RESUMO
BACKGROUND: Trastuzumab has been approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric carcinoma; however, relatively little is known about the role of HER2 in the natural history of this disease. PATIENTS AND METHODS: Patients enrolled in the INT-0116/SWOG9008 phase III gastric cancer clinical trial with available tissue specimens were retrospectively evaluated for HER2 gene amplification by FISH and overexpression by immunohistochemistry (IHC). The original trial was designed to evaluate the benefit of postoperative chemoradiation compared with surgery alone. RESULTS: HER2 gene amplification rate by FISH was 10.9% among 258 patients evaluated. HER2 overexpression rate by IHC was 12.2% among 148 patients evaluated, with 90% agreement between FISH and IHC. There was a significant interaction between HER2 amplification and treatment with respect to both disease-free survival (DFS) (P = 0.020) and overall survival (OS) (P = 0.034). Among patients with HER2-non-amplified cancers, treated patients had a median OS of 44 months compared with 24 months in the surgery-only arm (P = 0.003). Among patients with HER2-amplified cancers, there was no significant difference in survival based on treatment arm. HER2 status was not a prognostic marker among patients who received no postoperative chemoradiation. CONCLUSION: Patients lacking HER2 amplification benefited from treatment as indicated by both DFS and OS. CLINICAL TRIAL: INT-0116/SWOG9008 phase III.
Assuntos
Adenocarcinoma/genética , Neoplasias Esofágicas/genética , Junção Esofagogástrica/patologia , Amplificação de Genes , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Quimiorradioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Feminino , Fluoruracila/uso terapêutico , Gastrectomia , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Eniluracil is a potent, irreversible inactivator of dihydropyrimidine dehydrogenase, the major catabolic enzyme for 5-fluorouracil (5-FU). Pretreatment with eniluracil significantly increases plasma half-life, plasma concentration and oral bioavailability of 5-FU. This multicenter phase II trial was designed to estimate the 6-month survival rate in patients with metastatic adenocarcinoma of the pancreas treated with 5-FU and eniluracil. PATIENTS AND METHODS: One hundred and sixteen patients (61 with no prior chemotherapy and 55 with prior chemotherapy) were registered for treatment with eniluracil 50 mg (total dose) p.o. on days 1-7 and 5-FU 20 mg/m(2)/day p.o. on days 2-6 of a 28-day treatment cycle. RESULTS: In 106 patients evaluable for survival, the 6-month survival rate was 34% [95% confidence interval (CI) 22% to 47%, median survival 3.6 months] for patients who had not been treated previously with chemotherapy and 29% (95% CI 16% to 42%, median survival 3.4 months) for those who had received prior chemotherapy. For those patients with measurable disease, the confirmed response rates were 8% and 2%, respectively. The most common grade 3-4 toxicities were neutropenia (29% of patients) and diarrhea (12% of patients). Overall, 69% of patients experienced a grade 3 or worse adverse event during treatment. CONCLUSIONS: These results suggest that the combination of a 7-day course of eniluracil and a 5-day course of oral 5-FU has limited activity in patients with advanced pancreatic cancer, and is associated with a high frequency of clinically significant adverse events.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Uracila/análogos & derivados , Adenocarcinoma/patologia , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Diarreia/induzido quimicamente , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neutropenia/induzido quimicamente , Neoplasias Pancreáticas/patologia , Sobrevida , Resultado do Tratamento , Uracila/administração & dosagem , Uracila/farmacologiaRESUMO
BACKGROUND: Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases. We investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction. METHODS: A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to surgery plus postoperative chemoradiotherapy or surgery alone. The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day, plus 20 mg of leucovorin per square meter per day, for five days, followed by 4500 cGy of radiation at 180 cGy per day, given five days per week for five weeks, with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy. One month after the completion of radiotherapy, two five-day cycles of fluorouracil (425 mg per square meter per day) plus leucovorin (20 mg per square meter per day) were given one month apart. RESULTS: The median overall survival in the surgery-only group was 27 months, as compared with 36 months in the chemoradiotherapy group; the hazard ratio for death was 1.35 (95 percent confidence interval, 1.09 to 1.66; P=0.005). The hazard ratio for relapse was 1.52 (95 percent confidence interval, 1.23 to 1.86; P<0.001). Three patients (1 percent) died from toxic effects of the chemoradiotherapy; grade 3 toxic effects occurred in 41 percent of the patients in the chemoradiotherapy group, and grade 4 toxic effects occurred in 32 percent. CONCLUSIONS: Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection.
