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E I Kohorn

Publications and source records attributed to E I Kohorn.

At least 19 recordsLinked to original sources
PubMed2001

Serum levels of macrophage colony-stimulating factor in trophoblastic disease.

OBJECTIVES: The aims of this study were to measure levels of colony stimulating factor (CSF-1) in patients with trophoblastic disease, to determine whether such measurement may be useful to supplement measurement of the prognostically reliable human chorionic gonadotrophin (hCG), and to assess whether measurement of CSF-1 may be helpful in predicting requirement for chemotherapy in patients with hydatidiform mole. METHODS: Serial weekly serum samples were selected for CSF-1 assay from representative diagnostic groups of patients with trophoblastic disease: hydatidiform-mole with spontaneous resolution, low-risk post-hydatidiform-mole trophoblastic tumor, partial hydatidiform mole, high-risk metastatic gestational trophoblastic tumor, primary ovarian choriocarcinoma, and placental site trophoblastic tumor. hCG was measured by an in-house radioimmunoassay that measures all parts of the hCG molecule. CSF-1 was measured by radioimmunoassay with (125)I-labeled recombinant CSF-1. The upper level of normal CSF-1 was taken as 8 ng/ml. RESULTS: In this study of 45 patients with trophoblastic disease, some very high levels of CSF-1 were encountered. In a few patients there was dramatic correlation with hCG. Generally, however, CSF-1 and hCG did not correlate. CSF-1 was frequently not elevated when hCG was still significantly elevated and conversely CSF-1 was elevated when hCG was negative. CONCLUSION: The measurement of CSF-1 does not appear to be useful in managing trophoblastic disease as it does not correlate with the level of hCG. Occasionally, high levels of CSF-1 were found in patients with trophoblastic disease.

Adolescent↗
PubMed2000

Measurement of CA-125 in trophoblastic disease.

OBJECTIVES: Physicians treating hydatidiform mole are still seeking means of identifying those patients who will require chemotherapy. The standard accepted method is to follow human chorionic gonadotropin levels but CA-125 measurement has been suggested as a supplement that may be clinically useful. This study was undertaken to validate or refute the one previous study that addresses this issue. CA-125 was measured at the time of hydatidiform mole evacuation to determine (1) whether it would predict the need for chemotherapy and (2) whether it correlated with human chorionic gonadotropin and tumor load in following patients with hydatidiform mole and metastatic gestational trophoblastic disease. PATIENTS AND METHODS: CA-125 was measured in serial weekly samples selected from diagnostic groups of patients with trophoblastic disease. Sixteen patients had hydatidiform mole with spontaneous resolution, fourteen had nonmetastatic gestational trophoblastic tumor, and four had low-risk metastatic disease. Six patients had high-risk metastatic disease. Ten patients had partial hydatidiform mole and one of these required chemotherapy. One patient had primary ovarian choriocarcinoma and three had placental site tumor. RESULTS: The mean preevacuation CA-125 among the 15 patients with complete hydatidiform mole was 40.9 U/ml: 52.5 U/ml for 5 patients who required chemotherapy and 36.2 U/ml for 10 patients who did not require chemotherapy. There was no statistical difference between these values. There was no correlation of CA-125 with hCG. Frequently CA-125 became negative when hCG was still elevated. Among six patients with high-risk disease, CA-125 was elevated in four but in all six patients hCG remained elevated when CA-125 became negative. In nine patients with partial hydatidiform mole CA-125 was elevated prior to mole evacuation and then became negative. The patient with a tetraploid conceptus who required chemotherapy had negative CA-125. With placental site tumor CA-125 was negative, but it was elevated with ovarian choriocarcinoma. CONCLUSION: CA-125 levels do not provide reliable information in the management of patients with gestational trophoblastic disease.

Adult↗
PubMed1999

Oral contraceptive use and risk of gestational trophoblastic tumors.

