Biomedical subjects

J T Chambers

Publications and source records attributed to J T Chambers.

At least 19 recordsLinked to original sources

PubMed2005

Endometrial adenocarcinoma presenting in a premenopausal patient with tuberous sclerosis.

BACKGROUND: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. CASE: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. CONCLUSION: Caregivers must pay particular attention to signs and symptoms in non-verbal patients. Persistent irregular bleeding on oral contraceptive therapy warrants additional evaluation.

Adenocarcinoma↗

PubMed2003

Eosinophilia and uterine leiomyosarcoma.

BACKGROUND: Tumor-associated blood eosinophilia and tumor-associated tissue eosinophilia have been described in association with a spectrum of neoplasms. A case of uterine leiomyosarcoma exhibiting both blood and tissue eosinophilia is presented. CASE: A 67-year-old postmenopausal woman was evaluated for a 6-month history of postmenopausal bleeding. An office-based endometrial biopsy yielded atypical mesenchymal tissue with marked eosinophilic infiltrate suspicious for a uterine sarcoma, and the patient was referred to the gynecologic oncology service in a tertiary care hospital. There was evidence of leukocytosis and eosinophilia in preoperative laboratory assessment. The patient underwent an exploratory laparotomy, a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection. Histopathology confirmed a low-grade uterine leiomyosarcoma confined to the uterus. There was extensive infiltration of the tumor with eosinophils. The systemic leukocytosis and the absolute eosinophilia responded to surgical removal of the tumor, with normalization of values in the immediate postoperative period. CONCLUSION: A differential diagnosis of malignancy should be entertained during an evaluation of systemic eosinophilia.

Aged↗

PubMed2002

Low prevalence of abnormal cervical cytology in an institutionalized population with intellectual disability.

BACKGROUND: The present study was designed to determine the prevalence of abnormal cervical cytology in an institutionalized population with intellectual disability. METHOD: A retrospective review of charts for 162 women at a large state-owned facility was performed. Slides from 310 cervical Papanicolau smears were re-screened by a cytotechnologist and then reviewed by a pathologist. RESULTS: The prevalence of abnormal cytology (three out of 162 participants) and biopsy confirmed that the prevalence cervical dysplasia (one out of 310 smears) was low. CONCLUSION: The present preliminary study suggests that further investigation of the optimal interval for cervical cancer screening is warranted in this population.

Cytodiagnosis↗

PubMed2001

The activated macrophage colony-stimulating factor (CSF-1) receptor as a predictor of poor outcome in advanced epithelial ovarian carcinoma.

OBJECTIVE: We have previously shown that the macrophage colony-stimulating factor receptor (CSF-1R) and its ligand, CSF-1, together predict poor prognosis in epithelial ovarian carcinoma. The activated or phosphorylated form of CSF-1R (CSF-1Rphos) has been associated with enhanced invasive and metastatic potential. Our goal is to correlate CSF-1Rphos with known prognostic factors and to determine its role in predicting outcome in advanced ovarian cancer. METHODS: One hundred forty-two primary and forty-seven metastatic epithelial ovarian tumors from 98 patients were immunohistochemically stained using antibodies PY809 and PY723 against their respective tyrosine residues associated with local invasiveness and metastasis. chi2 analysis was used to correlate CSF-1Rphos staining and previously studied prognosticators within each group. Kaplan-Meier curves of survival were comparedusing the log-rank test with significance of P < 0.05. RESULTS: Forty-seven and nine-tenths percent (68/142) of primary tumors and forty-eight and nine-tenths percent (23/47) of metastatic tumors stained positive for PY809 and PY723, respectively. The PY809+ group was strongly associated with CSF-1R (P = 0.015) as was the PY723+ group (P = 0.025) in its respective subset. CSF-1Rphos by itself was not a predictor of survival or disease-free interval (DFI) in either the primary or metastatic group. However, when combined with CSF-1R in the metastatic group, the two together predicted worse survival (P = 0.007) and decreased DFI (P = 0.011). CONCLUSIONS: Phosphorylated tyrosine kinase receptors are detectable in a significant number of ovarian tumors. Staining strongly correlates with CSF-1R. PY723+ metastases coexpressing CSF-1R portend a highly significant decrease in survival and increased risk of recurrence which may serve to identify high-risk ovarian cancer patients.