Assuntos
Adenocarcinoma/cirurgia , Antimetabólitos Antineoplásicos/uso terapêutico , Junção Esofagogástrica/cirurgia , Fluoruracila/uso terapêutico , Neoplasias Gástricas/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Gastrectomia , Humanos , Leucovorina/uso terapêutico , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/radioterapia , Taxa de SobrevidaRESUMO
BACKGROUND & AIMS: Our long-term goal was to evaluate the role of p53 in the prognosis of gastric cancer. We previously showed a discrepancy between p53 expression and the presence of mutations when only exons 5-9 were examined. We then evaluated exon 4. METHODS: DNA was sequenced from 217 gastric cancers to detect exon 4 alterations. Codon 72 was examined by restriction enzyme digestion. RESULTS: Mutations were present in 3.2% of tumors. In addition, 2 polymorphic sites were found at codons 36 and 72. Polymorphisms at codon 36 were only found in 2 patients. In contrast, the codon 72 polymorphism was very frequent. The genotype frequency was arg/arg (54%), arg/pro (33%), and pro/pro (14%). The genotype of the polymorphic site varied with race (P = 0.001): 64% of whites had the arg/arg genotype, compared with 24% of blacks. The difference in genotype by site, sex, or histological tumor type was not statistically significant (P = 0.067). CONCLUSIONS: There are several exon 4 alterations in gastric cancers. These include the rare mutations and the very rare codon 36 polymorphism. The most common change is the codon 72 polymorphism, the genotype of which differs significantly with race. The more common arg/arg genotype in whites may explain why whites are more prone to develop cardiac cancer, whereas the more common proline allele in blacks may explain why they are more prone to develop antral cancers. Further studies are required to determine whether the codon 72 polymorphism affects patient predisposition to gastric cancer.
Assuntos
Carcinoma Medular/genética , Éxons/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/genética , Proteína Supressora de Tumor p53/genética , Adenocarcinoma Mucinoso/etnologia , Adenocarcinoma Mucinoso/genética , Apoptose/genética , Povo Asiático/genética , População Negra/genética , Tumor Carcinoide/etnologia , Tumor Carcinoide/genética , Carcinoma Medular/etnologia , Proteínas de Ligação a DNA/genética , Feminino , Mutação da Fase de Leitura , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Mutação Puntual , Polimorfismo Genético , Neoplasias Gástricas/etnologia , Transcrição Gênica/genética , População Branca/genéticaRESUMO
BACKGROUND: Appropriate adjuvant chemotherapy for resected head and neck cancer patients has yet to be defined. Multiple trials have noted trends toward improved disease-free survival and local control. The Southwest Oncology Group undertook a feasibility trial of postoperative cisplatin and radiotherapy followed by three cycles of cisplatin and 5-fluorouracil. METHODS: Patients with resected stage III or IV head and neck cancer received cisplatin, 100 mg/m2, on days 1, 22, and 43 of radiotherapy. This therapy was followed by three cycles of cisplatin, 100 mg/m2 or last tolerated dose, and 5-fluorouracil, 1000 mg/m2, on days 1 to 4 every 21 days. RESULTS: Seventy-two patients from 22 institutions were registered; 68 were evaluable. Sixty-eight patients received radiotherapy. Only 25 of 68 patients (36.7%) were able to complete all six cycles of chemotherapy. Forty-three of 68 patients (63%) completed all three cycles with radiotherapy. Toxicities were tolerable. One toxic death occurred. CONCLUSIONS: It is not feasible to deliver six cycles of chemotherapy postoperatively in the sequence described. Compliance issues need further exploration to define effective adjuvant chemotherapy for head and neck patients.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Fluoruracila/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
