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In contrast to adult humans, the epiglottis of other mammals and infant humans is situated close to the soft palate. It has been argued that this posture is maintained during swallowing, with food passing laterally around an intact airway. To test this supposition, the movement of the epiglottis in two contrasting mammalian species, pigs and ferrets, was studied by placing radiopaque markers on the epiglottis and soft palate. Swallowing was observed with videofluoroscopy while the animals were feeding on hard and soft foods, liquids, and food mixed with barium sulfate. Analysis of the images showed that bolus formation and downward movement of the epiglottis away from the soft palate were unvarying phenomena in both animals for all tested foods. The duration of the epiglottic movement was approximately 0.3 S for liquids and slightly longer for solids. Because swallowing never occurred past an upright epiglottis, the results of this study do not support the hypothesis that adult animals maintain a patent airway during swallowing. Instead, the epiglottis in nonhuman mammals downfolds similarly to that of adult humans during swallowing.

Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characterisitcs and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant.

Although the standard therapy of vulvar carcinoma remains radical surgery, this approach is accompanied by significant postoperative morbidity and psychological adjustment. Radical hemivulvectomy and ipsilateral superficial groin node dissection are increasingly used for patients with "early" or "microinvasive" disease. Two patients with an "early" vulvar carcinoma were treated conservatively and later developed recurrent disease. Despite further surgery and radiotherapy, both patients eventually died of disease. The case histories are described and the pertinent literature is discussed.

The survival of cervical carcinoma patients with paraaortic/high common iliac nodal metastases was evaluated by retrospective chart review during a 13-year interval. Thirty-three patients with cervical carcinoma and surgically documented nodal metastases received primary, extended-field radiation therapy. Overall 2-year and 5-year actuarial survival rates after diagnosis were 37% and 31%, respectively. Survival was analyzed in terms of the variables patient age, clinical stage, tumor histologic type, the presence of enlarged paraaortic/high common iliac lymph nodes, the extent of nodal involvement (microscopic versus macroscopic), the presence of intraperitoneal disease, and whether intracavitary brachytherapy was administered. The use of intracavitary radiation therapy was associated with improved local control and survival (P = 0.017). None of the other variables were statistically related to patient survival. Twenty-two of the patients died of cervical cancer and five are surviving without evidence of cancer. Four patients died of intercurrent disease. Two patients developed bowel-related radiation complications; both patients received chemotherapy concurrent with the radiation therapy. One of the two patients died of radiation enteritis. The use of extended-field radiation therapy does benefit a small group of patients and may result in extended patient survival.

Pure rhabdomyosarcomas of the female genital tract most commonly occur in infancy or childhood as sarcoma botryoides (embryonal rhabdomyosarcoma) and involve the vagina and cervix. Such tumors rarely occur in adults. A pure rhabdomyosarcoma of the uterus that arose in a postmenopausal patient is described. The pertinent literature is discussed.

Malignant melanomas of the female genital tract are uncommon lesions. A patient with multiple cutaneous, vulvar melanomas and a subsequent malignant melanoma of the cervix is described.

Hexamethylmelamine (altretamine, HMM) 260 mg/m2/day p.o. for 14 days followed by a 14-day drug-free interval was administered to 52 outpatients with advanced ovarian cancer who had previously been treated with chemotherapy. Prior to HMM, 92% (48/52) of these patients had received cisplatin and cyclophosphamide with or without doxorubicin. Two more patients received other cisplatin-based regimens. At the completion of HMM therapy, 15% (8/52) displayed no evidence of disease (NED). Of these eight patients, five are still alive 32 to 82 months after altretamine therapy (median follow-up of 46 months). At 41 months, one patient died of intercurrent illness with no clinical evidence of recurrence; the other two patients died of their disease at 21 and 31 months following HMM therapy. The median survival of the total group was 11 months: nine months for patients who did not respond to altretamine and 46+ months for patients with NED after altretamine (p less than 0.05). Intermittent oral administration of single-agent altretamine was well tolerated: eight patients reported moderate gastrointestinal symptoms, and only one patient reported severe gastrointestinal symptoms. Moderate neurologic toxicity was reported by five patients. No WBC fell below 2000 mm3 and platelet counts fell below 100,000 mm3 in only three patients; no patient experienced severe hematologic toxicity. In this series of patients, the overall response (15%) was comparable to or better than those reported for more toxic chemotherapeutic regimens. On the basis of these data and those reported by other investigators, HMM warrants consideration as a reasonable option in the management of recurrent or persistent ovarian cancer.

