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OBJECTIVE: Quality of life (QoL) for women with gynecologic malignancies is predictive of chemotherapy related toxicity and overall survival but has not been studied in relation to surgical outcomes and hospital readmissions. Our goal was to evaluate the association between baseline, pre-operative QoL measures and 30-day post-operative morbidity and health resource utilization by gynecologic oncology patients. METHODS: We analyzed prospectively collected survey data from an institution-wide cohort study. Patients were enrolled from 8/2012 to 6/2013 and medical record data was abstracted (demographics, comorbid conditions, and operative outcomes). Responses from several validated health-related QoL instruments were collected. Bivariate tests and multivariable linear and logistic regression models were used to evaluate factors associated with QoL scores. RESULTS: Of 182 women with suspected gynecologic malignancies, 152 (84%) were surveyed pre-operatively and 148 (81%) underwent surgery. Uterine (94; 63.5%), ovarian (26; 17.5%), cervical (15; 10%), vulvar/vaginal (8; 5.4%), and other (5; 3.4%) cancers were represented. There were 37 (25%) cases of postoperative morbidity (PM), 18 (12%) unplanned ER visits, 9(6%) unplanned clinic visits, and 17 (11.5%) hospital readmissions (HR) within 30days of surgery. On adjusted analysis, lower functional well-being scores resulted in increased odds of PM (OR 1.07, 95%CI 1.01-.1.21) and HR (OR 1.11, 95%CI 1.03-1.19). A subjective global assessment score was also strongly associated with HR (OR 1.89, 95%CI 1.14, 3.16). CONCLUSION: Lower pre-operative QoL scores are significantly associated with post-operative morbidity and hospital readmission in gynecologic cancer patients. This relationship may be a novel indicator of operative risk.
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Neoplasias de los Genitales Femeninos/cirugía , Servicios de Salud/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Periodo Preoperatorio , Calidad de Vida , Adolescente , Adulto , Anciano , Estudios de Cohortes , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Modelos Lineales , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Readmisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: Endometrial cancer is the most common gynecologic malignancy in the United States. Adjuvant radiotherapy in patients with intermediate risk disease (stage IB, IC, and occult stage II) is controversial. Despite no proven survival advantage, a significant number of women undergo this treatment annually. The purpose of this study was to compare the estimated health and economic outcomes for adjuvant whole pelvic radiotherapy to no treatment with salvage therapy for recurrence. METHODS: A decision analytic model was created to estimate the costs of adjuvant pelvic radiotherapy versus no adjuvant radiotherapy in patients with intermediate risk endometrial cancer. Data used was gathered from published literature and institutional data on costs. The model incorporates complications, recurrence rates, treatment of recurrence, and survival in each group. RESULTS: In the base case analysis, adjuvant pelvic radiation reduced the recurrence rate by 50%. Cost-effectiveness as measured by cost per recurrence prevented was highly sensitive to the probability of recurrence and the efficacy of adjuvant therapy. In our model the mean costs of Strategy 1 with observation and treatment reserved until the time of recurrence would be $5016. In contrast the mean cost of Strategy 2 which incorporated adjuvant radiotherapy would be $21,159. Cost per recurrence prevented based on the incremental cost-effectiveness is thus $225,215. In the highest risk subgroup, using the upper limit of the 90% confidence limit of efficacy seen in GOG Protocol 99, cost/recurrence prevented was approximately $50,000. Results did not differ when using parameters solely from GOG 99 or PORTEC. CONCLUSIONS: Although adjuvant pelvic radiation does not appear to improve survival for intermediate risk endometrial cancer patients, it does prevent recurrences, at a net positive cost compared to no therapy. Data are not currently available to incorporate quality of life information into cost-effectiveness analyses. Obtaining such data would allow cost/quality-adjusted life year gained to be estimated. This information is necessary to determine if the extra costs of adjuvant radiotherapy in patients with intermediate risk endometrial cancer are acceptable by current health care policy standards.