OBJECTIVES: We investigated p53 gene mutations in advanced gastric cancers by direct DNA sequencing, in order to determine the frequency of mutations in gastric cancers having different epidemiological backgrounds, tumors of the cardia were compared with those arising in the antrum or corpus. Intestinal type cancers were compared with diffuse or other histologic types. We have chosen to assess the frequency of mutations solely based on DNA sequencing. METHODS: Paraffin embedded tissues from 100 gastric cancers were evaluated. The mutational status of the p53 gene in exons 5 through 9 were determined by direct sequencing of PCR products. RESULTS: Mutations in exons 5, 6, 7 and 8 were found in 35 of 100(35%)stomach cancers. One tumor had mutations in both exons 5 and 8. No mutations were detected in exon 9. p53 gene mutations were significantly more frequent in cancers of the cardia (19/35; 54%) than the antrum and corpus (16/65 (25%)) (p < or = 0.005). p53 mutations were more frequent in intestinal type cancers (28/67; 42%) than diffuse cancers or other histologic types of cancer (7/33; 21%), but the difference was not statistically significant. CONCLUSIONS: Cancers of the cardia more frequently contain p53 mutations than do antral and corpus cancers, suggesting that cancers in the proximal and distal stomach evolve through different molecular pathways.
Assuntos
DNA de Neoplasias/análise , Genes p53/genética , Neoplasias Gástricas/genética , Sequência de Bases , Análise Mutacional de DNA , Humanos , Dados de Sequência Molecular , Fenótipo , Reação em Cadeia da Polimerase , Estômago/patologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Visits to physicians for genital herpes simplex virus (HSV) infection continue to increase. Most patients with symptomatic infections have recurrences, but no studies of the long-term clinical course of genital herpes are available. OBJECTIVE: To determine whether the frequency of HSV recurrences decreases over time. DESIGN: Observational cohort study. SETTING: University-based research clinic. PATIENTS: 664 persons with genital herpes followed for at least 14 months. MEASUREMENTS: Patients were classified as having initial or recurrent HSV-1 or HSV-2 infection. Patient-reported recurrences and observed recurrences were recorded in a database; more than 12,000 recurrences were analyzed. RESULTS: Median recurrence rates in the first year of follow-up were one and five per year in patients with newly acquired HSV-1 and HSV-2 infection, respectively; second-year rates were significantly lower in both groups. Patients presenting with recurrent HSV-2 infection had higher rates of recurrence in the first and second years and no significant decrease; significant decreases were detected with longer follow-up. One third of all patients experienced a decrease of two or more recurrences per year between years 1 and 2. Patients infected with HSV-2 who were followed for more than 4 years had a median decrease of two recurrences between years 1 and 5. However, 25% of these patients had an increase of at least one recurrence in year 5, illustrating the variability among HSV-infected persons. Decreases over time among patients who never received suppressive therapy were similar to decreases during untreated periods in patients who received suppressive therapy. CONCLUSIONS: Herpes simplex virus type 2 infection continues to be a chronic remitting illness. Over time, however, clinically significant reductions occur in a majority of patients. Physicians may wish to periodically assess the need for continued treatment with daily suppressive antiviral chemotherapy.
