Value of prognostic parameters in squamous cell carcinoma of the vulva

In a series of 137 patients with cancer of the vulva who had undergone radical surgery we investigated, by means of a Cox regression model, which combination of clinical variables and clinical as well as histopathological variables afforded the best prediction of survival/death from cancer and survival/death from other causes. Among clinical variables the best prediction was afforded by a combination of tumor site in the clitoris/not clitoris, tumor size greater or smaller than 40 mm, obesity/not obesity, and age. Among clinical and histopathological variables the best prediction was by a combination of groin node metastases/not groin node metastases, tumor site in the clitoris/not clitoris, degree of differentiation high/moderate + low, and age. The combination of clinical and histopathological variables had a significantly better predictive power than clinical variables alone. The best prognostic group in both combinations had a 5-year-survival for cancer of 98%, while the poorest prognostic group in the two combinations showed a 5-year survival for cancer of 19 and 9%. The best predictors of death from causes other than cancer were age and a poor general health. It is concluded that the poorest prognostic group is definitely under treated and that the best prognostic group is presumably over treated. Patients in poor general health and with a good cancer prognosis should receive a more conservative treatment.     

Granulosa cell tumors in Israel: a study of 172 cases

Data of an epidemiologic study of granulosa cell tumors in Israel are presented. During the 15-year period of the survey, 172 cases of granulosa cell tumors of the ovary were diagnosed. This represents a yearly incidence of 0.9/100,000 females. The incidence of occurrence was two times higher in women of European/American origin than in those of Asian/African origin. Most patients were 40 to 69 years old. The presenting symptoms were mainly those of abdominal distension and pain and changes in the menstrual pattern. Associated malignancy was relatively common. Carcinoma of the breast was present in 6.4% of patients and endometrial malignancy in 11%. Forty-five percent of patients were diagnosed at Stage I of the disease while 27% were detected at the advanced Stages, III and IV. Factors affecting the prognosis involved the clinical stage of the disease at diagnosis, the type of presenting symptoms, and to a limited extent, the age of the patient.     

Predictive factors with reference to low-risk of metastases in squamous cell carcinoma in the vulvar region

Among 122 patients operated upon for squamous cell carcinoma in the vulvar region 14 variables were investigated by a logistic regression analysis to determine their predictive value as to the presence/absence of metastases to the inguinal nodes. Factors of predictive value proved to be hyperchromasia, polymorphism, involvement of the clitoris, depth of invasion, and tumor size. On the basis of these variables, three different models of low-risk groups were set up. Model I comprised patients whose tumors showed slight hyperchromasia and did not involve the clitoris [metastatic rate: observed 0, estimated 2.1% (0.4-9.8%)]. Model II comprised patients whose tumors showed slight hyperchromasia, did not involve the clitoris, and measured less than 4 cm [metastatic rate: observed 0, estimated 1.6% (0.3-7.8%)]. Model III comprised patients whose tumors showed slight hyperchromasia, did not involve the clitoris, and had an invasion depth of less than or equal to 5 mm [metastatic rate: observed 0, estimated 1.3% (0.2-7.1%)].     

Bleomycin, vincristine, and methotrexate with citrovorum factor rescue in the treatment of advanced squamous cell carcinoma of the cervix

Fourteen patients with advanced or locally recurrent squamous cell carcinoma of the uterine cervix were treated with bleomycin, vincristine, and moderately high dose methotrexate with citrovorum rescue. Two patients (14%) had a partial response; no patient had a complete response. Two patients were felt to have significant bleomycin associated pulmonary toxicity. This chemotherapy regimen is not felt to be clinically useful in our patient population.     

Granular cell tumor of the clitoris in pregnancy

Granular cell tumors of the female genital organs represent 7-15% of all granular cell tumors reported in the literature. The majority of these genital lesions are located on the vulva. Granular cell tumor involving the clitoris is extremely rare and should be considered in the differential diagnosis of clitoral masses.     

KLE: a cell line with defective estrogen receptor derived from undifferentiated endometrial cancer

KLE is a cell line derived from a poorly differentiated endometrial carcinoma that is aneuploid with chromosome numbers ranging from 51 to 66 and 6-8 marker chromosomes demonstrated by G banding. Tumors harvested from five of five nude mice bearing an inoculum for more than a month resemble the original specimen, and electron microscopy shows microvilli, many junctional processes, glycogenation, and a prominent nucleolonema. The cell cytosol contains a specific binder for estradiol, but there is no estrogen receptor in the nucleus and in a study reported elsewhere (Raam et al., Breast Cancer Res. Treat. 2, 277 (1982) ) translocation to the nucleus fails to occur. The enzyme phenotype of this cell is human, non-HeLa.     

