Squamous-Cell Carcinoma of the Anal Canal

Techniques of Colorectal Surgery

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Squamous-Cell Carcinoma of the Anal Canal Philip H. Gordon, M.D. *

In recent years, renewed interest has been expressed in the management of patients with anal canal carcinoma. Disenchanted with the survival rates of radical surgical extirpation, Nigro and associates employed a preoperative course of chemotherapy and radiation prior to abdominoperineal resection. 27 Pathologic examination of the surgical specimens showed no residual carcinoma in many cases. Thus, what was intended to be preoperative adjuvant therapy was subsequently regarded as definitive therapy, with the byproduct being the preservation of anorectal function.

CLASSIFICATION AND TERMINOLOGY In any discussion of neoplasms of the anal region, it is imperative to have a clear understanding of their location and pathology. Unfortunately, confusion exists in this area. The lack of precision in reporting the exact location of a lesion or the inclusion of perianal as well as anal canal malignancies makes it inappropriate to compare the results of different forms of therapy from one series to another, because these series often compare dissimilar lesions. A brief review of the anatomy is therefore appropriate. Anatomy of the anal canal is described in more detail in the first two articles of this issue. The anal canal, which extends from the anorectal ring to the anal verge, is lined by different kinds of epithelium. l4 Below the dentate line is squamous epithelium; above the dentate line is columnar epithelium. This junction is not abrupt; for a distance of 6 to 12 mm above the dentate line, there is an area where columnar, cuboidal, transitional, or squamous epithelium may be found. This area, often referred to as the cloacogenic zone, has been considered to consist of unstable epithelium, and, because of its diversity, this epithelium gives rise to an interesting variety of neoplasms. The two areas of the anal canal also have different routes of lymphatic drainage, with neoplasms at or above the dentate line draining cephalad via the superior rectal lymphatics to the inferior mesenteric nodes and laterally along both the middle rectal vessels and inferior rectal vessels through the ischiorectal fossa to the internal iliac nodes. Lymph from the anal canal below the

*Director,

Division of Colon and Rectal Surgery, Sir Mortimer B. Davis jewish General Hospital, and Associate Professor, McGill University, Montreal, Quebec, Canada

Surgical Clinics of North America-Vol. 68, No.6, December 1988

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dentate line usually drains to the inguinal lymph nodes. However, if obstruction exists, lymph can drain to the superior rectal nodes or along the inferior rectal lymphatics to the ischiorectal fossa. For these reasons, it is appropriate to adopt the Classification of Histological Typing of Intestinal Tumors used by the World Health Organization 24 and the following dissertation has used their standardized nomenclature. In this classification, the anal canal is arbitrarily divided into the area above the dentate line, called the "anal canal," and the area below this line, called the "anal margin." Neoplasms of the anal margin include squamous-cell carcinoma, basal-cell carcinoma, Bowen's disease, and perianal Paget's disease. They will not be described here. In general, these neoplasms are treated satisfactorily by wide local excision. In the case of a squamous-cell carcinoma of the anal canal, delineation of the extent of the lesion is important. Recommendation for wide local excision pertains only if the dentate line is not involved. Should the lesion encroach upon the dentate line, therapeutic considerations should be the same as those for squamous-cell carcinoma of the anal canal. Neoplasms of the anal canal may be classified as carcinoma (squamous-cell, basaloid, mucoepidermoid, or adenocarcinoma, further divided into adenocarcinoma of the rectal type, that of the anal glands and ducts, and that within anorectal fistula) and malignant melanoma. Despite these histologic variations, from a therapeutic point of view, squamous-cell, basaloid (cloacogenic), and mucoepidermoid carcinomas can be considered together, and this article deals solely with these lesions. The most frequently encountered variety is the squamous-cell carcinoma. CLINICAL FEATURES Squamous-cell carcinoma of the anal canal presents at a median age of 60 years, and two thirds occur in women. 2, 16. 17, 21, 23 Presentation generally follows a long history of minor perianal problems such as bleeding, which occurs in about half the patients. 38 Other symptoms include pain and an anal mass. Almost one third of the patients in Stearns and Quan's series had an initial mistaken diagnosis of benign or inflammatory disease. The history and physical examination should describe the location and extent of the carcinoma. Anoscopy and proctosigmoidoscopy should be performed. Suspect inguinal lymph nodes should be biopsied. The liver should be screened for metastases by biochemical function studies as well as ultrasound. A chest radiograph should be obtained to rule out pulmonary metastases. NATURAL HISTORY Direct local extension and regional lymphatic spread is much more common than hematogenous metastases. 6 At the time of diagnosis, Boman and coworkers found that 88 per cent of lesions had penetrated beyond the mucosa. 2 Even with carcinoma limited to the submucosa, Frost and associates found 30 per cent of patients to have lymphatic metastases; if the muscle of the anal canal was infiltrated, 60 per cent of cases demonstrated nodal involvement. 12 In about half the cases, there is also extension to the rectal wall or perianal skin. 7 Invasion of the vaginal septum and mucosa is more common than involvement of the prostate or urethra. 6 Extensive cancers may infiltrate the muscular or bony walls of the pelvis. 7 At the time of initial diagnosis and treatment of squamous-cell carcinoma of the anal canal, pelvic lymph node metastases are present in 30 to 43 per cent of patients,2, 15, 23 and inguinal lymph node metastases are apparent in 15 to 36 per

