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Carcinoma of the Rectum: Current Management
Gastrointestinal and Hepatobiliary Malignancies
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Carcinoma of the Rectum: Current Management
Roger R. Dozois, M.D.,* Michael E. Pezim, M.D.,t and Leonard L. Gunderson, M.D.+
The principal goal of cancer surgery is to provide the greatest chance for cure while minimizing immediate and long-term disability. In recent years, the numerous approaches used to improve survival and the quality of life of patients after surgical treatment of rectal carcinoma have included earlier detection, sphincter-saving surgical procedures and adjuvant therapy for clinically resectable lesions, intraoperative radiotherapy for locally advanced tumors, and a more aggressive treatment for locally recurrent or distant, but isolated, spread of the disease.
EARLIER DETECTION The purpose of screening an asymptomatic population at risk for colorectal cancer is to detect tumors at an earlier stage, when treatment might be more successful. Whether such programs improve survival of patients with cancer of the rectum remains in question. Indeed, although a number of screening studies have shown a lower mean stage of disease at the time of detection in screened versus unscreened populations,6 both length bias and lead time bias complicate interpretation of such data. Endoscopy is the most accurate means of detecting rectal cancers but is not cost-effective as a screening tool. Although expensive and impractical for the general population, colonos copy is invaluable as a screening tool in selected groups of patients at risk for colorectal carcinoma. 6o These groups include patients who (1) have had a previous colon resection for cancer or colonic polypectomies, (2) have an obstructing carcinoma that does not *Consultant, Section of Gastroenterologic and General Surgery, and Consultant, Section of Colon and Rectal Surgery, Mayo Clinic and Mayo Foundation; and Associate Professor of Surgery, Mayo Medical School, Rochester, Minnesota tSenior Resident in Surgery, Mayo Graduate School of Medicine, Rochester, Minnesota :j:Consultant, Division of Radiation Oncology, Mayo Clinic and Mayo Foundation; and Professor of Oncology, Mayo Medical School, Rochester, Minnesota
Surgical Clinics of North America-Vol. 66, No.4, August 1986
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allow preoperative assessment of the proximal colon (early postoperative colonoscopy would appear to be valuable),8 (3) have a strong family history of colorectal carcinoma and colonic polyps, (4) have familial polyposis coli, (5) belong to a family with the "cancer family" syndrome, (6) have ulcerative colitis, especially if universal and present for more than 10 years, and (7) are more than 50 years of age and have rectal bleeding. Testing for fecal occult blood is more practical, but guaiac-based tests such as Hemoccult have serious limitations because of an unacceptable number of false-positive and false-negative tests. 3, 38 Moreover, and most troublesome, only 40 to 67 per cent of patients with proven colorectal cancers have a positive guaiac test. 15 What appears to be primarily responsible for false-negative Hemoccult tests is the conversion of heme to porphyrin, as occurs during intestinal transit or fecal storage. A new quantitative assay, the HemoQuant test, offers several advantages over guaiac-based screening tests. 58 In this procedure, the iron is removed from the hemoglobin heme and the fluorescence of the derived porphyrin is measured, thus including that important fraction of heme already converted to porphyrin during fecal transit. Also, this test is not affected by iron, ascorbic acid, vegetable peroxidase, or other substances known to interfere with guaiac tests. Results are calculated as hemoglobin equivalents and reported as milligram of hemoglobin per gram of stool. HemoQuant has been validated by recoveries of greater than 99 per cent for blood directly added to stools and of 88 per cent for ingested blood and by a close correlation with results of other quantitative tests. 3, 58 In a study comparing a single HemoQuant test per patient with six Hemoccult tests per patient, HemoQuant detected increased fecal hemoglobin levels in 97 per cent of all colorectal cancer patients, in 100 per cent of patients with asymptomatic colon cancer, and in 58 per cent of patients with large, premalignant (>2 cm) adenomas compared with positive Hemoccult tests in only 67, 43, and 17 per cent, respectively. 2
SPHINCTER-SAVING PROCEDURES FOR CLINICALLY RESECTABLE LESIONS Although opinion diverges on the treatment of carcinoma located in the lower third of the rectum (~5 cm above dentate line), there is general agreement that the classic abdominoperineal resection with a permanent end-sigmoid colostomy provides the otherwise healthy patient with the greatest opportunity for prolonged survival. Under certain circumstances, local excision may be another option (see below). Controversy persists, however, as to the extent of the resection required for carcinomas of the upper third (10 to 15 cm above dentate line) and, especially, of the middle third (5 to 10 cm above dentate line) of the rectum and as to the choice between the various sphincter-saving procedures now available, including low anterior resection, abdominosacral resection, and coloanal or pullthrough procedures. Regardless of which is chosen, the same basic anatomic and pathologic factors pertaining to rectal adenocarcinoma apply and should be adhered
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to strictly. If it is inadequate, a sphincter-saving procedure may avoid a stoma but jeopardize cure, the technical feat amounting to nothing more than an unfortunate mistake in surgical judgment. Equally tragic is the use of an abdominoperineal resection that is not indicated, because it leaves the patient with a permanent colostomy without improving survival. 18 Finally, to be a candidate for a sphincter-saving procedure, the patient must have adequate sphincter function preoperatively. Although this would appear to be obvious, not infrequently it is overlooked. One should not give the patient an anal colostomy to avoid the more easily managed abdominal stoma.
Low Anterior Resection This is the transabdominal removal of a malignant lesion from a site in the upper two thirds of the rectum, together with its regional lymphvascular tissues, and end-to-end anastomosis of the serosa-covered sigmoid with the non-serosa-covered rectum. 18 Indications and Technical Feasibility When considering the indications and technical feasibility of a low anterior resection, several pathologic and anatomic aspects must be taken into account. Pathologic factors that may influence adequacy of resection include intra- and extramural spread proximal and distal to the tumor. Proximal spread is not a major consideration because extensive resection of colon and proximal rectum along with the accompanying lymph-vascular pedicle does not interfere with re-establishment of colorectal continuity. Less than 1 per cent of the upper and middle rectal lymph drains through the pelvic lymph nodes,7 thus obviating extensive pelvic node dissection. Nonobstructing well-differentiated (Broders grade 1 or 2) adenocarcinoma rarely extends intramurally (distal spread) more than 1.5 cm, whereas an obstructing or poorly differentiated (Broders grade 3 or 4) tumor may do SO.25, 50 Similarly, retrograde extramural lymphatic spread is seen in less than 2 per cent of rectal carcinoma specimens, and it appears that, in all such instances, metastatic blockage of proximal lymphatic channels is responsible, 26 The shortest acceptable length of normal rectum below the inferior edge of a malignant lesion that will minimize local recurrence but optimize survival without compromising the safety of the anastomosis varies with the point of reference used and with the authors of papers on the subject. In reference to distal margin of resection, it is imperative to define how the measurements were made-that is, in vivo, before or after the rectum is freed during operation, or in vitro, on fresh or fixed specimens in the pathology laboratory. Lengths of distal margins ranging between 1 and 10 cm have been suggested. 24, 57, 64 Several surgical groups48, 66 have now confirmed the findings of Wilson and Beahrs67 that use of a margin as small as 2 cm does not adversely affect survival or local recurrence (Table 1). Whether the inferior mesenteric artery should be ligated at its origin from the aorta (high ligation) or below the origin of the left colic artery (low ligation) also remains controversial. Metastatic lymph nodes may be present (in 10 per cent of patients) within the short segment between the origins of the inferior mesenteric artery and the left colic artery.27 Their removal,
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Table 1. Survival and Recurrence Rate, by Length of Distal Margin after Low Anterior Resection* RECURRENCE. LENGTH OF
]>;0. OF
MARGIN, CMt
PATIENTS
o to <2
39
2 to <3 3 to <4 4 to <5
III
~5
155 95 156
MEAN SURVIVAL,
At 5 years
78 75 71 61 74
± ± ± ± ±
7 4 4 5 4
%:j:
At 10 years
57 66 50 47 56
± ± ± ± ±
10 5 5 5 4
%:j:
Anastomotic
Pelvic and Perirectal
8 5
10 10
4 8
6 8 8
5
*Modified from Wilson and Beahrs.67 tMeasured on fresh specimen in pathology laboratory. :j:Differences between groups are not statistically Significant.