BACKGROUND: Gestational trophoblastic disease refers to a spectrum of rare benign and malignant gynecologic disorders whose pathogenesis is not well understood. Recent studies from China and the United States have raised the hypothesis that long-term use of oral contraceptives before conception may increase the risk of gestational trophoblastic tumors. A multicenter case-control study of gestational trophoblastic tumors was undertaken to test this hypothesis. METHODS: Telephone interviews were conducted with 235 case patients, including 50 with gestational choriocarcinoma, and 413 control subjects matched on recentness of pregnancy, age at pregnancy, and area of residence. Relative risks (odds ratios) were computed by conditional logistic regression. Reported P values are two-sided. RESULTS: The relative risk estimate for ever having used oral contraceptives before the index pregnancy was 1.9 (95% confidence interval [CI] = 1.2-3.0), and the risk increased with duration of use (P for trend = .05). The estimate was highest for women who used oral contraceptives during the cycle in which they became pregnant (relative risk = 4.0; 95% CI=1.6-10), but there was no consistent pattern according to the time interval since last use. Separate analyses of choriocarcinoma and persistent mole yielded similar results, i.e., the relative risk estimates for oral contraceptive use were 2.2 (95% CI=0.8-6.4) and 1.8 (95% CI=1.0-3.0), respectively. Control for the number of sexual partners, which was independently associated with risk (P for trend = .05), did not materially change the results. CONCLUSIONS: This study, the largest to date, indicates that long duration of oral contraceptive use before conception increases the risk of gestational trophoblastic tumors. These findings may provide clues to the pathogenesis of this rare disease. Changes in use of oral contraceptives are not warranted, however, because the incidence attributable to oral contraceptive use is very low.

Adult↗
PubMed1999

Neoadjuvant chemotherapy for advanced ovarian cancer: long-term survival.

PURPOSE: The aim of this study was to compare the progression-free and overall survivals of women with advanced ovarian cancer treated with neoadjuvant chemotherapy followed by surgery with those treated conventionally with cytoreductive surgery followed by cytotoxic chemotherapy. MATERIALS AND METHODS: Fifty-nine consecutive women with advanced malignancies compatible with ovarian cancer based on (1) physical examinations, (2) computerized tomography scans, and (3) cytologic or histologic specimens and treated with platinum-based combination chemotherapy, i.e., neoadjuvant chemotherapy, were retrospectively reviewed. Forty-one subsequently underwent cytoreductive surgery. Their overall and progression-free survivals were compared to those of 206 consecutive women with Stage IIIC and IV epithelial ovarian cancers treated with conventional cytoreductive surgery followed by platinum-based combination chemotherapy during the same era. RESULTS: No statistical difference was observed in overall survival (P = 0.1578) or in progression-free survival between the group treated with neoadjuvant chemotherapy and the conventionally treated group (P = 0.5327) despite the neoadjuvant chemotherapy patients being statistically older (median age 67 years [range 44 to 85 years] vs a median age of 60 years [range 19 to 79 years] for conventionally treated patients; P < 0. 001) and having a statistically poorer performance status (P < 0. 001) than the conventionally treated group. Women undergoing cytoreductive surgery following neoadjuvant chemotherapy had a statistically improved overall survival (P < 0.0001) compared to those who did not undergo surgery. CONCLUSIONS: Neoadjuvant chemotherapy does not compromise the survival of women treated for advanced ovarian cancer. Prospective randomized trials comparing neoadjuvant chemotherapy to conventional therapy to determine quality of life experiences and cost/benefit outcomes are now appropriate for women presenting with advanced ovarian cancer.

Adult↗
PubMed1999

Adenocarcinoma in situ of the cervix: management and outcome.

