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Biomedical subjects

Harriet O Smith

Publications and source records attributed to Harriet O Smith.

At least 19 recordsLinked to original sources

Total pelvic exenteration: the Albert Einstein College of Medicine/Montefiore Medical Center Experience (1987 to 2003).

OBJECTIVE: To review the trends, modifications and results of 103 consecutive total pelvic exenterations (TPE) performed at the Montefiore Medical Center and Albert Einstein College of Medicine from 1987 to 2003. METHODS: All patients who underwent TPE from January 1987 to December 2003 were included. The medical record, complications, follow-up, clinical status and demographic information were entered in a database. The procedure performed, the method of urinary diversion, colonic diversion, pelvic floor support and vaginal reconstruction were documented. Surviving patients were surveyed regarding their satisfaction with the urinary diversion, the vaginal reconstruction and their sexual function since the surgery. RESULTS: 103 pts were identified. Indications for TPE were recurrent cancers of the cervix (95), endometrium (2), colon and rectum (5), vulva (1). Overall 5-year survival was 47%. 5-year survival for pts with recurrent cervix cancer was 48%. Six pts (6%) recurred >5 years after the TPE. 14 pts (14%) had ureteral anastomotic leaks (no difference between ileal conduit 9/65 (14%) versus 5/38 (13%) continent conduit (P = 0.92). 34 pts (89%) with continent conduits were "continent." 14 pts (17%) had wound complications. 4 pts (4%) had parastomal hernias. 5/11 (46%) pts who had a low rectal reanastomosis developed recurrence in the pelvis. 21/39 (54%) of pts with continent conduits would choose an ileal conduit if they had the option again. Long-term renal function was similar in pts with ileal and continent conduits. Mesh of any type for pelvic floor reconstruction is associated with infection and bowel/urinary fistulas. VRAM flaps for neovagina fill the pelvic dead space, reduce the risk of fistulas and 20/36 pts (55%) are sexually active. CONCLUSIONS: Our overall 5-year survival is encouraging, and modifications in surgical technique have improved the reconstructive phase. Low rectal anastomoses at TPE adversely affects survival. Many of our pts with continent urinary diversions would not choose this method again. Mesh of any type is associated with sepsis and bowel/urinary fistulas. VRAM for neovagina reduces fistula rate and are functional in >55% of pts. TPE remains a potentially curative option for these pts.

Adult↗

Incidence and survival rates for female malignant germ cell tumors.

OBJECTIVE: To evaluate 30-year, population-based trends in incidence and survival rates for malignant germ cell tumors originating within the female genital tract. METHODS: Surveillance, Epidemiology, and End Results data were used to identify malignant germ cell tumors (1973-2002). Overall and 5-year incidence rates, estimated annual percentage change, and survival rates were calculated and compared by age at diagnosis, race, stage, and histology. RESULTS: Of 1,262 cases, there were 414 (32.8%) dysgerminomas, 449 (35.6%) immature teratomas, 37 (2.9%) mature teratomas with malignant degeneration, and 362 (28.7%) mixed germ cell tumors. The 30-year, age-adjusted incidence rate per 100,000 women-years was 0.338, decreasing by 29.4% for dysgerminomas (P = .18) and by 31.5% for mixed germ cell tumors (P = .22). Other nonwhites had higher rates than whites and blacks, but dysgerminoma rates were higher in whites and other nonwhites than in blacks. Using the registries for expanded races, rates were higher for Asian/Pacific Islanders (P = .059) and Hispanics (P = .07). By age at diagnosis, 15-19 year olds had the highest rates and the only significant change in rates (37.5% increase, P = .008). The 5-year relative survival was 83.9%. Survival rates improved significantly over calendar time and varied by histologic subtype, race, stage of disease, and age at diagnosis. CONCLUSION: Over the past 30 years, germ cell tumor incidence rates have declined in women and differ from rising trends reported for testicular tumors. Survival rates have improved but were lower for older women and for nondysgerminoma subtypes.

Adolescent↗

Changing trends in gestational trophoblastic disease.

