C. Thomas Griffiths

Intensive Surgical and Chemotherapeutic Management of Advanced Ovarian Cancer

We have presented the background and rationale for initiating a program of intensive surgical and chemotherapeutic management of advanced ovarian cancer. Our goal of excising all tumor masses larger than 1.5 cm in diameter has been explained and our operative approach described. The necessity for nutritional support has been emphasized. Preliminary results among patients with Stage III disease treated by optimal operation and Adriamycin-cyclophosphamide chemotherapy are encouraging. Aggressive operations have been unsuccessful when employed as secondary treatment. The single most important contraindication to extensive operation is the inability to initiate effective chemotherapy in the postoperative period.

Central nervous system involvement by ovarian carcinoma. A complication of prolonged survival with metastatic disease

Six patients with epithelial ovarian cancer had clinical diagnoses of central nervous system (CNS) metastases during a four‐year period. A thorough review of the literature shows that involvement of the CNS by ovarian cancer is a rare phenomenon. Four of the six patients developed parenchymal brain metastases whereas carcinomatous meningitis was detected in the other two. These patients were younger and survived longer from initial diagnosis than the majority of women with ovarian cancer. Five of the six patients had previously received chemotherapy and had developed metastatic spread to extraperitoneal sites. Following extensive surgical resection, chemotherapy may provide intraperitoneal and systemic control, thereby extending survival and permitting occult CNS metastases to become apparent.

Cryopreserved autologous marrow infusion following high dose cancer chemotherapy

Abstract Seventeen patients with advanced malignancies received escalating doses of chemotherapy with adriamycin and cyclophosphamide. Sixty-five per cent of the courses produced circulating granulocyte counts of 500 cells/mm3 or less. Febrile episodes occurred in only 15% of courses and were seen only with doses of chemotherapy that produced granulocyte nadirs of less than 200 cells/mm3. There were no episodes of septicaemia. Ten of the 17 patients received an intensive dose followed by reinfusion of cryopreserved, autologous bone marrow. In 5 of these patients, recovery to 500 granulocytes/mm3 was more rapid following the intensive, marrow-supported course by comparison with the prior, less intensive, unsupported course. We conclude that higher doses of adriamycin and cyclophosphamide than are conventionally used can be given without serious toxicity. Autologous bone marrow reinfusion may have a role in reducing the period of drug-induced granulocytopenia, but effective storage and recovery of human bone marrow remains a major problem.

Combination chemotherapy with adriamycin-cyclophosphamide for advanced ovarian carcinoma

Combination chemotherapy with Adriamycin‐cyclophosphamide was employed after surgical treatment in 60 women with Stage III‐IV ovarian adenocarcinoma. Of 53 evaluable patients, objective response was noted in 34 of 41 (83%) without prior cytotoxic therapy but in only two of 12 (17%) who had failed a single alkylating agent or radiotherapy (P < .005). Complete response was confirmed by a negative biopsy at the site(s) of prior disease in 12 patients. Eleven of the 12 biopsy‐confirmed complete responses were achieved in patients without pretreatment palpable tumor. Twenty‐four out of 41 patients with palpable masses responded but only one was confirmed as complete. Confirmed complete responses had a median duration of 24 months, whereas the median duration of all other responses was only seven months. The median survival for patients in whom Adriamycin‐cyclophosphamide was the initial chemotherapy was 24 months. The median survival in patients with palpable tumor exceeds that of historical controls matched for age, tumor cell type, and grade (P = .05); the median survival for the confirmed complete responders has not been reached. The toxicity of this regimen was acceptable at doses of Adriamycin and cyclophosphamide of 45 mg and 500 mg/M2 body surface area, respectively. Extensive excision of tumor followed by effective combination chemotherapy offers the best current approach toward improved patient survival in advanced ovarian cancer.

Hypocalcemia — An Unusual Metabolic Complication of Breast Cancer

HYPOCALCEMIA as a complication of metastatic cancer is rare. It has been reported as occurring spontaneously in lung cancer,1 in response to successful treatment of carcinoma of the prostate2 , 3 a...

Intraperitoneal immunotherapy of epithelial ovarian carcinoma with Corynebacterium parvum