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Neoplasias Endometriales/radioterapia , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Árboles de Decisión , Neoplasias Endometriales/economía , Neoplasias Endometriales/cirugía , Femenino , Humanos , Recurrencia Local de Neoplasia/prevención & control , Radioterapia Adyuvante/economía , Factores de Riesgo , Resultado del TratamientoRESUMEN
To compare flap-specific complications of gracilis myocutaneous (GM) and rectus abdominis myocutaneous (RAM) flap neovaginal reconstructions after radical pelvic surgery. The study was a single-institution retrospective review of patients undergoing concurrent radical pelvic surgery with GM or RAM neovaginal reconstructions performed on a gynecological oncology service, 1978-2003. Flap-specific complications were compared between the techniques. Forty-four GM and 32 RAM neovaginal reconstructions were analyzed: plastic surgeons developed 12 (27%) GM and 4 (13%) RAM flaps, with all other flaps performed by gynecological oncologists. Primary procedures included 54 (71%) total pelvic exenterations, with partial exenterations or radical vulvovaginectomies in 16 (21%) and 6 (8%) patients, respectively. Forty (53%) patients had received radiation and 28 (36%) received chemoradiation before radical surgery. There were no significant differences in patient characteristics, other than more frequent use of continent urinary conduits (P < 0.001) and a trend for more frequent sidewall radiation (P < 0.1) in the RAM group, reflecting use in more recent patients (P < 0.001). Median follow-up is 28 months (range: 2 weeks to 216 months), with 5% acute operative mortality. Flap-specific complications were significantly increased in GM patients (P < 0.03). Overall flap loss was significantly increased in GM patients (P < 0.02). Thirty (59%) of 51 patients surviving for more than 12 months reported coitus, with no significant difference between the groups. Because of lower overall incidence of flap-specific complications and significantly lower incidence of flap loss compared with GM flap, RAM flap has become our technique of choice for neovaginal reconstruction concurrent with radical pelvic surgery.
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Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos , Vagina/cirugía , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Morbilidad , Procedimientos de Cirugía Plástica/efectos adversos , Recto del Abdomen/cirugía , Muslo/cirugíaRESUMEN
PURPOSE: To report our recent experience managing four patients with brain metastases of gestational trophoblastic neoplasia (GTN), coordinating systemic chemotherapy with early neurosurgical intervention or stereotactic radiosurgery and intensive supportive care during initial therapy to prevent early mortality. MATERIALS AND METHODS: A series of four consecutive patients with brain metastases from high-risk Stage IV GTN managed at our institution in 2003 and 2005. Patients were assigned FIGO stage and risk score prospectively. Because of concern for chronic toxicity resulting from concurrent moderate dose methotrexate and whole brain radiation, an individualized multidisciplinary approach was used to manage patients. RESULTS: All four women presented with brain and pulmonary metastases; one had multiple liver metastases. Neurological symptoms at presentation included grand mal seizures in 2 patients, left upper extremity hemiparesis and headache each in 1 patient, while 1 patient was asymptomatic. Index pregnancies were term pregnancies in all patients with interval from prior delivery ranging from 2 weeks to 4 years. Two had received prior chemotherapy for postmolar GTN prior to the index pregnancy with incomplete follow-up. Initial hCG values ranged from 26,400 to 137,751 mIU/ml; FIGO risk scores were > or =16 for all patients. Systemic combination chemotherapy was initiated with etoposide and cisplatin followed by moderate/high-dose (500-1000 mg/m(2)) methotrexate combinations. Craniotomy was used before or during the first chemotherapy cycle to extirpate solitary lesions in 3 patients, while stereotactic radiosurgery was administered after the first cycle to treat two brain lesions in the remaining patient. None received whole brain radiation or intrathecal methotrexate. In one patient, selective angiographic embolization was used to control hemorrhage from multiple liver metastases. Two patients required ventilator support early in treatment to allow stabilization from intrathoracic hemorrhage and neutropenic sepsis with respiratory distress syndrome, respectively. Hysterectomy was performed in one patient after completion of salvage chemotherapy. All have completed maintenance chemotherapy and are in prolonged remission (12-24 months). Neurologic sequelae include persistent left upper extremity dyskinesia and weakness in one patient, and episodic grand mal seizures and pseudoseizures in a second patient with a pre-existing seizure disorder. CONCLUSION: This case series documents the utility for a multidisciplinary approach to the treatment of brain metastases from GTN. Using early craniotomy or stereotactic radiosurgery combined with etoposide-cisplatin and moderate/high-dose methotrexate combination chemotherapy, we were able to stabilize patients early in their treatment and avoid whole brain radiation therapy or intrathecal chemotherapy.
