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Biomedical subjects

S H Quan

Publications and source records attributed to S H Quan.

At least 19 recordsLinked to original sources

Anal cancers. Squamous and melanoma.

The total experience at Memorial Sloan-Kettering Cancer Center with two types of anal cancers--squamous and malignant melanoma--is reviewed. The squamous type is much more common, and its anatomic distinction between that of the anal margin and the anal canal is important in its respective clinical and surgical management. The historical, purely surgical management of canal lesions has evolved into the current chemoirradiation management, followed by the surgical approach with improvement of the 5-year survival rate and salvage of rectums. Malignant melanoma, which is the much rarer anal cancer, is still occasionally salvageable, with the use of standard abdominoperineal resection.

Adult

Treatment of squamous cell carcinoma of the anal canal.

Progress in the prognosis of patients with squamous cell carcinoma of the anal canal has followed the use of multimodality therapy. From 1977 to 1985, 42 patients with squamous cell carcinoma of the anal canal were treated with mitomycin C (15 mg/m2) and 5-fluorouracil (750 mg/m2) on day 1, 5-FU (750 mg/m2/d) alone on days 2 to 5, and radiation therapy (3000 cGy) on days 7 to 28. They were evaluated 4 to 6 weeks after completion of the chemotherapy/radiation therapy protocol and received local excision, abdominoperineal resection, or both. Patient follow-up times ranged from 7 to 161 months, with a mean follow-up time of 71 months. Pathologic examination showed no residual carcinoma in 19 (45%) patients. The authors could not predict, based on clinical evaluation, which patients would have a complete response. Of the patients with a complete clinical response, 44% had tumor in the pathology specimen. Wide local excision was the most common initial operation (23 of 42 patients; 55%), with five of these patients subsequently requiring abdominoperineal resection. Anal continence was retained in 18 of 42 (43%) patients. Eleven patients experienced recurrent disease: six local recurrences, one distant, and four both local and distant. The 5-year overall survival rate was 82% and the 5-year disease-specific survival rate was 87%. There were no treatment related deaths. Preoperative tumor size was the only factor significantly related to survival. Contrary to other reports, tumor in the pathology specimen did not adversely affect long-term survival. Hence, patients should be treated after chemotherapy/radiation therapy with surgical therapy sufficient to control local disease.

Adult

Anorectal carcinoid tumors. Is aggressive surgery warranted?

The management of large carcinoid tumors of the anorectum is controversial. Most carcinoid tumors of the rectum and anus are early lesions, adequately treated by local excision. However, because of their relative rarity, the number of advanced cases seen at most institutions is small. Forty-three patients with anorectal carcinoid tumors were treated at our institution between 1960 and 1988 with complete follow-up. The median age of onset was 56 years. Eleven patients had no symptoms and the tumor was detected incidentally in eight additional patients with other diseases. Twenty tumors were larger than 2 cm in diameter and all patients had symptoms. Eight patients had another malignancy and three patients had ulcerative colitis. An association between ulcerative colitis and rectal carcinoid tumors is not widely appreciated. Eighteen tumors were treated by local excision, 16 by radical surgery, and nine underwent only biopsy. With complete resection of the primary lesion, local recurrence was never a problem. The median survival from diagnosis was 38 months in this series and 23 patients died of disease. After detection of metastases, the median survival time was 10 months. Tumors more advanced that T2 or larger than 2 cm in diameter were always fatal. All 13 patients with involved lymph nodes died of metastatic disease, with a median survival of 10 months, although one lived 9 years. Advanced rectal carcinoid tumors are aggressive malignancies. Adequate local excision controls regional disease but rectal carcinoid tumors are cured only when they are discovered before the T3 stage, measure less than 2 cm in diameter, and when lymph nodes are not involved. Consequently if a local excision permits complete resection, radical extirpative surgery will provide little benefit.

Adult

Conservative treatment of distal rectal cancer by local excision.

From 1954 through 1982, 57 patients with invasive, distal rectal cancer had a full-thickness local excision with curative intent. Prognostic criteria and need for further treatment were based on the histopathologic results of the operative specimen. The overall 5-year survival rate was 83.4%. The rectal cancer-specific mortality rate was 10.5%. None of the 27 patients without adverse prognostic factors died from rectal cancer, and for this group local excision alone was sufficient treatment. The only single factors associated with an adverse outcome were mucinous characteristics and full-thickness invasion. Ulceration alone and penetration into the muscularis propria alone were not adverse factors. In the presence of multiple adverse prognostic factors, mucinous characteristics or full-thickness penetration, local excision was inadequate treatment and an abdominal perineal resection was necessary.