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cent and are usually unilateral. 15,2.3,31,36 Lymphatic invasion occurs early, and nodal metastases were present in 30 per cent when smooth muscle was infiltrated and in 58 per cent when the carcinoma had extended to tissues beyond the sphincters. 10 Distant metastases are found at presentation in about 10 per cent of cases and usually involve the liver and lungs. 6

TREATMENT Traditional treatment of carcinoma of the anal canal has involved some form of operation. External-beam radiation has been used in some centers for several decades, either as primary therapy or in combination with operation. The various options will now be considered. Local Excision Even in the past, this form of treatment was reserved for patients with early lesions or well-differentiated lesions that involved only the submucosa. 20. 38 It had also been considered for individuals who were poor risks for an extensive operation or who refused radical excision. Survival rates following local excision are recorded in Table 1. Today, the role for this form of therapy is indeed very limited. The high local recurrence rates and low 5-year survival rates, combined with the availability of better therapy, point to different treatment options. Abdominoperineal Resection In most centers, squamous-cell carcinomas of the anal canal have been treated by abdominoperineal resection. Because of the relatively disappointing long-term survival rates, increasingly radical operations have been advocated. At Memorial Hospital, New York, procedures have included the Miles abdominoperineal resection, posterior or subtotal vaginectomy, radical pelvic lymphadenectomy, elective inguinal lymphadenectomy, and pelvic exenteration including cystectomy. 30 Despite these aggressive approaches, overall survival rates did not improve. Prior to 1944, the 5-year survival rate was 41 per cent, whereas the radical operations performed between 1944 and 1963 yielded a 57 per cent rate. However, a series of 65 patients seen between 1964 and 1970 had a 5-year survival rate of only 33 per cent, which was attributed to the patients' presenting with more advanced disease. 30 Reported 5-year survival rates after abdominoperineal resection have ranged from 24 to 62 per cent, with an average of about 50 per cent, in part reflecting the different referral patterns and extents of disease (Table 2). Some of the series with better survival rates may have included patients with anal margin lesions. Nigro Table 1. Results of Local Excision

AUTHOR

Dillard et aI' Hardcastle and Busseyl8 McConne1l21 Golden and Horselyl5* Beahrsl Greenall et aP'

NUMBER

LOCAL

5-YEAR

OF

RECURRENCE

SURVIVAL

YEAR

PATIENTS

(%)

(%)

1963 1968 1970 1976 1979 1985

4 8 4 134 21

ns

25 75 50 65 83 45

11

25 ns ns ns

64

*Unknown how many anal margin lesions were included. (Review of literature.) ns = Not stated.

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Table 2. Results of Abdominoperineal Resection

AUTHOR

Dillard et aI9 Hardcastle and Bussey'8 Morson and Pang'" McConnel2l Golden and Horsely15* Sawyers33 Welch and Malt"" O'Brien et al28 Boman et al2 Frost et al 12t Greenall et al'· Dougherty and Evans lO

NUMBER

LOCAL

5-YEAR

OF

RECURRENCE

SURVIVAL

YEAR

PATIENTS

(%)

(%)

1963 1968 1968 1970 1976 1977 1977 1981 1984 1984 1985 1985

40 83 131 21 487 40 43 21 114 109 103 79

ns 27 ns ns ns ns 37 ns 28 27 35 43

45 48 49 24 48 52 38 38 71

62 55 47

*Unknown how many anal margin lesions were included. (Review ofliterature.) tlncludes 16% of perianal lesions. ns = Not stated. suggested that the anatomic features of the anal canal limit the extent of surgery and that the profuse local blood supply and lymphatic drainage may promote local recurrence secondary to inadequate resection. 27 The perioperative mortality rate is 2 to 6 per cent. 2, Extended resection to include the external iliac obturator and hypogastric lymph nodes did not improve the survival rate. 36 When synchronous inguinal lymph-node metastases are present, the 5-year survival rate after lymphadenectomy and abdominoperineal resection is only 10 to 20 per cent. 15, I. The locoregional recurrence rate after abdominoperineal resection is 25 to 35 per cent. 17, 18

I.

