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The aim of this study was to evaluate the survival of gynecologic cancer patients diagnosed with deep vein thrombosis.We retrospectively reviewed the charts of patients admitted to our institution with gynecologic malignancy who were diagnosed with deep vein thrombosis (DVT) between 1984 and 1995. Data were collected regarding site, stage, histology, treatment, and proximity of DVT to treatment with surgery, chemotherapy, and radiotherapy. This study was limited to cases of ovarian, uterine, and cervical cancer. Descriptive statistics were generated and the survival of patients from the time of DVT was calculated using the Kaplan and Meier method. Cases were then matched by site, stage, histology, and age to controls without DVT to evaluate the effect of DVT on survival. A Cox regression model was used to assess the effect of multiple variables on survival.A total of 74 cases were identified. Ovarian, uterine, and cervical cancer accounted for 45, 27, and 28% of cases, respectively. Approximately 64% of patients had stage III or greater disease. The median survival of all patients from the time of DVT diagnosis was 7.8 months, with only about 20% of patients surviving at 5 years. Patients with cervical cancer or patients who had radiation therapy within 3 months of DVT diagnosis had significantly lessened survival (P0.01) than other patients with DVT. The survival of patients from the time of cancer diagnosis with venous thrombosis was significantly worse than a matched control group without DVT (P0.001). On multivariate analysis, there was a twofold greater risk of dying in those patients with gynecologic cancer and DVT.The development of DVT in conjunction with a gynecologic malignancy connotes a poor prognosis, especially in patients with cervical cancer. It is possible that this poor prognosis is related to the pathophysiology that results in venous thrombosis and not just the presence of cancer.

Vulvar cancer is an uncommon disease, marked by typical long delays in diagnosis due to lack of awareness by doctors and patients. The most common histology is squamous, although melanoma, sarcoma and adenocarcinoma occur less frequently. The predictable spread pattern of vulvar cancer to regional then distant lymphatics has allowed for improvements in survival largely due to radical surgical intervention. However, the significant morbidity from radical surgery has led to the search for better prognostic indicators and complementary therapeutic modalities to modify the extent of surgery in both early and advanced disease. En bloc radical vulvectomy and bilateral inguinal-femoral lymphadenectomy are rarely performed today: an early invasive stage has been defined where only limited excision is required. The extent of and the indications for inguinal lymphadenectomy for various clinical tumors and role of separate incisions have been clarified. When disease has spread to more than one inguinal node, adjuvant radiotherapy has replaced pelvic lymphadenectomy as the standard. Inguinal radiotherapy without groin dissection does not appear to be adequate therapy for most patients. The use of chemotherapy and radiation to shrink large tumors to allow surgical resection continues to be evaluated but has demonstrated excellent results to date. The utility of newer techniques of sentinel node mapping is also being evaluated in squamous cancers and melanoma to limit the extent of lymphadenectomy in patients with clinically normally lymph nodes.

