John R. Lurain

Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole

Gestational trophoblastic disease includes hydatidiform mole (complete and partial) and gestational trophoblastic neoplasia (invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor). The epidemiology, pathology, clinical presentation, and diagnosis of each of these trophoblastic disease variants are discussed. Particular emphasis is given to management of hydatidiform mole, including evacuation, twin mole/normal fetus pregnancy, prophylactic chemotherapy, and follow-up.

Laparoscopically assisted vaginal hysterectomy in a university hospital: report of 82 cases and comparison with abdominal and vaginal hysterectomy.

OBJECTIVE The objective of this study was to critically review the indications, outcomes, complications, and costs of laparoscopically assisted vaginal hysterectomy in comparison with abdominal and vaginal hysterectomy. STUDY DESIGN The operating room log was reviewed to determine the number and route of hysterectomies performed over a 1-year period. The charts of 50 consecutive laparoscopically assisted vaginal hysterectomies and 50 vaginal hysterectomies were reviewed. Charts from 50 selected abdominal hysterectomies were also reviewed. Information on patient characteristics, indications, complications, uterine weights, hospital stay, and patient costs were obtained and analyzed. RESULTS Of 509 hysterectomies, 82 were performed as laparoscopically assisted vaginal hysterectomies and 73 as vaginal hysterectomies. The patient characteristics and indications of the laparoscopically assisted group more closely matched those of the abdominal hysterectomy group. The complication rate in the laparoscopically assisted group was intermediate between the other two groups, but the hospital stay was significantly less. Patient cost for laparoscopically assisted vaginal hysterectomy was significantly greater than either abdominal or vaginal hysterectomy, in spite of the shortened hospital stay. CONCLUSIONS Laparoscopically assisted vaginal hysterectomy offers a technique to convert some abdominal hysterectomies into vaginal hysterectomies. It appears particularly useful when an adnexal indication for surgery exists. Uterine leiomyoma does not appear to be an indication for laparoscopically assisted vaginal hysterectomy. The costs are significant because of increased operating time and costs of disposable equipment.

Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia

Gestational trophoblastic neoplasia (GTN) includes invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. The overall cure rate in treating these tumors is currently >90%. Thorough evaluation and staging allow selection of appropriate therapy that maximizes chances for cure while minimizing toxicity. Nonmetastatic (stage I) and low-risk metastatic (stages II and III, score <7) GTN can be treated with single-agent chemotherapy resulting in a survival rate approaching 100%. High-risk GTN (stages II-IV, score ≥7) requires initial multiagent chemotherapy with or without adjuvant radiation and surgery to achieve a survival rate of 80-90%.

Natural history of hydatidiform mole after primary evacuation

From 1962 to 1978, 738 patients with hydatidiform mole were referred to the John I. Brewer Trophoblastic Disease Center of Northwestern University for follow-up and human chorionic gonadotropin (hCG) testing after evacuation. There was spontaneous regression of trophoblastic disease in 596 (80.8%) of the 738 patients. Of these 596 patients, regression occurred in 11 (1.8%) by day 10 after evacuation, in 124 (20.8%) between days 11 and 30, in 255 (42.8%) between days 31 and 60, and in 206 (34.6%) between days 61 and 170. Treatment with chemotherapeutic agents was required in 142 (19.2%) of the 738 patients; 125 (16.9%) of these had invasive mole (107 nonmetastatic and 18 metastatic) and 17 (2.3%) had choriocarcinoma (13 nonmetastatic and four metastatic). All 596 patients whose hCG titers declined spontaneously to normal levels have remained well and free of disease. All 142 treated patients experienced permanent remission. Thus, all 738 patients are well and free of disease 4 to 18 years after evacuation of the hydatidiform mole. The follow-up regimen described in this report furnishes information on natural history of molar pregnancies after evacuation and provides an excellent means by which all patients can be safely managed following termination of a hydatidiform mole.

Uterine Arteriovenous Malformations: Primary Treatment with Therapeutic Embolization

Uterine arteriovenous malformations are rare lesions that can cause massive vaginal bleeding and spontaneous abortions. The majority are either congenital or related to gestational trophoblastic disease. Hysterectomy has been the treatment with symptomatic uterine arteriovenous malformations by means of transcatheter embolization; three of the lesions were related to gestational trophoblastic disease and one was congenital. All were supplied by the uterine arteries that were subselectively embolized with particulate material. This resulted in prompt cessation of uterine hemorrhage. There were no complications, and one pregnancy was achieved. The three other women have normal menstruation and no recurrence of bleeding at follow-up 10-48 months after treatment. On the basis of this experience and that of others, embolotherapy should be the treatment of first choice in these lesions, as it appears safe and effective. Additionally, uterine function is preserved in patients who are usually reproductively active.

Defining the Interaction of HIV-1 with the Mucosal Barriers of the Female Reproductive Tract

ABSTRACT Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4+ target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection.