Antibodies↗

PubMed2001

Academic models of clinical care for women: the National Centers of Excellence in Women's Health.

Between 1996 and 1999, 18 academic health centers were awarded the designation of National Center of Excellence (CoE) in Women's Health by the Office on Women's Health within the Department of Health and Human Services and were provided with seed monies to develop model clinical services for women. Although the model has evolved in various forms, core characteristics that each nationally designated CoE has adopted include comprehensive, women-friendly, women-focused, women-relevant, integrated, multidisciplinary care. The permanent success of these comprehensive clinical programs resides in the ability to garner support of leaders of the academic health centers who understand both the importance of multidisciplinary programs to the clinical care they provide women and the education they offer to the future providers of women's healthcare.

Academic Medical Centers↗

PubMed2001

No BRCA1 germline mutation in a family with uterine papillary serous carcinoma: a case report.

The purpose of the study was to examine BRCA1 germline mutation and its relationship to BRCA1 expression in two patients, a mother and a daughter, both diagnosed with uterine papillary serous carcinoma (UPSC). DNA was screened for BRCA1 and BRCA2 germline mutations common in the Jewish population (185delAG, 5382insC, and 6174delT) by PCR-based assay and with a protein truncation test (PTT) to detect mutation in exon 11 of BRCA1 and exons 10 and 11 of BRCA2. BRCA1 expression in fixed tumor tissues was assessed by immunocytochemistry (IHC). No germline mutation in either BRCAI or BRCA2 gene was found in the two patients. Both samples showed reduced levels of BRCAI expression. Taken together, these results suggest that undetected or unscreened for germline mutation may be associated with occurrence of this rare tumor type in two members of the same family. Alternatively, an epigenetic mechanism such as BRCA1 promoter hypermethylation may be responsible for reduced expression of BRCA1 in the absence of DNA mutations.

Aged↗

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

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↗

PubMed1997

Stage IA uterine serous carcinoma: a study of 13 cases.

Although in endometrioid type endometrial carcinoma depth of invasion is a powerful predictor of extrauterine disease and survival, in serous carcinoma its importance is unclear. Recurrences and death in patients with serous tumors confined to the endometrium or an endometrial polyp have been reported. In other studies, however, the absence of myometrial invasion was correlated with a more favorable course. In an attempt to clarify this issue, we reviewed 13 completely staged, stage IA serous carcinomas with follow-up from 10 to 93 months (median 38), in which extensive histologic examination had been performed. Serous carcinoma was identified in an endometrial polyp in six cases, in an endometrial polyp and associated endometrium in four, and solely in the endometrium in three cases. No other histologic types of endometrial carcinoma were present, and there was no myometrial invasion. Multifocal serous intraepithelial carcinoma was also seen in 12 cases. Two of the patients died of disease with intraabdominal carcinomatosis at 10 and 14 months after presentation. The overall estimated survival was 83%, showing a relatively favorable prognosis. In conclusion, although the absence of histologically detected myometrial invasion may be associated with recurrences and death in serous carcinoma, an accurately assessed stage based on a careful histologic examination appears to be, at present, the most reliable predictor of survival.

Aged↗

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

Beta-core fragment (beta-core/UGF/UGP), a tumor marker: a 7-year report.