INTRODUCTION significant amount of exposure to general surgical techniques both during internship at the University of Pennsylvania Nineteen-hundred ninety-five is an important anniversary Hospital, then in the armed forces, and again during my year. It marks the centennial year since the performance of residency at Penn, where I spent a 4-month rotation on genthe first radical hysterectomy by John Goodrich Clark on eral surgery. In my case, I was very fortunate in that I spent April 26, 1895, at Johns Hopkins Hospital. A second imall of the time during my second year of residency on two portant event in 1895 was the discovery of X rays by Wilgynecologic services where we operated 6 days a week for helm Konrad Roentgen. Three years later Marie Sklodowska the entire year. Curie discovered radium. Thus, the constellation of events Despite the fact that Clark had been Professor of Gynecolnecessary for the successful management of cervical cancer ogy at the University of Pennsylvania from 1899 until his was made available. death in 1927, there never developed a strong tradition or The history of the development of the radical hysterecprogram in the use of radical pelvic surgery for gynecologic tomy is beautifully elucidated by Clark in a chapter from a cancer. After World War II there were a few feeble attempts 1907 textbook edited by Howard A. Kelly entitled ‘‘Gyneat establishing such a program that were soon abandoned cology and Abdominal Surgery.’’ In it, Clark reviewed the for what then was a safer and more effective treatment by historic events leading up to the first abdominal radical hysradiation therapy. terectomy, the technical problems associated with many of In 1954, the late Dr. Michael Newton who was a resident the early cases, and the factors involved in ensuring the with me in Obstetrics and Gynecology and was trained also complete removal of the cancer with maximum safety to the in general surgery was asked to develop a program of radical patient. Various issues were discussed such as pelvic node gynecologic surgery. Unfortunately, after about 6 months in involvement, the need for node removal, and the extent of this position he was offered the post as Chairman of the dissection, and later whether it was reasonable to continue newly developed Department of Obstetrics and Gynecology doing radical hysterectomy in view of the high morbidity at the University of Mississippi and left the University of and mortality observed in some of the early series of cases. In Pennsylvania. In the Spring of 1955 my chief, Dr. Franklin Chapter 16 of Hoskins and Rubin’s recent textbook entitled L. Payne, asked me if I would be willing to undertake the ‘‘Cervical Cancer and Preinvasive Neoplasia,’’ I outlined vacant position. With much trepidation I agreed. Two days the history of the development of radical hysterectomy later, I took the overnight train from Philadelphia to Boston throughout the latter part of the nineteenth century as well to the Pondville State Hospital where I met Dr. Langdon as the early part of the twentieth century. Parsons, whom Dr. Payne had contacted and made arrangements for my arrival. That day was a turning point in my thinking about how radical pelvic surgery should be done. PROLOGUE Dr. Parsons, a superb general and gynecologic surgeon, carI thought it would be helpful to describe the type of experiried out an anterior pelvic exenteration with urinary diverence and training which was available to many of us not sion to an isolated segment of ileum. Just roughly 6 or 7 long after World War II, when upon completion of a year’s hours of observation of this master surgical craftsman taught rotating internship most of us returned to military service me more than I had learned in all the years before. I shall before beginning our residencies in obstetrics and gynecolbe forever grateful to Dr. Parsons for the opportunity he ogy since residency positions were very limited by returning afforded me and for all that I learned on that day. This was essentially my fellowship. veterans who preceded us. This schedule provided me with a

In 1988, the International Federation of Gynecology and Obstetrics (FIGO) Cancer Committee changed the staging of endometrial carcinoma from a clinical one to a surgicopathologic one. The emphasis in the new FIGO system was changed to the pathologic findings in the uterus, cervix, adnexa, and pelvic and/or periaortic nodes, and peritoneal cytologic findings. The major changes in this staging system were (1) the use of the depth of myometrial invasion and (2) the identification of tumor cells in peritoneal cytologic examination and of invasion in the retroperitoneal lymph nodes. Preoperative endocervical curettage was no longer necessary. Currently, the high level of operability of patients with endometrial carcinoma makes this staging system a viable one, which will provide information about the need for additional treatment. The use of the grading system for the tumor also was refined to upgrade nuclear changes that were inappropriate for the architectural grade. In serous adenocarcinomas, clear cell adenocarcinomas, and squamous cell carcinomas, nuclear grading took precedence. Adenocarcinomas with squamous differentiation were graded according to the nuclear grade of the glandular component.

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.

With the ready availability of powerful desktop computers, the ability to manage large clinical databases has become practical. A computer can enhance the capability of a gynecologic oncology service to catalog, recall, and analyze data about patients, tumors, and therapies. While commercially available database packages can be used for this purpose, we have developed a custom database for tracking the clinical activity of a busy gynecologic oncology service. The system catalogs data about patients, admissions, tumors, and therapeutic modalities and uses this information to generate several useful reports. The reports are used for daily patient care, fellow and resident case statistics, and clinical research. What is unique about the system is that it is optimized for ease of use. The development of this tumor registry, its user friendliness, and advantages over a manual recordkeeping system are described. Unlike other tumor registries, our system is utilized on a daily basis for patient care. Therefore, the data being entered have an immediate usefulness in addition to being simultaneously added to the tumor register for retrospective clinical research. One may hypothesize that it would be useful if all gynecologic oncology services used a common computerized tumor registry that could allow for the sharing of information on a national or global Scale.

