Biomedical subjects
Publications and source records attributed to J R Lurain.
Recurrent vaginal clear cell adenocarcinoma was diagnosed in two DES-exposed patients 17 and 19 years after initial therapy. These cases demonstrate the need for continued clinical evaluation, since patients with clear cell carcinoma of the vagina seem to be at greater risk for developing late recurrences than patients with squamous cell carcinomas.
The majority (60-70%) of endometrial cancers express estrogen receptor. Typically, estrogen-receptor-positive endometrial tumors are associated with a more favorable outcome. Despite this, there is often a discrepancy between estrogen receptor expression and clinical outcome of the disease. Although little is known about the exact role of the estrogen receptor in endometrial malignancies, in breast cancer, where such information is abundant, a number of mutations of the estrogen receptor have been identified. To investigate whether mutations of the estrogen receptor gene occur in endometrial cancers we performed single-stranded conformational polymorphism analysis (SSCP) on 35 human endometrial tumors. We detected four point mutations in three different patients. Interestingly, all the mutations were detected in patients who had aggressive endometrial tumors (grade 3). Although we found the incidence of mutations of the estrogen receptor to be low (8.5%) and thus unlikely to be associated with the majority of endometrial cancers, further investigation is needed to elucidate the role of aberrant estrogen receptor expression in the progression of endometrial malignancies.
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.
OBJECTIVE: We tested whether serum pregnancy-associated major basic protein levels distinguish between benign and malignant trophoblastic disease. STUDY DESIGN: We compared serum pregnancy-associated major basic protein levels in seven patient groups: nonpregnant and pregnant controls, partial moles, complete moles, persistent moles, placental-site trophoblastic tumors, and choriocarcinoma. RESULTS: The results showed that patients with partial and complete moles had elevated serum pregnancy-associated major basic protein levels comparable to normal pregnancy. In contrast, patients with persistent mole, placental-site trophoblastic tumors and choriocarcinoma had low median serum levels comparable to those of the nonpregnant controls. Significant differences were shown between the complete and persistent mole groups (p = 0.0001) and between the complete mole group and the choriocarcinoma group (p = 0.0001); however, persistent moles were indistinguishable from choriocarcinoma (p = 0.2010). CONCLUSION: Serum pregnancy-associated major basic protein levels thus distinguish between benign disorders, such as pregnancy and partial and complete moles, and trophoblastic tumors, such as persistent moles and choriocarcinoma. The absence of elevated serum levels of pregnancy-associated major basic protein may be useful clinically to indicate a more aggressive or frankly malignant tumor.
PURPOSE: To evaluate clinical characteristics, treatment technique, and results in patients with gestational trophoblastic disease metastatic to the brain. MATERIALS AND METHODS: From 1962 to 1994, 26 (4.1%) of 631 patients who underwent treatment for trophoblastic disease had or developed evidence of brain metastases (patients were aged 14-43 years). All patients received multiagent systemic chemotherapy and whole-brain irradiation. Total doses of radiation were 2,386-4,000 cGy (200-300 cGy per fraction). No patient received intrathecal chemotherapy. Patients were divided into three groups: group A, symptomatic brain metastases at presentation; group B, asymptomatic or minimally symptomatic brain disease at presentation; and group C, development of brain metastases during systemic chemotherapy. RESULTS: The overall 5-year actuarial survival rate was 51%. Multivariate analysis findings indicated that age, preceding pregnancy event, human chorionic gonadotropin level, World Health Organization score, performance of craniotomy, and number of brain metastases did not influence survival. The difference in the 5-year overall survival rates between groups A (39%) and B (100%) was significant (P = .03). CONCLUSION: Gestational trophoblastic disease metastatic to the brain is curable with systemic chemotherapy and whole-brain irradiation. The authors suggest treatment with steroids, chemotherapy (etoposide, high-dose methotrexate [1 g/m2], dactinomycin, cyclophosphamide, and vincristine sulfate), and concurrent whole-brain irradiation (3,000 cGy in 200-cGy fractions).
BACKGROUND: To our knowledge, giant lymph node hyperplasia (Castleman disease) may present as a pelvic mass on magnetic resonance imaging (MRI). CASE: A postmenopausal woman with rapidly enlarging leiomyoma uteri was found to have a suspicious left adnexal mass mimicking an ovarian neoplasm on preoperative MRI. At laparotomy, the suspected uterus and normal ovaries were extirpated. In addition, a firm, 4 x 8-cm solid mass within the sigmoid colon mesentery was found and resected. The final histologic diagnosis was Castleman disease. CONCLUSION: Entities such as Castleman disease should be considered when assessing a pelvic mass. Characterization of the origin of pelvic masses can often be difficult, despite sophisticated diagnostic imaging studies such as MRI.
