Radiation Injuries of the Colon and Rectum

INFLAMMATORY DISORDERS OF THE COLON

0039-6109/93 $0.00 + .20

RADIATION INJURIES OF THE COLON AND RECTUM Daniel P. Otchy, MD, FACS, and Heidi Nelson, MD

Within 2 years of Rontgen's discovery of ionizing radiation in 1895, the detrimental effects of radiation on the gastroinestinal tract had been described. 86 Fiith and Ebeler in 191525 were the first to report cases of radiation-induced rectal strictures and fistulas. With time, radiationinduced injuries of the colon and rectum gained a reputation as infrequent but dreaded complications. These injuries were difficult to manage, and many surgeons were loathe to offer remedies other than fecal diversion. Between 10% and 25% of patients who sustained a radiation bowel injury died either as a direct result of the injury or as a result of complications from surgery to correct it. 17, 73 Today, because of a better understanding of the pathophysiology of radiation injuries and improvements in the available medical and surgical treatments, many of these complications can be brought to an acceptable outcome. BIOLOGIC EFFECTS OF RADIATION

Radiation energy produces its effects by creating free radicals from intracellular water. Free radicals cause breaks in the DNA helix, disrupting DNA transcription and replication, thereby leading to cell death during subsequent mitotic divisions. 9o Normal tissues and tumors show a radiation response at a rate proportional to their rate of proliferative turnover. When radiation is administered in the usual dose range of 150 to 250 cGy daily over several weeks, healthy tissue can repair a greater percentage of the daily radiation effects prior to the next dose than tumor

From the Division of Colorectal Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota

SURGICAL CLINICS OF NORTH AMERICA VOLUME 73 • NUMBER 5 • OCTOBER 1993

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cells can. 83 Over the course of treatment, normal healthy tissues are better able to repair the DNA damage, which results in a higher degree of tumor cell death than of normal cell death. Although there is a direct relation between the total dose of radiation and the incidence of radiation injury,36, 69 total dose is only one factor that contributes to radiation-induced injury. The dose of radiation delivered in each fraction is important because the greater the dose per fraction, the greater the injury incurred by healthy cells and the lower the likelihood that the injury will be repaired prior to the next dose. 32 To prevent an increase in the degree of damage to normal tissue, the total dose delivered must be decreased if the fraction size in increased. The volume of normal tissue being irradiated is also critical. A small area of bowel is capable of absorbing a greater degree of radiation without manifesting significant radiation injury. The type of radiation energy is of significance, as the degree of penetration is variable depending on the radiation source. As an example, a 25-MeV X-ray beam delivers twice the penetration of a cobalt-60 beam and will, therefore, distribute more energy to surrounding tissues. Whether the patient receives external-beam or intracavitary radiation or both is another determinant of injury. Clinical studies have demonstrated that patients who receive both external-beam and intracavitary radiation have a higher rate of complicationsP, 29 Finally, not all tissues are equally susceptible to the effects of radiation. 41 In many cases, the therapeutic dose range for tumors is similar to the toxic dose range for normal tissue. Because tolerance is tissue-specific, it is helpful to refer to "minimal tolerance dose" (TD 5/5) and "maximal tolerance dose" (TD 50/5). The TD 5/5 is defined as that dose that leads to clinical injury in 5% of patients within 5 years. The TD 50/5 is the dose that produces clinical damage in up to 50% of patients in 5 years. These values are similar for the small bowel and colon, 4500 to 6500 cGy. The rectum is somewhat more resistant to injury, as reflected by its TD5/5 and 50/5 values of 5500 and 8000 cGy, respectively.70 PATHOPHYSIOLOGY

Radiation exerts both direct and indirect effects on bowel, and these effects translate into acute and chronic manifestations of bowel injury, respectively.26, 50 The direct effects of ionizing radiation are manifested most acutely in those cells that are undergoing frequent mitosis, such as gastrointestinal epithelium. 90 Because the integrity of the mucosa depends on the frequent replacement of shed epithelial cells, radiation produces mucosal sloughing when the rate of cell loss outstrips the capacity of the crypt cells to replace the losses. As the cell renewal system continues to be impaired, microulcerations develop, and over time, they may coalesce to form macroscopic ulcers. Further changes in the submucosa, including edema, inflammatory cellular infiltrates, and capillary dilation, impair the, ability to absorb fluid and nutrients 41 and lead to

