Update on low malignant potential ovarian tumors.

Low malignant potential (LMP) ovarian tumors represent a small subset of epithelial ovarian cancers that were first identified 70 years ago but were recognized in a systematic way only within the last 30 years. These lesions afflict women at a much younger age than invasive ovarian cancer, behave in a more indolent manner, and have a much more favorable prognosis. The management of women with LMP tumors is primarily surgical; adjuvant therapy plays little role in early disease and its use in advanced disease is not well defined. Ongoing investigations are attempting to define prognostic factors that may assist clinicians in the appropriate application of postoperative therapy.

Sarcoidosis in a uterine leiomyoma.

Sarcoidosis is a granulomatous condition of unknown etiology. Though the lung and lymph nodes are most commonly involved, other organs may also be affected. Involvement of the female reproductive system is very uncommon and usually has been found in the endometrium or myometrium. A case is described of a 43-year-old nulligravida who presented for evaluation of a dry cough and who was found to have a pelvic mass. Preoperative evaluation revealed the presence of pulmonary sarcoidosis. At the time of exploratory laparotomy, a large, pedunculated fibroid was resected along with an inflammatory cyst. Histopathologic examination revealed the presence of sarcoid lesions within the fibroid. This is the first report of such a finding, and the implications are discussed.

Borderline ovarian tumors.

Borderline ovarian tumors (BOTs) represent a small subset of epithelial ovarian cancers that were first described more than 70 years ago. Recognized in a systematic way in only the last three decades, BOTs occur most often in women in their reproductive years but are associated with an excellent long-term prognosis. The management of these tumors is primarily surgical, with the role of medical therapy a topic of ongoing research and debate.

Contemporary surgical management of borderline ovarian tumors: a survey of the Society of Gynecologic Oncologists.

OBJECTIVE: The objective of this study was to review the current practice patterns regarding the surgical management of borderline ovarian tumors. METHODS: A one-page survey was mailed to the members of the Society of Gynecologic Oncologists (SGO), using the directory of the Society. The survey addressed the demographics of the respondent and the recommended staging procedure for presumed early-stage disease. RESULTS: Of the 660 surveys mailed, 274 (42%) were returned. Ninety-seven percent (267/274) of respondents advocate surgical staging. Of this group, 96% (257/267) perform peritoneal washings, 97% (259/267) sample the omentum, and 92% (245/267) submit random peritoneal biopsies. Eighty-eight percent (235/267) perform lymph node sampling: paraaortic biopsies by 89% (210/235) and pelvic biopsies by 97% (228/235). Of this latter group, 91% sample the external iliac chain, 82% submit hypogastric nodal tissue, and 70% remove obturator lymph nodes. CONCLUSION: Diversity exists in the surgical management of borderline ovarian tumors among members of the SGO who responded to this survey. Efforts to ensure a consistent approach to the management of borderline ovarian tumors are warranted.

The accuracy of a frozen section diagnosis of borderline ovarian malignancy.

While the accuracy of frozen section in the diagnosis of invasive ovarian neoplasms has been previously addressed, the frozen section diagnosis of borderline ovarian tumors has been less well characterized. The distinction between benign and borderline lesions is critical to the proper operative management of these patients. The records of 48 patients that had a frozen section diagnosis of borderline ovarian malignancy during surgical exploration between 1986 and 1993 were reviewed. Thirty-one patients were Stage I, 2 patients were Stage II, 10 patients were Stage III, and 5 patients were unstaged. Clarifying phrases were used frequently in the frozen section report, and these terms were categorized as "rule out" borderline tumor, borderline tumor, and "at least" borderline tumor. Of 33 cases with a frozen section report of borderline or at least borderline malignancy, no case were subsequently found to be benign. Errors in the intraoperative management could have occurred in 3 of 48 cases (6.25%), when benign neoplasms were thought to be of borderline malignancy on frozen section. However, in each of these cases, the clarifying term rule out was used, indicating the equivocal nature of the frozen section findings. Thirteen of the 48 patients (27.1%) were found to have a focus of invasive cancer within a borderline tumor on final pathologic review; the primary tumors in these 13 cases ranged in maximal diameter from 5 to 26 cm and were of varying histologic types. The level of experience of the pathologist responsible for the frozen section did not influence the accuracy of frozen section determination noted in this study. A frozen section evaluation identifying a borderline ovarian malignancy is accurate in excluding the presence of benign pathology. It is crucial to understand the meaning of specific clarifying terms used in frozen section diagnoses.

The effect of renal function on serum levels of CA 125.