however, does not appear to affect survival favorably, 12, 27, 47 suggesting that more proximal spread has already occurred. The feasibility of a safe, effective anastomosis between the left colon and the remaining rectum depends on several factors, including the characteristics of the tumor, the body habitus of the patient, and the ability and experience of the surgeon performing the operation. Larger tumors, those with extramural extension, and those with a lesser degree of differentiation (Broders grade 3 or 4) require wider distal and lateral margins and therefore are less amenable to anterior resection. Tumors located in the midrectum create a more technically demanding situation than do those in the upper third. A low anastomosis is performed more easily in women, in patients with a broad pelvis, and in thin patients. The operation is more difficult in men, because they usually have a narrower pelvis, and in obese patients. The experience, technical ability, and judgment of the surgeon are paramount in favoring low anterior resection over abdominoperineal resection. The surgeon should extend resection to a point below the tumor where continuity can be re-established conveniently without compromising cure, based on all the factors known regarding the cancer. In practice, the feasibility of a safe, effective anastomosis cannot be determined accurately until the rectum has been fully mobilized. The surgical technique described by Beahrs and colleagues 9 helps achieve this goal. Hand-Sewn Versus Stapled Anastomosis The hand-sewn technique permits direct and precise anastomotic approximation of the wall of the proximal segment to that of the distal segment. The layers are slightly inverted to minimize the possibility of leakage. For the majority of surgeons, use of a stapling device (EEA) may facilitate the achievement of this goal and lead to more frequent rectal preservation (10 to 15 per cent of cases) than otherwise might be possible. 11 On the other hand, unsuccessful attempts at completing a stapled anastomosis when it would have been feasible comfortably by the hand-sewn method may lead to an unwarranted abdominoperineal resection because of operative difficulties. Indeed, in a controlled, randomized evaluation of the two techniques, the hand-sewn technique was associated with fewer
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intraoperative complications and was as safe in preventing postoperative leakage. 11 Recently, there has been some concern over the possibility that a patient with a stapled anastomosis is at greater risk for local recurrence than one with a hand-sewn anastomosis. Whether this is true remains unclear because none of the reports suggesting such a possibility is derived from randomized, prospective, controlled trials. 5, 35, 51, 54 Those who favor one type of anastomosis over another do so because they have obtained reproducible and satisfactory results with it. Success with either technique depends on adequate exposure and blood supply and avoidance of tension. Surgeons should be familiar with both technical alternatives so that the proper one for a given situation can be used. On rare occasions, some midrectal tumors might be deemed too low for a safe low anterior resection, even with the stapling device. In such cases, other, less common techniques are available, including abdominosacral resection and coloanal anastomosis. However, we think that with the advent of staplers the role of such surgical approaches in the management of ordinary rectal cancer is limited. Abdominosacral Resection This procedure was championed primarily by Localio and colleagues for lesions located 7 to 11 cm from the anal verge in men and 5.5 to 10 cm from the anal verge in women. 4O We believe that such lesions usually can be resected by the low anterior approach by experienced colorectal surgeons. In Localio and Eng's series, anastomotic leaks were observed in 9.7 per cent of their patients, and temporary colostomy now is established routinely in men 65 years of age or younger.39 The operation provides no better functional results than those observed after anterior resection, and the 5-year survival is not improved. Coloanal Anastomosis This operation consists of anastomosing per anum the sigmoid colon to the dentate line of the remaining rectum stripped of mucosa. This procedure was devised by Parks and Percy46 to replace the earlier pull-through operations, which were plagued by complications and incontinence. The anastomosis may be hand sewn, as in the ileoanal anastomosis, or stapled by placing the distal purse-string suture from below, as proposed by Goligher. 23 A temporary colostomy frequently is required. This operation is followed by fewer complications than the previous pull-through operations and may provide an acceptable degree of continence, especially if a sigmoid pouch is added,45 but the indications for its use in the treatment of rectal cancer are unclear. It may also be of value for superficially invasive malignancies at the junction of the middle and lower thirds of the rectum, where a low anterior resection may prove technically impossible to do and yet may provide a more adequate resection than local excision. In the classic coloanal procedure, the denuded rectal stump is left in situ, and thus cancers of the lower third cannot be managed this way unless they have not invaded the muscularis. Clearly, such a determination cannot be made until the muscularis is removed. Lesions of the upper and middle
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thirds are more easily managed by hand-sewn or stapled anterior resection as discussed previously. One possible application of the coloanal procedure is in a failed very low anterior resection, in which an ultrashort rectal stump has disappeared into the mesorectal fat and the safe insertion of a distal purse-string suture is impossible. In such cases, rather than proceeding with an abdominoperineal resection, the surgeon may attempt a per anum mucosal proctectomy and coloanal anastomosis. Local Treatment Local eradication of low rectal cancers can be achieved by surgical excision,36 electrocoagulation,41. 56 or endocavitary irradiation 44 rather than by abdominoperineal resection. Of these options, surgical excision seems the most preferred because it yields specimens that can be assessed by the pathologist for adequacy of margins, extent of invasiveness, and potential for dissemination. Moreover, this approach still permits more radical treatment should the excised specimen dictate it. Destruction by electrocoagulation and, more recently, laser is less attractive because of the absence of an evaluable specimen. Although local excision may be curative lO in carefully selected situations, we prefer to reserve it for medically handicapped patients of high surgical risk because of our inability to predict accurately, prior to any surgical approach, who might be cured. Cancers that are well differentiated-especially those less than 3 cm in diameter, polypoid, and mobilemay be suitably treated by local excision, at least as a first step. As yet, however, no prospective, randomized trials comparing abdominoperineal resection with local treatment have been conducted. Overall, less than 5 per cent of rectal cancers are truly suitable for local excision. 37 To enhance exposure of the lower rectum and facilitate removal of benign rectal tumors, the Kraske method and the York-Mason technique may be useful. In the York-Mason procedure,42 a parasacral incision is made and carried through the muscle layers until the rectum is reached. Each layer is tagged to allow accurate reconstitution during closure. This ingenious approach may have a role in the management of benign tumors of the lower rectum and early cancers but, in our view, not in the management of typical rectal cancer unless the patient presents a considerable surgical risk or is totally opposed to a colostomy. ADJUVANT THERAPY FOR CLINICALLY RESECTABLE LESIONS The risk of local recurrence after "curative resection" for rectal cancers varies according to the degree of local tumor extension and the extent of lymph node involvement. The local recurrence rate for lesions with nodal involvement but tumor confined to the bowel wall (Astler-Coller classification) is 20 to 25 per cent; when nodes are negative but there is transmural growth, the recurrence rate is 30 to 35 per cent. Patients with both adverse prognostic factors have a nearly additive risk of local recurrence, 50 to 70 per cent. 13. 32, 52 The rate of local recurrence should be decreased with the addition of adequate doses of adjuvant irradiation, but this may not result