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Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Enfermedad Trofoblástica Gestacional/patología , Enfermedad Trofoblástica Gestacional/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Coriocarcinoma/patología , Coriocarcinoma/secundario , Coriocarcinoma/terapia , Cisplatino/administración & dosificación , Craneotomía , Ciclofosfamida/administración & dosificación , Dactinomicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Ácido Fólico/administración & dosificación , Humanos , Metotrexato/administración & dosificación , Estadificación de Neoplasias , Embarazo , Radiocirugia , Factores de Riesgo , Vincristina/administración & dosificaciónRESUMEN
OBJECTIVE: A phase I/II study of Doxil combined with whole abdomen hyperthermia was conducted in patients with refractory ovarian cancer. Liposomal doxorubicin combined with hyperthermia has been shown to increase both liposomal delivery and drug extravasation into tumour xenografts resulting in enhanced cytotoxic effects. PATIENTS AND METHODS: Thirty patients with either recurrent or persistent epithelial ovarian cancer were enrolled. All patients had either measurable or assessable disease. Patients received intravenous (IV) Doxil at a dose of 40 mg m-2 as a 1-h infusion followed by whole abdomen hyperthermia. The phase I portion of the study was performed to determine the maximal tolerated dose (MTD) of hyperthermia. Quality of life (QoL) was performed at baseline, prior to each cycle and every 3 months. Plasma pharmacokinetic studies were performed with the first cycle. RESULTS: Ten patients participated in the phase I portion of the study which demonstrated that the MTD of hyperthermia was 60 min after either average vaginal and rectal temperatures of 40 degrees C had been achieved or after 30 min of power application, whichever was shorter. All 30 patients were either paclitaxel and/or platinum resistant initially or developed resistant disease. The median number of prior chemotherapeutic regimens was three (range 2-8) and six patients had been previously treated with Doxil. There were three partial responses for a response rate of 10% (95% CI: [2%, 27%]) and eight patients (27%; 95% CI: [12%, 46%]) had disease stabilization. The median time to progression or death was 3.4 months (95% CI: [2.6, 5.2]) and the median survival was 10.8 months (95% CI: [8.8, 17.4]). Twelve patients (40%) experienced palmar-plantar erythrodysesthesia (PPE), but only four (13%) experienced grade 3-4 PPE toxicity. Doxil systemic exposure was higher in those with grade 3-4 PPE compared to those with no PPE. None of the patients had grade 3-4 thermal toxicity due to hyperthermia. QoL was not decreased in patients responding to therapy. CONCLUSIONS: Therapy with intravenous Doxil and whole abdomen hyperthermia for patients with platinum/paclitaxel resistant ovarian cancer is feasible and does not negatively impact quality of life.
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Antineoplásicos/uso terapéutico , Doxorrubicina/uso terapéutico , Hipertermia Inducida , Neoplasias Ováricas/terapia , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Terapia Combinada , Doxorrubicina/efectos adversos , Doxorrubicina/farmacocinética , Femenino , Humanos , Hipertermia Inducida/efectos adversos , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Calidad de VidaRESUMEN
The objective of this article is to compare the flap-specific complications associated with vertical (VRAM) and transverse (TRAM) rectus abdominis myocutaneous flap vaginal reconstructions performed during radical pelvic procedures. A retrospective chart review was performed to identify all patients who underwent VRAM and TRAM neovaginal reconstructions performed on the Gynecologic Oncology Service at Duke University Medical Center. Flap-specific complications were compared between the two techniques. From 1988 to 2003, 14 VRAM and 18 TRAM flap neovaginal reconstructions were performed on 32 women during the course of 22 (68%) total pelvic exenterations, 8 (25%) partial exenterations, and 2 (6%) radical vulvovaginectomies. Twenty-eight (88%) patients had been previously treated with radiation therapy or concurrent chemoradiation. Associated procedures included continent urinary conduit in 21 (66%), rectosigmoid reanastomosis in 8 (25%), and intraoperative or postoperative sidewall radiation therapy in 7 (22%) of patients. Overall median survival was 14 months (range: 2-week postoperative death to 65 months), with two (6%) acute postoperative mortalities. Fifteen flap-specific complications occurred in 12 (38%) patients, with no significant differences in flap type. Abdominal wound complications included four (12%) superficial wound separations, while one (3%) patient had a fascial dehiscence associated with complex fistulas that contributed to her death, but no patient developed incisional hernia. One patient each developed > 50% flap loss after TRAM and < 50% flap loss after VRAM flap, respectively. Four (12%) patients developed vaginal stricture or stenosis, two (6%) required percutaneous drainage of pelvic abscess or hematoma, and two (6%) developed rectovaginal fistula. Univariate analysis revealed a trend for increasing flap loss with body mass index > 35 (P = 0.056, Fisher exact two-tailed test), but there were no significant associations with other patient characteristics or flap-specific complications. Thirteen (62%) of 21 patients who survived >12 months reported coitus. Both VRAM and TRAM are reliable techniques for neovaginal reconstructions after radical pelvic surgery and have a similar distribution of flap-specific complications involving the donor and recipient sites.