OBJECTIVE: Serum assays for CA 125 are used to monitor disease status in patients undergoing treatment for epithelial ovarian cancer. While a number of benign gynecologic as well as benign and malignant nongynecologic conditions are associated with CA 125 elevations, the established "normal" range describes a healthy population of women. The metabolism and clearance of CA 125 is not well understood. Because mild degrees of renal impairment frequently occur in ovarian cancer patients, we investigated the effect of impaired renal function on basal CA 125 in a population of female dialysis patients. METHODS: Twenty-five women on hemodialysis were selected at random. Patients ranged in age from 29 to 87 years. Renal disease was secondary in most cases to diabetes mellitus or hypertension. The creatinine clearance was less than 10 cc/min for all patients. The duration of dialysis ranged from 3 months to 14 years. Serum levels of CA 125 were measured using monoclonal antibodies in an immunoradiometric assay. RESULTS: The mean of duplicate determinations for 23 of 25 (92%) patients fell within the normal range for otherwise healthy women (< 35 U/ml). There was no apparent correlation between CA 125 level and age, menopausal status, BUN, serum creatinine, adequacy of dialysis, or primary underlying diagnosis. Of the 2 patients (8%) with CA 125 levels above the normal range, 1 was premenopausal and the other was postmenopausal; their CA 125 elevations were marginal (49.81 and 50.51). CONCLUSIONS: The results of this study demonstrate that even marked renal insufficiency is not itself associated with significant elevations of CA 125 above the normal range selected for otherwise healthy women. The development of renal insufficiency during treatment for ovarian cancer should not alter the interpretation of serum levels of CA 125.

Lobular breast carcinoma metastatic to the vulva: a case report and literature review.

BACKGROUND: Six previous reports have documented a vulvar metastasis from breast cancer; one has noted involvement of the Bartholin's gland. CASE: A 53-year-old woman presented with an enlarging vulvar mass. Evaluation also identified a breast lesion. Surgical excision confirmed an invasive lobular breast carcinoma with a distant metastatic focus on the vulva. CONCLUSION: This is the first report in the English literature to document a vulvar metastasis from an invasive lobular carcinoma and the second to identify involvement of the Bartholin's gland. Careful gynecologic surveillance is needed in women with breast cancer.

Surgically documented responses to paclitaxel and cisplatin in patients with primary peritoneal carcinoma.

Intra-abdominal carcinomatosis indistinguishable from ovarian cancer may occur after removal of the ovaries or in association with surface ovarian involvement. Because its histologic pattern and behavior approximate those of ovarian cancer, this entity, known as primary peritoneal carcinoma, has been treated in a similar fashion--cytoreductive surgery followed by systemic chemotherapy. This review was undertaken to assess the efficacy of combination chemotherapy with paclitaxel and cisplatin, the current front-line chemotherapeutic regimen for ovarian cancer, in patients with primary peritoneal carcinoma. Sixteen patients diagnosed between January 1989 and July 1994 with primary peritoneal carcinoma were treated at the Hospital of the University of Pennsylvania. The records of the three patients whose initial chemotherapeutic regimen included paclitaxel and cisplatin were reviewed. An additional case from the Robert Wood Johnson Medical Center, Camden, New Jersey, was included. Pathologic review of all cases was conducted at the time of clinical management and again as part of this study. Reassessment laparotomy was performed in all patients after the completion of chemotherapy. Complete clinical information was available on all patients. All four patients presented with intra-abdominal carcinomatosis, and large volume (> 1 cm) residual disease was present following initial cytoreduction. Following chemotherapy, second-look laparotomy documented one complete pathologic response and three partial (>50% tumor volume reduction), but marked, responses. Combination chemotherapy with paclitaxel and cisplatin produces surgically documented responses in patients with primary peritoneal carcinoma.

Efficacy of frozen-section evaluation of uterine curettings in the diagnosis of ectopic pregnancy.

OBJECTIVE: This study was undertaken to examine the accuracy of frozen section for the identification of products of conception on curettage of patients undergoing surgery for suspected ectopic pregnancy. STUDY DESIGN: A retrospective analysis of 87 consecutive cases in which frozen-section assessment of an endometrial curettage specimen to identify products of conception was undertaken. A frozen-section diagnosis was considered correct if the final diagnosis concurred with the findings at frozen section. RESULTS: Eighty-one of 87 (93.1%) specimens were correctly identified at frozen section. Frozen section had a sensitivity of 78.3% and a specificity of 98.4%. The positive predictive value of frozen section in this population was 94.7% and the negative predictive value was 92.6%. No significant correlation was found regarding the attending pathologist at frozen section, preoperative human chorionic gonadotropin, or time of day at frozen section. CONCLUSIONS: Frozen section is accurate for the identification of products of conception on endometrial curettage in the evaluation of a suspected ectopic pregnancy.