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in an increased cure rate. Nevertheless, a decrease in the rate of local recurrence and its tremendous associated morbidity would be a significant accomplishment. 22 Opinion differs regarding the preferred sequence of operation and radiotherapy. The major advantage of preoperative radiotherapy is the potential destruction of cells that may spread at the time of operation. The obvious disadvantage is that many patients will receive unnecessary irradiation. With postoperative radiotherapy, however, one has the opportunity to select groups of patients at risk for local recurrence and exclude from further radiotherapy those at low risk or with previously undiagnosed, distant spread of their disease. Presumably, a well-designed combination of preoperative and postoperative radiotherapy (so-called sandwich approach) could offer the advantages of each approach. Preoperative Irradiation Although a modest improvement in survival was observed in selected subgroups of patients in one prospective, randomized trial of low-dose radiotherapy, 55 this was not duplicated in a recent trial that compared lowdose preoperative irradiation and operation with operation alone. 59 Higher doses may decrease local recurrence,61, 65 but controlled trials to examine this have not been carried out. Use of moderate doses of radiation preoperatively does not preclude the safe use of anterior resection, provided that healthy proximal bowel is used for the anastomosis, 53, 62 but the irradiated group may be at higher risk for development of thromboembolic and cardiovascular complications. 49 Postoperative Irradiation A number of prospective but nonrandomized studies have shown a decrease in the rate of local recurrence from an expected 35 to 50 per cent with operation alone to 6 to 8 per cent after postoperative irradiation (4500 to 5500 rads given over a 5- to 7-week period in high-risk patients; B2-3, Cl_3).34,68 In a randomized trial from the Gastrointestinal Tumor Study Group, patients with Duke's B or C lesions were randomized to operation alone (control arm) or to adjuvant treatment of postoperative irradiation (4000 to 4800 rads), postoperative chemotherapy (5-Huorouracil plus methylchloroethylcyclohexylnitrosourea), or a combination of both. 20,43 The only significant difference in disease-free survival was between the combined chemotherapy and radiotherapy adjuvant arm compared with operation alone (p < 0.009). In that study, it appears that the combined treatment did not result in a decreased incidence of distant metastasis but rather in a decrease in local recurrence. This suggests that, rather than acting systemically, the chemotherapy may have potentiated the local effect of irradiation.
INTRAOPERATIVE IRRADIATION IN MANAGEMENT OF LOCALLY ADVANCED DISEASE The experience in patients who, because of nonresectability, receive only irradiation as treatment for advanced rectal cancers attests to the
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inadequacy of this modality as the sole means of management. In an analysis of 123 patients treated with radical external beam irradiation without resection, local control was achieved in only 9 per cent, and the 5-year actuarial survival rate was only 2 per cent. 16 In patients with disease that is considered to be unresectable for cure-because of tumor fixation found at surgical exploration or clinical evaluation-preoperative radiotherapy has been used in an attempt to shrink the lesion, permitting resection and possibly improving local control and survival. Although resection ultimately may be possible in 50 to 75 per cent of these patients after 4500 to 5000 rads given over 6 weeks, the rate of local recurrence is still at least 35 to 45 per cent. 17. 19,61 There is some evidence that, when external beam irradiation is utilized postoperatively for residual disease after resection, local control may be enhanced. 4, 21, 63 Not surprisingly, however, the likelihood oflocal recurrence depends on the amount of disease left behind, varying from about 20 per cent with microscopic residual disease to about 50 per cent when gross tumor remains. The value of single-dose intraoperative electron radiotherapy (IORT) in combination with operation and external beam irradiation is being assessed at our institution. This technique permits the safe delivery of much higher doses of irradiation. With external beam techniques, the presence of dose-limiting organs such as the small bowel restricts doses to 4500 to 5000 rads in many patients. Even when the small bowel can be excluded, doses within boost fields usually are not carried beyond a total dose of 6000 to 7000 rads. The biologic effectiveness of single-dose irradiation is considered equivalent to two or three times that of the same quantity of fractionated external beam treatment. Therefore, the effective dose in the intraoperative boost field, when added to the 4500 to 5000 rads delivered in 25 to 28 fractions with external beam techniques, is 6500 to 8000 rads for an IORT dose of 1000 rads, 7500 to 9500 rads with a 1500-rad IORT dose, and 8500 to 11,000 rads with a 2000-rad IORT dose. 28 , 33 In early pilot studies at the Massachusetts General Hospital (MGH)29 and the Mayo Clinic, 30, 31 the addition of intraoperative irradiation in 67 patients appeared to improve local control and, possibly, survival. Most patients received 3 days of 5-fluorouracil therapy during the course of external irradiation. In the MGH group of 32 patients, survival was higher than that in previous patients treated with only external beam techniques with or without resection. In the group of patients who had residual disease and received IORT, although five of the seven had gross tumor left behind, survival rates paralleled those of the MGH external beam patients with microscopic residual disease. 4 In ongoing IORT trials at MGH, survival in the group who presented with recurrence is stable at approximately 40 per cent between 3 and 4 years, in contrast with an expected long-term survival of 5 to 10 per cent when treatment is by standard techniques. 33 The improved survival rate may be partly due to patient selection because those who were found to have metastasis prior to or at the time of exploration did not receive the intraoperative irradiation, and their survival is not reflected in the survival curves. In the Mayo Clinic IORT series of 35
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patients, survival results and local tumor control parallel results at MGH, although follow-up is too short to permit definitive conclusions. 3D The results of using IORT in the initially unresectable group reveal a significant advantage for the 16 patients who received IORT at MGH. This is particularly interesting because the patients were selected in a fashion similar to that for a previous group of 14 MGH patients treated only with preoperative external beam irradiation and resection. More patients in the IORT group had surgical transection of tumor with proven residual disease despite preoperative irradiation and resection (4 of 16 versus 1 of 14), and 75 per cent of specimens in both groups included gross disease persisting beyond the muscularis propria. No local recurrences occurred in the IORT group,33 compared with 43 per cent in the external beam groupY This technique needs further evaluation over a longer period, and randomized, controlled trials are being developed.
REOPERATION FOR METASTATIC OR RECURRENT RECTAL CANCER Most patients with recurrent rectal cancer have extensive local or widespread disseminated disease. However, a small number of patients with early stage of recurrence or distal but isolated spread (for example, to the lung, liver, or ovary) may be legitimate candidates for reoperation. The major obstacle thus far has been limitations in assessing the exact extent of the disease. The advent of carcinoembryonic antigen analysis, computed tomography, and magnetic resonance imaging has stimulated interest in "staging" these patients and reassessing the possible role of operation. Patients with liver metastasis confined to one lobe, especially if it is single, are suitable for resection with a reasonable chance of "cure. "1 Similar results have been obtained for solitary pulmonary metastasis in the absence of liver metastasis. 14 Finally, aggressive combined-modality approaches are being assessed, which involve preoperative external irradiation, gross or subtotal resection, and intraoperative radiotherapy with electrons or brachytherapy for lesions confined to the pelvis. Such formidable procedures, which may include abdominoperineal resection with partial sacrectomy or partial cystectomy, must be undertaken only for early recurrences and require a competent and experienced team with a colorectal surgeon, urologist, orthopedist, neurosurgeon, and radiotherapist.