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excessive secretion of mucus and eventual bleeding. Acute-phase changes generally produce self-limited symptoms of abdominal pain, mucous diarrhea, tenesmus, and rectal bleeding. The indirect effects of radiation are considerably more indolent and progressive and are associated with more serious consequences. 26 Late radiation damage is the result of progressive occlusive endarteritis and diffuse collagen deposition. 26,50 The obliterative vascular changes associated with chronic damage produce chronic blood flow reduction and ischemia. Mucosal telangiectases develop in response to this chronic ischemia, and submucosal hyalinization and fibrosis result from the ongoing cellulitis. The mucosal telangiectases are friable and may become the source of chronic blood loss. Over a period of months to years, progressive vasculitis may lead to necrosis, ulceration, or perforation. Ulceration is the most common histologic lesion. An ulcer may penetrate through the muscularis, causing peritonitis or abscess formation. Healing of the ulcers may lead to fibrosis and cicatrization with subsequent narrowing of the bowel lumen. RISK FACTORS

Several clinical conditions increase the risk of complications from radiation. 26 These conditions exert their effects either by increasing the exposure of normal tissue to radiation or by potentiating the effects of radiation. For example, thin elderly women, who have less soft tissue to protect them, are at higher risk of radiation damage. Similarly, several studies have demonstrated that patients who have pelvic small-bowel adhesions from laparotomy prior to radiation therapy have a higher incidence of radiation enteritis. 27, 47, 55 Conditions that potentiate the harmful effects of radiation include vascular diseases and chemotherapeutic agents. Conditions that contribute to vascular occlusion might reasonably be expected to potentiate the ischemic effects of radiation. OeCosse et aP7 demonstrated a significant association between hypertension, diabetes, and cardiovascular disease at the time of radiation therapy and the subsequent development of radiation enteritis. Although the carcinotoxic effects of radiotherapy can be enhanced by various chemotherapy agents,89 unfortunately, these drugs can also enhance the toxic effects manifested in normal tissue. Actinomycin 0, 5-fluorouracil, methotrexate, and doxorubicin have all been implicated.22, 77 Surgeons and radiation therapists can work together to decrease the exposure of normal tissue to radiation. If postoperative pelvic radiation is anticipated, the surgeon should attempt to exclude the small bowel from the pelvis. There are various means to achieve this, including closing the peritoneum of the pelvic floor after proctectomy, suturing the bladder to the sacral promontory, or filling the pelvis with omentum and suturing it in place. 18, 33, 72, 78, 91 More controversial methods include inserting a prosthetic mesh sling across the lower abdominal cavity or temporarily

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inserting an inflatable saline or silicone prosthesis in the pelvis until the radiation treatments are completed. 63 The radiation therapist can decrease exposure by focusing the treatments precisely on the tumor bed and potential sites of local and regional spread. Exposure of the small bowel can be minimized by positioning the patient prone and in the Trendelenburg position during treatment,91 by distending the bladder prior to each treatment, and by using multiple fixed or rotational fields. 81 Hyperfractional radiotherapy may also prove useful in reducing the incidence of late complications. 36 INCIDENCE AND PATTERNS OF INJURY

The true incidence of radiation injury is difficult to assess accurately. Most large series estimate the incidenceQf chronic radiation injury to be between 5% and 11 %,10, 17,35,40,54,55,60 with approximately20% of these patients requiring an operation. 12, 73 Krook et al44 reported a 6.7% incidence of bowel complications in their recent study of combined adjuvant radiation and chemotherapy for rectal cancer. The patterns of visceral injuries generally reflect the prevalence of the primary tumors being irradiated rather than the tolerance of the injured organ. Because pelvic malignancies are commonly irradiated, it is not surprising that the rectum is the most commonly injured organ. Because of its fixed position in the pelvis, the rectum, either alone or in combination with other areas of the bowel, is damaged in 70% to 90% of all patients with intestinal injuries. 4, 10, 17, 60, 82, 88 Damage to the remainder of the large bowel is less common. Those portions of the colon that may drop into the pelvis-the sigmoid, the cecum, and, occasionally, the transverse colon-are at risk. Injury to the hepatic flexure or descending colon is distinctly unusual. 27 Approximately 25% to 33% of visceral injuries involve the small bowel. 4, 10, 17, 40 The ability of the small bowel to change position within the abdomen decreases the risk of injury, whereas fixation of bowel in the pelvis increases the risk of radiation enteritis. Concomitant injuries to other adjacent organs are common,17, 20, 24 with as many as 55% of patients with intestinal complications having associated genitourinary tract injuries. 17 Fibrosis of the surrounding connective tissue frequently leads to the development of a frozen pelvis. ACUTE INJURIES

Although the acute effects of radiation begin within hours of the commencement of radiotherapy, most patients will not experience the symptoms of acute radiation injury until 3000 to 4000 cGy have been delivered. Acute colitis and proctitis are manifested by abdominal pain, diarrhea, tenesmus, and rectal bleeding. There is little value in pursuing an aggressive diagnostic evaluation in this clinical setting. If a procto-