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Neoplasias de los Genitales Femeninos/cirugía , Exenteración Pélvica , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias , Colgajos Quirúrgicos , Vagina/cirugía , Adulto , Anciano , Índice de Masa Corporal , Femenino , Humanos , Persona de Mediana Edad , Músculo Esquelético/cirugía , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Osteoblastoma-like osteosarcoma is a rare variant of osteosarcoma occurring in this instance in a highly unusual location: the lateral femoral condyle of a 13-year-old girl. The radiological features were non-aggressive and, although slightly unusual, were most suggestive of chondroblastoma.
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Epífisis/patología , Neoplasias Femorales/patología , Osteoblastoma/patología , Osteosarcoma/patología , Adolescente , Diagnóstico Diferencial , Femenino , Neoplasias Femorales/terapia , Cabeza Femoral/patología , Humanos , Osteoblastoma/terapia , Osteosarcoma/terapiaRESUMEN
Current radiographic techniques are useful for evaluating and managing patients with gynecologic malignancies. Lymphoscintigraphy may prove useful in limiting surgery in women with vulvar cancer who have negative sentinel groin nodes. Selected patients benefit from pretherapy MRI scanning to help determine treatment of cervical or endometrial malignancies. Sonographic techniques are helpful in discriminating benign from malignant adnexal or pelvic masses, and preoperative CT scans are helpful in determining the extent of advanced ovarian cancer. The FDG PET scans appear to help localize occult disease in patients with a variety of gynecologic malignancies. Further refinements of currently available techniques or newer techniques, however, are needed to increase the sensitivity for detection of subclinical or microscopic metastases in patients with gynecologic malignancies.
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Neoplasias de los Genitales Femeninos/diagnóstico por imagen , Tecnología Radiológica/métodos , Neoplasias Endometriales/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Neoplasias Ováricas/diagnóstico por imagen , Embarazo , Tomografía Computarizada por Rayos X , Neoplasias Trofoblásticas/diagnóstico por imagen , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Vaginales/diagnóstico por imagen , Neoplasias de la Vulva/diagnóstico por imagenRESUMEN
OBJECTIVE: The goal of this study was to estimate the clinical activity of paclitaxel in patients with persistent or recurrent carcinosarcoma of the uterus who have failed other treatments. METHODS: The Gynecologic Oncology Group (GOG) conducted a phase II study of paclitaxel 170 mg/m(2) (135 mg/m(2) in those with prior irradiation) intravenously every 3 weeks in patients with histologic confirmation of carcinoma and measurable disease who had failed appropriate local therapy. RESULTS: A total of 53 patients were entered into the study between September 1994 and January 1997; 44 patients were evaluable for response. The median age of the patients treated was 65 years (range: 38-79). Twenty-six patients had heterologous mixed mesodermal tumors (MMTs) and 18 patients had homologous tumors. A median of three courses were administered (range: 1-18). Fifteen patients had previous radiation therapy and 33 patients had failed prior chemotherapy. Eight patients (18.2%) had a response to paclitaxel: four patients had a complete response and four had a partial response. Neutropenia was the most common toxic effect. CONCLUSIONS: Paclitaxel had moderate activity in patients with carcinosarcoma of the uterus. The GOG is currently studying the combination of paclitaxel and ifosfamide versus ifosfamide alone for patients with advanced or recurrent carcinosarcoma of the uterus.