OBJECTIVE: The New Mexico Tumor Registry (NMTR) and Surveillance, Epidemiology and End Results (SEER) registries were utilized to determine (30+)-year trends in gestational trophoblastic disease and choriocarcinoma. STUDY DESIGN: Age-adjusted incidence rates of gestational trophoblastic disease per 100,000 woman-years (1973-2003) and ratios per live births and pregnancies were calculated using data abstracted from the NMTR and state vital records. SEER data (1973-2002) were used to calculate age-adjusted incidence rates, estimated annual percentage change (EAPC) and relative survival rates for choriocarcinoma. RESULTS: In New Mexico there were 1,153 cases affecting 377 non-Hispanic whites, 504 Hispanics and 241 American Indians, with respective incidence rates of 3.494, 5.150 and 9.991 (p < 0.0001). American Indian incidence rates decreased 53.3%, from 13.34 (1988-1992) to 6.23 (1998-2002). Within SEER (1973-2002), there were 504 gestational choriocarcinomas. The 30-year incidence rate was 0.132 and decreased by 37.7% (EAPC, -2.1% per year; p=0.0001)-by 40.1% for whites, 55.9% for blacks and 62.1% for others. However, over the previous 10 years, rates among blacks (0.097 vs. 0.259, p = 0.01) and for distant disease (0.044 vs. 0.071, p = 0.046) increased. CONCLUSION: Disparities in incidence rates by race/ethnicity in New Mexico are decreasing. An increase in rates among blacks and distant disease diagnosis may be the consequence of fewer regional trophoblastic centers in the United States.

Adolescent↗

Choriocarcinoma and gestational trophoblastic disease.

Gestational trophoblastic disease (GTD) encompasses a unique group of uncommon but interrelated conditions derived from placental trophoblasts. For the purposes of discussion GTD is the appropriate collective name for hydatidiform mole, whereas the term gestational trophoblastic neoplasia (GTN) is reserved for cases with persistent human chorionic gonadotropin (hCG) titer elevation after evacuation of hydatidiform mole, metastatic disease, or choriocarcinoma. Although the pathology and clinical behavior of CM and PM are different, the initial management of both conditions is surgical evacuation by suction curettage, determination of the baseline, and follow-up with (hCG) titers. There are guidelines for risk-factor scoring and a staging system that classifies untreated patients into distinct prognostic categories so that treatment outcomes can be objectively compared. The rates of GTN and choriocarcinoma are decreasing and survival has dramatically improved.

Chorionic Gonadotropin↗

Gestation trophoblastic diseases: management of cases with persistent low human chorionic gonadotropin results.

The finding of persistent low levels of human chorionic gonadotropin (hCG) raises concern, regardless of the antecedent history, and often provokes the evaluating physician to embark on further work-up. The USA hCG Reference Service was started in 1998 to aid physicians with these persistent low hCG cases. This article reviews the observations of the USA hCG Reference Service for 134 cases with persistent low hCG results. Examination of these cases provides clear insight for the appropriate management of those presenting with persistent low levels of hCG. Three distinct sources are discussed for persistent low hCG results: quiescence gestational trophoblastic disease, false-positive hCG results, and pituitary hCG.

Chorionic Gonadotropin↗

Cervical neoplasia complicating pregnancy.

This article reviews the key concepts regarding the counseling and management of cervical dysplasia and invasive cervical cancer diagnosed during pregnancy. Emphasis is placed on balancing the maternal and fetal well-being in collaboration with appropriate multidisciplinary teams. Information regarding appropriate diagnosis strategies and the impact of delay in treatment, subsequent prognosis, and treatment algorithms are discussed. Novel fertility-sparing techniques for cervical cancer and their impact on complications of future pregnancies are also discussed.

Algorithms↗

Paclitaxel and carboplatin with amifostine in advanced, recurrent, or refractory endometrial adenocarcinoma: a phase II study of the Southwest Oncology Group.

OBJECTIVES: To evaluate the response rate and progression free and overall survival of patients with advanced endometrial cancer treated with paclitaxel, carboplatin and amifostine. To evaluate the toxicity of amifostine when used in combination with carboplatin and paclitaxel. METHODS: Forty-seven eligible patients (median age: 66; range 45-82) with bidimensionally measurable advanced, recurrent, or refractory endometrial cancer were treated with carboplatin (AUC = 6), paclitaxel (175 mg/M2) and amifostine (740 mg/M2) every 4 weeks for 6 cycles or until disease progression or unacceptable toxicity. RESULTS: There were 4 CRs (8%) (2 confirmed, 2 unconfirmed) and 15 PRs (32%) (9 confirmed, 6 unconfirmed) for a total response rate of 40% (95% confidence interval [CI], 26% to 56%). The median progression-free survival (PFS) was 7 months (95% CI, 6-9 months) and a 6-month PFS rate of 64% (95% CI, 50% to 78%). The median overall survival was 14 months (95% CI, 12 to 17 months). Toxicity was tolerable. While 79% of patients developed Grade 3/4 neutropenia (30% Grade 3, 49% Grade 4), there were no episodes of Grade 4 febrile neutropenia and one episode of infection with grades 3-4 neutropenia. CONCLUSION: The combination of paclitaxel and carboplatin with amifostine was well reasonably tolerated in this cohort. The regimen demonstrated significant activity in endometrial cancer, comparable to other multi-agent chemotherapy programs in terms of response rate and survival, and with a favorable toxicity profile.

