The efficacy of adjuvant platinum-based chemotherapy in Stage I uterine papillary serous carcinoma (UPSC).

OBJECTIVE: To determine the efficacy of adjuvant platinum-based chemotherapy in Stage I uterine papillary serous carcinoma (UPSC). METHODS: A retrospective multi-institutional investigation was performed to identify surgically staged patients with Stage I UPSC who were (1) treated after surgery with 3-6 courses of platinum-based chemotherapy without radiation from 1990-2003, and (2) followed for a minimum of 12 months, or until recurrence. RESULTS: Six patients (IA-2, IB-3, IC-1) were treated with carboplatin (AUC 6) or cisplatin (50 mg/m2) alone. One patient recurred to the vagina, was treated with chemo-radiation, and is alive and well at 122 months. One patient recurred to the lung, liver, and brain, and died of disease at 24 months. The remaining 4 patients are alive with no evidence of disease 15-124 months (mean 62 months) after treatment. Two patients (IB-1, IC-1) were treated with cisplatin (50 mg/m2) and cyclophosphamide (1000 mg/m2), and both are alive and well with no evidence of disease 75 and 168 months after treatment. Twenty-one patients (IA-5, IB-13, IC-3) were treated with a combination of carboplatin (AUC 6) and paclitaxel (135 mg/m2-175 mg/m2). One patient recurred to the vagina after 3 cycles of carboplatin/paclitaxel, and was treated with chemo-radiation. She is now without evidence of disease 10 months after treatment. At present, all 21 patients with Stage I UPSC treated following surgical staging with carboplatin/paclitaxel chemotherapy are alive and well with no evidence of disease 10-138 months (mean 41 months) after treatment. CONCLUSION: Combination carboplatin/paclitaxel chemotherapy following surgery is effective in the treatment of Stage I UPSC.

Antisense inhibition of BRCA1 expression and molecular analysis of hereditary tumors indicate that functional inactivation of the p53 DNA damage response pathway is required for BRCA-associated tumorigenesis.

OBJECTIVE: The purpose of this investigation was to test the hypothesis that mutation of TP53 is a requirement for BRCA-associated cancer development. METHODS: A cell line experimentally deficient in BRCA1 protein was constructed using a regulatable antisense expression vector expressing 4000 bp from the BRCA1 cDNA. Changes in BRCA1, p53, and p21 protein levels were assayed by immunoblotting. Ovarian tumors with germline mutations in BRCA1 or BRCA2 were screened for mutations in TP53 by single-strand conformation polymorphism analysis. RESULTS: Antisense inhibition of BRCA1 protein caused p53 and p21 protein levels to rise, indicating that partial loss of BRCA1 function activates the p53 DNA damage response pathway. Somatic mutation of TP53 was observed in 7 of 14 BRCA-associated ovarian tumors. CONCLUSIONS: Our findings provide novel evidence that loss of BRCA1 function in human cells activates the p53 DNA damage response pathway and that loss of this pathway, by somatic mutation of TP53, is a likely requirement for BRCA-associated tumor development.

The efficacy of transvaginal sonographic screening in asymptomatic women at risk for ovarian cancer.

OBJECTIVE: The purpose of this study was to determine the efficacy of annual transvaginal sonography (TVS) as a screening method for ovarian cancer. METHODS: Annual TVS screening was performed on 14, 469 asymptomatic women from 1987 to 1999. Eligibility criteria included (1) all women >/= 50 years of age and (2) women >/= 25 years of age with a family history of ovarian cancer. Ovarian volume was calculated using the prolate ellipsoid (length x height x width x 0.523). An abnormal sonogram was defined by (1) an ovarian volume >10 cm(3) in postmenopausal women or >20 cm(3) in premenopausal women or (2) a papillary or complex tissue projection into a cystic ovarian tumor. All women with abnormal TVS had a repeat sonogram in 4-6 weeks. Patients with a persistently abnormal second screen had a serum CA-125 determination, tumor morphology indexing, and Doppler flow sonography, and were advised to have surgical tumor removal. RESULTS: One hundred eighty patients with persisting TVS abnormalities underwent exploratory laparoscopy or laparotomy. Seventeen ovarian cancers were detected: 11 Stage I, 3 Stage II, and 3 Stage III. Only three patients with Stage I cancers had a palpable ovarian mass on clinical examination. All patients with Stage I and II ovarian cancer are alive without recurrence 1.8-9.8 years (median, 4.5 years) after diagnosis. Two of the three Stage III patients have died of disease: one at 4.3 years and one at 7.7 years after detection. Four patients developed ovarian cancer within 12 months of a negative scan (FN): 2 Stage II, 2 Stage III. Three of these patients are alive with no evidence of disease 0.4, 1.9, and 5.5 years after diagnosis, and 1 patient has died of disease 0.7 years after diagnosis. Four patients developed ovarian cancer more than 12 months following a normal screen. All 4 presented clinically with Stage III disease. Two of these patients have died of disease and two patients are alive 1.5 and 2.1 years after diagnosis. TVS screening was associated with the following statistical variables: sensitivity, 81%; specificity, 98.9%; positive predictive value (PPV), 9.4%; and negative predictive value (NPV), 99.97%. After 46, 113 screening years, there have been 3 ovarian cancer deaths in the annually screened population and 2 ovarian cancer deaths in women receiving less than annual screening. The survival of ovarian cancer patients in the annually screened population was 95.0 +/- 4.9% at 2 years and 88.2 +/- 8.0% at 5 years. Excluding all cases of nonepithelial or borderline epithelial malignancies, the survival of patients with ovarian cancer in the annually screened population was 92.9 +/- 6.9% at 2 years and 83.6 +/- 10.8% at 5 years. CONCLUSIONS: (1) TVS screening, when performed annually, is associated with a decrease in stage at detection and a decrease in case-specific ovarian cancer mortality. (2) TVS screening does not appear to be effective in detecting ovarian cancer in which ovarian volume is normal.