Radical Radiation Some centers have for many years preferred primary radiation therapy to abdominoperineal resection for the treatment of patients with anal canal carcinoma and have reserved radical surgical techniques for those patients with residual carcinoma or with serious toxicity after radiation. Reluctance to employ radiation therapy has been attributable partly to the failure rates and the incidence of side effects. The techniques used included external-beam radiation alone4,8 and splitcourse external-beam and interstitial radiation. 29 Serious local radionecrosis or anal stricture necessitating operative management was reported in from 5 to 20 per cent of patients, with most recent reports lying at the lower end of this range. 4, 29 Approximately three quarters of the patients cured by radical radiation therapy or by radiation plus surgery for residual carcinoma retained normal anal function. 4, 29 Papillon29 reported local control rates of 90 per cent in patients with primary carcinomas less than 5 cm in diameter and of 76 per cent in patients with larger primary carcinomas. He suggested that, with appropriate attention to radiation technique, chemotherapy is not necessary except for patients with very advanced lesions. A review by Hintz and colleagues found a local failure rate of 33 to 42 per cent. 19 The advantage of interstitial radiotherapy is that it provides a high dose over a short time and spares adjacent tissues the harmful effects of irradiation. However, this technique is employed only in specialized c~nters. 29 Split-course radiotherapy has been effectively used by Papillon, who found only a 2.5 per cent rate of severe radionecrosis. 29 He reported on a combination of external-beam and interstitial radiation. Of 217 patients followed 3 years, 68 per cent were alive and well, with

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19 per cent dead from their carcinoma and 12 per cent of intercurrent disease. Among these 148 patients with complete remission, a remarkable 92.5 per cent had retained anal function. This figure represents 63 per cent of the originally treated patients. Of the 149 patients followed 5 years, 65 per cent were alive and well. Treatment with modern megavoltage external-beam radiation has resulted in 5-year survival rates of 18 to 79 per cent (Table 3). Treatment protocols for both dosage and duration differ from center to center. The series with the best survival rate may have included some anal margin carcinomas, which would favorably bias the results. The rates of serious complications (skin radiation necrosis, ulcerations, severe pain, fistulae, or sinus) following external-beam radiation depend on the radiation dosage and techniques and have generally been between 15 and 33 per cent. 4. 5. 32 It thus is disconcerting to read the report by Frost and associates, who, in their small series of patients treated by radiation therapy alone, found a minor complication rate of 33 per cent and a major complication rate of 77 per cent. l2 In their review, Hintz's group also found a major complication rate of 41 to 72 per cent. '9 Combination Chemotherapy and Radiotherapy In an effort to improve the dismal survival rates with radical operation alone, Nigro and his colleagues explored the use of preoperative adjuvant chemotherapy and radiotherapy.27 In this protocol, 5-fluorouracil was given as a continuous intravenous infusion for 4 days, and mitomycin C as a single intravenous bolus injection, in conjunction with 3000 cGy of external-beam radiation to the pelvis. The 5-fluorouracil infusion was subsequently repeated, and 6 weeks following the end of radiation therapy, abdominoperineal resection was performed. In one of their early reports, these authors noted that at operation, six of nine patients had no residual carcinoma. 3 They suggested that abdominoperineal resection might not be necessary if clinically complete regression of the carcinoma had followed combined radiation and chemotherapy and if a biopsy of the residual scar in the anal canal showed no microscopic disease. In a recent update in which their experience was combined with that obtained by a questionnaire survey of other medical centers, Nigro reported that among 104 patients treated by the combinedmpdality regimen, 31 underwent abdominoperineal resection with only nine having either gross or microscopic carcinoma; 62 underwent excision of the scar for biopsy purposes only, and of these, only one had microscopic carcinoma; and 11 had no operative procedure of any kind but had complete clinical regression of their Table 3. Results of Radical Radiation PER CENT REQUIRING NUMBER OF AUTHOR

Golden and Horsely15* Beahrs' Cummings BJ et aI' Cantril et al4 Frost et al12t Salmon et al"

YEAR PATIENTS

1976 1979 1982 1983 1984 1984

77 13 51 33 11

183

DOSE

ns ns 45-50 65-70 64-88 60-65

Gy Gy Gy Gy

OPERATION LOCAL (RECURRENCES RECURRENCE AND (%) COMPLICATIONS)

ns ns 20 12 18 34

5-YEAR SURVIVAL (%)

ns ns 26 22 45 37

*u nknown how many anal margin lesions were included. (Review of literature.) tMay have included some perianal lesions. ns = Not stated.