Monoclonal antibody X18A4 identifies an oncofetal fibronectin epitope distinct from the FDC-6 binding site.

OBJECTIVE: Oncofetal fibronectin reactive with antibody FDC-6 has been associated with trophoblastic implantation and chorion structural stability. Abnormal release of this fibronectin into cervical and vaginal secretions has identified patients at risk for preterm labor and delivery. The aim of this study was to determine whether trophoblast-derived oncofetal fibronectin contains other novel epitopes distinct from the FDC-6 binding site. STUDY DESIGN: Antitrophoblast fibronectin hybridomas were generated and screened by comparative immunoassays. One specific monoclonal antibody, X18A4, was identified and compared with antibody FDC-6 by immunocytochemical and immunoblot analyses. Both antibodies were also evaluated in "sandwich"-type double monoclonal immunosorbent assays. RESULTS: X18A4 and FDC-6 bind avidly and noncompetitively to distinct epitopes within oncofetal fibronectin. They exhibit similar immunohistochemical staining of the extracellular matrix within placental tissue, ovarian epithelial tumors, and cultured trophoblasts. However, in contrast to FDC-6, X18A4 has no detectable binding activity to human plasma fibronectin, and its binding to oncofetal fibronectin was unaffected by enzymatic deglycosylation. Immunoblot analyses of oncofetal fibronectin proteolytic digests suggest that X18A4 binds near or within the alternatively spliced type III connecting segment domain. CONCLUSIONS: X18A4 identifies and binds with high affinity to a new epitope within oncofetal fibronectin, distinct from the FDC-6 binding site. Because X18A4 displays no detectable binding to plasma fibronectin, it could be used as an important adjunctive antibody for enhancing the specificity of clinically based oncofetal fibronectin diagnostic assays.

Identification of oncofetal fibronectin in patients with advanced epithelial ovarian cancer: detection in ascitic fluid and localization to primary sites and metastatic implants.

BACKGROUND: The mechanisms by which metastatic ovarian cancer adheres to peritoneal surfaces are not well understood. A role for tumor-derived extracellular matrix adhesive molecules such as fibronectin (FN) has been proposed. Because oncofetal fibronectin (onfFN) isoforms function in the adhesion of trophoblasts and have been identified in association with several malignancies, we sought to study onfFN in patients with advanced epithelial ovarian cancer. METHODS: Total FN was identified with the nonspecific anti-FN monoclonal antibody CAF. OnfFN was identified using the specific monoclonal antibodies FDC-6 and X18A4. These antibodies were applied to: 1) ascitic fluid from advanced epithelial ovarian cancer patients and peritoneal fluid from patients without pathologic conditions and 2) tissue sections of primary lesions and metastatic ovarian cancer implants. Comparative histologic specimens included normal ovarian tissue and small bowel implants of endometriosis. RESULTS: When measured by sandwich enzyme-linked immunoadsorbent assay, all peritoneal fluids (32 malignant and 32 benign) contained marked quantities of total (CAF reactive) FN, although malignant ascites had higher concentrations than benign samples (173.2 +/- 36.8 microg/mL vs. 76.4 +/- 31.8 microg/mL; P = 0.001). Malignant ascites also had significantly higher levels of onfFN than benign peritoneal fluid (FDC-6: 3.4 +/- 0.6 vs. 0.9 +/- 0.2 microg/mL; and X18A4: 5.1 +/- 1.3 vs. 1.1 +/- 0.4 microg/mL; P = 0.0001). Immunohistochemical staining of malignant lesions revealed prominent localization of both CAF reactive FN and onfFN to the stroma surrounding epithelial tumor nests. More delicate fibrillar staining within tumor nests also was evident. In contrast, implants of endometriosis revealed strong stromal staining for CAF reactive FN but not for onfFN. CONCLUSIONS: These results demonstrate the presence of onfFN in advanced ovarian malignancies. We speculate that onfFN may participate in tumor-associated peritoneal adhesive interactions.

Allelotype analysis of uterine leiomyoma: localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q.