Tumor size in endometrial cancer

Tumor size was determined in 142 patients with clinical Stage I endometrial cancer treated primarily by total abdominal hysterectomy, bilateral salpingo‐oophorectomy, and lymph node biopsies between July 1979 and August 1988. Only 4% of patients with tumor size less than or equal to 2 cm had lymph node metastasis; this increased to 15% for tumors more than 2 cm and increased further to 35% when the entire uterine cavity was involved (multivariate P = 0.01). Five‐year survival was 98% for patients with tumors less than or equal to 2 cm, 84% with tumors more than 2 cm, and 64% with tumors involving the whole uterine cavity (Mantel‐Cox P = 0.005). For endometrial cancer patients with Grade 2 tumors and less than one‐half myometrial invasion, the risk of lymph node metastasis is often considered too low to justify adjuvant pelvic radiation therapy. This intermediate‐risk group is better defined by including tumor size as a prognostic factor. For this subgroup (Grade 2, less than one‐half endometrial invasion) there were no lymph node metastasis associated with tumors less than 2 cm, but 18% had nodal disease when tumors were larger than 2 cm. Tumor size is an important prognostic factor that is particularly helpful in directing adjuvant radiation therapy in patients without staging lymph node biopsies.

Familial ovarian cancer.

Abstract A family with epithelial ovarian carcinoma occurring in five members spanning three generations is presented. The pattern of appearance of the malignancies in this family is consistent with autosomal dominant transmission. The literature relating to familial ovarian cancer is reviewed and the management of women at risk for the development of ovarian cancer in these families is discussed.

Single-agent methotrexate chemotherapy for the treatment of nonmetastatic gestational trophoblastic tumors☆☆☆

OBJECTIVE Our purpose was to evaluate the efficacy and toxicity of single-agent methotrexate chemotherapy and to identify factors associated with chemotherapy resistance in patients with nonmetastatic gestational trophoblastic tumors. STUDY DESIGN A total of 337 patients with nonmetastatic gestational trophoblastic tumors (choriocarcinoma and invasive mole) received treatment at the Brewer Trophoblastic Disease Center of Northwestern University Medical School from 1962 through 1990. Of the 337 patients, 253 (75.0%) were treated initially with single-agent methotrexate 0.4 mg/kg intravenously daily for 5 days per treatment course repeated every 14 days. RESULTS All 337 patients with nonmetastatic gestational trophoblastic tumors were cured. Of the 253 patients initially treated with methotrexate, resistance developed in 27 (10.7%), 22 (8.7%) required a second agent (actinomycin D), 3 (1.2%) required multiagent chemotherapy, and 2 (0.8%) had a hysterectomy to achieve complete remission. Factors associated with the development of resistance were pretreatment human chorionic gonadotropin level > or = 50,000 mlU/ml (36%, p < 0.001), nonmolar antecedent pregnancy (26%, p < 0.02), and clinicopathologic diagnosis of choriocarcinoma (20.5%, p = 0.02). Significant methotrexate toxicity requiring a change to a second agent occurred in only 12 patients (4.7%), the most common side effect being severe stomatitis. CONCLUSIONS In a large series of patients with nonmetastatic gestational trophoblastic disease, single-agent methotrexate chemotherapy proved to be an extremely well-tolerated and effective treatment.

Treatment of low-risk metastatic gestational trophoblastic tumors with single-agent chemotherapy

OBJECTIVE Our purpose was to evaluate the efficacy and toxicity of single-agent chemotherapy and to identify risk factors associated with chemotherapy resistance in the treatment of low-risk metastatic gestational trophoblastic tumors. STUDY DESIGN We reviewed the records of all patients with gestational trophoblastic tumors treated with single-agent chemotherapy at the John I. Brewer Trophoblastic Disease Center of Northwestern University between 1962 and 1992. A total of 92 patients with low-risk metastatic gestational trophoblastic tumors by National Cancer Institute criteria were identified. Patients received methotrexate (n = 61), actinomycin D (n = 4), alternating methotrexate and actinomycin D (n = 5), or hysterectomy with methotrexate (n = 20) or actinomycin D (n = 2). RESULTS All 92 patients with low-risk metastatic gestational trophoblastic tumors were cured. Primary remission was achieved with initial single-agent therapy in 62 patients (67.4%). A second sequential single agent was used because of drug resistance in 20 patients (21.7%) or drug toxicity in 10 patients (10.9%). Only one patient (1%) needed multiagent chemotherapy to be cured. Adjuvant hysterectomy was performed in 22 patients (23.9%). Surgery was not required to remove resistant tumor foci. Chemotherapy toxicity, most commonly stomatitis, occurred in 36 patients (39.1%), but none of these effects was life threatening. Large vaginal metastasis was the only identifiable factor significantly associated with failure of initial single-agent chemotherapy (p = 0.03). CONCLUSION In this large series of patients with low-risk metastatic gestational trophoblastic tumors, sequential single-agent chemotherapy with methotrexate and actinomycin D provided safe and extremely effective treatment.