26 18 59 79 78 59

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disease. 26 All patients had been followed for a minimum of 2 years, and only 13 of the lO4 patients had died from anal canal carcinoma. Other centers have modified the original combined chemotherapy, radiation therapy, and surgery protocol in various ways, but all have confirmed the success of multimodality therapy in increasing the rate of control of the primary malignancy and in decreasing the number of patients who require abdominoperineal resection. ll. 35 The toxicity of the protocol recommended by Nigro has been mild to moderate, with stomatitis, diarrhea, and radiation mucositis and dermatitis being the most common side effects. Approximately 15 per cent of patients developed mild hematologic toxicity. Five per cent suffered severe toxicity associated with acute enterocolitis, but all recovered without long-term complications. 26 Higher rates of toxicity are experienced when chemotherapy is combined with larger doses of radiation.7. II Following the lead established by Nigro, combination chemotherapy and radiotherapy has become a popular and well-accepted form of therapy for squamouscell carcinoma of the anal canal. Controversy exists as to the relative importance of each of the components, and this uncertainty may help explain the numerous variations in dose scheduling that have been used, and indeed, the departures from the original combination of 5-fluorouracil and mitomycin C that have been made, including the use of bleomycin and cisplatin. 13 Deviations from the original radiation doses and the adoption of split-course radiotherapy have been tried. 7. 29 Results of several series are reported in Table 4. Many centers report excellent response rates, mostly in the 90 per cent range. However, follow-up is shorter than for other forms of treatment, often involving only several months. In 65 patients with a 5-year follow-up, Nigro projected a 5year survival rate of 83 per cent, which is, for the most part, better than the results of abdominoperineal resection or high-dose radiation therapy, although longer follow-up will be required. Controversy exists as to whether biopsies should be taken from the treatment site. Cummings and associates reported only a 6 per cent incidence of local recurrence after the patients were deemed to be clinically free of disease. 7 Nigro Table 4. Results of Combination Chemoradiation NUMBER OF PATIENTS

AUTHOR

YEAR

Cummings et aF

1984

16

Cummings et aF

1984

14

Sischy""

1985

33

Cummings 6 *

1986

18

Meeker et al 22

1986

19

Flam et aJll

1987

30

Nigro 26 t

1987

104

*Split-course therapy. tCollected series. 5-FU = 5-fluorouracil; MTC

=

COMPLETE REGRESSION (%)

FOLLOW· UP (MONTHS)

TYPE OF CHEMOTHERAPY

DOSE (GY)

5-FU MTC 5-FU MTC 5-FU MTC 5-FU MTC 5-FU MTC 5-FU MTC 5-FU MTC

50

94

48-84

25+25

100

30-48

55-65

91

12-108

24+24

89

6-30

30

88

41-50

87

30 (median) 9-76

30

93

24-132

mitomycin C.