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scopic examination is performed, the mucosa appears edematous, erythematous, and friable. Approximately 50% to 75% of all patients undergoing therapeutic pelvic irradiation will develop these symptoms. 4 , 29, 68 Acute proctitis is treated symptomatically. Tenesmus can be ameliorated with sitz baths and warm compresses. Steroid enemas can be effective for inflammation, and hydrophilic stool softeners may help control mucous diarrhea. At times, decreasing the amount of radiation by lowering the dose or decreasing the volume of tissue irradiated is necessary to relieve symptoms. A decrease of 10% in the daily dose usually is successful, and it is distinctly uncommon to have to discontinue therapy. Acute injury is self-limited and resolves within weeks after the completion of therapy. Most patients have no further problems. There is some evidence that patients who experience the worst acute reactions are at greater risk for late gastrointestinal complications. Unfortunately, however, even patients who experience no acute effects are still at risk of developing chronic complications. CHRONIC RADIATION INJURY

Chronic radiation injury of the colon and rectum can lead to a multitude of clinical problems. Patients may present with coloproctitis, ulceration, stricture, fistula formation, or perforation. They may also experience fecal incontinence, either because of direct radiation damage to the anal sphincter or as a consequence of late radiation effects on the pelvic nerves. 85 Finally, one must keep in mind that patients who survive 5 or more years after their first tumor may be at risk for the development of subsequent cancers within the radiation field. Eighty-five percent of all patients who develop radiation injury will present between 6 and 24 months after completion of radiation therapyY, 29, 60 The remaining 15% of patients may develop complications years, or even decades, after treatment. 35 In general, patients with rectal ulceration or proctitis present somewhat earlier in their course than those with strictures and fistulas. 76, 88 Most colorectal complications occur within the rectum and sigmoid. Clinical evaluation is best performed using proctosigmoidoscopy and barium enema or with total colonoscopy when this is technically feasible. However, because of the development of a frozen pelvis, with fixation or a narrowed and noncompliant rectum, it often is impossible to insert the endoscope beyond the rectosigmoid junction. 66 In those patients in whom an endoscopic examination is uncomfortable, examination under anesthesia may be required. Proctoscopic examination will frequently demonstrate edematous, pale, thickened mucosa with petechiae and will occasionally demonstrate strictures, ulcerations, and fistulas. The proximal extent of involvement can be defined with a barium enema. 29, 52 Typical findings on barium enema include the loss of distensibility with rectal or sigmoid foreshortening with or without fixed stenosis and stricturing. The mucosa may be ulcerated, with a thickened corrugated ap-

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pearance, or it may be smooth and featureless. The presence of retrorectal fibrosis is detected as an increase in the presacral space to more than 1 cm. Sinuses into pelvic tissues or fistulas into the bladder, vagina, or small bowel may be detected. If reflux into the terminal ileum can be accomplished, ileal damage may be assessed. The possibility that the presenting symptoms and clinical findings are attributable to a recurrence of the cancer for which the radiation was originally given must be kept in mind during the clinical evaluation. Supplementary tests and biopsies may be required to rule out recurrence. Proctitis and Bleeding

Sixty-five to seventy-five percent of patients with proctitis present within a year of completion or radiation therapy.29, 54 Most commonly, these patients have rectal bleeding caused by irritation of the fragile rectal mucosa by the passage of fecal matter. Bleeding may be accompanied by rectal pain, mucoid diarrhea, and tenesmus. Although most often the bleeding is of a slow chronic nature, over an extended period of time, sufficient blood loss can occur that transfusions are required. Rapid, torrential hemorrhage is rare, yet it may occur. The diagnosis is established by proctoscopic examination. The rectal mucosa appears erythematous, edematous, and friable, with diffuse telangiectasis. In severe cases, frank ulceration and necrosis may be detected. Colonoscopy may be difficult for technical reasons but may be helpful in excluding other sites of bleeding. Initial medical management is focused on avoiding constipation through dietary manipulation and stool softeners. Symptomatic relief is provided using oral analgesics. Although numerous other agents have been investigated for the treatment of radiation proctitis, favorable longterm results are rare. The best results have been demonstrated with sucralfate enemas. In a prospective study of 37 patients with radiationinduced proctosigmoiditis, treatment with 3.0 g of oral sulfasalazine and twice-daily 20-mg prednisolone enemas was compared with 2.0-g sucralfate enemas given with an oral placebo. Both treatments led to improvement. Sucralfate enemas not only significantly improved the response rates (clinical improvement in 95% of patients), but they were also better tolerated. Because sucralfate enemas are also less expensive, the authors concluded that they should be the preferred mode of short-term treatment. 43 Preliminary reports demonstrate that sodium pentosanpolysulfate, a mucosa-protecting synthetic sulfated polysaccharide, given orally may also be effective treatment in chronic radiation-induced proctitis. 34 Further studies of sodium pentosanpolysulfate are warranted before clinical application is accepted. Less conclusive results have been reported for the use of high-dose 5-aminosalicylic acid enemas,6, 84 topical steroid enemas,4, 26, 43 or oral sulfasalazine therapy.3o Although mild cases of proctitis with bleeding may continue over several months, most will resolve spontaneously or will stop with the