Fifty-two patients with advanced ovarian cancer were treated with single-agent hexamethylmelamine (HMM), 260 mg/m2 po per day for 14 days followed by 14 days off drug. All patients had been previously treated with chemotherapy. Of these patients, 92% (48/52) received cisplatin and cyclophosphamide +/- doxorubicin prior to hexamethylmelamine. Two additional patients received other cisplatin-based regimens. Fifteen percent (8/52) were found to have no evidence of disease (NED) at the completion of treatment with HMM. Five of these patients are alive at 12 to 65 months (median follow-up of 32 months); one patient died at 41 months of an intercurrent illness with no clinical evidence of recurrence; two patients died of recurrent tumor at 21 and 31 months. The median survival of the series of 52 patients is 11 months: 9 months for patients who did not respond versus 41 months for patients with NED post-HMM (P less than 0.05). The regimen was well tolerated: moderate gastrointestinal toxicity was reported by 8 patients; only one patient reported severe gastrointestinal toxicity. Moderate neurologic toxicity (primarily sensory) was reported by 5 patients, 3 patients experienced white counts less than 2000 or platelet counts less than 100,000, and no patient sustained severe hematologic toxicity. This moderate-dose intermittent regimen was associated with moderate toxicity and was well accepted by patients. The overall response is comparable to or higher than that reported for more toxic chemotherapy regimes. Based on these data and those recently reported by other authors, hexamethylmelamine should be considered in the treatment of recurrent ovarian cancer.

Two cases are presented which demonstrate histologically an endometrial response to endogenous hormones after pelvic teletherapy and brachytherapy in patients who have undergone lateral ovarian transposition. Reasons for such a response are briefly discussed.

Survival of ovarian carcinoma patients undergoing second-look laparotomy after primary surgery and adjunctive chemotherapy was evaluated by retrospective chart review. From August 1976 to August 1987, 102 patients with stage I-IV disease underwent second-look laparotomy. Optimal tumor debulking and early (stage I or II) disease were positively correlated with a negative second-look laparotomy. Of the 49 patients with a "negative" second look, 15 demonstrated recurrent tumor from 12.5 to 52.5 months after laparotomy. Of the 15 recurrences, 6 were documented more than 3 years following second look. Half of the 28 patients with stage III disease and a "negative" second look have demonstrated recurrent tumor. Fifty-three patients (52%) were found to have residual disease at second-look laparotomy. Initial chemotherapy (melphalan or multiple agent) and the adequacy of primary debulking surgery (optimal vs suboptimal) were not significant factors contributing to patient survival after a positive second look. However, the size of residual disease at second-look laparotomy was a significant factor in subsequent patient survival (P less than or equal to 0.01). Fifteen patients were free of gross disease at laparotomy, but had residual tumor on microscopic examination of the specimens submitted. These patients had a 2-year actuarial survival of 78%. Forty-seven percent have survived 5 or more years after second look. Nineteen patients with tumor implants 2 cm or smaller had 2- and 5-year actuarial survivals of 61 and 31%, respectively. Nineteen patients with tumor nodules larger than 2 cm in diameter had a 2-year actuarial survival of 6%. Only 1 of 19 patients with nodules greater than 2 cm could be effectively redebulked.