Development and characterization of a human ovarian cancer cell line which clones without agar in vitro

A new human ovarian cancer cell line has been initiated which clones without agar in vitro. The cell line has been characterized by growth of a tumor resembling the primary tumor in a nude mouse, by human lactic dehydrogenase isozyme pattern, by human karyotype, and by lack of contamination by other cell lines. Initial studies have demonstrated the presence of epidermal growth factor receptors in this cell line. The utility of this line for clonogenic studies is demonstrated by dose-response studies with doxorubicin, cisplatinum, and 13-cis-retinoic acid.     

Intensive inpatient therapy and survival in gestational trophoblastic disease

Metastatic gestational trophoblastic disease may be categorized into “good prognosis” and “poor prognosis” groups on the basis of the level of the pretreatment human chorionic gonadotropin titer, the location of metastases, the duration of disease, type of antecedent gestation, and the response of prior therapy. One hundred twenty-six patients with metastatic disease were treated from 1966 through 1979. All patients were treated as inpatients. Sixty-three “good prognosis” patients required an average of 65 days of intensive inpatient chemotherapy and all achieved sustained remission. Sixty-three “poor prognosis” patients were treated. Thirty-eight patients achieved sustained remission after an average of 112 days of intensive chemotherapy. Twenty-five patients (40%) succumbed to disease, after an average of 162 days of therapy. The probability of successful outcome of therapy falls rapidly after 150 days of treatment. Toxicity and deaths are reviewed.     

A prospective randomized study of doxycycline as a prophylactic antibiotic in patients undergoing radical hysterectomy

A prospective randomized study was undertaken to evaluate doxycycline as a prophylactic antibiotic in patients undergoing radical abdominal hysterectomy and pelvic lymphadenectomy. Although 69 patients were initially randomized, 64 patients (34 study, 30 control) are the basis of this report: 5 patients were omitted because large pelvic lymph nodes positive for tumor were found at laparotomy and radical hysterectomy was abandoned. The two study groups were similar in both preoperative and operative risk factors. There was a statistically significant reduction in the 7- and 14- day febrile index in the doxycycline group. The rate of cuff and/or pelvic cellulitis was 2.3 times higher in the control group. Thus, single-dose doxycycline as a prophylactic antibiotic reduced both febrile morbidity and the rate of serious infections in the radical hysterectomy patient.     

Renal metastases of malignant gestational trophoblastic disease: The use of intravenous urography in staging

Intravenous urography (IVU) was performed in 289 patients at the time of diagnosis of malignant gestational trophoblastic disease (GTD). Ninety-five percent of these studies were normal, and none of the urologic abnormalities detected provoked alteration of the patients' tumor-related therapy. In the detection of renal metastases, false-positive and false-negative intravenous urograms were encountered. It is concluded that IVU lacks sufficient sensitivity and specificity in the detection of renal metastatic GTD; alternate screening methods are recommended.     

The effectiveness of multidrug treatment by bleomycin, methotrexate, and cis-platinum in advanced vaginal carcinoma

A case of a female with advanced squamous carcinoma of the vagina is presented. Complete disappearance of the primary tumor and involved inguinal lymph nodes was achieved with three courses of the cis-platinum-containing chemotherapy regimen BMP administered prior to radiotherapy. The encouraging result obtained warrants the use of this combined treatment modality in other patients.     

Combination chemotherapy with cisplatin, vinblastine, and bleomycin for endodermal sinus tumor of the ovary

Four consecutive patients with endodermal sinus tumor of the ovary were treated following surgery with intensive combination chemotherapy consisting of cisplatin, vinblastine, and bleomycin. All four of these patients remain continuously free of recurrent disease from 22 to 43 months following their original diagnosis. Two patients developed severe pulmonary toxicity related to the administration of bleomycin. Both of these patients also experienced Raynaud's phenomenon. The two patients whose initial surgery consisted of unilateral salpingo-oophorectomy have regular, spontaneous menstrual cycles, and one of them has become pregnant twice following the completion of chemotherapy.     

Bone metastasis in vulvar carcinoma

Bone metastasis secondary to vulvar carcinoma, especially that involving distant bone, is an infrequent clinical entity. Three cases are reported in which the patients developed pathologic fractures within 8 months following radical surgery for advanced vulvar carcinoma. The incidence of bone metastasis secondary to vulvar carcinoma is reviewed.     

A new human cell line derived from a poorly differentiated endometrial adenocarcinoma

Establishment and characterization of an endometrial adenocarcinoma cell line are described. The tumor cells, designated AC-258, originated from a patient with a poorly differentiated adenocarcinoma of the endometrium. These cells have been passed in culture more than 102 times and have maintained their morphological and chromosomal integrity in a fashion suggestive of monocloning. Cells from passages 1, 58, and 102 were aneuploid. The average number of chromosomes per cell was 64.8, and 8–17 marker chromosomes per cell were identified and described. Histological evaluation of tumor explants from 3 passages grown in nude (athymic) mice revealed morphologic identity. The doubling time of AC-258 was 22 hr. No detectable estrogen- or progesterone-binding proteins were found. The AC-258 cell line provides researchers with another tool with which to investigate biochemical and biological properties of human cancer cells.     