Ovarian volume related to age.

OBJECTIVE: The goal of this study was to determine the relationship of ovarian volume to age, height, and weight in women undergoing transvaginal sonography. METHODS: Thirteen thousand nine hundred sixty-three women 25-91 years of age undergoing annual transvaginal sonography as part of the University of Kentucky Ovarian Cancer Screening Program were the subjects for this investigation. Each ovary was measured in three dimensions, and ovarian volume was calculated using the prolate ellipsoid formula (L x H x W x 0.523). Mean ovarian volume according to age was calculated for each decade of life. RESULTS: Data were obtained from 58,673 observations of ovarian volume. Mean ovarian volume was 6.6 +/- 0.19 cm(3) in women less than 30 years of age; 6.1 +/- 0.06 cm(3) in women 30-39; 4.8 +/- 0.03 cm(3) in women 40-49; 2.6 +/- 0.01 cm(3) in women 50-59; 2. 1 +/- 0.01 cm(3) in women 60-69; and 1.8 +/- 0.08 cm(3) in women >/=70. Mean ovarian volume was 4.9 +/- 0.03 cm(3) in premenopausal women and 2.2 +/- 0.01 cm(3) in postmenopausal women (P < 0.001). The use of exogenous estrogens was associated with a significant reduction in ovarian volume in women 40-59 years of age, but not in women >/= 60. Ovarian volume was unrelated to patient weight but was greater in tall women (>68 in.) than in short women (<58 in.). CONCLUSION: There is a statistically significant decrease in ovarian volume with each decade of life from age 30 to age 70. Mean ovarian volume in premenopausal women is significantly greater than that in postmenopausal women. The upper limit of normal for ovarian volume is 20 cm(3) in premenopausal women and 10 cm(3) in postmenopausal women.

Ovarian steroid cell tumors, not otherwise specified: a case report and literature review.

Steroid cell tumors, not otherwise specified, are rare ovarian sex cord-stromal tumors with malignant potential. The majority of these tumors produce steroids with testosterone being the most common. A case of a 46-year-old woman who presented with sudden onset of virilization and a pelvic mass is reported. Various aspects of the presentation, diagnosis, and treatment of these tumors are discussed.

Neuroendocrine signet ring cell adenocarcinoma of the endocervix.

Signet ring cell morphology in mixed carcinoma of the uterine cervix is not uncommon. It is rare for such morphology to predominate, however, and there are no reported cases of a signet ring cell adenocarcinoma (SRCA) of the endocervix with neuroendocrine differentiation. A 53-year-old woman presented with abnormal perimenopausal bleeding, and uterine curettings revealed a signet ring cell carcinoma. After clinical evaluation to eliminate a metastasis from an extra-uterine primary, the patient underwent surgical therapy and staging, and was treated with postoperative adjuvant chemoradiation. Pathologic evaluation found the tumor to arise from the endocervix and to be of predominant signet ring cell morphology. Immunohistochemical staining revealed that the tumor exhibited neuroendocrine differentiation and helped confirm its endocervical origin. The patient remains without evidence of disease 6 months after primary therapy. This is the first case report of endocervical SRCA with neuroendocrine differentiation (SRCA with features of carcinoid tumor). Discussion of this entity is provided.

Laparoscopy during pregnancy: a study of five fetal outcome parameters with use of the Swedish Health Registry.