Assuntos
Herpes Genital/virologia , Herpesvirus Humano 1/crescimento & desenvolvimento , Herpesvirus Humano 2/crescimento & desenvolvimento , Ativação Viral , Aciclovir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Herpes Genital/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVES: The care of patients with first episode and recurrent genital herpes differs with respect to therapy and source partner evaluation. Of 498 persons who presented with what appeared by history and symptoms to be a first episode of genital herpes, we identified 41 who had serologic evidence of remotely acquired herpes simplex virus 2 (HSV-2) infection. GOALS: To define the natural history of these individuals with previously unrecognized HSV-2 and to evaluate if any clinical or historical features could differentiate these people from persons with true first episode infection. STUDY DESIGN: Observational cohort study. RESULTS: Clinical overlap existed in the frequency of local symptoms, fever, and size of genital lesions between those with remotely acquired versus recently acquired genital herpes. The frequency of new sexual partners and recent sexual history were also similar in the two groups. However, on follow-up, the lesions of persons with remotely acquired HSV-2 healed more rapidly and subsequently recurred less frequently than those of true primary HSV-2. CONCLUSIONS: Even in a referral clinic with experienced clinicians, almost 10% of persons who are judged to have first episode genital herpes have evidence of remotely acquired HSV-2, suggesting that clinical differentiation of first episode genital herpes from previously acquired infection is difficult. Type-specific serologic testing assists the clinician in correctly classifying the infection and determining the potential source partner.
Assuntos
Anticorpos Antivirais/sangue , Herpes Genital/diagnóstico , Herpesvirus Humano 2/imunologia , Adolescente , Adulto , Diagnóstico Diferencial , Feminino , Herpes Genital/imunologia , Herpes Genital/terapia , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
In an exploratory study, levels of cadmium in whole-kidney and liver tissues of 314 subjects from the general population of the province of Quebec (Canada) were measured postmortem. Frequency distributions of cadmium concentrations were lognormal. As reported in similar studies, age and especially smoking habits were the main variables affecting cadmium concentrations. The geometric mean of whole kidney concentrations (wet weight) was 17.62 microg/g, with a minimum concentration of 2.25 microg/g and a maximum of 100.61 microg/g. Mean concentrations of cadmium in kidneys increased with age, reaching a plateau in the group 50 to 59 yr (29.49 microg/g), and falling slowly thereafter.
Assuntos
Cádmio/análise , Rim/química , Fígado/química , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quebeque , Fatores Sexuais , FumarRESUMO
PURPOSE: Fluorouracil (5-FU) continuous infusion is superior to 5-FU bolus in patients with advanced colorectal cancer, but the survival difference between the two treatments is small and, therefore, the difference in toxicity profile is crucial in choosing a treatment for individual patients. MATERIALS AND METHODS: We conducted a meta-analysis of all randomized trials that compared 5-FU bolus with 5-FU CI, based on individual data from 1,219 patients, to compare the toxicity of the two schedules of 5-FU administration and to identify predictive factors for toxicity. The toxicities considered were World Health Organization (WHO) grade 3 to 4 anemia, thrombopenia, leukopenia, neutropenia, nausea/vomiting, diarrhea, mucositis, and hand-foot syndrome. RESULTS: Hematologic toxicity, mainly neutropenia, was more frequent with 5-FU bolus than with 5-FU CI (31% and 4%, respectively; P < .0001). Hand-foot syndrome was less frequent with 5-FU bolus than with 5-FU CI (13% and 34%, respectively; P < .0001). There was no difference between the two treatment groups in terms of other nonhematologic toxicities. Independent prognostic factors were age, sex, and performance status for nonhematologic toxicities, performance status, and treatment for hematologic toxicities, and age, sex, and treatment for hand-foot syndrome. CONCLUSION: Based on a large data set, this study confirmed and quantified the toxicity profile of the two schedules of administration of 5-FU and allowed the identification of clinical predictors of toxicity.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/efeitos adversos , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Doenças Hematológicas/induzido quimicamente , Humanos , Infusões Intravenosas , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/efeitos dos fármacos , Náusea/induzido quimicamente , Prognóstico , Distribuição Aleatória , Taxa de SobrevidaRESUMO
Patients entered into Southwest Oncology Group gastric adjuvant protocol INT 0016 (SWOG 9008) after a "curative" gastric resection were assessed to determine practice patterns of more than 300 surgeons nationwide who performed "curative" gastric resections for 453 gastric cancer patients. The most common gastric resection performed was distal in 256 patients, proximal in 118, and total in 79. Extragastric organs resected were omentum (285), spleen (59), pancreas (18), and bowel (17). The extent of lymphadenectomy as staged by Japanese rules was 246 (54.2%) D0 resections, 173 (38.1%) D1 resections, 28 (6.2%) D2 resections, and 7 (1.5%) D3 resections. Staging of the cancer was poorly documented, with no statement made regarding the status of the primary cancer in 6 per cent, liver in 10 per cent, lymph nodes in 17 per cent, and omentum in 17 per cent. The greater the lymph node clearance, the greater the chance of resecting to a level of negative lymphatics, given that 45 per cent of nodes were involved when 10 or less were removed, whereas only 17 per cent were positive when more than 40 were cleared. The lack of adequate clearance of lymph nodes and poor documentation of tumor stage suggests that a more regimented surgical approach to this uncommon cancer is required.