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Antineoplásicos Fitogénicos/uso terapéutico , Carcinosarcoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/uso terapéutico , Neoplasias Uterinas/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos Fitogénicos/efectos adversos , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Paclitaxel/efectos adversosRESUMEN
The osmium(VI) nitrido complex TpOs(N)Cl(2) (1) has been prepared from K[Os(N)O(3)] and KTp in aqueous ethanolic HCl. It reacts rapidly with PhMgCl and related reagents with transfer of a phenyl group to the nitrido ligand. This forms Os(IV) metalla-analido complexes, which are readily protonated to give the analido complex TpOs(NHPh)Cl(2) (4). The nitrido-phenyl derivatives TpOs(N)PhCl and TpOs(N)Ph(2) react more slowly with PhMgCl and are not competent intermediates for the reaction of 1 with PhMgCl. Reactions of 1 with alkyl- and arylboranes similarly result in transfer of one organic group to nitrogen, leading to isolable borylamido complexes such as TpOs[N(Ph)(BPh(2))]Cl(2) (11). This is an unprecedented insertion of a nitrido ligand into a boron--carbon bond. Hydrolysis of 11 gives 4. Mechanistic studies suggest that both the Grignard and borane reactions proceed by initial weak coordination of Mg or B to the nitrido ligand, followed by migration of the carbanion to nitrogen. The hydrocarbyl group does not go to osmium and then move to nitrogen--there is no change in the atoms bound to the osmium during the reactions. It is suggested that there may be a general preference for nucleophiles to add directly to the metal--ligand multiple bond rather than binding to the metal first and migrating. Ab initio calculations show that the unusual reactivity of 1 results from its accessible LUMO and LUMO + 1, which are the Os = N pi* orbitals. The bonding in 1 and its reactivity with organoboranes are reminiscent of CO.
RESUMEN
Protonation of the Os(IV) amido complex TpOs(NHPh)Cl(2) (1) to give the aniline complex [TpOs(NH(2)Ph)Cl(2)]OTf (2) requires excess triflic acid (HOTf). Complex 1 is unreactive with HCl and other moderately strong acids. Consistent with the low basicity of 1, the aniline complex 2 is extremely acidic and is deprotonated by stoichiometric addition of weak bases such as Cl(-) or H(2)O. No reaction is observed between 1 and methyl triflate (CH(3)OTf) at ambient temperatures. Upon heating, CH(3)OTf removes the chloride ligands from 1 to give CH(3)Cl and the amidobis(triflate) complex TpOs(NHPh)(OTf)(2) (3). Attack at the amido nitrogen is not observed. Complex 1 is thus very inert to protonation and electrophilic attack at nitrogen. A deprotonated form of 1, TpOs[NPh(MgBr)]Cl(2) (4), is generated on reaction of PhMgBr with TpOs(N)Cl(2). Complex 4 is extremely basic and will protonate to 1 with weak acids such as CH(3)CN, DMSO, and acetic anhydride. Thus, 1 has a low acidity as well as a low basicity; it is both less acidic and less basic than aniline. The inertness of 1 is ascribed to partial Os-N pi bonding and to the oxidizing nature of the Os(IV) center.