In 1988 we published three papers describing immunoassay results for urine beta-core fragment as a marker of gynecological cancers. Many other papers have been published since, and three commercial immunoassays have been established. beta-Core fragment is called beta-core, UGF, or UGP by different commercial vendors. To avoid confusion we call it beta-core/UGF/UGP here. In this 7-year report, we compare the three commercial assays, establish cutoff limits, and use the Ciba-Corning kit for two large studies. The first was a retrospective study, measuring beta-core/UGF/UGP in gynecological cancer and control urines accumulated in our freezers (n = 486). The second is a first prospective study, testing over a 16-month period beta-core/UGF/UGP levels in urines of all new patients attending the Gynecology Oncology Clinic (n = 548). In the retrospective study, elevated beta-core/UGF/UGP levels ( > 1.9 ng/ml) were detected in 11% of urines from healthy individuals (n = 132), in 11% from women with benign gynecological disease (n = 196), in 44% from cervical cancer (n = 68), 56% from ovarian cancer (n = 54), and 47% from endometrial cancer (n = 38). Altogether, beta-core/UGF/UGP levels were elevated in 50% of 170 samples from gynecological cancers. Overall, sensitivity increased with advancing stage of malignancy. Sensitivity was 28% for stage I, 50% for stage II, 47% for stage III, and 68% for stage IV malignancies. In the prospective study very similar results were recorded. Elevated beta-core/UGF/UGP levels ( > 1.9 ng/ml) were detected in 11% of urines from healthy individuals (n = 99), 11% from individuals with benign gynecological disease (n = 196), 7% from women with carcinoma in situ (n = 28), in 42% of samples from cervical cancer (n = 69), 56% from ovarian cancer (n = 59), and 52% from endometrial cancer. Altogether, beta-core/UGF/UGP levels were elevated in 48% of 225 gynecological cancer samples. Overall, sensitivity increased with advancing stage of malignancy. Sensitivity was 29% for stage I, 66% for stage II, 60% for stage III, and 77% for stage IV malignancies. In both studies sensitivity for beta-core/UGF/UGP increased with advancing stage of disease. Sensitivity for cervical and endometrial cancers was slightly lower than that for ovarian malignancies. This difference may be due to the preponderance of advanced-stage-disease patients in the ovarian cancer group. beta-Core/UGF/UGP may be a general stage-dependent marker for all gynecological cancers. The same false-positive results and very similar sensitivity values were found in a retrospective and a prospective study. They confirm each other, and suggest a definitive false-positive rate and sensitivity of this tumor marker for gynecological cancers.

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↗

PubMed1996

Radiation therapy as exclusive treatment for medically inoperable patients with stage I and II endometrioid carcinoma with endometrium.

From 1975 to 1992, 54 patients with clinical Stage I and II endometrioid carcinoma of the endometrium, representing 3.5% of all such patients, were deemed medically inoperable and exclusively received radiation therapy. A cohort of 108 operable patients adjusted for age, clinical stage, and grade served as a control group. The 5-year actuarial cancer-specific survivals for patients with Stage I inoperable, Stage 11 inoperable, Stage I operable, and Stage II operable disease were 80, 85, 98, and 100%. The corresponding 5-year overall survival rates were 30, 24, 88, and 85%. Inoperable patients had a median disease-free interval of 36 months for clinical Stage I and 50 months for Stage II disease versus 74.5 and 77 months for the operable patients (P = 0.001). Inoperable patients with Stage I disease had a median survival of 37 months versus 50 months for Stage II (P = NS), with only 7 (13%) of these patients dying with endometrial cancer. Operable patients had a median survival of 75 and 79 months in Stage I and II, respectively, with 14 patients dying with endometrial carcinoma (13%). Stage I and II inoperable patients had significantly shorter survival than operable patients (P < 0.0001). More deaths from intercurrent disease occurred within the inoperable Stage I group than with the operable group (28 of 32 vs 3 of 15, P < 0.0001). Inoperable patients had a significantly shorter overall survival and more deaths due to intercurrent disease than operable patients (P < 0.0001). However, inoperable patients who did not die from intercurrent disease had a median 5-year survival which approaches that of operable patients. Our study demonstrates that exclusive radiation therapy is a well-tolerated and effective treatment for medically inoperable patients.

Adult↗

PubMed1996

Combination chemotherapy with etoposide, cisplatin, and doxorubicin in mixed müllerian tumors of the adnexa.

Eleven patients with ovarian (9) or fallopian tube (2) mixed müllerian tumors who underwent primary surgery at Yale New Haven Medical Center between 1986 and 1994 were treated with etoposide, cisplatin, and doxorubicin. Responses were observed in three (60%) of five evaluable patients with two complete (40%) and one partial (20%) response. Median survival time was 17 months with an estimated 3-year survival of 18%. Survival may have been improved with earlier stage disease, but survival was not significantly improved with optimal surgical cytoreduction in patients with advanced disease. Four patients required dose reductions for myelosuppression and there was one treatment related death. Toxicity was comparable to other combination chemotherapy regimens. EPA has modest therapeutic activity in ovarian and fallopian tube MMT.

