Robert F. Ryan

Regional chemotherapy for melanoma. A 35-year experience.

ObjectiveThe authors present their 35-year experience with intra-arterial chemotherapeutic regional perfusion of 1139 patients with melanomas, using an extracorporeal oxygenated circuit and heart-lung apparatus. Summary Background DataIntra-arterial chemotherapy produces improved responses in many tumors. By isolating and sustaining the area with extracorporeal oxygenated circulation, high doses can be delivered to the tumor area, limited only by local toxicity. Drug levels up to 10 times those achieved by systemic administration are obtained. MethodsTechniques for hyperthermic perfusion were developed for limbs, pelvis, head, neck, and skin of the breast. Melphalan (Burroughs Wellcome, Research Triangle Park, NC) was used in 753 patients. Combinations with melphalan or other drugs were used in remaining cases at temperature of 38 to 40 C for 30 to 60 minutes. ResultsChemotherapy perfusion followed by tumor excision or node dissection, was performed where indicated. The cumulative 10-year survival for patients with localized melanomas was 70%. For patients with local recurrences or satellites within 3 cm, survival was 61%. For those with regionally confined intransit tumors, survival was 30%; for those with regional node involvement, 38%; for those with intransit and nodal metastases, 16%; for those with distant metastases and perfusion—mainly to save functional limbs–survival was 7%. Multiple perfusions were performed in 158 patients with recurrent disease on 366 occasions. Patients with Indolent regionally confined melanomas were benefited by prolongation of useful life. ConclusionsSafe perfusion techniques are available for most anatomic regions. Increased chemotherapeutic doses are delivered to isolated areas limited only by local toxicity. Adjunct perfusion in poor prognosis stage I cases is useful in reducing local recurrence, and intransit or lymph node metastases. Regional perfusion reduces the need for major amputation. Multiple perfusion can be useful in treating recurrent chronic melanoma.

Malignant melanoma in the American Black.

Malignant melanoma in the American Black is an uncommon disease. Scattered reports have appeared in the literature indicating a somewhat different behavior and distribution from melanoma in the White patient. The last published report prior to the organization of the Tumor Registry at Charity Hospital of Louisiana on melanoma in the Black was in 1948 by Muelling when 28 cases were reported. From 1948 through 1974, 96 additional patients have been recorded in the Charity Hospital Registry which represents the largest reported experience in the American literature. The average age at diagnosis is 57.8 years as opposed to 53 years for White patients observed over the same time period. The ratio by sex is essentially equal in Blacks. The disease usually presents on the palmar or plantar surfaces of the hands or feet in the Black. In the registry data 51% occurred on the lower limb, 11% on the upper limb, 6% on the trunk, 6% on the genitalia, 1% on the head or neck, 13% were of extradermal origin, and 10% had unknown primary sites. The 5-year cumulative survival for all Black patients in this series is 27%. In contrast to the poor overall survival, a 78% 5-year survival has been achieved in Stage I patients treated with perfusion, wide excision, and regional lymph node dissection.

Metastatic melanoma of the gallbladder.

Metastatic involvement of the gallbladder in melanoma is rare, but constitutes the most common metastatic lesion involving this organ. Two cases of metastatic melanoma to the gallbladder with radiographic evidence of gallbladder abnormality prior to surgery are presented. These cases are compared to the nine previously reported cases of metastatic melanoma to the gallbladder with abnormal cholecystograms. All eleven cases presented with signs and symptoms compatible with cholecystitis. Nine of the eleven patients had a previous melanoma primary and most had other extrabiliary metastases. Associated cholelithiasis appeared to be only incidental. In addition, nine reported cases of “primary” biliary melanoma were reviewed. Clinical and pathologic presentations in the latter cases were similar to the former cases with metastases. Seventy‐eight percent had extrabiliary sites of metastasis at some time in the course of their disease, tending to refute the impression of “primary” biliary melanoma. Melanoma in the gallbladder is much more likely to have metastasized from a regressed skin primary than to have arisen de novo. The two reported cases and the 18 cases from the literature indicate that the physician must consider gallbladder metastasis in melanoma patients presenting with symptoms compatible with cholecystitis.

A new concept in the management of Marjolin's ulcers.

Marjolins ulcers have a grave prognosis, especially when regional nodes are involved. Recent studies suggest such cancers are in an immunologically privileged sites due to the dense scar tissue. The prognosis has been shown to be much worse for tumors not having a round cell infiltrate prior to surgery, as in Marjolins ulcers. The use of topical 5-fluorouracil (5-FU) induces a round cell infiltrate. Three case reports of large Marjolins ulcers are presented which were first treated with topical 5-FU. Radical ablative surgery was avoided in these patients with a successful outcome.

Squamous cell carcinoma of the parotid gland.