BACKGROUND: Ovarian failure is common after pelvic irradiation and is dependent upon radiation dose and patient age. This case report demonstrates the resumption of ovulation and pregnancy subsequent to this diagnosis. CASE: An enlarging abdominal mass was noted in a 28-year-old female 20 months after resection of a pelvic hemangiopericytoma. She had received postoperative adjuvant hemipelvic radiotherapy and subsequently developed amenorrhea and symptoms of hypoestrogenism. Serum follicle-stimulating hormone (FSH) was elevated. In light of the diagnosis of ovarian failure, the finding of an intrauterine pregnancy on an abdominal computed tomography scout film, performed to rule out a recurrence of the primary tumor, was unexpected. CONCLUSION: While amenorrhea and elevation in serum gonadotropin levels are common after pelvic irradiation, the clinician must be cognizant of the potential for resumption of ovulation after radiotherapy. The diagnosis of ovarian failure should be based on more than a single serum FSH level. Further, radiation changes in the endometrium and myometrium as well as in uterine blood flow may have an adverse effect on pregnancy outcome. We suspect these effects had an etiologic influence on the fetal growth retardation in this pregnancy.
The purpose of this study was to assess the ability of cytology to predict the results of colposcopically directed cervical biopsies in HIV-infected women. We performed a case-control study of 52 HIV(+), 31% of whom had AIDS, and 57 HIV(-) women referred to two tertiary care centers for colposcopy from July 1991 to November 1993. All 57 HIV(-) controls and 27 HIV (+) cases underwent colposcopy for evaluation of an abnormal Pap smear. The remaining HIV(+) cases (n = 25) had colposcopy as part of their routine assessment. In women with abnormal Pap smears, colposcopic biopsy agreed with the Pap smear results in 83% of 24 HIV(+) women and 65% of 37 controls (chi 2; P = 0.34). For patients with low-grade SIL on Pap smear, 14% of HIV(+) and 11% of HIV(-) women had moderate or severe dysplasia on biopsy (P = 0.52). The positive predictive value of an abnormal Pap smear was 96% in HIV(+) women vs 78% in noninfected patients (P = 0.05). In the overall series of 52 HIV(+) women, the Pap smear did not match the biopsy in 44% of patients and was less severe than the cervical biopsy results in 91% of these mismatches. The Pap smear had a sensitivity of 57%, a specificity of 92%, a positive predictive value of 96%, and a negative predictive value of 39%, when compared to biopsy results in HIV-seropositive patients. Pap smears missed 43% of biopsy-proven intraepithelial lesions in this series of HIV (+) women. However, when abnormal, the Pap smear was no worse in predicting the presence and degree of an intraepithelial lesion in HIV(+) women than in noninfected women. These characteristics may justify immediate treatment of HIV(+) women at the time of colposcopy after an abnormal Pap smear given its high positive predictive value.
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.
Three patients with cervical carcinoma underwent laparoscopic descending colostomy. The indications for colostomy included severe radiation proctitis, enterovaginal fistula secondary to progressive pelvic tumor, and large bowel obstruction from progressive pelvic tumor. Two patients were treated with laparoscopic descending end colostomy with creation of a Hartman's pouch, and the third patient underwent laparoscopic descending loop colostomy. The techniques utilized are discussed.
Aggressive multimodality therapy with an appropriate combination of chemotherapy and adjuvant radiotherapy and surgery has resulted in a cure for most patients with high-risk, metastatic gestational trophoblastic tumors. The EMA-CO chemotherapy regimen, employing etoposide, high-dose methotrexate, actinomycin D, cyclophosphamide and vincristine, is highly effective and well tolerated. Complete response rates of 80-94% and survival rates of 82-100% have been reported. For patients with central nervous system metastases, whole brain irradiation is given simultaneously with the initiation of combination chemotherapy employing a high-dose methotrexate infusion. Surgical procedures, especially hysterectomy and thoracotomy, may be useful for the purpose of removing known foci of chemotherapy-resistant disease. Subsequent salvage chemotherapy with cisplatin and bleomycin in combination with etoposide will result in a cure for almost all patients. The factors that are most important in determining response to treatment in patients with metastatic, high-risk disease are metastases to sites other than the lung and vagina, more than eight metastases, previous failed chemotherapy and a World Health Organization score > or = 8.