Adenocarcinoma↗

Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study.

OBJECTIVES: To assess the activity of vinorelbine in women with recurrent or resistant epithelial ovarian cancer following treatment with platinum and paclitaxel in terms of survival rate at 6 months, objective response rate (in the subset of patients with bidimensionally measurable disease), and health-related quality of life. METHODS: Seventy-nine evaluable patients with progressive ovarian cancer following platinum and taxane therapy received vinorelbine 30 mg/m(2) days 1 and 8 of a 21-day treatment cycle. RESULTS: Six-month survival rate for the entire group was 65% (95% CI: 54-75%) and median survival was 10.1 months (95% CI: 7.7-13.6 months). In the 71 women with measurable disease, 0 complete and 2 partial responses were observed (RR = 3%) (95% CI: 0.3-10%). Patients reported substantial symptom-related distress at baseline, which persisted, but did not worsen, during treatment. Patients also had impaired physical functioning at baseline and this continued to decline during treatment. CONCLUSIONS: The 6-month survival rate achieved with salvage vinorelbine is comparable to the results obtained with other salvage therapies in patients with relapsed ovarian cancer. During the initial 10 weeks of treatment, vinorelbine did not appear to be effective in alleviating the symptom-related distress or progressive impairment of physical functioning associated with this disease.

Adult↗

Gestational trophoblastic neoplasia in American Indians.

OBJECTIVE: To analyze gestational trophoblastic neoplasia (GTN) trends among American Indians (AI) using population-based data. STUDY DESIGN: GTN incidence, by race and age, was calculated using data collected by the New Mexico Tumor Registry over 29 years (1973-2001). Live birth, pregnancy and women at risk were tabulated using data derived from the state's vital record annual reports and from the registry. Statistical methods included trends analysis and Poisson regression. There is no national registry in the United States for all GTN. Therefore, the Surveillance, Epidemiology and End Results (SEER) database was used to identify choriocarcinoma cases in American Indians between 1973 and 1999. RESULTS: Within New Mexico, 1,082 cases of GTN were identified among 752,374 live births and 904,831 pregnancies, with ratios of 1:695 and 1:836, respectively, affecting 234 AI, 355 non-Hispanic whites (NHW), 463 Hispanic whites (HW) and 30 other nonwhites. Ratios per live births (pregnancy), respectively, were significantly higher in AI (AI 1:439 [1:487], NHW 1:739 [1:949], HW 1:783 [1:903]), as was age-adjusted incidence per 100,000 woman-years (AI 10.62, NHW 3.53, HW 5.15; all P<.0001). Using Poisson models with live birth and woman-year denominators, AI were found to be at increased risk for all GTN histologic subsets (complete, partial and invasive hydatidiform mole and choriocarcinoma). Of 524 total gestational choriocarcinoma cases identified within SEER, 8 (1.8%) affected American Indians; of them, 7 were from New Mexico. CONCLUSION: In New Mexico, AI continue to be at higher risk of GTN than are other groups. Given the rarity of choriocarcinoma within SEER, especially among AI, the New Mexico dataset provides the best available estimate of trends in U.S. AI GTN risk.

Black or African American↗

TLK-286.

Telik Inc is developing TLK-286, a modified glutathione analog prodrug, for the potential treatment of cancer.

Animals↗

Trends in gestational choriocarcinoma: a 27-year perspective.

OBJECTIVE: To evaluate trends in incidence and survival rates for gestational choriocarcinoma with the use of population-based data. METHODS: Overall and 5-year average age-adjusted incidence rates were computed with the Surveillance, Epidemiology, and End Results program public-use database. Differences by age at diagnosis, race, stage, registry, and over calendar time were compared by Poisson regression, and survival censored for deaths other than choriocarcinoma by log-rank tests and Cox's proportional hazard ratios. RESULTS: Between 1973 and 1999, 450 cases were recorded. The annualized age-adjusted incidence rate for choriocarcinoma was 0.133 per 100,000 woman-years and decreased by 49.7% (2.8% per year). By race (whites, blacks, and others), incidence rates declined by 62.3%, 27.2%, and 54.3%, respectively. In the Poisson model evaluating incidence rates, age, race, registry, and stage were significant main effects. Compared with whites, the relative risk was higher for blacks (2.14, 95% confidence interval [CI] 1.60, 2.86) and others (2.30, 95% CI 1.67, 3.18). Rates were highest in Utah and lowest in Iowa. By age at diagnosis, rates were higher in 20-39-year-olds. The 5-year relative survival rate was 89.5%. Censored survival was significantly lower among blacks (whites 92.4%, blacks 84.9%, others 87.1%, P = .045), for advanced disease (localized 94.5%, regional 92.9%, distant 87.1%, P = .02), and with increasing age at diagnosis (P = .017). Age and calendar time significantly influenced censored survival independent of stage and registry. CONCLUSION: Gestational choriocarcinoma incidence rates have declined and survivals have improved, but blacks continue to have higher incidence and lower survival rates.