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. The primary approach to endometrial cancer is surgery, which has been used for staging and treatment since the adoption of the Federation of Obstetrics and Gynecology system in 1988. Pilot studies and the Gynecologic Oncology Group have researched this system extensively and have emphasized the findings that could be defined only by pathologic study of the uterus, adnexa, retroperitoneal lymph nodes, and peritoneal cytologic findings. Preoperative endocervical evaluation is no longer necessary unless gross invasion of the cervix is suspected. However, initial histologic findings can identify patients at high risk, that is, those with high grade adenocarcinomas, clear cell carcinomas, adenosquamous carcinomas, and papillary serous adenocarcinomas. Intraoperative pathologic evaluation of the uterus by frozen section, which reveals depth of invasion into the myometrium and correlation with tumor grade, can identify patients for whom lymph node sampling should be performed.

Tamoxifen is an estrogen antagonist/agonist often associated with antiestrogenic effects such as hot flushes and vaginal dryness in premenopausal women. Estrogenic side-effects, such as thromboembolic phenomena and endometrial proliferation has been reported in postmenopausal women. Paradoxically, tamoxifen has also been shown to be capable of increasing estrogen levels in premenopausal women. Since tamoxifen is being used more frequently in this group of women, potential adverse effects are only now being recognized. Two cases of premenopausal women who developed symptomatic endometriomas while on tamoxifen for breast cancer, are reported. Stimulation of endometriosis should be considered when pain and an ovarian mass develops in a woman on tamoxifen. The unique effects of tamoxifen in premenopausal women may contribute to this even in the presence of regular ovulation.

In order to determine whether optimal surgical debulking in Stage IV epithelial ovarian cancer impacts survival, a retrospective review of patients treated at the University of Pennsylvania Cancer Center (UPCC) from 1984 to 1995 diagnosed with Stage IV epithelial ovarian cancer was performed. Data were collected regarding grade, histology, reason for allocation to Stage IV, extent of surgery performed and residual disease at initial staging procedure, major perioperative complications, first-line chemotherapy regimen, length of inpatient hospital stay, outcome at second-look laparotomy, follow-up, and survival. For the purposes of this study, optimal cytoreduction was defined as a residual disease of 2 cm or less. Forty-seven patients with Stage IV epithelial ovarian cancer identified in the Society of Gynecologic Oncologists (SGO) Database at UPCC are included. Fourteen of 47 (30%) were optimally cytoreduced at the time of their staging procedure. Twenty-six of 47 (55%) were deemed Stage IV by virtue of positive pleural effusion cytology only. Twenty-one of 47 (45%) had intraparenchymal liver involvement or metastatic disease outside of the abdomen. The median survival of the suboptimally debulked group was 17 months, while median survival in the optimal group was 37 months (P = 0.0295). These data suggest that Stage IV epithelial ovarian cancer patients with less than 2 cm residual disease have a survival advantage over patients with greater than 2 cm residual.

A case report and review of the world literature are presented to examine all the reported cases of cervical carcinoma manifesting as pulmonary lymphangitic carcinomatosis in order to better understand this rare condition. The clinical and pathologic features of this disease process are reviewed, as are potential treatment options. We present the first reported case of an immunocompromised patient with cervical carcinoma and pulmonary lymphangitic metastasis with a prospective diagnosis made by transbronchial biopsy. Given that this condition carries a uniformly fatal prognosis, unwanted therapy may result from a missed diagnosis. A prospective pathologic diagnosis by transbronchial biopsy may guide appropriate therapy in these patients.

The Center for Disease Control (CDC) recently added invasive cervical cancer to its list of surveillance case-defining diseases, and also included cervical dysplasia, carcinoma in situ , and pelvic inflammatory disease (PID) in the classification system. There are several reported cases of cervical cancer in AIDS patients that behaved in an unusually aggressive fashion and responded poorly to therapy. In light of the above-reported cases, it may be expected that cervical cancer may manifest itself in unusual ways in HIV-positive women. A case of aggressive cervical cancer in an AIDS patient with PID is reported. She was admitted with PID and newly diagnosed cervical cancer with recurrent fever spikes despite adequate antibiotic coverage. An aspiration of a presumed psoas abscess revealed metastatic squamous call carcinoma. These data suggest that not only are HIV-infected women at risk for aggressive and unusual presentations of cervical cancer, but also that coexistent pelvic infection may contribute to development and spread of the disease. Immunosuppression from the virus may increase the incidence and severity of neoplasia. Data suggest that cervical cancer in HIV-infected women is often of advanced stage and responds poorly to treatment. Unique treatment approaches may need to be developed as conventional strategies do not seem to be adequate. More research is required to determine what these strategies should be. Lastly, universal HIV screening of women with either PID or cervical cancer seems prudent.