Aged↗

PubMed1996

Parametrial involvement, regardless of nodal status: a poor prognostic factor for cervical cancer.

OBJECTIVE: To evaluate the effect of resection of central disease when the parametria are involved by tumor in high-risk stage I cervical cancer patients. METHODS: Thirty-two patients with high-risk stage I cervical cancer who underwent radical hysterectomy and had pathologic findings of positive lymph nodes (N = 13), positive parametria (N = 7), or both (N = 12) were identified retrospectively. The effects of various histopathologic findings on disease-free interval and survival were evaluated, including the effect of resection of central disease with and without positive nodal disease. Kaplan-Meier survival curves were compared with the log-rang test. Multivariate analyses using a stepwise regression model were performed. RESULTS: Compared with other histologies, adenocarcinoma was associated with a significantly shorter disease-free interval (P = .037). Among patients with parametrial involvement lymph node status did not affect disease-free interval or survival. However, when patients with positive lymph nodes were examined, the additional finding of parametrial positivity significantly worsened both disease-free interval (P = .039) and survival (P = .036). When the 19 patients with positive parametria, regardless of lymph node status, were compared with those with positive lymph nodes alone, the former group had a significantly shorter disease-free interval (P = .038). The tumor recurred in 12 of these 19 patients; all cases involved the pelvis, with a median time to recurrence of 15 months. Multivariate analysis showed that adenocarcinoma histology (P = .038) and parametrial involvement (P = .043) were independent, poor prognostic indicators for disease-free interval. CONCLUSION: Involvement of the parametria, regardless of lymph node status, and adenocarcinoma histology confer a poor prognosis in high-risk patients undergoing radical hysterectomy. Caution should be used when contemplating resection of bulky tumors as part of primary therapy if the parametria appear to be involved by tumor.

Adenocarcinoma↗

PubMed1996

Modulation of platinum sensitivity and resistance by cyclosporin A in refractory ovarian and fallopian tube cancer patients: a phase II study.

Our objective was to assess the activity of cyclosporin A (CsA) used as a chemomodulator of carboplatin in refractory ovarian and fallopian tube cancer patients. Fifty-one patients (47 epithelial ovarian, 1 ovarian mixed mesodermal tumor, and 3 fallopian tube carcinomas) were enrolled in a prospective Phase II trial of CsA and carboplatin. CsA was infused as a loading dose of 10 mg/kg over 5 h, followed by carboplatin infused over 30 min at an AUC of 6 mg/ml x min, then a 24-h continuous infusion of 11.6 mg/kg CsA. The patients received this protocol as second- to sixth-line therapy and had received between 1 and 3 prior platinum-based regimens. Eight patients received more than six cycles every 28 days, 34 patients received three to six cycles; and 9 patients received only one or two cycles. Thirty-eight patients were evaluable for objective response, and in an additional nine patients, CA-125 was the only marker of response. Four patients had no marker of disease. Of evaluable patients, 74% were platinum resistant. There were nine objective responses (one complete and eight partial responses) for an overall response rate in evaluable patients of 24%, with a median duration of response of 7 months (range, 3-38+ months). No responses were seen in patients who had received only one or two cycles of therapy. Among the strictly defined platinum-resistant patients, there was an overall 14% response rate, including one partial response seen after five prior regimens of chemotherapy including paclitaxel, and one ongoing complete response for 38+ months. Among the rest of the patients (those who were potentially platinum sensitive), there was an overall 50+ response rate; four of five responses were seen in patients with a platinum-free interval of <24 months, with only one response seen in a patient with a platinum-free interval of >24 months. Of evaluable patients, 34% had stable disease for a duration of 3-19 months. The most common grade 3 or 4 toxicity, thrombocytopenia, was seen in 22% of the patients. Hypertension, which responded to medications, was seen in 18% of the patients during the CsA infusion. We concluded that this CsA/carboplatin regimen is active in potentially platinum-sensitive patients and compares well with the expected response rate of 30% in patients with a platinum-free interval <24 months who are retreated with platinum. Moreover, this regimen had modest but real activity in platinum-resistant patients.

Adult↗