The CA 125 radioimmunoassay has been increasingly used to monitor the course of patients with ovarian epithelial carcinomas. The purpose of this report is to describe our experience in the use of this assay and to better define its clinical utility. Fifty-one patients had serum CA 125 follow-up during primary chemotherapy. All 51 patients demonstrated either a normal CA 125 level at the completion of chemotherapy or a substantial fall in CA 125 values with treatment. In 48 of 51 patients, the drop in CA 125 levels was temporally related to the clinical regression or remission of tumor. Forty of these patients underwent second-look laparotomy; 23 patients (58%) had residual disease. A total of 45 patients had serum CA 125 determinations at the time of second-look laparotomy. Eight patients with microscopic disease and 11 of 18 patients with gross residual disease had a "negative" (less than 35 U/ml) CA 125 level. The predictive value of an elevated CA 125 level was 1.00. However, the predictive value of a negative value was only 0.50. Hence, a negative CA 125 level cannot be a substitute for a second-look laparotomy. Only 7 of 18 patients (39%) with gross residual disease at second-look surgery had an elevated CA 125 level. Patients with an elevated CA 125 and gross residual tumor at the second-look laparotomy uniformly demonstrated large, bulky disease. Furthermore, the survival of patients with gross residual disease at second-look laparotomy correlated with the preoperative CA 125 value. Serum CA 125 determinations also show promise in the follow-up of patients with a negative second-look laparotomy. The serum CA 125 level from patients with a "negative" second-look laparotomy can become elevated months before recurrent disease is appreciated.

Twenty patients have undergone pelvic exenteration at the University Hospital of the Pennsylvania State University from 1979 to 1985. The majority of operations were performed for cancers of the cervix or vagina that recurred following radiotherapy. Operative mortality was 5.0%. Of those surviving the procedure, 16 patients (84%) were rehospitalized for complications that occurred more than 30 days after exenteration. The majority of these involved the gastrointestinal or urinary tracts. Fifty-eight percent of the complications requiring surgical intervention occurred more than 1 year after surgery while 74% of the complications managed conservatively occurred within 1 year of surgery. The 2-year survival for all patients was 70%; survival decreased to 58% at 5 years. The most important risk factor for reduced survival was the extension of tumor laterally into the surgical margins.

The case report of a patient with pelvic fibromatosis is described. Excision of the tumor without sacrificing organs or major vessels was performed. Although not malignant, this tumor can be life-threatening due to its locally invasive properties. A variety of therapeutic options are discussed.

Forty-two patients with malignant, mixed mesodermal tumors of the uterus were identified by retrospective chart review. Only 2 patients were premenopausal at the time of diagnosis. Six of the patients had previously received pelvic radiotherapy. Surgical/pathologic findings were inconsistent with clinical staging in 17 of the patients. Patients with stage I tumors were found to have extrauterine extension of tumor in 39% of the cases. Overall, 2- and 5-year actuarial survival rates were 40 and 18%, respectively. The surgical extent of disease was a major prognostic factor in patient survival (P = 0.006). Patients with tumors showing no invasion or invasion limited to the inner two-thirds of the myometrium also demonstrated a significant survival advantage as compared to those with deeper myometrial invasion (P = 0.02). However, no statistically significant relationship was demonstrated between survival and patient age, the nature of the sarcomatous element (homologous or heterologous), or the presence of cervical involvement. Patients with recurrent or persistent disease did poorly; only 4 patients have survived more than 1 year after documentation of recurrent disease. Two patients had prolonged disease stabilization with radiotherapy and cisplatin. Another patient with pulmonary metastases had a 6-month, complete response to cisplatin.

From 1982 to 1987, 24 patients with recurrent carcinoma of the cervix underwent scalene lymph node biopsy prior to exploration for exenteration. Patients with palpable nodes were excluded from the study. There was no significant morbidity associated with the procedure. None of the 24 patients was found to have metastases to the scalene lymph nodes. From this study it would seem unjustifiable to perform this procedure on all patients undergoing evaluation for exenteration.

Between June 1976 and January 1986, 94 evaluable patients with stage I–IV disease underwent second-look laparotomy as part of their treatment for ovarian epithelial carcinomas. Stage and residual tumor size after initial debulking surgery demonstrated a significant association with absence of disease at reexploration. Forty-nine patients (52%) had no evidence of disease at second-look laparotomy. Thirty patients (32%) had macroscopic residual tumor, and 15 patients (16%) had microscopic disease at reexploration. Patients with a negative second-look laparotomy had an excellent prognosis; uncorrected 2- and 5-year survival rates exceed 90%. None of the patients with stage I or II disease developed recurrent tumor after a negative second-look laparotomy. However, 7 of the 25 (28%) patients with stage III disease and a negative second-look have demonstrated recurrent carcinomas. Recurrences were documented from 15.4 to 51.7 months after second-look laparotomy and were located within the abdominal cavity. Life table methods demonstrated improved survival for patients with microscopic disease as compared to those with gross tumor at second-look survery. Both groups had similar mean patient ages and tumor stage distributions. Patients with microscopic residual disease had uncorrected 2- and 5-year survival rates of 76 and 64%. The 2-year uncorrected survival rate for patients with gross tumor at second-look laparotomy was 25%. Thirty patients with macroscopic disease at second-look laparotomy underwent a repeat attempt at tumor debulking. Seventeen patients completed second-look surgery with residual disease less than 1 cm in maximum dimensions. Life table methods demonstrated improved survival when residual disease was less than 1 cm. Regardless of residual tumor size after reexploration, patients with gross tumor had a worse survival than those with microscopic disease.