Adolescent↗

Phase II trial of single agent carboplatin followed by dose-intense paclitaxel, followed by maintenance paclitaxel therapy in stage IV ovarian, fallopian tube, and peritoneal cancers: a Southwest Oncology Group trial.

OBJECTIVE: To improve the survival of women with stage IV epithelial ovarian cancer the Southwest Oncology Group conducted a phase II trial examining two novel treatment strategies: (a) modification of the chemotherapy regimen (carboplatin/paclitaxel) based on evidence of response during treatment and (b) "maintenance therapy," with the monthly administration of single agent paclitaxel (maximum 2 years). METHODS: Individuals with histologically documented stage IV ovarian, fallopian tube, or peritoneal cancers initially received a maximum of 3 courses of single agent carboplatin (AUC 6), with the decision to administer a subsequent course based on specific response criteria (i.e., declines in serum CA-125 or shrinkage of measurable mass lesions). This was followed by single agent paclitaxel (150 mg/m(2)), delivered every 2 weeks for a maximum of 6 courses, again based on evidence of continued response to the treatment program. Finally, in the absence of disease progression or unacceptable toxicity, patients received single agent paclitaxel (175 mg/m2) for a maximum of 24 monthly courses. The primary study end point was 2-year overall survival, which was to be compared to the survival of a previously published historical control population [stage IV ovarian cancer patients treated with a "standard" cisplatin/paclitaxel regimen (GOG 111; McGuire WP, N Eng E J Med 1996; 334:1)]. This analysis was employed to determine if this novel strategy was worthy of further clinical investigation in a controlled clinical trial. RESULTS: There were 53 patients entered this multicenter study, of whom 50 were evaluable for toxicity and 51 for survival. There were 2 treatment-related deaths. Grades 2 and 3 neutrotoxicity were observed in 18 and 4% of patients, respectively. There were no major treatment-related protocol violations. The overall 2-year survival was 48% (95% CI, 34-62%), compared to 60% for the historical control group. CONCLUSIONS: While this trial demonstrated the feasibility of delivering a treatment regimen requiring frequent alternations in therapy based on predetermined changes in objective parameters of response, further exploration of this specific management approach does not appear warranted in stage IV ovarian cancer, based on the survival outcome compared to a reasonably similar historical control population. As this trial demonstrates, the prospective determination of clinical end points in a phase II study (e.g., 2-year survival) that will lead to continued evaluation of a particular investigative strategy in a large-scale randomized trial can be an effective method to reduce the bias and uncertainty often associated with this complex decision process.

Adult↗

Persistent low levels of human chorionic gonadotropin: A premalignant gestational trophoblastic disease.

OBJECTIVE: This study was undertaken to evaluate the significance of persistent low-level human chorionic gonadotropin (hCG) titers (usually <50 IU/L) in the absence of clinical evidence of pregnancy or gestational trophoblastic disease. STUDY DESIGN: The USA hCG Reference Service consulted on 114 cases with persistent low levels of hCG; 51 had false-positive hCG results. The remaining 63 cases had real hCG results and are presented here. RESULTS: Antecedent gestational events included hydatidiform mole (27), pregnancy (35), and gestational trophoblastic neoplasm (1). Forty of the 63 (64%) cases received therapy, including chemotherapy (38), hysterectomy (2), or both (10). Despite treatment, in all cases, low hCG titers persisted. After 1 to 4.5 years of low titers, four women had a sudden rapid increase in hCG levels, and malignant disease was confirmed or clearly suggested (gestational trophoblastic neoplasm [3] and placental site trophoblastic tumor [1]). Invasive trophoblast antigen (ITA) is a marker of invasive cytotrophoblast cells. ITA was measured in 38 of the cases with persistent low hCG, in all cases ITA accounted for less than 25% of the hCG concentration. It was also determined in the 4 cases indicated with malignant disease, accounting for more than 80% of the hCG. CONCLUSION: The presence of persistent low-level hCG titers defines a subset of women with preinvasive or quiescent gestational trophoblastic disease. ITA effectively detected the presence or absence of invasive cells in these cases. The recommended management of the quiescent disease is close surveillance without therapy until malignant disease detected.