REFERENCES 1. Adson, M. A.: Diagnosis and surgical treatment of primary and secondary solid hepatic tumors in the adult. Surg. Clin. North Am., 61:181-196, 1981. 2. Ahlquist, D. A., and Beart, R. W., Jr.: Use offecal occult blood tests in the detection of colorectal neoplasia. Probl. Gen. Surg., 2:200--210, 1985. 3. Ahlquist, D. A., McGill, D. B., Schwartz, S., et al.: HemoQuant, a new quantitative assay for fecal hemoglobin: Comparison with Hemoccult. Ann. Intern. Med., 101:297-302, 1984.
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4. Allee, P. E., Gunderson, L. L., and Munzenrider, J. E.: Postoperative radiation therapy for residual colorectal carcinoma. (Abstract.) Int. J. Radiat. Oncol. BioI. Phys., 7:1208, 1981. 5. Anderberg, B., Enblad, P., Sj6dahl, R., et al.: Recurrent rectal carcinoma after anterior resection and rectal stapling. Br. J. Surg., 71:98-100, 1984. 6. Axtell, L. M., Asire, A. J., and Myers, M. D.: Cancer patient survival. (Report no. 5, DHEW Publication [NIH] 77-992.) Bethesda, National Cancer Institute, 1976. 7. Bartholdson, L., Hultborn, A., Hulten, L., et al.: Lymph drainage from the upper and middle third of the rectum as demonstrated by 19BAu. Acta Radiol. [Ther.] (Stockh.), 16:352-360, 1977. 8. Bat, L., Neumann, G., and Shemesh, E.: The association of synchronous neoplasms with occluding colorectal cancer. Dis. Colon Rectum, 28:149--151, 1985. 9. Beahrs, O. H., Kiernan, P. D., and Hubert, J. P., Jr.: An Atlas of the Surgical Techniques of Oliver H. Beahrs. Philadelphia, W. B. Saunders Company, 1985. 10. Beart, R. W., Jr., and Biggers, 0.: Local excision of rectal cancer. Probl. Gen. Surg., 2:240-243, 1985. 11. Beart, R. W., Jr., and Kelly, K. A.: Randomized prospective evaluation of the EEA stapler for colorectal anastomoses. Am. J. Surg., 141:143--146, 1981. 12. Busuttil, R. W., Foglia, R. P., and Longmire, W. P., Jr.: Treatment of carcinoma of the sigmoid colon and upper rectum. Arch. Surg., 112:920-923, 1977. 13. Cass, A. W., Million, R. R., and Pfaff, W. W.: Patterns of recurrence following surgery alone for adenocarcinoma of the colon and rectum. Cancer, 37:2861-2865, 1976. 14. Cooperman, A. M.: Hepatic and pulmonary metastases from colorectal cancer. In Kodner, 1., Fry, R. D., and Roe, J. P. (eds.): Colon, Rectal, and Anal Surgery-Current Techniques and Controversies. St. Louis, C. V. Mosby, 1985, pp. 218-230. 15. Crowley, M. L., Freeman, L. D., Mottet, M. D., et al.: Sensitivity of guaiac-impregnated cards for the detection of colorectal neoplasia. J. Clin. Gastroenterol., 5:127-130, 1983. 16. Cummings, B. J., Rider, W. D., Harwood, A. R., et al.: Radical external beam radiation therapy for adenocarcinoma of the rectum. Dis. Colon Rectum, 26:30-36, 1983. 17. Dosoretz, D. E., Gunderson, L. L., Hedberg, S., et al.: Preoperative irradiation for unresectable rectal and rectosigmoid carcinomas. Cancer, 52:814-818, 1983. 18. Dozois, R. R., DeCalan, L., and Beahrs, O. H.: Low anterior resection for carcinoma of the rectum: When, how, and how low? In Beahrs, O. H., Higgins, G. A., and Weinstein, J. J. (eds.): Colorectal Tumors. Philadelphia, J. B. Lippincott, 1986, pp. 171-184. 19. Emami, B., Pilepich, M., Willett, C., et al.: Effect of preoperative irradiation on resectability of colorectal carcinomas. lnt. J. Radiat. Oncol. BioI. Phys., 8:1295-1299, 1982. 20. Gastrointestinal Tumor Study Group: Prolongation of the disease-free interval in surgically treated rectal carcinoma. N. Engl. J. Med., 312:1465-1472, 1985. 21. Ghossein, N. A., Samala, E. c., Alpert, S., et al.: Elective postoperative radiotherapy after incomplete resection of a colorectal cancer. Dis. Colon Rectum, 24:252-256, 1981. 22. Gilbert, S. G.: Symptomatic local tumor failure following abdomino-perineal resection. Int. J. Radiat. Oncol. BioI. Phys., 4:801-807, 1978. 23. Goligher, J. C.: Use of circular stapling gun with peranal insertion of anorectal pursestring suture for construction of very low colorectal or colo-anal anastomoses. Br. J. Surg., 66:501-504, 1979. 24. Goligher, J. C., Duthie, H. L., Dedombal, F. T., et al.: Abdomino-anal pull-through excision for tumours of the mid-third of the rectum: A comparison with low anterior resection. Br. J. Surg., 52:323--335, 1965. 25. Grinnell, R. S.: Distal intramural spread of carcinoma of the rectum and rectosigmoid. Surg. Gynecol. Obstet., 99:421-430, 1954. 26. Grinnell, R. S.: Lymphatic block with atypical and retrograde lymphatic metastasis and spread in carcinoma of the colon and rectum. Ann. Surg., 163:272-280, 1966. 27. Grinnell, R. S., and Hiatt, R. B.: Ligation of the inferior mesenteric artery at the aorta in resections for carcinoma of the sigmoid and rectum. Surg. Gynecol. Obstet., 94:526--534, 1952. 28. Gunderson, L. L., Beart, R. W., and O'Connell, M. J.: Current issues in the treatment of colorectal cancer. In Davis, S. (ed.): CRC Critical Reviews in Oncology/Hematology. Boca Raton, Florida, CRC Press, in press.