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addition of medical treatments. In contrast, Gilinsky et aJ29 demonstrated that patients with moderate to severe proctitis who require transfusions and have associated significant bowel dysfunction rarely stop bleeding with medical means and most often require surgical or endoscopic intervention. The simplest and most expeditious surgical means to resolve rectal bleeding is the creation of a colostomy. Theoretically, diversion of the fecal stream prevents constant irritation of the friable rectal mucosa. Unfortunately, the creation of a colostomy is neither risk free nor completely successful in eradicating symptoms. This procedure has been reported to have as much as a 79% complication rate,29 with 20% to 40% of patients continuing to bleed from the rectal stump. 4,29 For this reason, resectional therapy is at times most appropriate. Partial proctectomy with low anterior resection, and complete proctectomy with a coloanal anastomosis or abdominal perineal resection have all been performed with various degrees of success. These procedures are discussed in greater detail later in the text. Until recently, when medicinal remedies failed to control the gastrointestinal bleeding, patients were forced to choose between the expense and hazards of long-term blood transfusions and the uncertainties of surgical intervention. Several centers have now reported the use of laser photocoagulation as a valuable third alternative. 2, 3, 7, 13,48,58 Telangiectases are obliterated using laser energy delivered through a flexible endoscope. Multiple treatments delivered over 3 to 6 months may be required to obliterate vascular lesions completely. Both argon and neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers have been used successfully to stop transfusion-dependent bleeding in radiation proctitis. Whether either of these forms of laser is preferable is yet to be determined. Although the laser treatment series are all of small size (fewer than 10 patients), these reports are uniformly optimistic. Reported complication rates as high as 20% to 25% have generally reflected minor complications such as ileus, tenesmus, or abdominal pain. 2, 3 No serious complications or deaths have occurred. Enthusiasm for this modality is tempered by the fact that laser therapy does not appear to be a permanent solution. Recurrence of telangiectases, as well as recurrent bleeding, has been reported in some patients less than 1 year after laser therapy.2,48 Ulceration

Rectal ulcers tend to occur earlier than the other major colorectal complications of radiation therapy, with most being identified 4 to 12 months after the completion of treatment. 17 Ulceration most frequently develops on the anterior rectal wall at the level of the cervix, 4 cm from the anal verge. Rectal ulcers tend to be shallow, with thick margins and a yellow-gray coloration. Radiation-induced ulcers may be asymptomatic or may be associated with exquisite and disabling pain. There is no

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correlation between the size of the ulcer and the severity of the symptoms. The possibility that an ulceration represents recurrence of cancer must always be considered, and a biopsy must be obtained. Specimens should be taken from the margin of the ulcer, both to increase its yield and to decrease the incidence of fistula formation at the biopsy site. 9,24,60 Most ulcerations will respond to medical treatments as outlined above for proctitis. Sucralfate enemas appear to be particularly beneficial.42 In severe cases, fecal diversion may be required to relieve symptoms and to promote healing. Despite diversion, some ulcers do not respond and may progress to fistulization or perforation. Stricture

Progressive fibrosis of the muscular layer of the bowel can lead to stricture formation. A symptomatic stricture is the most common indication for surgical intervention in patients with colorectal radiation injury.4, 27, 55 Strictures are frequently in the mid to upper rectum but are not uncommonly seen within the sigmoid colon. Although the majority of strictures develop and become symptomatic within 2 years of radiation treatments, Galland and Spencer27 reported that strictures are the most likely complication to present 15 to 30 years after therapy. Patients present with complaints of increased straining at stool, decreased caliber of stool, and abdominal pain and cramping. The extent of endoscopy will be limited by the stricture, and therefore, dilute barium enema studies must be relied on to assess the stricture and the proximal bowel. Strictures are often several centimeters in length and taper gently at either end, thereby denoting a benign process. In rare cases, the barium enema appearance of the stricture mimics that of a malignant process, with abrupt and irregular overhanging mucosal edges. If the diagnosis of cancer cannot be excluded endoscopically, a laparotomy may be necessary. Minimal stenosis with mild symptoms may be acceptably managed with stool softeners and enemas. Most patients with symptomatic rectal strictures are best treated with a diverting colostomy. In some patients, the acute swelling associated with the stricture will subside, reopening the lumen and allowing restoration of intestinal continuity after several months. 4 If the stricture persists and the patient is a good surgical candidate, resection of the rectal stricture should be considered. For more proximally located strictures, resection and primary anastomosis is the procedure of choice. Fistula