Assuntos
Gastrectomia/métodos , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias Gástricas/cirurgia , Documentação/normas , Gastrectomia/estatística & dados numéricos , Humanos , Japão , Excisão de Linfonodo , Prontuários Médicos , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Estados Unidos/epidemiologiaRESUMO
PURPOSE: The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU. DESIGN: Individual data of 1,219 patients included in six randomized trials served as the basis for this meta-analysis, which was conducted by an independent secretariat in close collaboration with the investigators. RESULTS: Tumor response rate was significantly higher in patients assigned to 5-FU CI than in patients assigned to 5-FU bolus (22% v 14%; overall response odds ratio, 0.55; 95% confidence interval [95% CI], 0.41 to 0.75; P = .0002). Overall survival was also significantly higher in patients assigned to 5-FU CI (overall hazards ratio [HR], 0.88; 95% CI, 0.78 to 0.99; P = .04), although the median survival times were close. Multivariate analyses showed that randomized treatment and performance status were the only two significant predictors of tumor response, whereas the same plus primary tumor site were independent significant predictors of survival (patients with rectal cancer did somewhat better). Grade 3 or 4 hematologic toxicity was more frequent in patients assigned to 5-FU bolus (31% v 4%; P < 10(-16)), whereas hand-foot syndrome was more frequent in the 5-FU CI group (34% v 13%; P < 10(-7)). CONCLUSION: 5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Neoplasias Colorretais/mortalidade , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do TratamentoRESUMO
The projection point of the axis of the anterior column of the acetabulum on the outer table of the iliac wing was determined in 15 adult bony hemipelves. The optimal entry point for lag screw fixation in the anterior column was located 16 +/- 3.9 mm superior to the midpoint of the line connecting the apex of the sciatic notch with the notch between anterior superior iliac spine and anterior inferior iliac spine, and 46 +/- 5.9 mm superior to the acetabular rim. The mean inclination of the projected axis was 90.6 degrees +/- 5.0 degrees in the sagittal plane and 29.0 degrees +/- 4.4 degrees in the transverse plane. These data may facilitate insertion of a lag screw into the anterior acetabular column and minimize the risk of articular violation or cortical penetration because there is a narrow margin of safety. The lag screw placement also may be aided by palpating the anterior column with a finger and by intraoperative fluoroscopy for visualization of the hip joint and the anterior column in the obturator or pelvic outlet views.