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29. Gunderson, L. L., Cohen, A. C., Dosoretz, D. D., et al.: Residual, unresectable, or recurrent colorectal cancer: External beam irradiation and intraoperative electron beam boost ± resection. Int. J. Radiat. Oncol. BioI. Phys., 9:1597-1606, 1983. 30. Gunderson, L. L., Martin, J. K., Beart, R. W., et al.: Intraoperative radiation for colorectal cancer. In Abe, S., and Dobelbower, R. (eds.): Intraoperative Radiation Therapy. Boca Raton, Florida, CRC Press, in press. 31. Gunderson, L. L., Martin, J. K., Jr., Earle, J. D., et al.: Intraoperative and external beam irradiation with or without resection: Mayo pilot experience. Mayo Clin. Proc.", 59:691-699, 1984. 32. Gunderson, L. L., and Sosin, H.: Areas of failure found at reoperation (second or symptoQlatic look) following "curative surgery" for adenocarcilloma of the rectum: Clinicopathologic correlation and implications for adjuvant therapy. Cancer, 34:1278-1292, 1974. 33. Gunderson, L. L., Tepper, J. E., Biggs, P. J., et al.: Intraoperative ± external beam irradiation. Curro Probl. Cancer, 7:1-69, 1983. 34. Hoskins, R. B., Gunderson, L. L., Dosoretz, D. E., et al.: Adjuvant postoperative radiotherapy in carcinoma of the rectum and rectosigmoid. Cancer, 55:61-71, 1985. 35. Hurst, P. A., Prout, W. G., Kelly, J. M., et al.: Local recurrence after low anterior resection using the staple gun. Br. J. Surg., 69:275-276, 1982. 36. Jackman, R. J.: Conservative management of selected patients with carcinoma of the rectum. Dis. Colon Rectum, 4:429-434, 1961. 37. Killingback, M. J.: Indications for local excision of rectal cancer. Br. J. Surg., 72(Suppl.):S54-S56, 1985. 38. Lifton, L. J., and Kreiser, J.: False-positive stool occult blood tests caused by iron preparations: A controlled study and review ofliterature. Gastroenterology, 83:860-863, 1982. 39. Localio, S. A., and Eng, K.: Abdominosacral resection. In Beahrs, O. H., Higgins, G. A., Weinstein, J. J. (eds.): Colorectal Tumors. Philadelphia, J. B. Lippincott, 1986, pp. 185-190. 40. Localio, S. A., Eng, K., and Coppa, G. F.: Abdominosacral resection for midrectal cancer: A fifteen-year experiellce. Ann. Surg., 198:320-324, 1983. 41. Madden, J. L., and Kandalaft, S. I.: Electrocoagulation as a primary curative method in the treatment of carcinoma of the rectum. Surg. Gynecol. Obstet., 157:164-179, 1983. 42. Mason, A. Y., and Malt, R. A.: Transsphincteric Surgery for Low Rectal Cancer; Surgical Techniques Illustrated. Boston, Little Brown and Co., 1977, pp. 71-90. 43. Mittelman, A., Holyoke, E., Thomas, P. R. M., et al.: Adjuvant chemotherapy and radiotherapy following rectal surgery: An interim report from the Gastrointestinal Tumor Study Group (GITSG). In Salmon, S. E., and Jones, S. E. (eds.): Adjuvant Therapy of Cancer III. New York, Grune & Stratton, 1981, pp. 547-557. 44. Papillon, J.: Resectable rectal cancers: Treatment by curative endocavitary irradiation. J.A.M.A., 231:1385-1387, 1975. 45. Parc, R., Frileux, P., Tiret, E., et al.: Resection and colo-anal anastomosis with colic reservoir for rectal carcinoma. (Abstract.) Br. J. Surg., 72(Suppl.):SI29, 1985. 46. Parks, A. G., and Percy, J. P.: Resection and sutured colo-anal anastomosis for rectal carcinoma. Br. J. Surg., 69:301-304, 1982. 47. Pezim, M. E., and Nicholls, R. J.: Survival after high or low ligation of the inferior mesenteric artery during curative surgery for rectal cancer. Ann. Surg., 200:729-733, 1984. 48. Pollett, W. J., and Nicholls, R. J.: The relationship between the extent of distal clearance and survival and local recurrence rates after curative anterior resection for carcinoma of the rectum. Ann. Surg., 198:159-163, 1983. 49. Porter, N. H., and Nicholls, R. J.: Pre-operative radiotherapy in operable rectal cancer: Interim report of a trial carried out by the Rectal Cancer Group. Br. J. Surg., 72(Suppl.):S62-S64, 1985. 50. Quer, E. A., Dahlin, D. C., and Mayo, C. W.: Retrograde intramural spread of carcinoma of the rectum and rectosigmoid: A microscopic study. Surg. Gynecol. Obstet., 96:24-30, 1953. 51. Reid, J. D. S., Robins, R. E., and Atkinson, K. G.: Pelvic recurrence after anterior resection and EEA stapling anastomosis for potentially curable carcinoma of the rectum. Am. J. Surg., 147:629-632, 1984.
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52. Rich, T., Gunderson, L. L., Lew, R., et al.: Patterns of recurrence of rectal cancer after potentially curative surgery. Cancer, 52:1317-1329, 1983. 53. Roberson, S. H., Heron, H. C., Kerman, H. D., et al.: Is anterior resection of the rectosigmoid safe after preoperative radiation? Dis. Colon Rectum, 28:254-259, 1985. 54. Rosen, C. B., Beart, R. W., Jr., and Ilstrup, D. M.: Local recurrence of rectal carcinoma after hand-sewn and stapled anastomoses. Dis. Colon Rectum, 28:305--309, 1985. 55. Roswit, B., Higgins, G. A., Jr., and Keehn, R. J.: Preoperative irradiation for carcinoma of the rectum and rectosigmoid colon: Report of a National Veterans Administration randomized study. Cancer, 35:1597-1602, 1975. 56. Salvati, E. P., and Rubin, R. J.: Electrocoagulation as primary therapy for rectal carcinoma. Am. J. Surg., 132:583-586, 1976. 57. Sauer, I., and Bacon, H. E.: Influence of lateral spread of cancer of the rectum on radicability of operation and prognosis. Am. J. Surg., 81:111-119, 1951. 58. Schwartz, S., Dahl, J., Ellefson, M., et al.: The "HemoQuant" test: A specific and quantitative determination of heme (hemoglobin) in feces and other materials. Clin. Chern., 29:2061-2067, 1983. 59. Second Report of an MRC Working Party: The evaluation of low dose pre-operative x-ray therapy in the management of operable rectal cancer; results of a randomly controlled trial. Br. J. Surg., 71:21-25, 1984. 60. Shinya, H., Hsu, M., and Cwern, M.: Colonoscopy. Probl. Gen. Surg., 2:211-218,1985. 61. Stevens, K. R., Jr., Allen, C. V., and Fletcher, W. S.: Preoperative radiotherapy for adenocarcinoma of the rectosigmoid. Cancer, 37:2866--2874, 1976. 62. Stevens, K. R., Jr., Fletcher, W. S., and Allen, C. V.: Anterior resection and primary anastomosis following high dose preoperative irradiation for adenocarcinoma of the recto-sigmoid. Cancer, 41:2065-2071, 1978. 63. Turner, S. S., Vieira, E. F., Ager, P. J., et al.: Elective postoperative radiotherapy for locally advanced colorectal cancer: A preliminary report. Cancer, 40:105--108, 1977. 64. Vandertoll, D. J., and Beahrs, O. H.: Carcinoma of rectum and low sigmoid: Evaluation of anterior resection of 1,766 favorable lesions. Arch. Surg., 90:793-797, 1965. 65. Walz, B. J., Kodner, 1. J., Fry, R., et al.: Preoperative irradiation in two schedules for rectal cancer. (Abstract.) Int. J. Radiat. Oncol. BioI. Phys., 9(Suppl. 1): 109-110, 1983. 66. Williams, N. S., Dixon, M. F., and Johnston, D.: Reappraisal of the 5 centimetre rule of distal excision for carcinoma of the rectum: A study of distal intramural spread and of patients' survival. Br. J. Surg., 70: 150-154, 1983. 67. Wilson, S. M., and Beahrs, O. H.: The curative treatment of carcinoma of the sigmoid, rectosigmoid, and rectum. Ann. Surg., 183:556--563, 1976. 68. Withers, H. R., Cuasay, L., and Mason, K. A.: Elective radiation therapy in curative treatment of cancer of the rectum and rectosigmoid colon. In Stroehlien, J. R., and Romsdahl, M. M. (eds.): Gastrointestinal Cancer. New York, Raven Press, 1981, p. 351. Mayo Clinic 200 First Street S.W. Rochester, Minnesota 55905
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Carcinoma of the Rectum: Current Management
Roger R. Dozois, M.D.,* Michael E. Pezim, M.D.,t and Leonard L. Gunderson, M.D.+
The principal goal of cancer surgery is to provide the greatest chance for cure while minimizing immediate and long-term disability. In recent years, the numerous approaches used to improve survival and the quality of life of patients after surgical treatment of rectal carcinoma have included earlier detection, sphincter-saving surgical procedures and adjuvant therapy for clinically resectable lesions, intraoperative radiotherapy for locally advanced tumors, and a more aggressive treatment for locally recurrent or distant, but isolated, spread of the disease.