Radiation-induced fistulas may form between any two or more adjacent organs. Although the median time for fistula development is 18

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months after radiation therapy, some patients first present two or three decades after completion of treatment. 17 Rectovaginal fistulas, which present as vaginal discharge, are the most common type. 29 Rectal bleeding and perineal excoriation, which are frequently present, are also debilitating and distressing to these patients. Fistulas commonly occur in patients who have had other radiation complications earlier in their courses. As with ulceration and stricture, the possibility of a local cancer recurrence must be evaluated. When the fistula develops after a particularly long period of time, it is less likely to be secondary to a recurrent malignancy. Full radiologic and endoscopic evaluation of the gastrointestinal and genitourinary tracts should be completed to assess the extent of disease, to define which organs are involved, and to look for any concomitant injuries. Rectovaginal fistulas from radiation require surgery. Local repairs should not be attempted, as they invariably fail because of the chronic ischemia and poor healing qualities of the surrounding tissues. 17, 56 The two most important guiding principles for successful repair are that well-vascularized tissue be used to reconstruct the local anatomy and that fecal diversion be performed to allow adequate healing. In the past, most patients with a rectovaginal fistula have been treated with fecal diversion alone because of the technical difficulties and the high complication rate of reparative surgery. 53 Unlike other benign rectovaginal fistulas, in which diversion is often temporary, radiation-induced fistulas almost never heal, and these stomas must be viewed as permanent. 4 For patients unwilling to accept a permanent stoma for what is in reality a benign condition, many types of tissue transfers have been advocated for delivering vascularized tissue to close the fistula defect. These methods include the use of the omentum,5 gracilis muscle,31 adductor muscle,37 and rectus abdominis muscle. 37 In each of these tissue interposition techniques, the colonic defect is closed using a perineal approach. The vascularized tissue is positioned in the rectovaginal septum at the site of the fistula, and the vaginal mucosa is reapproximated. Even though these methods have met with some success, none has been widely accepted. Many surgical centers are now taking a more aggressive approach to the treatment of these fistulas and are achieving good success rates by resecting the involved segment and restoring intestinal continuity with a coloanal anastomosis. 11, 16,23,49,57,62 This and other surgical options are discussed in the surgical management portion of the text. Perforation

Perforation of the colon is a distinctly uncommon late complication of radiation therapy.4, 17 Perforation most commonly occurs within areas of irradiated small intestine, often just proximal to an area of stricture. 60 Free peritoneal perforation will present, much like any perforation, with signs and symptoms of peritonitis. Alternatively, progressive necrosis of

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the bowel wall may lead to a chronic perforation, most commonly in the rectosigmoid. 50 Encasement of the viscera by a fibrinous envelope may prevent free peritoneal perforation. The necrotic area is insulated from the parietal peritoneum, and the fibrinous envelope also prevents absorption of toxic products and minimizes systemic signs. Patients with chronic perforation can represent a diagnostic dilemma, presenting with chronic pelvic pain and incomplete colonic obstruction. When a perforation is diagnosed, resuscitation with intravenous fluids, administration of antibiotics, and prompt surgical intervention are indicated. The perforated segment should be resected. The combination of irradiated bowel and peritonitis should dissuade even the most confident surgeon from performing a primary anastomosis in this circumstance. A colostomy should be fashioned at the proximal end of the resection and the distal end oversewn or fashioned as a mucous fistula if distal obstruction is present or eminent. Induction of Cancer

Although the development of colorectal carcinoma after abdominal and pelvic radiotherapy is well documented, a direct cause-and-effect relation has not been proved. Despite the lack of direct evidence, there are sufficient circumstantial clinical data8, 15, 21, 39, 45, 51, 59, 61, 79 and experimental animal data l9, 46 to support the concept of cancer induction. Radiation has been found to be a potent carcinogen in animal models. 19, 46 By exposing the colon of rats to between 2500 and 6500 rad, Denman et aP9 were able to induce the development of adenocarcinoma in as many as 47% of the animals by 7.5 months. Although this observation cannot necessarily be applied to the human colon, Sandler and Sandler,74 in a comprehensive analysis, calculated that the relative risk in humans of developing colorectal cancer after irradiation for gynecologic malignancy is increased two fold to three fold. Several studies have observed higher than expected mortality rates from rectal cancer in women who have received radiation for cervical carcinoma21 or benign uterine bleeding. 61 , 71, 78 The risk appears to be unrelated to any apparent link between gynecologic and rectal malignancy. 75 Black and Ackerman8 have set forth three criteria for establishing whether a cancer was induced by prior radiotherapy: (1) a minimum of 10 years between exposure to radiation and subsequent tumor development; (2) severe radiation-induced changes in the immediate vicinity of the tumor; and (3) a relatively great exposure of the large bowel to irradiation. Although the majority of radiation-induced cancers do occur after a latent period of more than 10 years, the two largest reported series of these patients both observed a peak incidence 5 to 10 years after radiotherapy.15, 39 Likewise, severe radiation damage in the bowel adjacent to a cancer is present in 70% to 85% of cases but is not universally present. 15, 39 Although one would expect high-dose radiation to be essential for the induction of colorectal cancer, in fact, the opposite may be