OBJECTIVE: The aim of this study was to review the management and outcome of patients with adenocarcinoma in situ of the cervix and to evaluate the significance of endocervical cone margin status in these patients. METHODS: A retrospective review of records between January 1988 and December 1996 identified 40 patients with adenocarcinoma in situ on cone biopsy for whom complete information was available. The median follow-up was 38 months. RESULTS: The mean age was 37 years, and the mean parity was 1.3. Fifty-three percent of the patients had prior abnormal cervical cytology. The initial Pap smear that led to the patient's referral was abnormal in 39 (98%). Initial cervical biopsies showed adenocarcinoma in situ and/or glandular dysplasia in 28 (70%), squamous dysplasia in 2 (5%), chronic inflammation in 2 (5%), and no pathologic changes in 2 (5%) patients. Initially no biopsies were performed in 3 (7.5%) patients and the results of 3 (7.5%) biopsies were unknown. Subsequently, all patients had cone biopsies. The endocervical margins were positive for glandular abnormalities in 24% of cold knife cones (CKC), 75% of LEEPs, and 57% of laser cones. The ectocervical margins were positive for squamous and/or glandular abnormalities in 8% of CKCs, 13% of LEEPs, and 57% of laser cones. ECCs above the cone were obtained in 28 patients, and only 1 (3%) was positive. The definitive treatment was hysterectomy in 27, repeat cone in 5, and no additional therapy in 8 patients. The pathology showed residual disease in 44% of treated patients. From 16 cone biopsies with negative margins who had subsequent treatment, there was residual disease in 5 (31%) specimens (1 adenocarcinoma in situ, 1 mild glandular dysplasia, 3 glandular atypia). From 16 cones with positive margins who had subsequent treatment, there was residual disease in 9 (56%) specimens. The patients with negative ECCs above the cone regardless of margin status had residual disease in 58% of treated specimens. CONCLUSION: Women with adenocarcinoma in situ of the uterine cervix had residual disease in 31% of cases with negative margins in cone biopsies and/or with negative ECCs and in 56% of cases with positive endocervical margins. LEEP cones had higher rate of positive endocervical margins (75%) compared to CKC (24%) and laser cone (57%). If maintaining reproductive capacity is desired, we would recommend CKC; however, this does not guarantee absence of the disease.

Adenocarcinoma↗
PubMed1998

CA 125 may not reflect disease status in patients with uterine serous carcinoma.

BACKGROUND: Although CA 125 level correlates with response to therapy in patients with serous carcinoma of the ovary, the utility of CA 125 in patients with high risk or metastatic endometrial carcinoma has not been established. METHODS: CA 125 was tested as a marker of disease status in patients with endometrial serous carcinoma (SC) undergoing adjuvant chemotherapy. All patients received monthly intravenous chemotherapy with cisplatin, cyclophosphamide, and doxorubicin at standard doses (median number of courses, 6; range, 2-8 courses). Serum CA 125 was measured at diagnosis and before each course. After the completion of chemotherapy, patients were examined every 3 months and the CA 125 level was measured. RESULTS: A total of 220 serum specimens from 15 patients with invasive SC were analyzed. All five patients who died of disease had clinical or radiographic evidence of tumor, which CA 125 elevation did not precede or predict. One patient with advanced disease at staging never had an elevated CA 125 level but died of disseminated disease 14 months after diagnosis. At last follow-up, 3 patients who were without evidence of disease > 36 months from diagnosis had significant false-positive elevations in their CA 125 level (>50 u/mL) lasting 1, 2, and 4 months, respectively, during therapy. The sensitivity for advanced disease was only 57% at presentation. CONCLUSIONS: CA 125 may reflect advanced stage disease and portend a poor prognosis, but may not add information to that gained by history and physical examination, preoperative studies, or surgery that already is mandated by this high risk histology. This circulating marker appears to have limited utility in monitoring the effects of adjuvant therapy for SC, and may not predict recurrence in the absence of other clinical findings.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Effective treatment of stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy.