Assuntos
Acetábulo/anatomia & histologia , Acetábulo/lesões , Parafusos Ósseos , Fraturas Ósseas/cirurgia , Idoso , Antropometria , Cadáver , Feminino , Fluoroscopia , Fraturas Ósseas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , PalpaçãoRESUMO
The topoisomerase-1 inhibitor, topotecan, was tested in 48 eligible patients with advanced colorectal cancer. The patients had no prior chemotherapy and a Southwest Oncology Group performance status of 0-2. Topotecan was administered intravenously at 1.5 mg/m2/day for five days and repeated every 21 days. The major toxicity was hematologic with 19 out of 48 (40%) patients having grade IV granulocytopenia and 4 out of 48 (8%) patients demonstrating grade IV thrombocytopenia. Two patients (4%) demonstrated partial response. Thirty patients have died and the Kaplan-Meier estimate of median survival is 9 months (95% confidence interval; 7-16 months). Topotecan in this dose and schedule does not appear active in patients with advanced colorectal cancer.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Topotecan/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Progressão da Doença , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Topotecan/administração & dosagem , Topotecan/efeitos adversosRESUMO
Hepatocellular carcinoma remains a highly chemoresistant neoplasm. In this study of the topoisomerase I inhibitor topotecan a response rate of 13.9% (95% confidence interval 4.7%-29.5%) was obtained utilizing a five consecutive day bolus infusion schedule. There were no complete responses and the median survival was only eight months. Furthermore, treatment with topotecan produced significant toxicity with two-thirds of patients experiencing life-threatening (grade 4) neutropenia. When used in this dose and schedule, topotecan does not appear to be effective for patients with advanced hepatocellular carcinoma.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Topotecan/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Neoplasias Hepáticas/enzimologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Inibidores da Topoisomerase I , Topotecan/efeitos adversosRESUMO
Topotecan (NSC 609099) is a camptothecin analogue that demonstrated activity against a variety of human tumors in preclinical studies. A phase II trial was performed with topotecan given to patients with locally advanced or metastatic adenocarcinoma of the stomach. Topotecan was administered IV Bolus over 30 minutes on a daily X 5 schedule, every three weeks, with a starting dose of 1.5 mg/m2. Twenty patients were entered onto the study, all of whom were eligible. All patients were evaluable for toxicities. Half of these patients experienced at least one Grade 4 hematologic toxicity, comprised of either granulocytopenia or leukopenia (4 patients with both, 3 patients with grade 4 granulocytopenia, and 2 patients with only grade 4 leukopenia). Other non-life threatening (Grade 3) toxicities included nausea (2 patients), weakness (2 patients), weight loss (1 patient), blurred vision (1 patient), diarrhea (1 patient) and malaise/fatigue/lethargy (1 patient). Two patients achieved a partial response, for an overall response rate of 10% (95% confidence interval of 1.2 to 31.7%). The median survival for the 20 patients was five months.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Topotecan/uso terapêutico , Adulto , Idoso , Agranulocitose/induzido quimicamente , Antineoplásicos/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Inibidores da Topoisomerase I , Topotecan/efeitos adversosRESUMO
This cohort study of 182 women attending a sexually transmitted disease clinic evaluated the hypothesis that women colonized by lactobacilli have decreased acquisition of vaginal infections. During a 2-year follow-up, 50 women acquired bacterial vaginosis (BV), 25 acquired symptomatic vulvovaginal candidiasis (VVC), and 7 acquired vaginal trichomoniasis. By multivariate analysis, utilizing Cox proportional hazards modeling with time-dependent covariates, acquisition of BV was independently associated with lack of vaginal H2O2-producing lactobacilli (hazard ratio [HR] = 4.0, P < .001) or presence of only non-H2O2-producing lactobacilli (HR = 2.2, P = .02). Acquisition of BV was associated with having a new sex partner (HR = 2.5, P = .004) and with douching for hygiene (HR = 2.1, P = .05). Absence of lactobacilli did not increase acquisition of VVC. Trichomoniasis was associated only with having a new sex partner (HR = 4.7, P = .05). These results support the hypothesis that H2O2-producing vaginal lactobacilli protect against acquisition of BV but do not protect against VVC or vaginal trichomoniasis.