Chorionic Gonadotropin↗

Ethnic differences at risk for gestational trophoblastic disease in New Mexico: A 25-year population-based study.

OBJECTIVE: The purpose of this study was to compare gestational trophoblastic disease incidence rates with the use of population-based data. STUDY DESIGN: All incident cases between 1973 and 1997 and live birth, pregnancy, and women at risk were tabulated with the use of data that were derived from the New Mexico Tumor Registry and Vital Records and Health Statistics Annual Reports. Statistical methods included trends analyses, odds ratios, and Poisson regression. RESULTS: Of 939 total cases, 312 non-Hispanic white women, 399 Hispanic white women, 201 American Indian women, and 27 other women were affected. Age-adjusted incidence rates were significantly higher for American Indian women (11.16%) compared with non-Hispanic (3.57%) or Hispanic white women (5.32%); the probability value was <.001. When live birth (1:438 women) and pregnancy (1:486 women) denominators were considered, American Indian women alone were at increased risk, and the ratio increased by 56% over 25 years. American Indian women were also at increased risk for partial mole (relative risk, 4.03; 95% CI, 2.57-6.31), invasive mole (relative risk, 26.7; 95% CI, 7.81-93.14), and choriocarcinoma (relative risk, 6.29; 95% CI, 1.81-22.66) variants. CONCLUSION: American Indians are at increased risk relative to the other predominant ethnic groups in New Mexico. Age-adjusted standardization provided a reproducible measurement that may be applicable across other registries.

Adolescent↗

Primary plasmacytoma arising in an endocervical polyp with detection of neoplastic cells on papanicolaou test. A case report and review of the literature.

Primary plasmacytomas of the female genital tract are extremely rare and present a substantial diagnostic challenge. Five cases morphologically representing plasmacytomas and localized to the uterine cervix have been reported previously; however, only 1 was shown to be monotypic for immunoglobulin light-chain expression. We report the case of a 37-year-old woman who had highly atypical plasma cells on her Papanicolaou test. A clinically detected endocervical polyp was removed and revealed a plasmacytoma, the diagnosis of which was substantiated by demonstrating monotypic lambda-light-chain restriction and a clonal immunoglobulin heavy-chain gene rearrangement. The cytologic and histopathologic findings of plasmacytomas of the uterine cervix are discussed, including the utility of immunophenotypic and molecular techniques to confirm the neoplastic diagnosis.

Adult↗

Trimetrexate in the treatment of recurrent or advanced leiomyosarcoma of the uterus: a phase II study of the Gynecologic Oncology Group.

OBJECTIVE: This study was conducted to determine the objective response of trimetrexate in patients with advanced or recurrent leiomyosarcoma of the uterus. METHODS: Eligibility was restricted to patients with measurable disease who had received no more than one prior chemotherapy regimen, who had adequate bone marrow, renal, and hepatic function, and who had recovered from previous therapy. Trimetrexate was begun at 5 mg/m2/day orally for 5 days every other week, with dose modifications specified by study design. RESULTS: Of 28 patients entered into the study, 27 were evaluable for toxicity and 23 for response. Prior therapy included radiation (7 patients) and/or chemotherapy (10 patients). Measurable disease was extrapelvic in 20 cases and confined to the pelvis in 3. The overall response rate was 4.3%; there were no complete responses and 1 partial response. Toxicities were mild to moderate with no treatment-related deaths. Hematological toxicity was most common, consisting of leukopenia (grade 1 to 2, 8 patients; grade 3 or 4, 2 patients), thrombocytopenia (grade 1 to 2, 10 patients; grade 3 or 4, 1 patient), and anemia (grade 1 to 2, 6 patients; grade 3 or 4, 4 patients. Severe (grade 3 or 4) nonhematologic toxicity was uncommon: nausea/vomiting/gastrointestinal (3 patients) and neurological (1 patient). Progression-free and overall survival, in months, was 2.2 (range: 0.9-13.4) and 7.2+ (range: 1.0-13.4+), respectively. CONCLUSION: Although toxicity is acceptable, trimetrexate at this dose and schedule is ineffective therapy for patients with recurrent leiomyosarcoma. Further development of this specific regimen for this indication is unwarranted.

Administration, Oral↗