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.

Ovarian carcinoma disseminates primarily through the shedding of cells into the peritoneal cavity and subsequent implantation onto peritoneal surfaces. Accurate evaluation of the extent of disease is important both at initial surgical evaluation for staging and at second-look operations to determine the necessity of further therapy. Techniques used for such assessment include node sampling, peritoneal washings, and random biopsies of peritoneal surfaces. Although random biopsies are used by some, others have found them to be of negligible value in the absence of gross disease. The use of cytologic smears of peritoneal surfaces offers a simple method by which cells from a large surface area may be evaluated, and uses equipment readily available to the gynecologist. We compared results of 125 cytologic smears with washings and biopsy specimens obtained during 33 laparotomies for ovarian carcinoma. Cytologic smears identified disease in 48 of 125 sites, whereas biopsy identified only 29 areas of disease. Thirteen of the positive Papanicolaou smears were obtained from clinically disease-free areas. Although the cytologic evaluation of the parietal peritoneal surfaces was more frequently positive than were biopsy specimens, each method identified disease in 16 patients when paired with standard techniques of examination and washing. We conclude that the peritoneal cytologic smear offers an alternative method of further evaluating the extent of disease, particularly when no gross evidence of extraovarian disease is detected.

The purpose of this study was to obtain information about the public's awareness and perception of the discipline of gynecologic oncology. The marketing of cancer care and related services has resulted in substantial funding being allocated to market individual institutions. However, little has been done to educate patients to the fact that there are physicians specifically trained who possess special expertise in the care of specific types of malignancy. The members of The Division of Gynecologic Oncology at The Hospital of the University of Pennsylvania asked each new patient to complete an anonymous questionnaire hoping to learn more about her prior knowledge of the specialty of gynecologic oncology and her perceptions of our discipline. Presented is the analysis of the answers provided by the 200 participants. The conclusion is that the public in general is poorly informed of gynecologic oncology as a specialty and consequently may not be taking advantage of optimal cancer care already available. Thus, as a specialty we must institute programs to educate and enlighten patients.

The purpose of this study was to evaluate the ability of the pathologist to assess intraoperatively the hysterectomy specimen in patients with endometrial carcinoma. The past few years have seen the definition of prognostic variables that predict the ultimate outcome of patients with endometrial carcinoma. As a result, the International Federation of Gynecology and Obstetrics (FIGO) revised the staging system to take into account such prognostic factors as grade, depth of myometrial penetration by tumor, cervical involvement, adnexal metastasis, peritoneal cytology, and involvement of pelvic and para-aortic lymph nodes. The need for node evaluation has led to considerable controversy as to whether all hysterectomies for Stage I disease should be performed by gynecologic oncologists. To help predict which patients will need node sampling, several published studies have shown that determination of depth of myometrial penetration can be accomplished by gross evaluation of the uterine specimen, and even more accurately on frozen section. These studies recorded excellent results, but were limited to evaluation by pathologists with specific expertise in gynecologic pathology. The current study evaluated the ability to assess tumor grade, depth of invasion, and presence of cervical invasion by intra-operative evaluation of sixty hysterectomy specimens from patients with clinical Stage I disease. The gross and frozen section reports used for this study were produced by anatomic pathologists ranging in experience level from lecturer to professor, with varying levels of experience in gynecologic pathology. Our results indicate that the level of experience of the pathologist does not affect the ability to accurately assess the specimen for the parameters described. This, in turn, allows the surgeon to correctly determine the need for lymph node sampling in 94% of cases.