Histiocytosis-X in gynecology

(1) Histiocytosis-X can manifest itself in virtually every organ, but in gynecology it is an absolute curiosity. (2) Differential diagnosis must exclude specific and nonspecific ulcerations and granulations such as syphilis, tuberculosis, Boeck's disease, and also neoplastic processes like lymphomas, sarcomas, carcinomas, and malignant diseases of the hemopoietic system. (3) The diagnosis by light microscopy alone, as in our case, may be insufficient; therefore, electron microscopy should be used. As soon as the diagnosis is confirmed histologically, an extensive examination of all organs is necessary in order to establish an exact prognosis and an optimal plan of therapy. (4) Because of the unknown etiology of histiocytosis-X, a causal treatment is not yet possible. In spite of this, with a symptomatic, individualized therapy by means of excision, low-dose irradiation and cytotoxic agents a 5-year survival of 90% was obtained for the patients. (5) Because of its rarity and multidisciplinary character, histiocytosis-X is a challenge to interdisciplinary and interregional cooperation. Though not being a malignoma in the strict sense, diagnosis, therapy, and in part prognosis are not essentially different from a malignant disease.     

Pretreatment laparotomy in carcinoma of the cervix

In cases of advanced carcinoma of the uterine cervix, control of regional pelvic disease is not always equated with survival. While early disease often does remain localized within the pelvis, more advanced cervical cancers are observed to metastasize to paraaortic nodes and to distant sites. This study reports a surgical protocol designed to define extent of disease in patients having invasive cervical carcinoma prior to administering primary radiation therapy. Three questions have been raised: (1) Which individual patients have disease outside the pelvis? (2) Is it possible to modify therapy to control disease outside the pelvis and thereby influence survival? (3) Are positive paraaortic nodes found at pretreatment laparotomy indicative of systemic spread of disease? This pretreatment laparotomy was done on 127 patients, 31 of whom were found to have positive paraaortic nodes (24.4%). Sixteen patients had metastatic disease within the peritoneal cavity. Standard pelvic radiotherapy was subsequently given, supplemented with a paraaortic field in those cases with positive paraaortic nodes. Survival was not significantly different in patients with or without paraaortic nodal disease. It was further noted that 17 of the 31 patients (54.8%) who had positive paraaortic nodes later had distant metastases (median time 8 months), compared to $\text{24}\text{96}$ (25.0%) with negative nodes having a median time to metastases of 10 months.     

Pseudoobstruction of the colon complicating choriocarcinoma

Colonic pseudoobstruction is an enigmatic condition which can mimic mechanical obstruction clinically and lead to spontaneous cecal perforation. A patient who was treated for choriocarcinoma developed colonic pseudoobstruction and appropriate evaluation permitted nonsurgical management. The etiologies, diagnosis, and management of colonic pseudoobstruction are discussed.     

Action of 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) against untreated human ovarian cancers in the murine xenograft assay

The activity of 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) was determined in nine untreated human ovarian cancer specimens, using the murine subrenal capsule xenograft assay. Tumor cytotoxic effect was demonstrated in seven out of the nine tumors implanted. The drug was well tolerated by the test animals. Tiazofurin may prove to be an effective chemotherapeutic agent in the treatment of ovarian cancer.     

Advanced and recurrent carcinoma of the ovary treated with a combination of cyclophosphamide,doxorubicin, and cytosine arabinoside

Twenty-six patients with advanced or recurrent epithelial ovarian carcinoma, FIGO Stages III and IV, were treated with combination chemotherapy using cyclophosphamide, doxorubicin, and cytosine arabinoside (CARA). In 17 cases, CARA was initiated following failure to single-agent chemotherapy, in all cases, melphalan. Nine patients with advanced cancer received CARA as their primary chemotherapy after maximum cytoreductive surgery. The overall response rate was 27%; however, in patients without prior chemotherapy the response rate was 44%. There were 6 complete responders, 1 partial responder, 13 patients with stable disease, and 6 who failed to respond to therapy. Four of six complete responders had remission durations greater than 10 months. The median progression free interval (PFI) of patients with residual tumor diameters less than 2 cm was significantly longer (P ? 0.04) than the PFI of patients with greater initial tumor burden. The median PFI of complete responders was significantly longer (P = 0.007) than PFI of patients with less than complete response. Previously untreated patients had longer median PFI than those who had failed previous chemotherapy (P = 0.07). The major dose-limiting toxicity of CARA was thrombocytopenia. Other myelosuppression was moderate and no cardiotoxicity was encountered.     

Microinvasive squamous carcinoma of the vulva: present status and reassessment

A retrospective analysis of 24 patients with early invasive squamous carcinoma was performed. No nodal metastases were noted in these patients. Based on a review of the literature, no absolute definition of microinvasive carcinoma could be formulated, but a treatment outline has been formulated based on depth of invasion for Stage I lesions.