Twenty-one (8%) of 264 consecutive evaluable patients with clinical stage 1 endometrial carcinoma had histologic evidence of pelvic and/or para-aortic lymph node metastases. DNA flow cytometry was performed on both the primary tumor and nodal metastasis. Seventeen of 21 sets could be analyzed. Overall, 11 (65%) of the primary carcinomas were aneuploid. Nine of 17 (53%) had consistent ploidy patterns when the primary tumor and lymphatic metastasis were compared. The remaining 8 (47%) had aneuploid primaries with diploid nodal metastases. Five (83%) of the 6 patients with diploid primary tumors were alive without evidence of disease compared to 3 of 11 (27%) patients with aneuploid tumors (P < 0.05). Other predictors of disease outcome included tumor histology, lymph vascular space invasion, and depth of myometrial invasion. Ploidy status of the lymphatic metastasis was not important in terms of overall survival. All 8 patients with para-aortic nodal metastases had aneuploid primary carcinomas compared to 4 (44%) of 9 patients with pelvic node involvement only (P < 0.01). Mean survival was 31 months for patients with para-aortic node metastases compared to 51 months for patients with only pelvic node metastases. Comparison of survival curves among these two groups demonstrated a significant survival advantage in patients with regional nodal metastases (P = 0.032). S-phase fraction of both the primary tumor and lymphatic metastasis did not correlate with survival or predict disease outcome. DNA index of the primary tumor, as a continuous variable, was inversely proportional to survival, demonstrating poorer survivorship with incremental increases of DI. Ploidy status of the lymph node metastasis was an inconsistent reflection of the primary tumor's expression and behavior and, therefore, little additional information was gained by knowledge of the lymphatic ploidy status.
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.
OBJECTIVE: To define the role of flow cytometry as a prognostic indicator in early cancers of the uterine cervix. METHODS: Flow cytometry was used to determine ploidy, DNA index, and S-phase fraction on 141 samples from the tumors of 53 women with stage IB cancers of the cervix treated by radical hysterectomy and pelvic lymphadenectomy as primary therapy. Multiple samples of the same tumor were analyzable for 47 (89%) of the subjects. One-way analysis of variance for the multiple samples was used to compare the heterogeneity of flow cytometry data, both within each tumor and between patients. Flow cytometry results, as well as previously described clinical and pathologic prognostic factors, were correlated to recurrence and survival using Cox regression hazard ratios and Kaplan-Meier estimates. RESULTS: We found DNA aneuploidy in 25 (47%) of the cancers, with a mean (+/- standard error) DNA index of 1.52 +/- 0.07. The mean S-phase fraction was 7.6 +/- 0.4% for diploid tumors and 9.2 +/- 0.4% for aneuploid tumors. The cancers from 24 women (45%) were homogeneously diploid, 18 (34%) were consistently aneuploid, and five (9%) had mixed diploid/aneuploid samples. Analysis of variance of the multiple samples for each woman revealed a greater standard deviation (SD) between patients than within any individual tumor for both DNA index (ratio of between SD to within SD 2.1; P < .0001) and S-phase fraction (ratio 1.6; P < .0001). Of the previously described clinical and pathologic prognostic factors, only depth of invasion, expressed as either percent of cervical wall thickness or as thirds, was correlated with recurrence or survival. Neither the DNA index nor S-phase fraction correlated significantly with recurrence or survival. CONCLUSIONS: These results suggest that alterations in the DNA content or proliferative activity of early invasive cancers of the uterine cervix do not reflect biologic behavior in terms of recurrence or survival, and that this behavior is not due to tumor heterogeneity.
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OBJECTIVE: To evaluate the efficacy and toxicity of a regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine in patients with metastatic, high-risk gestational trophoblastic tumors. METHODS: Twelve women with metastatic gestational choriocarcinoma received 64 treatment cycles. All met the National Cancer Institute criteria for high-risk gestational trophoblastic tumors. Response was evaluated by monitoring serial serum beta-hCG levels. Toxicity was recorded using standard World Health Organization criteria. RESULTS: There was no life-threatening toxicity. Neutropenia necessitating a 1-week delay of treatment occurred with only eight treatment cycles (12.5%) and deferral of vincristine and cyclophosphamide with three cycles. Anemia requiring transfusion complicated only two cycles. Peripheral neuropathy in two patients was treated by discontinuing vincristine. Other toxicities included nausea and vomiting, diarrhea, stomatitis, alopecia, conjunctivitis, thrombocytopenia, and fever. Ten of the 12 subjects experienced a complete response. Two had partial responses and one with an initial complete response had relapse 4 months after completing therapy; all three were successfully salvaged with cisplatin-based chemotherapy. Overall survival was 100%, and all 12 patients are disease-free with a median follow-up of 26 months. CONCLUSIONS: Chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine is well tolerated and highly effective for metastatic, high-risk gestational trophoblastic disease.