DNA flow cytometry (FCM) data and estrogen receptor (ER) and progesterone receptor (PR) status were studied in three cases of low-grade stromal sarcoma (LGSS). One case was a primary presentation and the remaining two were recurrent tumors. DNA FCM showed a DNA index (DI) equal to 1.00, consistent with a diploid cell population, for four of the six specimens studied. The other two showed near-diploid populations. Proliferation indices (PI) were low in two of the patients' tumors (8.0 and 12.7%). These findings are consistent with the clinical history of LGSS and its propensity for indolent growth, long intervals between recurrences, and generally favorable prognosis. In case 2, a patient with several recurrences, the PI was increased to 20.3% in a specimen from the first recurrence. She subsequently recurred within 1 year with a more aggressive tumor, characterized by a mitotic index of greater than 10 mitoses/10 high-power fields (HPF), absence of ER and PR, and an aneuploid population (DI = 1.19). Receptor data, obtained by dextran-coated charcoal assay, showed that all tumors except the aggressive recurrence in case 2 had high ER (average 316 fmole/mg protein) and high PR (average 753 fmole/mg protein) levels. These ER and PR data are similar to the two other reports in the literature and the usual clinical response to progestational therapy was demonstrated. Further studies will help define the possible role of FCM and ER and PR determinations in patients with LGSS. These preliminary data suggest that they may be of prognostic significance.

Thirteen patients with a variety of advanced gynecologic malignancies were administered BCG via the dorsal lymphatics of the lower extremity in addition to standard accepted forms of therapy. Prolonged febrile courses, lymphangitis and suppurative adenitis were observed along the lymphatic pathway of the injected lower limbs. There was no correlation between reaction to a standard anergy panel and survival. There was also no correlation between reaction to a standard anergy panel and the inflammatory response to intralymphatic BCG (ILP-BCG). There was, however, a positive correlation between the inflammatory response to ILP-BCG and survival. Intralymphatic administration of immunostimulants may conceivably be of value as ancillary therapy for use in gynecologic malignancy. However, complications of this approach to immunotherapy are significant and the method should not be used until complications are decreased.

Since the route of administration of BCG may have an important function in immunotherapy, we investigated intralymphatic administration to direct BCG to the lymph nodes. Multiple injections of high doses of BCG were administered to 6 rhesus monkeys via the dorsal lymphatics of the lower limb. A suppurative lymphadenitis was observed along the lower limb and in the inguinal area in 5 of the 6 monkeys. However, many of the complications reported with other routes of administration were not observed. Granulomatous reactions and histiocytic responses developed in lymph nodes on the injected sides of the pelvis and distant nodes as well as in the liver. The intralymphatic route is the method by which high doses of nonspecific immunostimulants were delivered to regional lymph nodes. The efficacy of this approach remains to be established in tumor-bearing animals and humans.

Thirty-six cases of carcinoma of the cervix with positive pelvic or para-aortic nodesdiagnosed 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 weekshas been used. Of 26 patients avaiable for foloowup 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 an- implications for further therapy are discussed.

One hundred endometrium specimens have been studied with flow cytometry for DNA analysis (FCDA) and a proliferative enzyme marker, 5′-nucleotide phosphodiesterase (5′-NPD). FCDA data showed that aneuploidy was present in only 5 of 40 cancer specimens. However, with corrected histograms, a higher DNA value was observed in the G2/M (6%) of all cancer compared with noncancer specimens (4%). Thus, FCDA can be a useful diagnostic aid for endometrial cancer. The determination of 5′-NPD was done with a quenching method based on the use of 5′-(5-iodo-3-indoxyl)-thymidine phosphodiester as a substrate and 4′,6-diamidino-2-phenylindole for DNA. This method could qualitatively define which population of the cell cycle had a higher enzyme level and also quantitatively gave the enzyme units per cell. It was found that 12.5% of all cancer specimens had 5′-NPD activity in the G0/G1 cells and 87.5% in the S and/ or G2/M cells, whereas in the noncancer specimens 5′-NPD was found in 28.5% of the G0/C1 cells and 71.5% of the specimens had 5′-NPD in the S and/or G2/M cells. Furthermore, the concentration of 5′-NPD was found to be five times higher in the G2/M cells of the cancer specimens than that in the noncancer specimens. However, in the hyperplasia specimens, the activity was only two times higher in the same cell cycle fraction than in the normal specimens. The results of this investigation provided for the first time evidence that this exonuclease activity alters in the cell cycle fractions and that a decrease in the enzyme activity in G0/G1 cells and an increase in G2/M cells may be a useful marker for neoplastic development in human endometrial cancer.