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PURPOSE: In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. PATIENTS AND METHODS: Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. RESULTS: Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). CONCLUSION: Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias Endometriales/tratamiento farmacológico , Tamoxifeno/uso terapéutico , Anciano , Anciano de 80 o más Años , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estadificación de Neoplasias , Análisis de SupervivenciaRESUMEN
OBJECTIVE: The aims of this study were to substantiate the previously reported activity of ifosfamide in patients with advanced, persistent, or recurrent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determine whether the addition of cisplatin results in an improved response or survival. Secondarily, we sought to determine the toxicity of ifosfamide-cisplatin in this patient population. METHODS: Patients were randomized to receive ifosfamide (1.5 g/m(2)/day) times 5 days every 3 weeks for eight courses with mesna uroprotection, with or without cisplatin (20 mg/m(2)/day) times 5 days. No patient had received previous chemotherapy. RESULTS: Of 224 patients entered on this study, 30 were ineligible for a variety of reasons, leaving 194 evaluable patients. Early in the study, the dose of the combination regimen was reduced by 20% (1 day) because of toxicity. The investigational arms were balanced for age, grade, and Gynecologic Oncology Group performance status. Percentages of adverse effects reported in 191 patients receiving chemotherapy included (ifosfamide/cisplatin-ifosfamide) grade 3 or 4 granulocytopenia (36/60), grade 3 or 4 anemia (8/17), grade 3 or 4 central nervous system toxicity (19/14), and grade 3 or 4 peripheral neuropathy (1/12). Treatment may have contributed to the deaths of 6 patients treated with full doses of ifosfamide and cisplatin for 5 days. The proportion of patients responding to ifosfamide alone versus ifosfamide-cisplatin therapy was (0.36 versus 0.54) overall, 0.47 versus 0.61 for pelvic, 0.21 versus 0.54 for lung, and 0.33 versus 0.40 for "other" metastatic sites of measurable disease. The relative odds ratio of response adjusted for measurable sites of disease was 1.82 (P = 0.03, one-tailed test; 95% lower confidence limit, 1.06). Progression-free survival (PFS) and survival data suggest that the combination offers a slight prolongation of PFS (relative risk, 0.73; 95% upper confidence limit, 0.94; P = 0.02, one-tailed test), but no significant survival benefit (relative risk, 0.80, 95% upper confidence limit, 1.03; P = 0.071, one-tailed test). CONCLUSION: The addition of cisplatin to ifosfamide appears to offer a small improvement in progression-free survival over ifosfamide alone in the management of advanced carcinosarcoma of the uterus; the added toxicity may not justify the use of this combination.
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Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinosarcoma/tratamiento farmacológico , Ifosfamida/uso terapéutico , Neoplasias Uterinas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Persona de Mediana EdadRESUMEN
PURPOSE: The aim of this study was to compare survival and recurrence in clinical and surgical stage I-II papillary serous (PS), clear cell (CC), and endometrioid (EM) cancers of the endometrium and examine the prognostic utility of myometrial invasion. METHODS: Clinical, surgicopathologic, and survival data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. Prognostic variables examined included age, stage, grade, myometrial invasion, lymph-vascular space invasion (LVSI), and histology. PS and CC histologic subtypes were compared as both common category and discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Statistical analyses were performed using chi(2), Fisher's exact, and Wilcoxon rank sum tests, Cox regression analysis, and Kaplan-Meier survival analysis. RESULTS: PS tumors accounted for 9%, CC for 3%, and EM for 88% of cases. Recurrences were more frequent among PS (38%) and CC (22%) compared with EM (9%) (P < 0.001 and 0.08, respectively), and PS recurred more frequently than EM3 alone (20%) (P = 0.06). Among PS, CC, and EM3 patients with recurrences there were no statistical differences in the proportion that received preoperative or postoperative radiotherapy or chemotherapy. Prognostic factors for shorter survival included age >=60, surgical stage III+IV, presence of LVSI, histology (PS, CC, or EM3), and >=50% myometrial invasion. The estimated 5-year survival of PS+CC patients with <2 mm myometrial invasion is 0.56 compared to 0.93 for EM patients (P < 0. 001). PS + CC tumors confined to the endometrium had a 5-year survival of 0.60 compared to 0.98 and 1.00 for EM and EM3, respectively. The 5-year survival for surgically staged IA patients (0.57) was not different from stages IB and IC combined (0.53) (P = 0.72). The 5-year survival for surgical stage I + II PS + CC patients (0.56) was comparable to that for clinical stage I + II PS + CC patients (0.46) and remained significantly smaller than that for EM patients (0.86) (P < 0.001). CONCLUSION: Recurrences are more frequent among PS and CC tumors compared with EM and among PS compared with EM3. When controlled for surgical stage I-II tumors, 5-year survival for PS + CC patients remains comparable to that of clinical stage I-II patients and below that of EM. Prognostic factors for survival in PS and CC patients include age, stage, and LVSI. PS, CC, and EM3 subtypes together are predictors of poor survival. Thorough extended surgical staging is indicated in PS and CC tumors, and prospective trials of aggressive adjuvant therapies for surgical stage I-II tumors are needed to improve outcome in PS and CC patients.