Assuntos
Candidíase Vulvovaginal/prevenção & controle , Peróxido de Hidrogênio/metabolismo , Lactobacillus/fisiologia , Vaginite por Trichomonas/prevenção & controle , Vagina/microbiologia , Vaginose Bacteriana/prevenção & controle , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine if fetal growth restriction and prematurity are observed with subclinical shedding of herpes simplex virus (HSV) at the onset of labor. METHODS: Within 48 hours of delivery, cultures were taken from the cervix and external genitalia of 15,923 asymptomatic pregnant women without symptoms or signs of genital HSV infection; results were positive for HSV in 57. Each of these 57 women were compared with a control group composed of the three culture-negative women delivering immediately before and the three delivering immediately after each woman shedding HSV. RESULTS: The median birth weight for infants born to the 57 women with asymptomatic shedding was 3050 g, compared with 3360 g among the 342 women without asymptomatic shedding, a statistically significant difference (P < .002). These differences were due to very low birth weight (LBW) among the five infants of women with subclinical viral shedding secondary to recently acquired primary genital herpes; these five infants had a median gestational age of 33 weeks, compared with 37 weeks for the 14 infants of mothers with nonprimary, first-episode disease and 39 weeks for the 33 infants of women with reactivation disease, also a significant difference (P = .018). CONCLUSIONS: Asymptomatic genital shedding of HSV at the onset of labor because of subclinical primary genital HSV infection is associated with preterm delivery. Women who acquire genital HSV-2 before pregnancy and are shedding subclinically at the onset of labor experience no increase in adverse outcome. Thus, prevention of the prematurity and LBW associated with genital herpes means that acquisition of the infection in late pregnancy must be prevented.
Assuntos
Herpes Genital/complicações , Herpes Genital/virologia , Início do Trabalho de Parto , Trabalho de Parto Prematuro/etiologia , Complicações Infecciosas na Gravidez/virologia , Simplexvirus/isolamento & purificação , Peso ao Nascer , Estudos de Casos e Controles , Colo do Útero/virologia , Feminino , Genitália Feminina/virologia , Idade Gestacional , Humanos , Recém-Nascido , GravidezRESUMO
Fifteen cadaveric adult bony hemipelvis specimens and 30 adult dry bone specimens were obtained to evaluate the configuration of the anterior column of the acetabulum and to develop a safe path for screw placement into it. Each cadaveric specimen was sectioned at 1-cm intervals, beginning at the level of the inferior border of the acetabulum (junction between the anteroinferior edge of the acetabulum and the most anterolateral edge of the superior ramus of the pubic bone). The plane of the cross-section was perpendicular to the anterior column. The projection of the medial acetabular boundary on the anterior column was determined by analysis of each cross-section. Results showed that the average width of the anterior column at 1.0, 2.0, and 3.0 cm superior to the inferior acetabular boundary is 31.0 +/- 4.7, 34.2 +/- 5.1, and 39.4 +/- 6.2 mm, respectively. At 1.0 cm superior to the inferior margin of the acetabulum, the average medial angulation for 0.5-, 1.0-, and 1.5-cm entry points lateral to the pelvic brim were 24.9 +/- 4.4 degrees, 35.5 +/- 5.2 degrees, and 44.4 +/- 6.6 degrees, respectively. At 2.0 cm superior to the inferior acetabular margin, the corresponding average medial angulation for 0.5-, 1.0-, 1.5-cm entry points were determined to be 29.2 +/- 5.5 degrees, 38.6 +/- 5.9 degrees, and 48.1 +/- 5.7 degrees, respectively. At 3.0 cm superior to the inferior acetabular margin, these angles were found to be 20.7 +/- 4.3 degrees, 29.4 +/- 6.0 degrees, and 39.3 +/- 5.9 degrees, respectively. All of the above mentioned angles are with respect to the perpendicular of the longitudinal axis of the anterior column without violation of the hip joint. Screws placed 1.0 cm lateral to the pelvic brim at the levels of 1.0, 2.0, 3.0, and 4.0 cm superior to the inferior acetabular margin and directed perpendicular to the anterior column penetrated the hip joint.