EARLIER DETECTION The purpose of screening an asymptomatic population at risk for colorectal cancer is to detect tumors at an earlier stage, when treatment might be more successful. Whether such programs improve survival of patients with cancer of the rectum remains in question. Indeed, although a number of screening studies have shown a lower mean stage of disease at the time of detection in screened versus unscreened populations,6 both length bias and lead time bias complicate interpretation of such data. Endoscopy is the most accurate means of detecting rectal cancers but is not cost-effective as a screening tool. Although expensive and impractical for the general population, colonos copy is invaluable as a screening tool in selected groups of patients at risk for colorectal carcinoma. 6o These groups include patients who (1) have had a previous colon resection for cancer or colonic polypectomies, (2) have an obstructing carcinoma that does not *Consultant, Section of Gastroenterologic and General Surgery, and Consultant, Section of Colon and Rectal Surgery, Mayo Clinic and Mayo Foundation; and Associate Professor of Surgery, Mayo Medical School, Rochester, Minnesota tSenior Resident in Surgery, Mayo Graduate School of Medicine, Rochester, Minnesota :j:Consultant, Division of Radiation Oncology, Mayo Clinic and Mayo Foundation; and Professor of Oncology, Mayo Medical School, Rochester, Minnesota
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allow preoperative assessment of the proximal colon (early postoperative colonoscopy would appear to be valuable),8 (3) have a strong family history of colorectal carcinoma and colonic polyps, (4) have familial polyposis coli, (5) belong to a family with the "cancer family" syndrome, (6) have ulcerative colitis, especially if universal and present for more than 10 years, and (7) are more than 50 years of age and have rectal bleeding. Testing for fecal occult blood is more practical, but guaiac-based tests such as Hemoccult have serious limitations because of an unacceptable number of false-positive and false-negative tests. 3, 38 Moreover, and most troublesome, only 40 to 67 per cent of patients with proven colorectal cancers have a positive guaiac test. 15 What appears to be primarily responsible for false-negative Hemoccult tests is the conversion of heme to porphyrin, as occurs during intestinal transit or fecal storage. A new quantitative assay, the HemoQuant test, offers several advantages over guaiac-based screening tests. 58 In this procedure, the iron is removed from the hemoglobin heme and the fluorescence of the derived porphyrin is measured, thus including that important fraction of heme already converted to porphyrin during fecal transit. Also, this test is not affected by iron, ascorbic acid, vegetable peroxidase, or other substances known to interfere with guaiac tests. Results are calculated as hemoglobin equivalents and reported as milligram of hemoglobin per gram of stool. HemoQuant has been validated by recoveries of greater than 99 per cent for blood directly added to stools and of 88 per cent for ingested blood and by a close correlation with results of other quantitative tests. 3, 58 In a study comparing a single HemoQuant test per patient with six Hemoccult tests per patient, HemoQuant detected increased fecal hemoglobin levels in 97 per cent of all colorectal cancer patients, in 100 per cent of patients with asymptomatic colon cancer, and in 58 per cent of patients with large, premalignant (>2 cm) adenomas compared with positive Hemoccult tests in only 67, 43, and 17 per cent, respectively. 2
SPHINCTER-SAVING PROCEDURES FOR CLINICALLY RESECTABLE LESIONS Although opinion diverges on the treatment of carcinoma located in the lower third of the rectum (~5 cm above dentate line), there is general agreement that the classic abdominoperineal resection with a permanent end-sigmoid colostomy provides the otherwise healthy patient with the greatest opportunity for prolonged survival. Under certain circumstances, local excision may be another option (see below). Controversy persists, however, as to the extent of the resection required for carcinomas of the upper third (10 to 15 cm above dentate line) and, especially, of the middle third (5 to 10 cm above dentate line) of the rectum and as to the choice between the various sphincter-saving procedures now available, including low anterior resection, abdominosacral resection, and coloanal or pullthrough procedures. Regardless of which is chosen, the same basic anatomic and pathologic factors pertaining to rectal adenocarcinoma apply and should be adhered
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to strictly. If it is inadequate, a sphincter-saving procedure may avoid a stoma but jeopardize cure, the technical feat amounting to nothing more than an unfortunate mistake in surgical judgment. Equally tragic is the use of an abdominoperineal resection that is not indicated, because it leaves the patient with a permanent colostomy without improving survival. 18 Finally, to be a candidate for a sphincter-saving procedure, the patient must have adequate sphincter function preoperatively. Although this would appear to be obvious, not infrequently it is overlooked. One should not give the patient an anal colostomy to avoid the more easily managed abdominal stoma.
Low Anterior Resection This is the transabdominal removal of a malignant lesion from a site in the upper two thirds of the rectum, together with its regional lymphvascular tissues, and end-to-end anastomosis of the serosa-covered sigmoid with the non-serosa-covered rectum. 18 Indications and Technical Feasibility When considering the indications and technical feasibility of a low anterior resection, several pathologic and anatomic aspects must be taken into account. Pathologic factors that may influence adequacy of resection include intra- and extramural spread proximal and distal to the tumor. Proximal spread is not a major consideration because extensive resection of colon and proximal rectum along with the accompanying lymph-vascular pedicle does not interfere with re-establishment of colorectal continuity. Less than 1 per cent of the upper and middle rectal lymph drains through the pelvic lymph nodes,7 thus obviating extensive pelvic node dissection. Nonobstructing well-differentiated (Broders grade 1 or 2) adenocarcinoma rarely extends intramurally (distal spread) more than 1.5 cm, whereas an obstructing or poorly differentiated (Broders grade 3 or 4) tumor may do SO.25, 50 Similarly, retrograde extramural lymphatic spread is seen in less than 2 per cent of rectal carcinoma specimens, and it appears that, in all such instances, metastatic blockage of proximal lymphatic channels is responsible, 26 The shortest acceptable length of normal rectum below the inferior edge of a malignant lesion that will minimize local recurrence but optimize survival without compromising the safety of the anastomosis varies with the point of reference used and with the authors of papers on the subject. In reference to distal margin of resection, it is imperative to define how the measurements were made-that is, in vivo, before or after the rectum is freed during operation, or in vitro, on fresh or fixed specimens in the pathology laboratory. Lengths of distal margins ranging between 1 and 10 cm have been suggested. 24, 57, 64 Several surgical groups48, 66 have now confirmed the findings of Wilson and Beahrs67 that use of a margin as small as 2 cm does not adversely affect survival or local recurrence (Table 1). Whether the inferior mesenteric artery should be ligated at its origin from the aorta (high ligation) or below the origin of the left colic artery (low ligation) also remains controversial. Metastatic lymph nodes may be present (in 10 per cent of patients) within the short segment between the origins of the inferior mesenteric artery and the left colic artery.27 Their removal,
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Table 1. Survival and Recurrence Rate, by Length of Distal Margin after Low Anterior Resection* RECURRENCE. LENGTH OF
]>;0. OF
MARGIN, CMt
PATIENTS
o to <2
39
2 to <3 3 to <4 4 to <5
III
~5
155 95 156
MEAN SURVIVAL,
At 5 years
78 75 71 61 74
± ± ± ± ±
7 4 4 5 4
%:j:
At 10 years
57 66 50 47 56
± ± ± ± ±
10 5 5 5 4
%:j:
Anastomotic
Pelvic and Perirectal
8 5
10 10
4 8
6 8 8
5
*Modified from Wilson and Beahrs.67 tMeasured on fresh specimen in pathology laboratory. :j:Differences between groups are not statistically Significant.