OBJECTIVE: Our purpose was to compare five fetal outcome variables between laparoscopy and laparotomy performed during pregnancy with use of the Swedish Health Registries from 1973 to 1993. STUDY DESIGN: A dataset was produced by linking computerized records from three Swedish Health Registries. The dataset includes records for women who were delivered between 1973 and 1993 and had an operation within 1 year before giving birth. The data were divided according to surgical procedure(s) and grouped according to diagnostic code(s). The following end points were studied in singleton births: birth weight, gestational duration, intrauterine growth restriction, congenital malformations, stillbirths, and neonatal deaths. In the analysis confounding by maternal age and parity, year of birth of the infant, maternal smoking, period of involuntary infertility, and maternal cohabitation was taken into consideration. A chi 2 analysis was used to compare proportions. Variables were stratified with use of the Mantel-Haenszel procedure. Risk ratios were calculated for observed/expected ratios when outcomes for the total population were compared or as odds ratios when laparoscopy and laparotomy cohorts were compared. Expected values were calculated from the total population of women with singleton pregnancies. RESULTS: The study covered 2,015,000 deliveries in Sweden from 1973 to 1993. Data for this study were restricted to singleton pregnancies who had nonobstetric operations between the fourth and twentieth weeks of pregnancy. Too few laparoscopic procedures were performed after 20 weeks to allow comparison. A total of 2181 laparoscopies and 1522 laparotomies met criteria for analysis. There were no significant differences between the two groups in any demographic variable. Pregnancies with operations were compared with the total population for birth weight, gestational duration, growth restriction, infant survival, and fetal malformations. On the basis of relative risks, there was an increased risk for infants in both laparoscopy and laparotomy groups to weigh < 2500 gm, to be delivered before 37 weeks, and to have an increased incidence of growth restriction compared with the total population. There was no difference between laparoscopy and laparotomy in cumulative infant survival up to 1 year (odds ratio 0.85, 95% confidence interval 0.48 to 1.51). There was no difference in the rate of fetal malformations between laparoscopy (risk ratio 1.09, 95% confidence interval 0.90 to 1.11), laparotomy (risk ratio 1.08, 95% confidence interval 0.85 to 1.11), and the total population. CONCLUSION: There is no difference in five fetal outcome variables for patients undergoing laparoscopy versus laparotomy in singleton pregnancies between 4 and 20 weeks of gestation.

Laparoscopy during pregnancy. A survey of laparoendoscopic surgeons.

OBJECTIVE: The purpose of this study was to survey the Society of Laparoendoscopic Surgeons (SLS) for their experience with laparoscopy during pregnancy and to develop a database on the safety and complications of laparoscopy in pregnancy. STUDY DESIGN: A survey questionnaire was mailed to 16,329 laparoscopic surgeons from the SLS mailing database. Seven questions were asked: number of laparoscopic procedures in pregnancy, type of operation, gestational age, intraoperative and postoperative complications, insufflation agent and insufflation pressure. Only surgeons who had performed laparoscopic procedures in pregnancy were asked to return surveys. RESULTS: One hundred ninety-two (1.2%) surveys were returned. Complete information was available on 413 laparoscopic cases. There were five intraoperative complications, including inadvertent placement of a Veress needle into a pregnant uterus. There were 10 postoperative complications. CONCLUSION: This is the first report to specifically address the safety and complications of laparoscopy in pregnancy. This study suggests that laparoscopy may be safe during pregnancy; however, it was limited by the biases of surveys and retrospective studies.

Evaluation of 3-Day Course of Doxycycline for the Treatment of Uncomplicated Chlamydia trachomatis Cervicitis.

OBJECTIVE: The purpose of this study was to compare the efficacy of a 3-day course of doxycycline to a standard 7-day course for treating uncomplicated chlamydia cervicitis. METHODS: During an 18-month period, 77 women with uncomplicated chlamydia cervicitis were randomized to receive either a 3-day or a 7-day course of doxycycline (100 mg twice daily). Tests of cure were performed 3 weeks after completion of therapy with the Amplicor polymerase chain reaction (PCR) assay (Roche Molecular Systems, Branchburg, NJ). Demographics, therapeutic results, and side effects for the two groups were compared. RESULTS: Seventy-three patients completed the study: 35 in the 3-day group and 38 in the 7-day group. There were no significant differences in age, gravidity, or parity between the groups. There was a 94% (33/35) cure rate in the 3-day group and a 95% (36/38) cure rate in the 7-day group (P = 1.0). Thirty-four percent and 32% of the patients in the 3- and 7-day groups reported side effects, respectively; there was no significant differences between the 3- and 7-day groups in regard to population demographics, patient compliance, therapeutic outcome, or side effects. CONCLUSIONS: A 3-day course of doxycycline appears to be as effective as a 7-day course of doxycycline for the treatment of uncomplicated chlamydia cervicitis.