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Adenocarcinoma de Células Claras/patología , Carcinoma Endometrioide/patología , Cistadenocarcinoma Papilar/patología , Neoplasias Endometriales/patología , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/cirugía , Cistadenocarcinoma Papilar/mortalidad , Cistadenocarcinoma Papilar/cirugía , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/cirugía , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND: Chlorpheniramine is known to cause drowsiness, and this side effect has a potential to impair performance and could be a factor in accidents. METHODS: Therefore, to establish the prevalence of this drug in pilot fatalities of aviation accidents, a postmortem toxicology database--maintained at the Civil Aeromedical Institute--was examined for the presence of chlorpheniramine in the fatalities, occurred during 1991-1996. RESULTS: There were 47 (2.2%) accidents involving chlorpheniramine. Of these, 16 had only chlorpheniramine at 109 ng.ml-1 (n = 4) in blood and 1412 ng.g-1 (n = 12) in liver. Other drugs were also present in the remaining 31 cases, wherein chlorpheniramine concentrations were 93 ng.ml-1 (n = 18) in blood and 747 ng.g-1 (n = 12) in liver. Ninety-five percent of all quantitated blood values were at or above the therapeutic level (10 ng.ml-1), giving a 100 ng.ml-1 (n = 21) mean blood value. The drug's mean liver concentration from all cases was 1080 ng.g-1 (n = 24). The average blood value was approximately 10 times higher than the therapeutic value. CONCLUSIONS: The presence of other drugs did not appear to significantly alter the blood chlorpheniramine level, but no such correlation could be established with the hepatic value. The approximate 10-fold increase in the liver concentration was consistent with the general trend of drug distribution in the hepatic compartment. However, the contribution of postmortem redistribution of the drug to alter its concentration cannot be entirely ruled out. This study suggests that chlorpheniramine was present in some aviation fatalities at levels higher than therapeutic levels.
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Accidentes de Aviación/mortalidad , Clorfeniramina/efectos adversos , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Fases del Sueño/efectos de los fármacos , Accidentes de Aviación/estadística & datos numéricos , Accidentes de Aviación/tendencias , Autopsia , Clorfeniramina/análisis , Clorfeniramina/metabolismo , Antagonistas de los Receptores Histamínicos H1/análisis , Antagonistas de los Receptores Histamínicos H1/metabolismo , Humanos , Hígado/química , Medicamentos sin Prescripción/efectos adversos , Medicamentos sin Prescripción/análisis , Medicamentos sin Prescripción/metabolismo , Vigilancia de la Población , Prevalencia , Factores de Riesgo , Detección de Abuso de Sustancias , Distribución Tisular , Estados Unidos/epidemiologíaRESUMEN
During the past 5 years the International Society for the Study of Trophoblastic Disease and the International Gynecological Cancer Society have moved to modify the staging system for trophoblastic disease by combining the staging of the International Federation of Gynecology and Obstetrics (FIGO) with the scoring system of the World Health Organization (WHO). By making significant changes in both, the classification will be more acceptable worldwide leading to uniform use by physicians reporting management results in trophoblastic disease. This is the report of the Rome Workshop, which will be presented for ratification to the FIGO Staging Committee in September 2000.
RESUMEN
PURPOSE: Progestins have definite activity against advanced or recurrent endometrial carcinoma. Both parenteral and oral progestins yield similar serum levels and response rates, which range from 18% to 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectively) than previously reported. The present study sought to confirm this earlier study of oral MPA, to assess the importance of prognostic factors such as histologic grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate. PATIENTS AND METHODS: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized to receive oral MPA either 200 mg/d or 1, 000 mg/d until unacceptable toxicity intervened or their disease progressed. RESULTS: Among 145 patients receiving the low-dose regimen, there were 25 complete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) complete and 10 (6%) partial responses for an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 months for the low-dose and high-dose regimens, respectively. Median survival durations were 11.1 months and 7.0 months, respectively. The adjusted relative odds of responding to the high-dose regimen compared with the low-dose regimen was 0.61 (90% confidence interval, 0.36 to 1.04). Prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor concentration. Compliance with oral therapy was documented with serum levels 1 month after starting therapy, when possible. MPA levels were commensurate with the assigned dose and schedule. CONCLUSION: Oral MPA is active against endometrial carcinoma. Response to progestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides no evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 mg/d orally. In fact, the trends suggest the opposite. The use of oral MPA 200 mg/d is a reasonable initial approach to the treatment of advanced or recurrent endometrial carcinoma, particularly those lesions that are well-differentiated and/or progesterone receptor-positive (> 50 fmol/mg cytosol protein). Patients with poorly differentiated and/or progesterone receptor levels less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate.