however, does not appear to affect survival favorably, 12, 27, 47 suggesting that more proximal spread has already occurred. The feasibility of a safe, effective anastomosis between the left colon and the remaining rectum depends on several factors, including the characteristics of the tumor, the body habitus of the patient, and the ability and experience of the surgeon performing the operation. Larger tumors, those with extramural extension, and those with a lesser degree of differentiation (Broders grade 3 or 4) require wider distal and lateral margins and therefore are less amenable to anterior resection. Tumors located in the midrectum create a more technically demanding situation than do those in the upper third. A low anastomosis is performed more easily in women, in patients with a broad pelvis, and in thin patients. The operation is more difficult in men, because they usually have a narrower pelvis, and in obese patients. The experience, technical ability, and judgment of the surgeon are paramount in favoring low anterior resection over abdominoperineal resection. The surgeon should extend resection to a point below the tumor where continuity can be re-established conveniently without compromising cure, based on all the factors known regarding the cancer. In practice, the feasibility of a safe, effective anastomosis cannot be determined accurately until the rectum has been fully mobilized. The surgical technique described by Beahrs and colleagues 9 helps achieve this goal. Hand-Sewn Versus Stapled Anastomosis The hand-sewn technique permits direct and precise anastomotic approximation of the wall of the proximal segment to that of the distal segment. The layers are slightly inverted to minimize the possibility of leakage. For the majority of surgeons, use of a stapling device (EEA) may facilitate the achievement of this goal and lead to more frequent rectal preservation (10 to 15 per cent of cases) than otherwise might be possible. 11 On the other hand, unsuccessful attempts at completing a stapled anastomosis when it would have been feasible comfortably by the hand-sewn method may lead to an unwarranted abdominoperineal resection because of operative difficulties. Indeed, in a controlled, randomized evaluation of the two techniques, the hand-sewn technique was associated with fewer
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intraoperative complications and was as safe in preventing postoperative leakage. 11 Recently, there has been some concern over the possibility that a patient with a stapled anastomosis is at greater risk for local recurrence than one with a hand-sewn anastomosis. Whether this is true remains unclear because none of the reports suggesting such a possibility is derived from randomized, prospective, controlled trials. 5, 35, 51, 54 Those who favor one type of anastomosis over another do so because they have obtained reproducible and satisfactory results with it. Success with either technique depends on adequate exposure and blood supply and avoidance of tension. Surgeons should be familiar with both technical alternatives so that the proper one for a given situation can be used. On rare occasions, some midrectal tumors might be deemed too low for a safe low anterior resection, even with the stapling device. In such cases, other, less common techniques are available, including abdominosacral resection and coloanal anastomosis. However, we think that with the advent of staplers the role of such surgical approaches in the management of ordinary rectal cancer is limited. Abdominosacral Resection This procedure was championed primarily by Localio and colleagues for lesions located 7 to 11 cm from the anal verge in men and 5.5 to 10 cm from the anal verge in women. 4O We believe that such lesions usually can be resected by the low anterior approach by experienced colorectal surgeons. In Localio and Eng's series, anastomotic leaks were observed in 9.7 per cent of their patients, and temporary colostomy now is established routinely in men 65 years of age or younger.39 The operation provides no better functional results than those observed after anterior resection, and the 5-year survival is not improved. Coloanal Anastomosis This operation consists of anastomosing per anum the sigmoid colon to the dentate line of the remaining rectum stripped of mucosa. This procedure was devised by Parks and Percy46 to replace the earlier pull-through operations, which were plagued by complications and incontinence. The anastomosis may be hand sewn, as in the ileoanal anastomosis, or stapled by placing the distal purse-string suture from below, as proposed by Goligher. 23 A temporary colostomy frequently is required. This operation is followed by fewer complications than the previous pull-through operations and may provide an acceptable degree of continence, especially if a sigmoid pouch is added,45 but the indications for its use in the treatment of rectal cancer are unclear. It may also be of value for superficially invasive malignancies at the junction of the middle and lower thirds of the rectum, where a low anterior resection may prove technically impossible to do and yet may provide a more adequate resection than local excision. In the classic coloanal procedure, the denuded rectal stump is left in situ, and thus cancers of the lower third cannot be managed this way unless they have not invaded the muscularis. Clearly, such a determination cannot be made until the muscularis is removed. Lesions of the upper and middle
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thirds are more easily managed by hand-sewn or stapled anterior resection as discussed previously. One possible application of the coloanal procedure is in a failed very low anterior resection, in which an ultrashort rectal stump has disappeared into the mesorectal fat and the safe insertion of a distal purse-string suture is impossible. In such cases, rather than proceeding with an abdominoperineal resection, the surgeon may attempt a per anum mucosal proctectomy and coloanal anastomosis. Local Treatment Local eradication of low rectal cancers can be achieved by surgical excision,36 electrocoagulation,41. 56 or endocavitary irradiation 44 rather than by abdominoperineal resection. Of these options, surgical excision seems the most preferred because it yields specimens that can be assessed by the pathologist for adequacy of margins, extent of invasiveness, and potential for dissemination. Moreover, this approach still permits more radical treatment should the excised specimen dictate it. Destruction by electrocoagulation and, more recently, laser is less attractive because of the absence of an evaluable specimen. Although local excision may be curative lO in carefully selected situations, we prefer to reserve it for medically handicapped patients of high surgical risk because of our inability to predict accurately, prior to any surgical approach, who might be cured. Cancers that are well differentiated-especially those less than 3 cm in diameter, polypoid, and mobilemay be suitably treated by local excision, at least as a first step. As yet, however, no prospective, randomized trials comparing abdominoperineal resection with local treatment have been conducted. Overall, less than 5 per cent of rectal cancers are truly suitable for local excision. 37 To enhance exposure of the lower rectum and facilitate removal of benign rectal tumors, the Kraske method and the York-Mason technique may be useful. In the York-Mason procedure,42 a parasacral incision is made and carried through the muscle layers until the rectum is reached. Each layer is tagged to allow accurate reconstitution during closure. This ingenious approach may have a role in the management of benign tumors of the lower rectum and early cancers but, in our view, not in the management of typical rectal cancer unless the patient presents a considerable surgical risk or is totally opposed to a colostomy. ADJUVANT THERAPY FOR CLINICALLY RESECTABLE LESIONS The risk of local recurrence after "curative resection" for rectal cancers varies according to the degree of local tumor extension and the extent of lymph node involvement. The local recurrence rate for lesions with nodal involvement but tumor confined to the bowel wall (Astler-Coller classification) is 20 to 25 per cent; when nodes are negative but there is transmural growth, the recurrence rate is 30 to 35 per cent. Patients with both adverse prognostic factors have a nearly additive risk of local recurrence, 50 to 70 per cent. 13. 32, 52 The rate of local recurrence should be decreased with the addition of adequate doses of adjuvant irradiation, but this may not result
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in an increased cure rate. Nevertheless, a decrease in the rate of local recurrence and its tremendous associated morbidity would be a significant accomplishment. 22 Opinion differs regarding the preferred sequence of operation and radiotherapy. The major advantage of preoperative radiotherapy is the potential destruction of cells that may spread at the time of operation. The obvious disadvantage is that many patients will receive unnecessary irradiation. With postoperative radiotherapy, however, one has the opportunity to select groups of patients at risk for local recurrence and exclude from further radiotherapy those at low risk or with previously undiagnosed, distant spread of their disease. Presumably, a well-designed combination of preoperative and postoperative radiotherapy (so-called sandwich approach) could offer the advantages of each approach. Preoperative Irradiation Although a modest improvement in survival was observed in selected subgroups of patients in one prospective, randomized trial of low-dose radiotherapy, 55 this was not duplicated in a recent trial that compared lowdose preoperative irradiation and operation with operation alone. 59 Higher doses may decrease local recurrence,61, 65 but controlled trials to examine this have not been carried out. Use of moderate doses of radiation preoperatively does not preclude the safe use of anterior resection, provided that healthy proximal bowel is used for the anastomosis, 53, 62 but the irradiated group may be at higher risk for development of thromboembolic and cardiovascular complications. 49 Postoperative Irradiation A number of prospective but nonrandomized studies have shown a decrease in the rate of local recurrence from an expected 35 to 50 per cent with operation alone to 6 to 8 per cent after postoperative irradiation (4500 to 5500 rads given over a 5- to 7-week period in high-risk patients; B2-3, Cl_3).34,68 In a randomized trial from the Gastrointestinal Tumor Study Group, patients with Duke's B or C lesions were randomized to operation alone (control arm) or to adjuvant treatment of postoperative irradiation (4000 to 4800 rads), postoperative chemotherapy (5-Huorouracil plus methylchloroethylcyclohexylnitrosourea), or a combination of both. 20,43 The only significant difference in disease-free survival was between the combined chemotherapy and radiotherapy adjuvant arm compared with operation alone (p < 0.009). In that study, it appears that the combined treatment did not result in a decreased incidence of distant metastasis but rather in a decrease in local recurrence. This suggests that, rather than acting systemically, the chemotherapy may have potentiated the local effect of irradiation.