SQUAMOUS-CELL CARCINOMA OF THE ANAL CANAL

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found only 1 of 62 patients in whom regression was clinically complete to have a positive biopsy. The latter finding suggests a biopsy may not be necessary. Inguinal Lymph Nodes If prophylactic lymph node dissection were performed in all cases of carcinoma of the anal canal, the yield of metastases would lie somewhere between 10 and 30 per cent. 39 In the series reported by Steams and Quan,38 60 of 82 patients having prophylactic groin dissections had negative nodes. Based on these statistics, and in view of the high morbidity and mortality rates, the risk of the added procedure outweighs the benefit, and prophylactic groin dissection is not recommended. The simultaneous appearance of inguinal metastases is an ominous sign: only 2 of 14 such patients survived 5 years. 38 In contrast, later inguinal metastases carry a better prognosis: after radical groin dissection, 5-year survival rates of 50 to 75 per cent have been documented. 12, 17, 37, 39 Cummings reported that elective radiation of clinically normal inguinal nodes greatly reduces the risk of late node failure and carries little morbidity. Only 1 of 38 such patients had a late recurrence in the inguinal area after combination chemotherapy and radiotherapy, In series in which the inguinal areas were not treated electively, the late nodal recurrence rate was 15 to 25 per cent. 2, 29, 38 Metastases Cummings discussed a number of drugs that have been used in treatment. 6 These have included 5-Huorouracil, bleomycin, methyl-CCNU, vincristine, doxorubicin, and cisplatin. Combinations of agents have also been used such as bleomycin, vincristine, methotrexate, and leucovorin. All combinations have resulted in only partial responses. Patterns of Failure After treatment by either radical surgery or radical radiation, relapse is more common in the pelvis than in extrapelvic organs. After abdominoperineal resection, Bowman and colleagues reported a recurrence rate of 37 per cent (73 per cent of these in the pelvis only and pelvic combined with distant metastases in another 12 per cent).2 The median survival after the diagnosis of pelvic recurrence in patients previously treated by abdominoperineal resection is about 9 months. 16 After radical radiation therapy, Cummings and associates reported that when recurrence (including residual carcinoma) developed, 68 per cent were locoregional. All their patients with distant metastases also had pelvic recurrence, 8 Cummings noted that the pattern of recurrence after chemoradiation differs from that after radiation alone or surgery alone. The latter techniques are associated with moderately high rates of pelvic recurrence, either alone or associated with distant metastases, whereas after radiation and chemotherapy, distant metastases are found more frequently as the only apparent sites of failure. This is difficult to explain, as chemotherapy is a systemic form of treatment. In Nigro's collected series of 104 patients, 8 of the 13 who died had distant metastases only, and five had both local and distant failure. In the Princess Margaret Hospital series, 6 of 55 patients treated with combination therapy had recurrence at distant sites only compared with 0 of 51 with distant metastases only among those treated by radical radiation alone. The overall rate of late distant metastases is about 10 to 15 per cent and is similar, whether the principal treatment was radical radiation5 or radical surgery? SUMMARY Squamous-cell carcinoma of the anal canal should be differentiated from anal margin carcinoma because of differences in the recommended treatment and

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prognosis. Traditional treatment of squamous-cell carcinoma by abdominoperineal resection produces 5-year survival rates in the 50 per cent range. Radical radiation has shown to be effective for the control oflocal disease, but treatment complications have been cause for concern. Reported 5-year survival rates have ranged from 40 to 80 per cent. Treatment with a combination of radiation and chemotherapy results in a response rate of about 90 per cent and a projected 5-year survival rate of 83 per cent. Strong proponents exist for the combination chemoradiation, whereas others favor radical radiation therapy. Only a prospective clinical trial will determine the treatment of choice. What has evolved in the controversy is that abdominoperineal resection should be reserved for residual or recurrent disease or for the complications of radiation therapy.

REFERENCES 1. Beahrs OH: Management of cancer of the anus. AJR 133:790, 1979 2. Boman BM, Moertel CB, O'Connell MJ, et al: Carcinoma of the anal canal: a clinical and pathological study of 188 cases. Cancer 54:114, 1984 3. Buroker TR, Nigro N, Bradley G, et al: Combined therapy for cancer of the anal canal: a follow up report. Dis Colon Rectum 20:677, 1977 4. Cantril ST, Green JP, Schall G, et al: Primary radiation therapy in the treatment of anal carcinoma. lnt J Radiat Oncol BioI Phys 9:1271, 1983 5. Cummings BJ: The place of radiation therapy in the treatment of carcinoma of the anal canal. Cancer Treat Rev 9:125, 1982 6. Cummings BJ: Current management of epidermoid carcinoma of the anal canal. Gastroenterol Clin North Am 16:125, 1987 7. Cummings BJ, Keane TJ, Thomas GM, et al: Results and toxicity of the treatment of anal canal carcinoma by radiation therapy or radiation therapy and chemotherapy. Cancer 54:2062, 1984 8. Cummings BJ, Thomas GM, Keane TJ, et al: Primary radiation therapy in the treatment of anal canal carcinoma. Dis Colon Rectum 25:778, 1982 9. Dillard BM, Spratt JS Jr, Ackerman LV, et al: Epidermoid cancer of anal margin and canal: review of 79 cases. Arch Surg 86:772, 1963 10. Dougherty BG, Evans HL: Carcinoma of the anal canal: a study of 79 cases. Am J Clin Pathol 83:159, 1985 11. Flam MS, John MJ, Mowry PA, et al: Definitive combined modality therapy of carcinoma of the anus: a report of 30 cases including results of salvage therapy in patients with residual disease. Dis Colon Rectum 30:495, 1987 12. Frost DB, Richards PC, Montague ED, et al: Epidermoid cancer of the anorectum. Cancer 53:1285, 1984 13. Glimelius B, Graffman S, Pahlman L, et al: Radiation therapy of anal carcinoma. Acta Radiol Oncol 22:273, 1983 14. Goldberg SM, Gordon PH, Nivatvongs S: Essentials of Anorectal Surgery. Philadelphia, JB Lippincott, 1980, p 161 15. Golden GT, Horsely JS III: Surgical management of epidermoid carcinoma of the anus. Am J Surg 131:275, 1976 16. Greenall MJ, Quan SMQ, Decosse JJ: Epidermoid cancer of the anus. Br J Surg 72(Suppl):597, 1985 17. Greenall MJ, Quan SHQ, Urmarcher C, et al: Treatment of epidermoid carcinoma of the anal canal. Surg Gynecol Obstet 161:509, 1985 18. Hardcastle JD, Bussey HJR: Results of surgical treatment of squamous cell carcinoma of the anal canal and anal margin seen at St. Mark's Hospital 1928-66. Proc Roy Soc Med 61:629, 1968 19. Hintz BL, Choryulu KKN, Sudersanam A: Anal carcinoma: basic concepts and management. J Surg Oncoll0:141, 1978 20. Holm WH, Jackman RJ: Anorectal squamous-cell carcinoma: conservative or radical treatment? JAMA 188:241, 1974