The optimal management of stage II carcinoma of the endometrium remains to be established. We reviewed our experience in treating 42 patients with stage II endometrial cancer by surgery, radiation, or combined radiation and surgery at the Hospital of the University of Pennsylvania. The overall 5-year survival was 47.6%. The 5-year survivals of patients treated by surgery only, radiation only, or combination radiation and surgery were 68.5, 36.5, and 46.1%, respectively, which were not significantly different. Histologic grade was found a significant prognostic factor but type of cervical involvement was not. Major complication rates were similar in each treatment group. We conclude that the majority of patients with stage II endometrial carcinoma are best treated by combination radiation and surgery, but in a select subset of patients, radical hysterectomy and lymphadenectomy constitute a reasonable treatment option.

The physician population delivering obstetric care in Philadelphia between 1950 and 1970 was contacted to ascertain their use of diethylstilbesterol (DES) during pregnancy. Of the 31.8% of the physicians who responded to the questionnaire, 71.8% used DES during pregnancy and 12.7% desired assistance in review of their records. During the 6 years from the initial survey, 830 young women exposed to DES in utero were periodically screened for cervicovaginal abnormalities and clear cell adenocarcinoma. Of these 830 patients 61.7% were found to have cervicovaginal abnormalities, and 65.9% of the patients showed either adenosis or evidence of the prior existence of vaginal adenosis. Eight patients were treated for clear cell adenocarcinoma. Two cases were detected while asymptomatic. Seven of the patients are living with no evidence of cancer, and two of these have survived over 5 years.A project, designed to locate the population at risk to diethylstilbestrol (DES) exposure in utero in the greater Philadelphia area from 1950-1970, was implemented by contacting area physicians who might have used the drug in their practices on pregnant women. 216 (31.8%) physicians responded to the questionaire; 155 (71.8%) responded that they had used DES. During the 6 years from initial survey, 830 young women exposed to DES in utero were periodically screened for cervicovaginal abnormalities and clear cell adenocarcinoma. Gross structural cervicovaginal abnormalities were found in 512 (61.7%) of the individuals evaluated. In 38 patients, vaginal adenosis existing alone was documented. In another 279 patients, metaplasia alone was noted in the vagina, and in another 230 patients, both metaplasia and adenosis coexisting in varying degrees were found. Thus, 547 (65.9%) showed either adenosis or evidence of the prior existence of vaginal adenosis. 8 patients with clear cell adenocarcinoma of the vagina or cervix were seen; each individual was born during the decade of the 1950s. 2 cases were detected while asymptomatic; 7 of the patients are living with no evidence of cancer, and 2 of these have survived over 5 years. These results showed a much lower incidence of significant dysplastic squamous changes (1.1%) than that of earlier reports, emphasizing the subjective element of earlier, more alarming reports.

Flow cytometric DNA analysis data (FCDA) were obtained from 324 samples provided through the Gynecology-Oncology Clinic. These samples consisted of 294 combined endoectocervical and vaginal smears and 30 peritoneal washings. Using a conventional scheme for G0/G1, S + G2/M and the coefficient of variation with computer correction for the cell-cycle kinetics, it was possible to assign a diagnostic Class I, II, III or V similar to that used by the Cytology Laboratory. These data were then compared with the histopathologic and colposcopic diagnoses. The correlation between FCDA and cytologic results were essentially similar to the previous data obtained from only endocervical sampling. The most interesting finding in this study was the recognition of an FCDA pattern showing a higher DNA content in the G0/G1 and the early S regions in 70 of 94 (74.5%) of samples from patients with condyloma acuminata. All condyloma samples were diagnosed either by cytologic, histopathologic, or colposcopic examination, or a combination of two or three. All biopsy specimens were then reviewed by one pathologist to verify any discrepancies. The relationship of this pattern to the viral etiology of this disease is discussed with the three methods of diagnosis and electron microscopic observations. It is suggested that, based on this study. FCDA analysis of pap smears may also be useful in determining the presence of condyloma in a gynecology clinic. The potential value of FCDA analysis from peritoneal washings for the diagnosis of gynecologic cancer can not be ascertained in this preliminary investigation because of insufficient samples.

This is a study of 243 radical hysterectomy and pelvic lymphadenectomy procedures performed for gynecologic malignancy. The term “problem” radical hysterectomy was applied to those patients with one of the following conditions: (1) recent cervical conization (within 21 days), (2) previous total or supravaginal hysterectomy, (3) pregnancy, or (4) previous pelvic radiation. There were 88 patients in these categories. One hundred and fifty-five patients had none of these predisposing problems which might influence operative or postoperative complications. There were two deaths (0.82 per cent). There was no statistically significant difference in operative injuries to the bladder, ureters, or rectum or in the mean operative time and mean blood loss across the categories. However, there was a statistically significant difference across the categories in postoperative complications, both major and minor. The greatest incidence of such complications occurred in patients who had previous radiation therapy and the second greatest incidence was in patients who had recent cervical conization. Pregnant patients had the least number of complications.