PURPOSE: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC. METHODS AND MATERIALS: This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using 226Ra or 137Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using 192Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy. RESULTS: The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94% (18 patients). The 5-year actuarial OS for Stage I UPSC patients treated with HDR vaginal apex brachytherapy and chemotherapy who underwent complete surgical staging was 100% (15 patients). The 5-year actuarial OS for the 20 Stage I UPSC patients treated with combinations of pre- and postoperative LDR brachytherapy and postop WART was 65%. None of the 6 surgically staged UPSC patients treated with LDR radiation and WART/WPRT developed recurrent disease. For patients with FIGO Stage IA, IB, and IC UPSC who underwent complete surgical staging, the 5-year actuarial DFS by depth of myometrial invasion was 100, 71, and 40%, respectively (p = 0.006). The overall salvage rate for local and distant recurrence was 0%. Complications following HDR vaginal apex brachytherapy included only Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicity in 16% of patients. However, complications from patients treated with WART/WPRT, and/or LDR brachytherapy, included RTOG grade 3 and 4 toxicity in 15% of patients. CONCLUSION: Patients with UPSC should undergo complete surgical staging, and completely surgically staged FIGO Stage I UPSC patients can be effectively and safely treated with HDR vaginal apex brachytherapy and chemotherapy. Both OS and DFS of patients with UPSC are dependent on depth of myometrial invasion. The salvage rate for both local and distant UPSC recurrences is extremely poor. Complications from HDR vaginal apex brachytherapy were minimal.

Adult↗
PubMed1998

Necrosis of myometrial choriocarcinoma with fulminating sepsis complicating chemotherapy for trophoblastic tumor.

We report a patient who developed metastatic gestational choriocarcinoma following delivery of a normal, healthy child that, however, was anemic and required blood transfusion. The patient developed secondary postpartum hemorrhage over a period of several weeks and required curettage and myometrial contractants to control the bleeding. At the time of diagnosis the patient had extensive pulmonary metastases and ultrasound showed full penetration of the myometrium by tumor. Immediately following the second course of chemotherapy with etoposide, methotrexate, and actinomycin D, alternating with cyclophosphamide and vincristine, the patient developed sepsis associated with a uteroperitoneal fistula and required hysterectomy. The sepsis was associated with disseminated intravascular coagulopathy and adult respiratory distress syndrome. However, the patient's tumor was exquisitely sensitive to chemotherapy and with good intensive care unit support and chemotherapy the survived without residual scar except for the loss of reproductive function. There are two lessons to be learned from these events: (1) The syndrome of secondary postpartum hemorrhage with a fetus that is anemic spells a diagnosis of choriocarcinoma; and (2) color Doppler flow vaginal ultrasound performed at the time of presentation of trophoblastic tumors may be useful to show full penetration of the myometrium by tumor which may be a warning of possible scar rupture in a subsequent pregnancy.

Adult↗
PubMed1998

Nonmetastatic gestational trophoblastic neoplasia. Role of ultrasonography and magnetic resonance imaging.

OBJECTIVE: To determine whether routine imaging using grey-scale ultrasound, pulse and color Doppler flow, endovaginal ultrasound and magnetic resonance imaging (MRI) provide information that significantly helps determine therapy in patients with nonmetastatic gestational trophoblastic disease. STUDY DESIGN: A literature search was performed to seek all publications in English and German that reported on investigations of imaging by ultrasound and MRI in patients with a diagnosis of trophoblastic tumor without evidence of metastases. Studies performed to make a diagnosis of hydatidiform mole were excluded. Included were studies that investigated the clinical usefulness and efficacy of these imaging methods in the diagnosis of invasive mole as a visual confirmation of the diagnosis based on human chorionic gonadotropin (hCG) and histology. Furthermore, the usefulness and efficiency of imaging in determining the effectiveness of chemotherapy were investigated. RESULTS: Analysis of these reports showed that lesions are detectable by imaging modalities at relatively high levels of hCG but may not be visualized at lower levels of hCG, when chemotherapy is nevertheless indicated and the diagnosis of neoplasia is fully justified. Moreover, myometrial lesions have been observed by MRI in patients who subsequently achieved spontaneous resolution of their disease without chemotherapy. At lower levels of hCG (< 700 mIU/mL), intramyometrial lesions may not be visualized by either ultrasound or MRI. Myometrial abnormalities may persist with resolution of the tumor. Thus, the sensitivity of either method is no better than 70% and the specificity is even lower. CONCLUSION: Weekly serial levels of serum hCG remain the most accurate, reliable and definitive arbiter of treatment management. Pelvic ultrasound or MRI need not be an integral part of pretreatment assessment. Imaging techniques are expensive yet not decisive in managing nonmetastatic trophoblastic disease. This finding applies to nonmetastatic disease only. With metastases, ultrasound, MRI and computed tomography do play an integral role in diagnosis, staging and management.