Adenocarcinoma

Recurrent epidermoid cancer of the anus.

Of 83 patients with recurrent epidermoid cancer of the anus, 67 had tumors in the anal canal and 16 had tumors at the anal margin. Local pelvic or perineal recurrence after abdominoperineal resection of tumors in the canal had a poor prognosis. Median survival after combination chemotherapy and megavoltage irradiation was 14 months. With irradiation alone, median survival was 7 months, although nearly half of these patients had been treated with orthovoltage techniques. Untreated patients with visceral metastases had a median survival of 8 months, but no improvement in survival was seen after treatment with chemotherapy. In contrast, patients who had metastases in inguinal lymph nodes had a 55% 5-year survival rate after inguinal dissection. Patients with tumors at the anal margin did not have visceral metastases. This is an important difference between tumors arising in the canal and those arising at the anal margin. Local excision was satisfactory treatment for 90% of the patients who had local recurrence in the perianal skin; abdominoperineal resection was rarely required. Inguinal lymph node metastases from margin cancer are uncommon, but three of five such patients survived 5 years after groin dissection. A combination of 5-fluorouracil, mitomycin C, and radiation therapy was used for patients with pelvic recurrence after abdominoperineal resection of epidermoid cancer of the anal canal. In this study, there was no evaluation of the role of megavoltage irradiation alone at the recommended doses of 5500 to 6000 rad for these patients. Some patients with visceral metastases respond to combination chemotherapy, but median survival is not improved; evaluation of new chemotherapeutic regimens is required. Patients with canal tumors metastatic to inguinal nodes should be treated by groin dissection as their prognosis is relatively good. Local recurrence of tumors at the anal margin can be satisfactorily treated by further local excision; those patients with margin tumors metastatic to inguinal nodes require groin dissection.

Antineoplastic Combined Chemotherapy Protocols

Improved survival in epidermoid carcinoma of the anus in association with preoperative multidisciplinary therapy.

From 1972 to 1983, we treated 78 patients who had primary epidermoid carcinoma of the anus. Forty-four of these patients were treated by protocol, while 34 patients were not treated according to protocol. Protocol consisted of fluorouracil (750 mg/m for 5 days) and mitomycin (10 to 15 mg/m on day 1), followed sequentially by 3000 rad (30 Gy) over three weeks, followed by surgery. There were 20 local excisions and 29 abdominoperineal resections in the protocol group, and 11 local excisions and 14 abdominoperineal resections in the nonprotocol group. In the protocol group, 26 patients (59%) had no residual cancer in their operative specimens, while only ten (29.9%) of the nonprotocol patients had no remaining cancer. Four (11.7%) of the 34 nonprotocol patients had pathologically positive inguinal nodes, compared with only three (4.5%) of 44 protocol patients. Thirty-four (77%) of 44 protocol patients remained free of disease, while ten patients experienced local or pelvic recurrence. In contrast, only 17 (50%) of 34 patients in the nonprotocol group remained free of disease. Of 17 recurrences, five were at distant sites. The status at this writing of all patients in the protocol group was 32 (75%), with no evidence of disease, four alive with disease, and eight dead of or with disease. Of the untreated patients, only 11 (32%) remained without evidence of disease, two were alive with disease, and 19 were dead of or with disease. Smaller carcinoma size (less than 5 cm, 27 of 32 had no evidence of disease), younger age, female gender, and deep infiltration also predicted a statistically significant survival advantage after protocol treatment. Controlled, prospective, multi-institutional trials should stratify for these factors when comparing new treatment modalities.

Adult

Epidermoid cancer of the anal margin. Pathologic features, treatment, and clinical results.

Epidermoid cancer of the anal margin should be distinguished from that in the canal because of its different clinical and pathologic characteristics, the suitability of local excision for its treatment, and its better overall prognosis. In addition, margin cancer rarely metastasises to visceral sites. Forty-eight patients with epidermoid cancer of the anal margin were reviewed. Two refused treatment, 4 had palliative therapy for advanced, inoperable disease, 31 had local excision, and 11 were treated by abdominoperineal resection. Local excision provided satisfactory results with a corrected 5 year survival of 88 percent, although locoregional recurrence developed in 46 percent of these patients during follow-up. A second local excision or inguinal lymphadenectomy provided good results in the patients with recurrence. Abdominoperineal resection did not provide better overall survival figures.

