John J. Mikuta

Endometrioid carcinoma of the ovary. A clinicopathologic study of 75 cases

A clinicopathologic study of 75 endometrioid carcinomas of the ovary was carried out. Thirty‐six of the patients were in clinical Stages I and II and 39 in Stages III and IV. There were 49 histologically “pure” endometrioid carcinomas. the remaining 26 showed histologic admixtures of other neoplasms of Müllerian derivation. Thirty‐six of the 75 cases were adenoacanthomas. By histologic grading, 45 were classified as Grades 1 and 2, 30 as Grades 3 and 4. Thirteen of the ovaries with carcinoma also harbored endometriosis. in 11 patients, there was a concomitant endometrial carcinoma. the 5‐ and 10‐year survival figures for the entire series were 40.5% and 32.7%. Survival did not differ significantly between various subgroups or with different modalities of treatment and correlated best with clinical staging. Five‐year survival was 92.5% in Stage I and 27.8%, 3.7%, and 0% in Stages II, III, and IV.

Results of radiation therapy given after radical hysterectomy

Two hundred twelve patients with carcinoma of the cervix, Stage I (193 patients) and Stage II (19 patients), were treated by radical hysterectomy at the Hospital of the University of Pennsylvania during the period from 1955–1977. Pathology reports were evaluated for the presence of the following factors thought to indicate an unfavorable prognosis: (1) positive pelvic lymph nodes (31 patients); (2) parametriat extension (22 patients); and (3) infiltration of the margin of resection (14 patients). Fifty‐one high risk patients (HR) with one or more of these pathologic findings have five and ten year survivals of 55% and 30%, respectively. This compares with five‐ and ten‐year survivals of 87% and 85%, respectively, for patients without these findings. Local recurrences were noted in 20/50 (40%) HR patients versus 23/159 (13.2%) non‐HR patients (P < .001). A retrospective analysis revealed that 21 of 50 evaluable HR patients received adjunctive postoperative pelvic irradiation (HR‐XRT). Although the reduction in local recurrence in the treated group approached statistical significance, 5/21 versus 15/29 (0.1 > P > 0.05), the five‐ and ten‐year survival did not differ significantly. Twenty‐four patients initially treated with surgery received definitive radiation therapy for local recurrence. The five‐ and ten‐year survivals from the time of recurrence were 22% and 15%. Our findings suggest that postoperative irradiation may be beneficial in controlling local disease in a subgroup of radical hysterectomy patients who are at high risk for recurrence. Since the ultimate incidence of extra pelvic metastasis for the high risk and the recurrent group is 32% and 67%, respectively, however, it appears that improved survival awaits the development of effective systemic adjuvant therapy.

Malignant struma ovarii

Malignant struma ovarii is a very rare tumor, with considerable disagreement concerning the necessary histologic features for malignancy. The prognosis with patients with a malignant struma ovarii is difficult to make because of inadequate follow-up of the reported cases and long clinical courses. In most cases the patients responded well to surgical treatment but sometimes patients have died from malignant struma ovarii, in particular, if there is metastasis. There is evidence that radioactive iodine is effective in treating metastatic struma. The present case reports the use of intraperitoneal chronic phosphate for metastatic intraperitoneal disease, with thyroid suppression. Long-term follow-up will be necessary to properly evaluate this therapy. Prophylactic administration of thyroid hormone should be considered in cases of malignant struma ovarii.

Squamous carcinoma of the vagina: Treatment, complications and long-term follow-up

Seventy-five cases of primary squamous cell carcinoma of the vagina treated at the University of Pennsylvania are reviewed with long-term follow-up presented. These comprised 2.5% of all female genital malignancies treated during 1958 to 1980 inclusive. Patients treated during that time with non-squamous cell cancers have been excluded. Patients are analyzed with regard to stage, therapy, complications, and survival. Sixty-five percent of patients were stage I or II. Five-year survival for the entire group was 45%. Patients treated with radical surgery other than exenteration did well, with 7 of 8 surviving 5 years. Serious treatment complications were mostly related to radiation therapy and primarily involved the bowel and bladder. Three patients died of complications. Recurrence carried a grave prognosis as 30 of 33 patients with recurrence died of disease. Most recurrences were diagnosed within the first year following treatment. Patients with advanced disease were more likely to have distant recurrences. Although radiation therapy is generally the treatment of choice, radical surgery can yield excellent results when used in carefully selected patients. With meticulous attention to radiation dosage and technique it is hoped that treatment morbidity can be reduced. Optimal treatment of advanced disease may require some form of adjuvant systemic therapy.

Treatment of para-aortic nodes in carcinoma of the cervix.