Corynebacterium parvum was administered intraperitoneally to 21 patients with epithelial ovarian cancer. Nineteen patients had surgically measurable disease and two received adjuvant therapy. Surgically confirmed responses were documented in six of 19 patients (31.6%), with two complete responses (10.5%) and four partial responses (21.1%). Three patients (15.8%) had stable disease, and 10 patients (52.6%) had disease progression. The mean survival of the patients who had a complete response was 35.5 months; the four patients who had a partial response the mean survival was 26.6 months, and of the nonresponders the mean survival was 12.6 months (p less than 0.02). The mean survival of the entire group was 18.2 months. Initial response and patient survival correlated with the amount of disease pretreatment. Thus six responding patients had less than or equal to 5 mm maximum diameter tumors, that is, minimal residual disease. Toxicity in the 86 courses of therapy included abdominal pain in 78% of cases, fever in 56%, nausea in 40%, and vomiting in 22%. Stimulation of cytotoxic lymphocytes resulted from the administration of C. parvum, which induced a significant increase of both intraperitoneal natural killer lymphocyte cytotoxicity and antibody-dependent cell-mediated cytotoxicity in six of nine patients tested; these two types of cytotoxicity correlated with response to therapy and may be partially responsible for the surgically documented tumor regression. While the clinical usefulness of intraperitoneal C. parvum is limited because of its toxicity, intraperitoneal immunotherapy may prove useful in patients with minimal residual ovarian cancer when more refined agents become available.

PUNCH BIOPSY OF THE CERVIX.

Abstract 1. 1. Three hundred and four consecutive patients with carcinoma in situ, carcinoma in situ with early stromal invasion and early invasive cancer of the cervix were studied for the purpose of evaluating the accuracy of cervical biopsy using a sharp punch and endocervical curette. 2. 2. The accuracy of punch biopsy in the detection of 159 cases of carcinoma in situ and carcinoma in situ with early stromal invasion was 96.9 per cent. 3. 3. The diagnostic accuracy of punch biopsy and endocervical curettage in 144 cases of carcinoma in situ alone and with early stromal invasion was 90 per cent. 4. 4. The necessity for diagnostic conization in patients with abnormal cervical cytology or preinvasive lesions has been exaggerated as has the fear of missing invasive cancer by the use of punch biopsy techniques. In only one patient in this series was invasive carcinoma not diagnosed preoperatively, a figure comparing quite favorably with reported series of conizations.

Radiation therapy in stage II ovarian carcinoma. The influence of histologic grade

Between September 1968, and December 1975, 40 patients with Stage II epithelial tumors of the ovary were treated at the Joint Center for Radiation Therapy. Thirty‐six patients had undergone a total abdominal hysterectomy and bilateral salpingo‐oophorectomy (BSOH) with attempted total removal of disease, and all patients received postoperative pelvic irradiation. The five‐year actuarial relapse‐free survival rate is 66% and the overall survival rate 70% for the entire group of patients. The histology was reviewed in all cases and graded for the percentage of solid vs. papillary or glandular tumor in the specimen. Of the 36 patients treated with a BSOH, 18 had well‐differentiated tumors defined as containing less than a 10% solid architectural pattern. There have been no relapses in this group of patients. In contrast, 9 of 18 patients with moderately or poorly differentiated tumors containing a 10% or more solid pattern have relapsed; five diffusely in the abdomen, two in the pelvis, and two in the lungs or pleura. It appears that a BSOH followed by pelvic irradiation is sufficient treatment for Stage II patients with well‐differentiated tumors showing less than a 10% solid pattern. In contrast, patients with less well‐differentiated tumors have a high risk of relapse outside of the pelvis and need additional treatment. Alternative treatment options are discussed.

Malignant hemangioendothelioma of the uterus.

Abstract In the entire world literature, there are only seven reported cases of malignant hemangioendothelioma arising in the uterus. An eighth case, reported here, was a 17-year-old girl who lived for 8 years after curettings and subsequent hysterectomy revealed malignant hemangioendothelioma of the endometrium with extension to the left ovary. Pelvic recurrences were temporarily controlled with chemotherapy, X-ray treatment, and repeated surgery. However, the patient eventually succumbed to massive growth of malignant hemangioendothelioma in the pelvis, with extension into the inferior vena cava and left external iliac vein. Growth within blood vessel lumens was also striking in the surgical specimens of recurrent tumor. Microscopically, the important diagnostic feature was the presence of numerous capillaries lined by malignant endothelial cells.

Ovarian cancer cachexia—Surgical interactions

Abstract The woman with advanced ovarian carcinoma presents unusual risks for complications of cancer therapy. The combined effects of mechanical disruption of gastrointestinal function and the metabolic demand of large tumor burden can produce severe nutritional depletion. The additional stress of extensive surgery may exceed the capacity of the host to meet demands for wound healing and control of infection. Isotonic dextrose infusion inhibits the physiologic adaptation of the host to surgical injury and contributes to postoperative morbidity. Fourteen patients with advanced ovarian carcinoma at high risk for postoperative complications received total parenteral nutrition with hypertonic glucose and essential amino acids. Their hospital course compares favorably with that of two other groups receiving isotonic glucose—11 retrospective high-risk controls and 3 concurrent low-risk patients. We conclude that total parenteral nutrition is a safe and cost-effective means of reducing morbidity and mortality after extensive surgery for selected, high-risk patients with Stage III or IV ovarian carcinoma.