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true. Palmer and Spratt61 found that patients who had received low-dose irradiation for benign gynecologic conditions had a greater chance (3.32%) of developing rectal cancer than those who received high-dose irradiation (1.42%) to treat cancer of the cervix. Denman et aP9 found that doses of 4500 rad caused the highest incidence of colon cancer in rats compared with higher or lower doses. Data from these series do not strictly fulfill the stringent criteria outlined by Black and Ackerman but are suggestive of a relation between radiation and subsequent cancer. Radiation-induced colorectal cancers are more often of mucinous histologic type (25% to 60% of cases) than are cancers in non-irradiated patients (10% of cases),15, 39, 45 The fact that these cancers are of a different histologic type and that all colon cancers induced by radiation in rats were mucinous adenocarcinomas 19 lends further support to the concept that these carcinomas are radiation induced. The outcome for patients presenting with a colorectal cancer in an irradiated field is poor. In a large series of patients, Castro et aP5 reported a 5-year survival rate of just 20%. The poor prognosis may be related, in part, to the high incidence of mucinous tumors as well as to the debilitating effects of chronic radiation injury. Resection of these cancers carries a higher mortality (5%) and morbidity (22%) than operations for ordinary colorectal cancer because of the difficulties of operating in an irradiated field. 39 It seems evident that patients who have received pelvic radiation should be considered to be in i1 high-risk category for the development of colorectal cancer. Colonoscopic surveillance at regular intervals beginning 5 years after radiotherapy is highly recommended for these patients. SURGICAL ALTERNATIVES FOR CHRONIC INJURIES Preoperative Preparation

The majority of these operations are of an elective nature and allow ample opportunity for complete preoperative evaluation and preparation of the patient. Any alterations in fecal continence should be elicited from the patient and the adequacy of the anal sphincter mechanism determined by physical examination and anal manometry. It serves little purpose to undertake a heroic resection of a colorectal injury in the presence of a poorly functioning sphincter that has beer.. damaged by prior surgery or radiation. The status of the original malignancy must also be assessed. It is unconscionable to submit a patient to an extensive reconstruction in the face of extensive local or distant recurrence. The extent of the radiation injury should be completely evaluated. The frequency with which injuries to the genitourinary tract and small bowel occur concomitantly with colorectal injuries demands full evaluation of these areas prior to surgery. Barium study of the small bowel may reveal unsuspected strictures or fistulas. Cystoscopy may confirm the presence

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of radiation cystitis or cancer. An intravenous urogram can delineate the position of the ureters bilaterally and identify the presence of hydronephrosis attributable to encasement of the ureter by fibrosis or recurrent cancer. If there is displacement or obstruction of a ureter or if a pelvic dissection is contemplated, bilateral ureteral stents should be placed preoperatively. Nutritional and biochemical abnormalities should be corrected prior to surgery. Acute or chronic pelvic sepsis should be controlled, and this may require proximal fecal diversion. The bowel should be prepared using an oral lavage solution combined with both oral and intravenous antibiotics. General Principles

The abdomen should be entered through a standard midline incision, as this incision provides access to the entire abdominal cavity while leaving all quadrants available for potential stoma placement. During the procedure, the underlying goal of the operation must be kept in mind. Mobilization and resection should be minimized and focused on accomplishing the desired goal. Bowel that is grossly affected by radiation typically appears pale with grayish white coloration. Often, the loops of bowel are densely matted together, and extensive interloop fibrosis causes the loss of distinct planes of dissection. Unnecessary dissection of these loops should be avoided. Overaggressive attempts at dissection simply for the sake of freeing up the bowel are unnecessary and may lead to vascular compromise, to enterotomies, and to fistula formation. The surgeon must keep in mind that healing is impaired in bowel that has received more than 4500 cGy and that any suture line is at increased risk of leak and fistula formation. Diverting Stomas