Thirty‐six cases of carcinoma of the cervix with positive pelvic or para‐aortic nodes diagnosed by lymph node scan, lymphangiogram, and/or biopsy have received radiation therapy to the para‐aortic nodal area at the Hospital of the University of Pennsylvania. Megavoltage radiation delivering a tumor dose of approximately 5000 rads in 5 weeks has been used. Of 26 patients available for followup for 2 years, 11 were alive; of 8 followed for 5 years, 4 were alive. The severe complication rate was 19.5%, with a 5.5% mortality. Conclusions and implications for future therapy are discussed.

Plasma estrogens in postmenopausal women.

Abstract The concentration of plasma estrone and estradiol was measured in different groups of postmenopausal women; including physiologic menopause, castration menopause, and those who in addition to menopause had diabetes, hypertension, or cardiac disease. The mean values for estrone were 41 pg. per milliliter and for estradiol 13 pg. per milliliter. There was no statistical difference in the levels of plasma estrogen in all groups of postmenopausal women studied. In 3 individuals, studies of estrogens in ovarian vein blood suggested a nonovarian origin of estrogen.

Extended-field radiation therapy in early-stage cervical carcinoma: Survival and complications

Four hundred fifteen patients with early-stage cervical carcinoma were explored via a transperitoneal approach for radical hysterectomy at the Hospital of the University of Pennsylvania between January 1, 1960, and December 31, 1985. Twenty-four of these patients were found to have histologic documentation of para-aortic lymph node metastases. Twenty-one patients (88%) were treated primarily with extended-field radiotherapy. Forty-eight percent of these patients have survived greater than 5 years from diagnosis. Six patients have been followed more than 10 years after initial treatment. All six are alive although one patient has recurrent disease that was diagnosed at 164 months. Patients with adenocarcinoma or adenosquamous carcinoma had a survival significantly lower than that of those with squamous cell cancers (p = 0.022). Complications included one treatment-related death from multiple fistulas and sepsis, one vesicovaginal fistula, two enteric fistulas, and two small bowel obstructions. The major morbidity rate was 19%. Extended-field radiation is effective therapy for para-aortic nodal metastasis associated with early-stage squamous cell carcinomas of the cervix but carries a considerable morbidity rate. Other modalities such as combined chemotherapy and radiation may be necessary for adenocarcinoma.

Para-aortic nodal metastases in early cervical carcinoma: long-term survival following extended-field radiotherapy.

From 1960 to 1979 there were a total of 14 patients followed at the University of Pennsylvania with early cervical carcinoma who had histologically documented metastases to the para-aortic nodes and who were treated with extended-field radiotherapy. Thirteen of these patients were stage IB and one was stage IIA. All patients underwent exploratory laparotomy and lymph node dissection, followed by extended-field radiotherapy. Six patients are alive with NED for greater than 5 years; one patient is alive with NED at 3 years. An additional patient is now alive and well almost 3 years from a biopsy documented recurrence treated with chemotherapy, and 6 years from initial diagnosis. Thus 8 of 14 patients have enjoyed a long-term survival. Five patients experienced severe treatment-related morbidity. Two had long-term survival, two died of disease, and one died of radiation complications with NED on autopsy. Each of the six patients that died of disease had recurrences at distant sites. One also had a pelvic recurrence. These patients appear to have a prognosis quite different from that of patients with locally advanced cervical cancer metastatic to the para-aortic nodes and deserve aggressive treatment. The need for adjuvant systemic therapy is stressed.

Treatment of Advanced and Recurrent Endometrial Cancer with Cisplatin, Doxorubicin, and Cyclophosphamide'

Twenty-five patients with recurrent or advanced-stage endometrial cancer were treated with cisplatin, doxorubicin, and cyclophosphamide (PAC) from May 1982 to November 1987. A retrospective chart analysis was performed to evaluate the effect of treatment on survival and progression-free interval. Toxicity was moderate. Neutropenia was the most common side effect. Age, performance status, and tumor cytoreduction were statistically significant predictors of survival time (P less than 0.03). In the 17 evaluable patients, the response rate was 47%. PAC is an active regimen in the treatment of endometrial cancer. Larger prospective studies are needed to evaluate whether tumor cytoreduction is important in the treatment of this disease.

Preoperative evaluation and staging of endometrial cancer

Preoperative examination of a patient for whom a diagnosis of endometrial cancer has been made by office biopsy or dilatation and curettage includes careful history taking and physical examination, with emphasis on the pelvic examination, blood tests, and imaging evaluations of the pelvis, abdomen and chest, and other specific studies related to medical operability.