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21. McConnell EM: Squamous carcinoma of the anus: a review of 96 cases. Br J Surg 57:1:>9, 1970 22. Meeker WR Jr, Sickle-Santanello BJ, Philpott G, et al: Combined chemotherapy, radiation and surgery for epithelial cancer of the anal canal. Cancer 57:525, 1986 23. Morson BC: The pathology and results of treatment of squamous cell carcinoma of the anal canal and anal margin. Proc Roy Soc Med 53:416, 1960 24. Morson BC: Histologic Typing of Intestinal Tumors 62-65. Geneva, World Health Organization, 1976 25. Morson BC, Pang LSC: Pathology of anal cancer. Proc Roy Soc Med 61:623, 1968 26. Nigro ND: Multidisciplinary management of cancer of the anus. World J Surg 11:446, 1987 27. Nigro ND, Vaitkevicius VK, Considine B: Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 17:354, 1974 28. O'Brien PH, Jenrette JM, Wallace KM, et al: Epidermoid carcinoma of the anus. Surg Gynecol Obstet 155:745, 1982 29. Papillon J: The responsibility of radiologists in the preservation of breast and rectum in cancer treatment. Clin Radiol 37:303, 1986 30. Quan SHQ: Anal and para-anal tumors. Surg Clin North Am 58:591, 1978 31. Salem PA, Habboubie N, Anaissie E, et al: Effectiveness of cisplatin in the treatment of anal squamous cell carcinoma. Cancer Treat Rep 69:891, 1985 32. Salmon RJ, Fenton J, Asselain B, et al: Treatment of epidermoid anal canal cancer. Am J Surg 147:43, 1984 33. Sawyers JL: Current management of carcinoma of the anus and perianal. Am Surg 43:424, 1977 34. Sischy B: The use of radiation therapy combined with chemotherapy in the management of squamous cell carcinoma of the anus and marginally resectable adenocarcinoma of the rectum. Int J Radiat Oncol Bioi Phys 11:1587, 1985 35. Sischy B, Remington JJ, Hinson EJ, et al: Definitive treatment of anal canal carcinoma by means of radiation therapy and chemotherapy. Dis Colon Rectum 25:685, 1982 36. Stearns MW, Urmacher C, Sternberg SS, et al: Cancer of the anal canal. Curr Prob Cancer 4:1, 1980 37. Stearns MW Jr: Abdominoperineal resection for carcinoma of the rectum. Dis Colon Rectum 17:612, 1974 38. Stearns MW Jr, Quan SHQ: Epidermoid carcinoma of the anorectum. Surg Gynecol Obstet 131:953, 1970 39. Welch JP, Malt RA: Appraisal of the treatment of carcinoma of the anus and anal canal. Surg Gynecol Obstet 145:837, 1977 Sir Mortimer B. Davis Jewish General Hospital 3755 Cote Ste Catherine Road Suite A 333 Montreal, Quebec H3T 1E2 Canada