Chronic rectal bleeding requiring blood transfusions, as well as symptomatic strictures and painful rectal ulcers not responding to medical management, are indications for colostomy. In approximately 50% of patients, the inflammation associated with these maladies subsides after several months of diversion, and healing permits restoration of intestinal continuity. 4, 65 Unfortunately, 20% of patients who undergo colostomy closure will have a return of symptoms requiring a second diverting stoma. 4 For patients with a rectovaginal fistula, it is often best to create a stoma initially, even if an attempt at repair or resection is anticipated. This will allow the inflammation at the fistula site to resolve prior to the definitive surgery. In general, the sigmoid colon should not be used for colostomy formation. The likelihood that it has sustained some degree of radiation injury is high, even if it appears normal on gross examination. When

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irradiated colon is used, the incidence of necrosis, retraction, and fistula formation is higher. 17, 20, 38 The proximal transverse and descending colon rarely receive radiation exposure and are the best segments to use for creation of a stoma. DeCosse et all 7 confirmed this view, reporting a 53% complication rate for sigmoid colostomies compared with 8% for descending and transverse colostomies. If rectal resection is anticipated for a later date, a transverse colostomy is preferred. This prevents vascular compromise of the sigmoid and descending colon, a segment crucial for future reconstruction. Because of the frequent occurrence of synchronous damage to the ileum, diversion using a loop or end-ileostomy usually is not a good option. If possible, the stoma should not be brought out through irradiated skin. Such skin has poor wound healing properties and can contribute to the risk of mucocutaneous separation. The bowel that is brought out must be extensively mobilized to eliminate any tension of the mesentery. If the bowel to be used for the stoma has been exposed to radiation, an additional centimeter or two of bowel should be exteriorized beyond what is normally used for a stoma. Irradiated bowel tends to contract significantly after the stoma is matured, and the additional exteriorization will help prevent retraction and stoma necrosis. Segmental Colectomy

Right colectomy is most commonly performed in concert with resection of a segment of ileum for radiation injury to the small bowel. Attempts at ileoileal anastomosis are usually ill advised because of the likelihood that the terminal ileum harbors radiation effects. Even though the terminal ileum and cecum appear normal, they are too frequently involved with radiation changes to be used safely for anastomosis. For resection of the terminal ileum and right colon, it is best to extend the resection to include the proximal right colon and to perform the anastomosis to non-irradiated bowel at the hepatic flexure. When there is radiation injury involving the sigmoid or the upper rectum, the status of the distal 6 to 10 cm of the rectum must be assessed. If the distal rectum has only mild to moderate radiation changes, a rectosigmoid resection with a low anterior anastomosis can be performed safely. If the lower rectum is extensively involved with radiation changes or if there is significant colonic necrosis, a rectosigmoid resection with a Hartmann pouch and proximal stoma is advised. The stoma can be closed in 3 to 6 months when the acute changes in the rectum have subsided. Palmer and Bush60 have used this approach in 60 patients. They performed 31 low anterior anastomoses and reported a 6% anastomotic leak rate. The chief disadvantage of the Hartmann procedure is the difficulty in doing the second-stage anastomosis. It is often difficult to mobilize the oversewn rectum from the surrounding dense radiation fibrosis. With the development of the circular stapler, this problem is diminished because the stapler is introduced per anum, and less of the

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remnant rectum requires mobilization. Using such a technique, Palmer and Bush were able to close 18 of 24 colostomies successfully. Because the microvasculature of the rectum is invariably damaged, it is of paramount importance that the proximal colon brought down for the anastomosis be normal, healthy bowel. The cut edge of the bowel should have pulsatile bleeding. The splenic flexure should always be mobilized to assure a tension-free anastomosis. The suture line should be wrapped with omentum to enhance healing. The anastomosis can be handsewn or stapled. If a stapler is used, one should bear in mind that the rectal tissue may be thicker than usual, and thicker staples should be considered. Despite all the precautions, it is at times prudent to create a temporary proximal diverting stoma. A contrast study can be performed in 8 weeks, and if there are no leaks at the anastomosis, the stoma can be closed. Proctectomy and Other Options

A permanent diverting colostomy is an acceptable surgical alternative for patients who are poor surgical risks, who have unresectable recurrent cancer, or who are unwilling to accept the potential risks of reparative or resectional surgery. In contradistinction to this, patients who enjoy good general health and who have a normal distal rectum and anal sphincter mechanism can undergo proctectomy with restoration of intestinal continuity using either a low colorectostomy or a coloanal anastomosis. These operations can be performed safely even when the fistula or stricture is within 1 to 2 cm of the anal sphincters. The chief technical difficulty of these operations is the safe removal of the rectum from the fibrotic, contracted, frozen pelvis. The rectal canal forms a rigid tunnel at the level of the anterior peritoneal reflection. This tunnel can be enlarged by sharply incising the fibrotic tissue in the midline anteriorly. Attempting to perform this maneuver in a lateral direction puts the ureters at considerable risk of injury and does not open the space as effectively. Marks49 has reported success using an abdominal-trans sacral approach for low rectal injuries. This approach allows the surgeon to suture the proximal colon under direct vision to the last centimeter of the distal rectum. The operation commences with the patient in the supine position. The colon is mobilized and the rectum transected as low in the pelvis as can comfortably be performed. The proximal freed bowel is placed in the presacral space so that it can be drawn easily through the transsacral incision. A proximal transverse colostomy is created, and the abdomen is closed. The patient is placed in a decubitus position, and a transsacral incision is made. A portion of the sacrum and the coccyx is resected, and the rectum is identified. The rectum is then dissected out, leaving a l-cm rectal stump. The proximal colon is brought down and sewn to the stump. Marks and Mohiudden50 performed this operation on 20 patients with no deaths, but with three anastomotic leaks, two of which necessitated reoperation for a successful result.