Fresh frozen plasma prophylaxis for hereditary angioedema during pregnancy. A case report.

BACKGROUND: Hereditary angioedema (HAE) is an uncommon disorder of the complement system due to a deficiency or dysfunction of the inhibitor of the first component of complement (C1 INH). Clinically, HAE is characterized by episodic abdominal pain or edema of the extremities, face, larynx and vulva. Laryngeal edema is potentially lethal and accounts for mortality rates as high as 30%. Therapy is divided into short-term (fresh frozen plasma) and long-term (antifibrinolytic agents, hormonal therapy) prophylaxis, or acute treatment (epinephrine, steroids, antihistamines). CASE: An 18 year-old, primiparous woman presented with a history of multiple episodes of abdominal pain, swelling of abdomen and extremities. A diagnosis of hereditary angioedema was made based on the patient's and family's history and on decreased levels of C1 INH and complement component 4. Standard prophylactic methods were contraindicated due to potential teratogenic effects. Fresh frozen plasma given twice weekly over 2.5 months resulted in reduction in the number and severity of attacks and allowed successful completion of pregnancy. CONCLUSION: This is the first report of fresh frozen plasma therapy as a means of long-term prophylaxis in a pregnant woman. Fresh frozen plasma may serve as an alternate mode of long-term prophylaxis if the standard agents (antifibrinolytic, hormone) are unsuccessful or contraindicated.

Maternal and fetal effects of laparoscopic insufflation in the gravid baboon.

STUDY OBJECTIVE: To test the hypothesis that intraabdominal pressures (IAP) associated with abdominal insufflation for laparoscopic procedures can alter pulmonary and hemodynamic values in the pregnant baboon and hemodynamic values in the fetus. DESIGN: A descriptive physiologic study. SETTING: Animal research facility at Scott and White Memorial Hospital, Temple, TX. PARTICIPANTS: Four pregnant baboons at 120 +/- 7 days' gestation. INTERVENTIONS: The baboons underwent general anesthesia, Swan-Ganz and arterial catheter placement, and abdominal insufflation at 10 and 20 mm Hg IAP for 20-minute intervals at each pressure. The following end points were measured: maternal heart rate (MHR), mean arterial pressure (MAP), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), pulmonary artery pressures (PAP), central venous pressure (CVP), systemic vascular resistance (SVR), ventilator rate (VR), oxygen saturation, and end-tidal carbon dioxide (CO2). Fetal heart rate and fetal growth values were measured, and umbilical artery Doppler flow studies were performed. MEASUREMENTS AND MAIN RESULTS: The PCWP (p <0.026), CVP (p <0.0012), and PAP (p <0.046) were significantly increased at 20 mm Hg IAP; CO decreased as IP increased. The MAP, MHR, and SVR did not change significantly with increased IAP. The only significant change in pulmonary values was the increase in peak airway pressure (p <0.001). The VR was increased from an average of 18 to 41 breaths/minute in an attempt to maintain adequate oxygen saturation and to normalize end-tidal CO2 when IAP was increased to 20 mm Hg. Respiratory acidosis (pH <7. 35, partial pressure of carbon dioxide >50 torr) was demonstrated in three of four animals within 20 minutes at an IAP of 20 mm Hg. Results of Doppler flow studies on the effects of the fetuses were unaltered immediately after this procedure compared with baseline measurements. Normal interval growth was demonstrated 2 weeks after the procedure. CONCLUSION: The baboon mothers and fetuses had no adverse effects at an IAP of 10 mm Hg, but may have significant cardiovascular and respiratory alterations associated with IAP of 20 mm Hg.

Erythema nodosum associated with streptococcal infection in pregnancy.

