favorable comments on this excellent and courageous paper. I will not comment on the technical aspects of management, but make some observations about radiation and its effects on tissues. Radiation enteritis is not a good term. It implies an inflammatory change, while really it is a problem of ischemia. The telangiectasia in the submucosa appear as soon as three months after radiation. These are fragile, thin-walled vessels which can lead to the severe hemorrhagic complications that were reported. Later on, proliferation of the subintimal tissues leads to occlusion and diminished
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muscular blood flow. This is followed by fibrosis and contracture. Was this sequence in fact seen, of hemorrhage first, followed later by the complications related to contracture? We have investigated in the dog the problem of radiation damage to small intestine and ways of reducing this damage. A Thiry fistula, or isolated segment of small bowel, was transplanted to the subcutaneous tissue of the abdomen. One end of the segment was a mucous fistula. A nylon snare was placed around the vascular pedical and exteriorized below the xiphoid so that it could be occluded prior to irradiating this isolated segment of bowel. Both tumor cells and normal cells when they are anoxic are more resistant to radiation. By making the small bowel temporarily ischemic and therefore anoxic, we hoped to protect it. The vascular pedicle was occluded during the radiation therapy. The mucosa of the bowel, which was temporarily anoxic, was less damaged by irradiation than the unprotected bowel. Even up to 3,000 rad we found considerable protection in the acute stages of damage. We have not done the experiments to see whether this could afford protection from late damage. With this kind of “biologic trick” and new radiotherapy technics such as “dynamic shaping” of the fields during therapy to reduce the exposure of viscera, these complications may eventually be just a bad memory.
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John C. Russell (closing): We share with Dr. Dunphy his concern about the possible effect of “pretreatment laparotomy” in enhancing subsequent radiation bowel injury. In a retrospective study, LoIudice and co-workers [24] showed that previous abdominal surgery is a statistically significant factor predisposing to radiation bowel injury. However, to our knowledge there are no randomized, prospective studies looking specifically at the effects of pretreatment laparotomy. We hope that such data will soon become available, as more patients undergo exploration prior to radiotherapy. Dr. Patterson very nicely stressed the ischemic nature of radiation bowel injury. Other authors have found a sequence of acute hemorrhagic injuries followed by the development of fibrosis. In reviewing our data we could not confirm this sequence. As also noted by Dr. Patterson, anoxia provides relative protection against radiation damage. Pitressin infusion into the superior mesenteric artery decreases the severity of radiation injury of the small bowel in laboratory animals. Experimental work with beta-aminopropionitrile and certain phosphorothioates as radioprotectors of normal, oxygenated cells and limited clinical trials with metronidazole as a radiosensitizer of anoxic tumor cells, suggest that in the future pharmacologic manipulations during radiotherapy may lessen the incidence of radiation-induced gastrointestinal injuries.
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