Squamous cell carcinoma involving the parotid gland is an aggressive and rapidly advancing lesion which if not recognized and treated early will result in a high morbidity and mortality. We reviewed 30 patients with squamous cell carcinoma involving the parotid gland. Twenty-four patients had had previous epidermoid skin lesions in an area known to drain to the parotid gland and three resulted from direct extension into the gland from an overlying skin carcinoma, whereas only three were primary lesions of the gland. Patients who presented with involvement of the gland more than 4 months after excision of the skin lesion had a poor prognosis. Patients with epidermoid skin cancer in areas with a propensity to secondarily involve the parotid gland must be closely followed after treatment of the primary skin lesion.

Value of perfusion in pelvic surgery

SINCE the over-all five-year survival rate for rectal carcinoma is approximate ly 50 per cent, it is obvious that half of all patients with rectal carcinoma will have to be cared for through stages of the disease where none of the known surgical or radiologic measures will benefit the patient. Surgical procedures which aim at control of the disease are most valuable when applied to sharply localized rectal cancers and it has been abundant ly demonstrated that applicat ion of such methods to more extensive forms of cancer results in progressively declining survival rates¢ It is questionable whether anatomic extension of surgical procedures modifies this relationship. In any event, the limits of this approach eventually will be reached by even the most radical types of surgery. Palliation for patients with locally advanced pelvic cancer is usually achieved by additional surgical procedures performed on normal portions of the gastro-intestinal, genitourinary or central nervous systems. Thus, there is clearly a need for addit ional methods to control the disease, as well as a need for methods of palliation which are directed against the disease itself ra ther than the remaining normal structures. Chemotherapy has been employed hopefully to accomplish these objectives. This report concerns our experiences in the application of chemotherapy by arterial perfusion in the management o15 a,tvanced pelvic neoplasms.

Osteogenic sarcoma of the mandible: a plea for radical initial surgery.

A total of 24 cases of osteogenic sarcoma of the mandible have been reported to the SEER Program of the National Cancer Institute from 1973 to 1983. Out of 14 patients whose disease was staged as regional, only 9 were eligible for 5-year survival figures and only 2 are alive, for a 23 percent 5-year cure. For those patients staged as localized, only four of six eligible for 5-year cure survived, for a 66 percent 5-year survival. Considering all patients reported to SEER who were eligible for 5-year cure, the rate is 40 percent. We believe this reflects the practice of localized resection of these tumors. At Charity Hospital of Louisiana at New Orleans there have been 10 cases of osteogenic sarcoma of the mandible since 1948. There have been no 5-year survivors for those operated on by other services, usually by local resection. On the Tulane Plastic Surgery Service, a total of six cases of osteogenic sarcoma of the mandible were treated by radical surgery with 100 percent survival from 11 to 22 years.

Salvage of stage IV intraoral squamous cell carcinomas with preoperative 5-fluorouracil

A regimen for improving the salvage rate for Stage IV squamous cell carcinoma of the tongue, alveolar ridge and floor of mouth is presented. This method utilizes pre‐operative sensitization of the tumor and regional lymph nodes by the topical application of 5‐fluorouracil (5‐FU) in the form of Efudex (Roche). The drug must be used topically at the tumor skin or tumor–mucous membrane interface to utilize the sensitizing properties of skin or mucous membrane. Further response is obtained by direct injections of 5‐FU into the tumor. Later intravenous (IV) drip of 5‐FU can be used particularly at the time of surgical resection. During the period of preparation until sensitized to 5‐FU, patients must be restored to positive nitrogen balance and concurrent infections are controlled. Because of the importance of nutrition in restoring immunity, a feeding gastrostomy for these patients is recommended. The definitive surgery must include all bone that is involved, as 5‐FU alone will not sterilize the bone. Of 15 patients who underwent the regimen outlined in this study, 12 of the patients with Stage IV intra‐oral squamous cell carcinoma have had their primary tumor controlled for 17 months to 5 years at the time of this report.

Method for the prevention of firm breasts from capsular contraction.

The permeability of inflatable silicone implants to water creates a diffusion gradient which may result in a continuous early disparity between the volume of the implant and its fibrous capsule. We submit suggestive evidence that the addition of 50 ml of water to the desired volume of normal saline in an inflatable implant may be a helpful adjunct in the prevention of firm breasts due to capsular contracture.

One-stage cervical esophageal and pharyngeal reconstruction for a fourth primary cancer.

This case is presented to describe how an ellipse of skin taken with a pectoralis major musculocutaneous flap can be sewn in a spiral fashion to make a water-tight tube to replace the cervical esophagus. While this case may represent a technical triumph of the use of musculocutaneous flaps, we cannot help but feel it is a hollow victory because of the patients addiction to cigarettes and alcohol. While constant attention and hard work have kept her alive for 16 years, with four primary cancers of the oral cavity, pharynx, and proximal esophagus, continued use of alcohol and cigarettes (Fig. 7) may well defeat our technical advances.