Chorionic Gonadotropin↗
PubMed1998

Staging and assessing trophoblastic tumors. A possible solution to an intractable problem.

The present situation of staging gestational trophoblastic tumors by the system of the International Federation of Obstetrics and Gynecology (FIGO) and of scoring systems of risk factors in such tumors is examined critically. A solution for resolving staging and scoring difficulties is offered by combining the present FIGO staging with the accepted standardized World Health Organization system.

Adult↗
PubMed1997

Pharmacokinetic and phase I trial of intraperitoneal carboplatin and cyclosporine in refractory ovarian cancer patients.

PURPOSE: The feasibility and pharmacokinetics of cyclosporine (CsA) delivered intraperitoneally (IP) have not been previously explored. We performed a pharmacokinetic study of IP CsA followed by a phase I dose-escalation trial of the combination of IP CsA and carboplatin in refractory ovarian cancer patients. PATIENTS AND METHODS: A pilot study was performed of three patients who received 1, 10, and 20 mg/kg IP CsA alone. Subsequently, a phase I trial of 35 patients was performed between April 1990 and April 1993. Whole-blood and IP fluid CsA concentrations were measured at serial time points. The highest dose delivered IP was 34.6 mg CsA/kg in combination with carboplatin (250 mg/m2 or 300 mg/m2, depending on creatinine clearance), which was not dose-escalated. The area under the concentration-time curve (AUC) for CsA and half-life (T1/2) were calculated. Objective and serologic responses were noted, and toxicity was graded using the National Cancer Institute common toxicity criteria. RESULTS: The feasibility of delivering IP CsA alone was established. We observed a 1,000:1 ratio between IP fluid and blood concentrations at 20 mg CsA/kg. Pharmacokinetic analysis confirmed that at 20 mg CsA/kg, there was an IP fluid-to-blood AUC ratio of 600:1 in favor of peritoneal exposure. At the highest dose delivered, 34.6 mg CsA/kg, the mean IP CsA levels of 1,110 micrograms/ mL were tolerated moderately well and the IP fluid-to-blood ratio of 1,000:1 was maintained. Blood and IP CsA concentrations were analyzed in the presence and absence of IP carboplatin. At 20 mg CsA/kg, there was no difference in either mean blood CsA levels (0.9 microgram/ mL) or mean IP CsA concentrations (1,000 micrograms/mL) obtained in the absence or presence of carboplatin. The most common toxicity in the phase I study was anemia, seen in 66% of patients. Common toxicities at the maximum CsA dose delivered (34.6 mg/kg) were anemia, leukopenia, thrombocytopenia, and hypertension. In this trial, three objective responses (two complete and one partial) were observed for a duration of 3 to 11 months. Control of platinum-resistant ascites was an important feature, noted in five of eight patients. CONCLUSION: We have established the feasibility of delivering IP CsA up to doses of 34.6 mg/kg in conjunction with carboplatin, and the sustaining of IP fluid to blood ratios of 1,000:1. The IP administration of CsA resulted in a favorable ratio of exposure for the peritoneal cavity compared with systemic exposure, indicating a therapeutic advantage of this approach with a significant decrease in systemic toxicity. We recommend that 34.6 mg/ kg of IP CsA be tested as a phase II dose in combination with carboplatin in refractory ovarian cancer patients. This report provides the groundwork for future studies using IP CsA, both as a chemomodulator of platinum and of multidrug resistance.