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 chromic 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.

Eighty-five patients underwent a surgical staging procedure during a 2-year period. Fifty-eight of these patients were evaluated in relation to the histologic grade of their squamous carcinoma of the cervix. An increased incidence of extrapelvic lymph node metastasis is associated with poorly differentiated tumors and with parametrial extension of the primary tumor regardless of histologic grade. Surgical staging is suggested for patients with parametrial extension of their tumor or for patients with poorly differentiated tumors.

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.

Cytoplasmic estrogen receptor levels (ER) were measured in ovarian epithelial malignancies from 44 patients using a dextran-coated charcoal assay with analysis of the data by Scatchard plots. In 31 cases, progesterone receptor levels (PR) were also determined. In untreated patients, 68.8% of malignancies were ER-positive (greater than or equal to 10 fmole receptor/mg protein) and 35.0% were PR-positive (greater than or equal to 50 fmole/mg protein). Receptor levels in ovarian epithelial malignancies were not dependent on patient age, menopausal status, tumor stage, or histologic grade. However, ovarian endometrioid carcinomas contained significantly more PR than other histologic variants (P less than 0.02). Excluding endometrioid carcinoma, tissues from patients treated with chemotherapy contained less ER and PR than tissues from untreated patients. ER-positive tumors from three patients assayed before cyclophosphamide or combination chemotherapy became ER-negative after therapy. In addition, tamoxifen increased cytoplasmic PR (124 to 333 fmol/mg) and decreased cytoplasmic ER (65 to 4 fmol/mg) in a single patient with endometrioid carcinoma.

Thirty-six patients with primary ovarian carcinoma who had 42 second-look procedures performed are reported. Twenty-three patients had no tumor found at the second-look celiotomy and were given no further treatment. Thirteen patients had tumor at the second-look procedure and were continued on therapy. Six patients have died with disease and all had a positive second-look celiotomy. Two patients have died with leukemia but with no evidence of ovarian cancer, one after a negative second-look and the other a negative third-look. No patient with a negative second-look celiotomy has died with disease. A correlation with respect to the findings at the second-look was found with respect to the stage of disease and the amount of residual tumor at the initial surgery. The use of the second-look celiotomy in patients with disease in the early stages and in patients treated with irradiation is discussed, along with the utilization of the laparoscopy.

Malignant gestational trophoblastic disease arising after term pregnancy is associated with a poorer prognosis than postmolar trophoblastic disease [1]. Choriocarcinoma coexistent with intrauterine pregnancy has also been reported [2]. The case described herein represents the rare occurrence of a term pregnancy in a patient with preexisting metastatic choriocarcinoma and serves to underscore the need for adequate contraception in the follow-up of patients treated for malignant gestational trophoblastic disease.

The nomenclature of the lymph node groups draining the pelvic organs has been poorly standardized. This has impaired understanding of the natural history of gynecologic malignancies and led to difficulties in communication among specialists treating those diseases. In order to assess the extent of this problem, members of the Society of Gynecologic Oncologists and other physicians treating pelvic malignancy were asked to label a diagram of the pelvic lymph nodes. The lack of uniformity in the answers confirms the need for a simple, clinically relevant system of nomenclature. Such a system is proposed.

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.

The average postoperative stay for 45 patients undergoing radical vulvectomy with femoral and inguinal lymphadenectomy was 37 days. Five patients were treated with oral zinc sulfate for at least 7 days prior to surgery. The incidence of wound infection was decreased, and the average postoperative stay was reduced to 18 days.

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.

1. 1. The total mortality in 18 patients treated by pelvic exenteration for carcinoma of the cervix was 16.6 per cent. 2. 2. There were 14 postoperative complications in 12 patients, the most serious of which were 3 instances of intestinal obstruction. 3. 3. Of the 15 patients who left the hospital, 6 have died of tumor recurrence and one of perforation of the colon with peritonitis but without evidence of recurrence at necropsy. Eight patients are living from 18 months to 7 years without evidence of tumor.