A retrospective study was performed in which patients with both bowel obstruction and ovarian carcinoma admitted to the gynecologic oncology service at the Milton S. Hershey Medical Center between July 1, 1980, and June 30, 1987, were examined. Thirty-three patients were identified who fulfilled the inclusion criteria for bowel obstruction that did not occur in the postoperative period. Historical, physical, nutritional, and laboratory variables thought to contribute to patient survival were evaluated by a retrospective chart review. Survival time was not significantly related to presence or absence of tumor at obstruction, type of intervention whether medical or surgical, patient age, or interval from initial diagnosis of ovarian cancer to obstruction. Survival time was found to be significantly related to the prognostic index initially proposed by H. B. Krebs and D. R. Goplerud [Obstet. Gynecol. 61, 327-330 (1983)], P = 0.002. This prognostic index incorporates a multifactorial assessment of patient status including age, nutritional status, tumor spread, ascites, and prior chemotherapy and radiotherapy and can be used to evaluate patients at the time of presentation with intestinal obstruction and to help select optimal treatment for palliation.

From September 1972 to September 1987, thirty-six patients with stage II carcinoma of the endometrium were treated with external-beam radiotherapy to the pelvis, a single intracavitary application of cesium-137, and extrafascial hysterectomy with adnexectomy. Patients were followed for a median of 54.4 months. Overall 2- and 5-year actuarial survival rates were 83 and 58%, respectively. Survival was analyzed in terms of the independent variables surgical stage, presence of a gross cervical lesion, and residual disease within the myometrium or cervix. Factors contributing to patients survival were analyzed by the log-rank method. The 12 patients with a gross cervical lesion had an adverse prognosis, as compared to those without such a lesion (P less than 0.05). Seven of the twelve patients (58%) with a cervical lesion at clinical staging demonstrated persistent or recurrent disease. The presence of extrauterine disease at surgery was a major prognostic factor in patient survival (P less than 0.01). All six patients with extrauterine disease expired 2.3 to 53.0 months after hysterectomy. Two patients with persistence of disease expired 2.3 and 7.5 months after hysterectomy. Eleven patients developed recurrent disease 2.1 to 56.5 months after hysterectomy. All presented with distant metastases. Four of the thirteen patients with persistent or recurrent disease had no residual tumor within the myometrium.

One hundred fifty-five patients with cervical cancer not amenable to radical surgery underwent selective, paraaortic lymphadenectomy and exploratory laparotomy prior to the initiation of radiotherapy. Fifty-one patients underwent transperitoneal lymphadenectomy; the remainder had the procedure performed using the extraperitoneal approach. Twenty-six patients (17%) were found to have metastatic disease to the paraaortic lymph nodes. The incidence of paraaortic metastases increased with advancing clinical stage. Twenty-four of the 26 patients were treated with extended-field radiotherapy which did not exceed 5100 cGy to the paraaortic region. Twenty-three percent of the patients with positive paraaortic nodes had documented intraperitoneal tumor. Two- and five-year actuarial survival rates for patients with paraaortic metastases were 35 and 27%, respectively. Approximately 4.6% of patients undergoing a selective paraaortic lymphadenectomy derived therapeutic benefit from the information supplied by the procedure. Using a Cox model, tumor histology, status of the paraaortic lymph nodes, tumor size, and presence of intraperitoneal disease were statistically significant prognostic factors in patient survival. Tumor size and presence of intraperitoneal disease were major predictors Of patient Survival.