Antineoplastic Agents↗
PubMed1996

Malignant uterine smooth muscle tumors: role of etoposide, cisplatin, and doxorubicin (EPA) chemotherapy.

BACKGROUND: Nearly 80% of patients with malignant uterine smooth muscle tumor will suffer local relapse and/or distant metastases after initial surgical resection. There is no convincing evidence that the addition of pelvic radiation improves the outcome. However, adjuvant chemotherapy might be an appropriate therapeutic modality. METHODS: Between 1986 and 1991, 13 consecutive patients with malignant uterine smooth muscle tumors were treated at Yale-New Haven Hospital with a combination chemotherapy containing etoposide 100 mg/M2 on days 1 and 2, cisplatin 50 mg/M2 on day 1, and doxorubicin 50 mg/M2 on day 1, repeated every 28 days. Six patients had Stage I disease, one patient had Stage III disease, and six patients had Stage IV disease. The number of cycles ranged from 2 to 9. RESULTS: The median follow-up was 30 months (range 4-81). The mean overall survival for the group was 43.1 +/- 6.7 months, with the progression-free interval of 25.5 +/- 8.0 months. Of the seven patients with evaluable disease, one patient had complete response and one had partial response (total response rate of 28.6%). Of the six patients treated adjuvantly, three recurred at 9, 33, and 59 months (recurrence rate of 50%). CONCLUSIONS: We conclude that this combination has only modest activity against malignant uterine smooth muscle tumors at the schedule and doses tested.

Adult↗
PubMed1996

Uterine papillary serous carcinoma treated with intraperitoneal cisplatin and intravenous doxorubicin and cyclophosphamide.

This study was designed to evaluate the efficacy of intraperitoneal cisplatin and intravenous doxorubicin and cyclophosphamide in patients with uterine papillary serous carcinoma. Sixteen patients with uterine papillary serous carcinoma underwent complete surgical staging and placement of an intraperitoneal port. Postoperatively, they received cisplatin (100 mg/m2) given intraperitoneally and doxorubicin (50 mg/m2) intravenously and cyclophosphamide (600 mg/m2) intravenously every 4 weeks for 6 cycles. The intraperitoneal ports did not function in 3 patients immediately following surgery. The remaining 13 patients constitute the study group. The patients ranged in age from 37 to 77 years. There were 1 patient with Stage IA, 3 with Stage IB, 2 with Stage IIB, 2 with Stage IIIA, 2 with Stage IIIC, 1 with Stage IVA, and 2 with Stage IVB. At the end of surgery no gross residual disease remained except for 1 patient who had less than 1-cm nodules in the peritoneal cavity. Eleven of the patients underwent 6 cycles of chemotherapy, 1 patient underwent 3 cycles, and 1 patient underwent 1 cycle. A total of 71 cycles of chemotherapy were given. All patients developed alopecia. Two patients developed neutropenic fever, one was treated with antibiotics, the other patient died from urosepsis. One patient had a > 15% decrease in left ventricular ejection fraction which led to a dose reduction of doxorubicin. One patient had a urinary tract infection and one patient developed a port infection which necessitated its removal. Seven patients have died, 1 is alive with disease, and 5 patients are alive with no evidence of disease. Five of the 7 patients with extrauterine disease have died of disease. One is alive with disease and the other is free of disease. The media survival of these patients was 34 months with an overall 3 years survival of only 24.1%. Although the protocol was reasonably well tolerated, the overall survival did not differ from that of a similar group of patients treated at our institution with intravenous chemotherapy. There was a high incidence of dysfunction of the intraperitoneal ports (25%). This approach with intraperitoneal cisplatin presents no therapeutic advantage for these patients.

Adult↗