INTRAOPERATIVE IRRADIATION IN MANAGEMENT OF LOCALLY ADVANCED DISEASE The experience in patients who, because of nonresectability, receive only irradiation as treatment for advanced rectal cancers attests to the
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inadequacy of this modality as the sole means of management. In an analysis of 123 patients treated with radical external beam irradiation without resection, local control was achieved in only 9 per cent, and the 5-year actuarial survival rate was only 2 per cent. 16 In patients with disease that is considered to be unresectable for cure-because of tumor fixation found at surgical exploration or clinical evaluation-preoperative radiotherapy has been used in an attempt to shrink the lesion, permitting resection and possibly improving local control and survival. Although resection ultimately may be possible in 50 to 75 per cent of these patients after 4500 to 5000 rads given over 6 weeks, the rate of local recurrence is still at least 35 to 45 per cent. 17. 19,61 There is some evidence that, when external beam irradiation is utilized postoperatively for residual disease after resection, local control may be enhanced. 4, 21, 63 Not surprisingly, however, the likelihood oflocal recurrence depends on the amount of disease left behind, varying from about 20 per cent with microscopic residual disease to about 50 per cent when gross tumor remains. The value of single-dose intraoperative electron radiotherapy (IORT) in combination with operation and external beam irradiation is being assessed at our institution. This technique permits the safe delivery of much higher doses of irradiation. With external beam techniques, the presence of dose-limiting organs such as the small bowel restricts doses to 4500 to 5000 rads in many patients. Even when the small bowel can be excluded, doses within boost fields usually are not carried beyond a total dose of 6000 to 7000 rads. The biologic effectiveness of single-dose irradiation is considered equivalent to two or three times that of the same quantity of fractionated external beam treatment. Therefore, the effective dose in the intraoperative boost field, when added to the 4500 to 5000 rads delivered in 25 to 28 fractions with external beam techniques, is 6500 to 8000 rads for an IORT dose of 1000 rads, 7500 to 9500 rads with a 1500-rad IORT dose, and 8500 to 11,000 rads with a 2000-rad IORT dose. 28 , 33 In early pilot studies at the Massachusetts General Hospital (MGH)29 and the Mayo Clinic, 30, 31 the addition of intraoperative irradiation in 67 patients appeared to improve local control and, possibly, survival. Most patients received 3 days of 5-fluorouracil therapy during the course of external irradiation. In the MGH group of 32 patients, survival was higher than that in previous patients treated with only external beam techniques with or without resection. In the group of patients who had residual disease and received IORT, although five of the seven had gross tumor left behind, survival rates paralleled those of the MGH external beam patients with microscopic residual disease. 4 In ongoing IORT trials at MGH, survival in the group who presented with recurrence is stable at approximately 40 per cent between 3 and 4 years, in contrast with an expected long-term survival of 5 to 10 per cent when treatment is by standard techniques. 33 The improved survival rate may be partly due to patient selection because those who were found to have metastasis prior to or at the time of exploration did not receive the intraoperative irradiation, and their survival is not reflected in the survival curves. In the Mayo Clinic IORT series of 35
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patients, survival results and local tumor control parallel results at MGH, although follow-up is too short to permit definitive conclusions. 3D The results of using IORT in the initially unresectable group reveal a significant advantage for the 16 patients who received IORT at MGH. This is particularly interesting because the patients were selected in a fashion similar to that for a previous group of 14 MGH patients treated only with preoperative external beam irradiation and resection. More patients in the IORT group had surgical transection of tumor with proven residual disease despite preoperative irradiation and resection (4 of 16 versus 1 of 14), and 75 per cent of specimens in both groups included gross disease persisting beyond the muscularis propria. No local recurrences occurred in the IORT group,33 compared with 43 per cent in the external beam groupY This technique needs further evaluation over a longer period, and randomized, controlled trials are being developed.
REOPERATION FOR METASTATIC OR RECURRENT RECTAL CANCER Most patients with recurrent rectal cancer have extensive local or widespread disseminated disease. However, a small number of patients with early stage of recurrence or distal but isolated spread (for example, to the lung, liver, or ovary) may be legitimate candidates for reoperation. The major obstacle thus far has been limitations in assessing the exact extent of the disease. The advent of carcinoembryonic antigen analysis, computed tomography, and magnetic resonance imaging has stimulated interest in "staging" these patients and reassessing the possible role of operation. Patients with liver metastasis confined to one lobe, especially if it is single, are suitable for resection with a reasonable chance of "cure. "1 Similar results have been obtained for solitary pulmonary metastasis in the absence of liver metastasis. 14 Finally, aggressive combined-modality approaches are being assessed, which involve preoperative external irradiation, gross or subtotal resection, and intraoperative radiotherapy with electrons or brachytherapy for lesions confined to the pelvis. Such formidable procedures, which may include abdominoperineal resection with partial sacrectomy or partial cystectomy, must be undertaken only for early recurrences and require a competent and experienced team with a colorectal surgeon, urologist, orthopedist, neurosurgeon, and radiotherapist.
REFERENCES 1. Adson, M. A.: Diagnosis and surgical treatment of primary and secondary solid hepatic tumors in the adult. Surg. Clin. North Am., 61:181-196, 1981. 2. Ahlquist, D. A., and Beart, R. W., Jr.: Use offecal occult blood tests in the detection of colorectal neoplasia. Probl. Gen. Surg., 2:200--210, 1985. 3. Ahlquist, D. A., McGill, D. B., Schwartz, S., et al.: HemoQuant, a new quantitative assay for fecal hemoglobin: Comparison with Hemoccult. Ann. Intern. Med., 101:297-302, 1984.
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