Adult

Treatment of epidermoid carcinoma of the anal canal.

Epidermoid carcinoma of the anal canal should be differentiated from that of the anal margin because of the different clinical presentations, pathologic characteristics, treatments and prognosis. The traditional treatment for carcinoma of the canal, abdominoperineal resection, produced a 55 per cent absolute five year survival rate but at the expense of permanent colostomy. Initial treatment with 5-fluorouracil and mitomycin C combined with external beam radiation therapy reduced the size of the tumor in 72 per cent of the patients and, with subsequent local excision or abdominoperineal resection, resulted in a 78 per cent survival rate in five years. The long term results from combined treatment are better than abdominoperineal resection alone with preservation of anal function in 45 per cent of the patients.

Adult

Patterns of pelvic recurrence following definitive resections of rectal cancer.

Patterns of local and distant recurrences following resections for rectal cancer provide clinical perspective for multidisciplinary prevention and follow-up programs. From 1968 to 1976 at Memorial Hospital, 412 patients with potentially curable rectal cancer were treated by anterior (AR) or abdominoperineal (APR) resections. First sites of recurrences were categorized as pelvis, liver, distant viscera, and intraabdominal/retroperitoneal sites. Pelvic recurrences were further evaluated according to the location of the tumor, type of resection, and stage of disease. Among the 412 cases, 182 (44.2%) patients developed recurrence, of which 105 (57.6%) were pelvic. Pelvic recurrence was the predominating site either alone (55 of 103) or with concomitant extra-pelvic sites (50/79). In instances of single-site first recurrence, pelvic failure was recognized earliest at 19.1 months, which was significantly earlier than single-distant visceral sites at 34.9 months. Pelvic recurrence was selectively related to various categories of the Dukes and modified Dukes staging systems. Dukes stage significantly predicted pelvic recurrence rates for Dukes A verus B. Astler-Coller stages of B2 and C1 were associated with significantly lower rates of pelvic recurrence (29.7% and 22.1%, respectively) than C2 cancers. The incidence of pelvic recurrence was significantly increased for low and mid rectal cancers as compared with cancers at or above 12 cm. The type of resection utilized (APR versus AR) was associated with no difference in the rate of pelvic recurrence, except for the few patients in whom AR was performed for low rectal Dukes C cancers. Patients with pelvic recurrence had an ultimate disease-free survival of only 3.8% as compared with patients with no pelvic recurrence of whom 77% remained alive without disease or went on to die of other causes. The timing and predominance of pelvic failure in rectal cancer with its own treatment-related morbidity and overall dismal survival outcome justifies organized multidisciplinary efforts to prevent such failure and prospective trials of comprehensive follow-up programs to evaluate improved cure rates or palliation.

Female

Preoperative chemotherapy and radiation therapy in the management of anal epidermoid carcinoma.

Management of epidermoid carcinoma of the anus has been primarily surgical in the past. Since it is a relatively rare entity, meaningful survival statistics are difficult to obtain. Five-year survival rates fall between 35 and 68% in patients treated with surgery and/or radiotherapy. Based on preliminary studies indicating promising results with the use of mitomycin C and 5-fluorouracil (5-FU) chemotherapy combined preoperatively with radiation therapy, these authors initiated a protocol in 1973 utilizing this multimodality approach. The preoperative treatment consisted of mitomycin C 15 mg/m2 IV bolus on day 1 and 5-FU 750 mg/m2/24 hours continuous infusion for five days. Radiation followed chemotherapy and consisted of 3000 rad given at 200 rad per day for 15 fractions. Of 37 patients entered on the protocol, 30 had primary disease and seven had been previously treated and had local recurrences. Median follow-up has been 28 months (range, 5-74 months). Of 31 patients with measurable lesions, 29 (94%) had major clinical responses (CR + PR) to the combined chemotherapy and radiation. Pathologic responses were also impressive with 53% (17/32) showing no evidence of residual tumor in the subsequently resected surgical specimen. Of the 37 patients treated, seven (19%) have had recurrences. The recurrence rate was 4/17 (24%) for those who had local excision following complete response to therapy as opposed to 3/18 (17%) for those treated by abdominoperineal resection. Thus it appears that the combination of preoperative mitomycin C and 5-FU with radiotherapy is effective at least in significantly downstaging this uncommon malignancy. Its ultimate effect on recurrence rate and overall patient survival awaits longer follow-up.