Uterine leiomyoma is a benign smooth muscle tumor of the myometrium and is the most commonly encountered neoplasm in women of reproductive age. As for most benign tumors, the pathogenesis of leiomyoma remains obscure, especially at the molecular genetic level. The purpose of this study was to perform a genome-wide allelotype analysis to identify potential sites of tumor suppressor gene inactivation. Fifty-two cases of uterine leiomyoma were subjected to allelotype analysis by using matched pairs of tumor and blood DNA. Loss of heterozygosity (LOH) was assessed at 61 microsatellite markers distributed throughout the genome and representing all 41 chromosome arms. In general, LOH was very rare except on chromosome 7q, where LOH was observed in 34% of all informative tumors. Fine-deletion mapping with 25 microsatellite markers from the 7q22 region revealed a minimal deletion unit of approximately 4 cM, bounded by the markers D7S2453 proximally and D7S496 distally, that probably harbors a novel tumor suppressor gene involved in the etiology of this tumor.

Informe preliminar sobre la vigilancia epidemiológica en un estudio de campo en gran escala con vacuna antipoliomielítica de administración oral / Preliminary report on the control epidemiological in a case study with the polio vaccine applied orally

Consideramos que este estudio de campo fue oportuno y pertinente. Nuestras observaciones son demasiado anticipadas para justificar conclusiones. En los próximos meses se dispondrá de nuevos datos. Los hallazgos obtenidos sólo se presentan a título de información sobre la marcha del trabajo realizado ya(AU)

Publicado en inglés en Scientific Publication 50:445-456, 1960

Informe preliminar sobre la vigilancia epidemiológica en un estudio de campo en gran escala con vacuna antipoliomielítica de administración oral / Preliminary report on the control epidemiological in a case study with the polio vaccine applied orally

Consideramos que este estudio de campo fue oportuno y pertinente. Nuestras observaciones son demasiado anticipadas para justificar conclusiones. En los próximos meses se dispondrá de nuevos datos. Los hallazgos obtenidos sólo se presentan a título de información sobre la marcha del trabajo realizado ya(AU)

Informe preliminar sobre un estudio de campo en gran escala con vacuna cox-lederle de virus poliomielítico atenuado, administrada por vía oral, en el Condado de Dade (Miami) Florida / Preliminary report on a case study on the use of tha cox-lederle vaccine, administered via oral methods in Dade County Florida

1. El trabajo presenta los datos preliminares de un estudio de campo hecho en el condado de Dade, Florida, en que fueron vacunadas 412.000 personas con una sola dosis, administrada por vía oral, de vacuna antipoliomielítica trivalente Cox-Lederle de virus vivo atenuado

2. Se informa sobre los estudios de anticuerpos poliomielíticos neutralizadores en 594 individuos que carecían de anticuerpos de uno o más tipos de virus poliomielítico antes de la vacunación oral. La eficacia de la vacuna, medida por su capacidad de producir anticuerpos en estos individuos, fue la siguiente: 95 por ciento para el tipo 1, 97 por ciento para el tipo 3 y 78 por ciento para el tipo 2

3. Nuestra experiencia nos lleva a creer que los estudios de campo en gran escala de la vacuna antipoliomielítica de administración oral pueden y deben ser llevados a cabo en los grupos sociales y geográficos y grupos de edad en los cuales se proyecta, en definitiva, utilizar la vacuna(AU)

Publicado en inglés en Scientific Publication 50:435-444, 1960

Informe preliminar sobre un estudio de campo en gran escala con vacuna cox-lederle de virus poliomielítico atenuado, administrada por vía oral, en el Condado de Dade (Miami) Florida / Preliminary report on a case study on the use of tha cox-lederle vaccine, administered via oral methods in Dade County Florida

1. El trabajo presenta los datos preliminares de un estudio de campo hecho en el condado de Dade, Florida, en que fueron vacunadas 412.000 personas con una sola dosis, administrada por vía oral, de vacuna antipoliomielítica trivalente Cox-Lederle de virus vivo atenuado

2. Se informa sobre los estudios de anticuerpos poliomielíticos neutralizadores en 594 individuos que carecían de anticuerpos de uno o más tipos de virus poliomielítico antes de la vacunación oral. La eficacia de la vacuna, medida por su capacidad de producir anticuerpos en estos individuos, fue la siguiente: 95 por ciento para el tipo 1, 97 por ciento para el tipo 3 y 78 por ciento para el tipo 2

3. Nuestra experiencia nos lleva a creer que los estudios de campo en gran escala de la vacuna antipoliomielítica de administración oral pueden y deben ser llevados a cabo en los grupos sociales y geográficos y grupos de edad en los cuales se proyecta, en definitiva, utilizar la vacuna(AU)