BACKGROUND: Erythema nodosum (EN) is a condition characterized by the presence of painful erythematous nodules on the pretibial aspects of the lower extremities. EN is thought to be a local inflammatory, immune-mediated reaction to a number of systemic antigenic stimuli. This condition is noted most often in women between menarche and menopause and is associated with certain drugs, infections, and pregnancy. However, no reports in the literature describe EN as a result of streptococcal infection during pregnancy. CASE: A 21-year-old, white woman, G(3)P(0020), presented at 13 weeks gestation with a 2-week history of erythematous, tender lesions on the pretibial aspects of both legs consistent with EN. The patient reported having had a "flu-like" illness at the same time the lesions developed. The "flu" symptoms resolved within 10 days without medical intervention, but the lesions on her legs persisted. An initial antistreptolysin-O (ASO) titer was elevated at 960 Todd units (normal values: preschool and adults <85; school-age and young adults <170). Six days later, she presented to the emergency department with complaints consistent with a urinary-tract infection. She was empirically treated with a 10-day course of amoxicillin, 500 mg t.i.d. Although the patient was treated with amoxicillin for a presumed urinary-tract infection (which was culture-negative), the lesions resolved after her completion of the antibiotics. Twelve weeks later, a repeat ASO was within normal limits. The EN lesions did not recur. CONCLUSION: Although many etiologic factors are identified as causes of EN, the condition is usually self-limiting, requiring only minimal supportive measures until it resolves. A careful history should be obtained and a physical examination performed to exclude other causes. If a recent streptococcal infection is identified or presumed, a 10- to 14-day course of antibiotics is warranted.

Acute pelvic inflammatory disease after tubal sterilization. A report of three cases.

Pelvic inflammatory disease (PID) is considered to be rare or nonexistent following tubal sterilization. The purpose of this report is to describe three cases of surgically diagnosed acute PID in women previously sterilized by bilateral tubal ligation who presented over a one-year period. All three patients presented with an acute abdomen, fever and elevated white blood cell count. Our experience suggests that PID following tubal sterilization is more common than previously described and can present a diagnostic dilemma.

Hyperbaric oxygen therapy following radical vulvectomy: an adjunctive therapy to improve wound healing.

The objective of the study was to evaluate the effect of postoperative hyperbaric oxygen (HBO) therapy on wound breakdown following radical vulvectomy. A prospective, observational study was performed on patients undergoing radical vulvectomy from October 1990 to March 1993 at Scott and White Memorial Hospital, Temple, Texas. HBO therapy was initiated in the postoperative period. Retrospective review of all patients coded as radical vulvectomy from 1987 to 1990 provides for a historical comparison. Eight patients were enrolled in the study. Six patients had radical vulvectomies with lymph node dissections (LND) and two did not. One wound breakdown was observed in the HBO-treated patients. Retrospective review identified 22 patients as having undergone radical vulvectomy with or without LND. Seven of 9 patients with LND and 3 of 13 without LND had wound breakdowns. A significant difference (P = 0.035) was found comparing patients treated with LND and HBO to retrospective controls with LND. Hospitalization was shorter in the HBO-treated patients. This small study showed a reduction in wound breakdown for patients undergoing radical vulvectomy with LND and HBO therapy compared to similar patients not treated with HBO. This observation supports the need for randomized studies examining the efficacy of HBO therapy in this group of patients.

Performance of the syva direct fluorescent antibody assay for Chlamydia in a low-prevalence population.

Chlamydia trachomatis is the most common reportable sexually transmitted disease (STD) in the United States. In the 1980s, rapid diagnostic tests for chlamydia began to replace more cumbersome tissue culture methods. Current data on rapid antigen detection assays demonstrate acceptable sensitivity, specificity, and predictive values in populations with a high prevalence of chlamydia. Few studies report the performance of these assays in a low-prevalence obstetric and gynecologic (Ob/Gyn) population, This study compares the most commonly used direct fluorescent antibody (DFA) assay (Syva Microtrak) with tissue culture (TC) in a low-prevalence population. Endocervical specimens (775) were tested from women at risk for chlamydia infection, and the prevalence was found to be 7.7%. The DFA assay demonstrated a sensitivity of 80% and a specificity of 97% compared with TC. The positive and negative predictive values were 72% and 98%, respectively. The results of this study indicate that the Syva DFA assay lacks the sensitivity and positive predictive value for routine use in Ob/Gyn populations with a lowprevalence of C. trachomatis.

Inadvertent administration of prostaglandin E1 instead of prostaglandin F2 alpha in a patient with uterine atony and hemorrhage.

A woman underwent cesarean delivery for premature labor, breech presentation, and ruptured membranes. Placenta accreta associated with uterine atony and severe hemorrhage was diagnosed. Prostaglandin E1 instead of prostaglandin F2 alpha was inadvertently administered in an effort to control the hemorrhage. The resulting complications included profound hypotension, disseminated intravascular coagulation, and ventricular tachycardia.

Paget's disease of the scrotum: a case report and review of current literature.

A case of extramammary Paget's disease of the scrotum is presented. A patient was diagnosed by biopsy and treated for squamous cell carcinoma in situ of the scrotum. Following surgery, the tumor was found to be extramammary Paget's disease. Management consisted of treatment with 5-fluorouracil followed by wide local excision. The current literature is reviewed briefly.