Adult

Myosarcomas of the small and large intestine: a clinicopathologic study.

A retrospective study was made of 38 myosarcomas of the small and large intestines (34 leiomyosarcomas and 4 malignant leiomyoblastomas). Endoenteric, small, and noninvasive tumors were successfully treated by simple wedge excision, cautery snare removal, or segmental bowel resection with a high 5-yr cure rate of 86% (12/14). Exo-enteric tumors often invaded adjacent structures or perforated into the peritoneal cavity. Extensive resection procedures, including pancreaticoduodenectomy, abdominoperineal resection, and pelvic exenteration salvaged only 13% (2/16) of these patients. Three clinicopathologic factors adversely affected prognosis: i) tumor size greater than 5 cm in diameter, ii) extra-intestinal invasion or free perforation, and iii) high histopathologic grade of malignancy. The presence of none, one, two, or three of these adverse factors gave decreasing 5-yr survival rates of 100, 44, 31, and 0%, respectively. These observations suggest use of a multimodal treatment program that may minimize treatment failure from local as well as distant disease.

Adolescent

Anorectal melanoma.

Primary malignant melanoma of the anorectum is a rare and virulent malignancy associated with an extremely poor prognosis in spite of aggressive initial therapy. Fifty-one patients with this disease were treated at Memorial Sloan-Kettering Cancer Center during the last 50 years and only six (12%) survived five years. This report views in detail 36 of the patients treated since 1950. In this group there was a female predominance (21 females, 15 males), and median age was in the 6th decade (range 27-75). Common presenting symptoms were pain, bleeding, mass or "hemorrhoids" of 1-12 months duration. In two-thirds, of the cases, a radical surgical approach was attempted. Other therapy included local excision alone or combined with groin dissection, local excision followed by delayed rectal resection and local tumor destruction by cryosurgery or fulguration. Mean survival was 21.5 months. Three patients had palliative treatment only with radiation therapy. Histopathologic study of 30 lesions showed that two-thirds were bulky or polypoid lesions and two-thirds showed junctional changes. The virulent prognosis of primary anorectal melanoma appears directly related to tumor size and thickness. Although all four of the five-year survivors had radical surgery, the three whose tumors could be measured had superficial lesions. In general, curative efforts by radical surgery were no more effective than local treatment by excision or cryosurgery. One patient, however, did have a thin lesion but also had nodal metastases and survived over five years after radical surgery. Although these data suggest that radical resection may cure patients with lesions thinner than 3 mm, it does not exclude the possibility that local excision might also be curative. For larger lesions that have not been cured by radical surgery, more conservative local approaches by excision or cryotherapy might be the optimum way of achieving local palliation.

Adult

Malignant retrorectal tumors: 28 years' experience at Memorial Sloan-Kettering Cancer Center.

From 1949 to 1977, 39 patients with localized malignant retrorectal tumors were treated at Memorial Sloan-Kettering Cancer Center. Chordomas were the most frequent histologic type (38 per cent of patients) followed by neurogenic tumors (15 per cent) chondrosarcomas, hemangiopericytomas, and embryonal adenocarcinomas (8 per cent each). Treatment consisted of surgical excision in 28 patients (18 of whom received adjuvant radiotherapy and/or chemotherapy). Ten patients were treated nonsurgically, receiving radiation and/or chemotherapy alone. Large tumors were most successfully managed by a combined surgical approach consisting of exploratory celiotomy, rectal mobilization, and bilateral hypogastric artery (with middle sacral artery and vein) ligation, followed by transsacral tumor excision with incontinuity sacrectomy. For all treated patients, survival at 5, 10, 15 and 20 years was 69 per cent, 50 per cent, 37 per cent and 20 per cent, respectively. Long-term disease-free survival (17 to 25 years post treatment) was noted in six patients. [Key words: Tumor(s), retrorectal, malignant; Tumor(s), treatment].

Adolescent