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Antineoplásicos Hormonales/administración & dosificación , Carcinoma/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Acetato de Medroxiprogesterona/administración & dosificación , Administración Oral , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/sangre , Carcinoma/sangre , Carcinoma/diagnóstico , Carcinoma/metabolismo , Carcinoma/mortalidad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Neoplasias Endometriales/sangre , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/mortalidad , Femenino , Humanos , Acetato de Medroxiprogesterona/efectos adversos , Acetato de Medroxiprogesterona/sangre , Persona de Mediana Edad , Pronóstico , Receptores de Progesterona/metabolismo , Recurrencia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: The aim of this study was to identify similarities and differences in epidemiologic and surgicopathologic staging results for papillary serous (PS) and clear cell (CC) endometrial cancers compared with endometrioid (EM) carcinoma of the endometrium. METHODS: Clinical and surgicopathologic data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. PS and CC histologic subtypes were compared both as a common category and as discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Fisher's exact test was used to compare proportions with unordered categories (2x2 tables), while the chi(2) test for trend was used to compare proportions in 3x2 tables with ordered categories. Differences in medians were compared with the Wilcoxon rank-sum test. RESULTS: PS tumors accounted for 8%, CC for 2%, and EM for 90% of cases. Overall, 14% of tumors were changed to a different postoperative histology including 64% of PS, 50% of CC, and 8% of EM. Postoperative histology changes were 4% for EM1 and 21% for EM3. PS, CC, and EM3 had more surgical sampling performed than for other EM. Rates for lymph node dissections were similar for EM3 (81%), PS (72%), and CC (67%) tumors, although metastases were more frequent for PS and CC compared with EM3. When PS tumors were confined to the endometrium, paraaortic metastases occurred in 13%. LVSI increased with EM grade and was highest for PS and CC. Upstaging to surgical stage III-IV occurred in 47% of PS, 39% of CC, and 12% of EM. The majority of PS and CC tumors were confined to the inner one-third of the myometrium, compared with EM tumors, where grade correlated with depth of myometrial invasion. Extrauterine metastases occurred in 55% of PS and 45% of CC tumors confined to the inner one-half, compared with 17% of EM3. CONCLUSION: Frequent changes from preoperative to postoperative histology and grade may contribute to misassignment of preoperative and intraoperative risk as determined by depth of myometrial invasion for PS and CC patients. The higher frequency of extrauterine metastases in PS and CC tumors compared with EM3, despite similar surgical sampling rates, supports a more virulent behavior. The poor correlation between depth of myometrial invasion and risk for extrauterine metastases helps to explain poorer survival in PS and CC patients, in addition to more frequent upstaging. These results support routine extended surgical staging for women with preoperative or intraoperative diagnosis of PS and CC tumors. Intraoperative assessment of tumor grade and histology may be indicated and warrants further investigation.
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Adenocarcinoma de Células Claras/epidemiología , Adenocarcinoma de Células Claras/patología , Carcinoma Endometrioide/epidemiología , Carcinoma Endometrioide/patología , Cistadenocarcinoma Papilar/epidemiología , Cistadenocarcinoma Papilar/patología , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/patología , Adenocarcinoma de Células Claras/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/cirugía , Cistadenocarcinoma Papilar/cirugía , Neoplasias Endometriales/cirugía , Femenino , Humanos , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
MRI was performed on the spinal roots, brachial and lumbar plexuses of 14 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Hypertrophy of cervical roots and brachial plexus was demonstrated in eight cases, six of whom also had hypertrophy of the lumbar plexus. Of 11 patients who received gadolinium, five of six cases with hypertrophy and one of five without hypertrophy demonstrated enhancement. All patients with hypertrophy had a relapsing-remitting course and a significantly longer disease duration. Gross onion-bulb formations were seen in a biopsy of nerve from the brachial plexus in one case with clinically evident nodular hypertrophy. We conclude that spinal root and plexus hypertrophy may be seen on MRI, particularly in cases of CIDP of long duration, and gadolinium enhancement may be present in active disease.