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Parks and coworkers62 utilized a mucosal proctectomy and coloanal sleeve anastomosis for radiation-induced injuries. The operation is performed with the patient in the lithotomy position. The abdominal portion is commenced by mobilizing the left colon, including the splenic flexure. The rectum is dissected very close to the rectal wall to preclude injury to the ureters and nerves. Rectal dissection continues until necrotic tissue is reached, and the rectum is transected at this level. If a fistula is present, it is left untouched; if a stricture is present, it is fully dilated from above or below. Proximally, non-irradiated bowel is divided where it has a good blood supply. Through the anal canal, the distal rectal mucosa is infiltrated submucosally with a solution containing epinephrine. The rectal mucosa is then excised circumferentially from the dentate line until the level of transection is reached. The proximal colon is next brought down through the muscular rectal tube past the area of fistula or stricture and anastomosed to the anal mucosa transanally. A proximal diverting colostomy is created. Cooke and DeMoor 16 achieved good results using the Parks technique in 37 patients, 28 of whom had rectovaginal fistulas. Just two patients developed anastomotic leaks, and 75% achieved full continence by the I-year follow-up. Norwacki57 performed coloanal sleeve anastomosis for the repair of rectovaginal fistulas in 24 patients. Eleven patients had a simultaneous repair of a vesicovaginal fistula. One postoperative death occurred. The functional results were reported as good in 18 of the surviving 23 patients. Norwacki pointed out that in some patients, stripping of the rectal mucosa can be difficult, and he recommended surgical curettage in this circumstance. The promising results achieved with coloanal sleeve anastomosis have made it the procedure of choice for definitive repair of rectovaginal fistulas and low rectal strictures. Bricker et aPl advocated using an onlay patch graft of viable proximal colon for repair of rectovaginal fistulas and low rectal strictures. They argued that resection of the irradiated rectum is difficult and that the muscular tube through which the colon is passed may stricture, leading to renewed problems for patients undergoing a coloanal sleeve anastomosis. In their method, dissection of the rectum is kept to a minimum, and the presacral space need not be entered. The anterior wall of the rectum is opened starting at the peritoneal reflection down through the extent of the fistula or stricture. If the sigmoid is unaffected by radiation and its blood supply is intact, it can be used as the graft. The sigmoid is divided from the descending colon, and the proximal sigmoid end is turned down into the pelvis and laid over and anastomosed to the now-opened strictured or fistulized rectum. The descending colon is anastomosed end-to-side to the most cephalad portion of the sigmoid loop. A diverting colostomy is always utilized. Of 21 patients operated on, Bricker et aF7 were successful in 19. 11 Eighteen of these had a satisfactory to excellent functional result. Successful performance of this procedure utilizing anastomotic staplers has recently been described. 80 Finally, for those patients who cannot be reconstructed and who are symptomatic despite a diverting colostomy, the surgeon may need to

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resort to an abdominoperineal resection. The resulting perineal wound may heal poorly because of the prior radiation. Healing of the pelvic cavity can be enhanced by packing it with omentum or a muscle transfer.

SUMMARY

Approximately 5% to 10% of patients receiving abdominopelvic radiation therapy will develop a colon or rectal injury. Thorough evaluation of the patient to determine the extent of the injury and the presence of concomitant lesions and to rule out recurrent malignancy is urged. Many radiation complications can be managed with medical regimens. Although colostomy remains a valuable and frequently utilized mode of treatment, it is by no means the sole alternative when surgical intervention is required. Rectal resection with colorectal or coloanal anastomosis can be performed safely for some injuries involving the distal rectum. Surgery for irradiated bowel should be focused on minimizing dissection to minimize injuries and on providing healthy non-irradiated tissues to provide adequate blood supply to promote healing. Patients who have received abdominopelvic radiation are at greater risk of developing colorectal cancer, and cancer surveillance should be commenced 5 years after completion of therapy.

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