RESUMEN
The paper describes Russia's first diagnosed case of Erdheim--Chester disease (systemic histiocytosis) in a 65-year-old man who has been long treated for Ormond's disease (idiopathic retroperitoneal fibrosis). It also gives the data available in the literature on the pathogenetic components of these diseases and on the similarity of many clinical, laboratory, and morphological characteristics of these two immunoinflammatory diseases and covers the issues of their differential diagnosis. Invasive procedures with a careful morphological/immunomorphological examination of biopsy specimens obtained from affected tissues are shown to be necessary for accurate diagnosis.
Asunto(s)
Errores Diagnósticos , Enfermedad de Erdheim-Chester/diagnóstico , Inmunoglobulina G/inmunología , Fibrosis Retroperitoneal/diagnóstico , Anciano , Diagnóstico Diferencial , Humanos , Masculino , Federación de RusiaRESUMEN
BACKGROUND: This trial was designed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) and to identify patient populations most likely to benefit from the combination. PATIENTS AND METHODS: Patients with one prior systemic therapy for advanced disease were eligible. Docetaxel (75 mg/m(2) on day 1) was administered alone or with ganetespib (150 mg/m(2) on days 1 and 15) every 3 weeks. The primary end points were progression-free survival (PFS) in two subgroups of the adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH) and mutated KRAS (mKRAS). RESULTS: Of 385 patients enrolled, 381 were treated. Early in the trial, increased hemoptysis and lack of efficacy were observed in nonadenocarcinoma patients (n = 71); therefore, only patients with adenocarcinoma histology were subsequently enrolled. Neutropenia was the most common grade ≥3 adverse event: 41% in the combination arm versus 42% in docetaxel alone. There was no improvement in PFS for the combination arm in the eLDH (N = 114, adjusted hazard ratio (HR) = 0.77, P = 0.1134) or mKRAS (N = 89, adjusted HR = 1.11, P = 0.3384) subgroups. In the intent-to-treat adenocarcinoma population, there was a trend in favor of the combination, with PFS (N = 253, adjusted HR = 0.82, P = 0.0784) and overall survival (OS) (adjusted HR = 0.84, P = 0.1139). Exploratory analyses showed significant benefit of the ganetespib combination in the prespecified subgroup of adenocarcinoma patients diagnosed with advanced disease >6 months before study entry (N = 177): PFS (adjusted HR = 0.74, P = 0.0417); OS (adjusted HR = 0.69, P = 0.0191). CONCLUSION: Advanced lung adenocarcinoma patients treated with ganetespib in combination with docetaxel had an acceptable safety profile. While the study's primary end points were not met, significant prolongation of PFS and OS was observed in patients >6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Anciano , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Docetaxel , Femenino , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Humanos , L-Lactato Deshidrogenasa/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas p21(ras)/genética , Taxoides/administración & dosificación , Resultado del Tratamiento , Triazoles/administración & dosificaciónRESUMEN
AIM: To characterize a group of patients with IgG4-related disease (IgG4-RD) in a Russian population and to evaluate the efficiency of rituximab therapy. SUBJECTS AND METHODS: In 2009 to 2011, at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, 30 patients (16 men and 14 women; mean age 44 years) were diagnosed with IgG4-RD that was confirmed by determination of serum IgG4 levels and immunohistochemical study of biopsy samples stained for IgG4-positive plasma cells. Seven patients received rituximab therapy. RESULTS: It was assumed at baseline that there were different types of neoplasias in 12 (40%), non-Hodgkin's and Hodgkin's lymphomas in 10 (33.3%), Sjögren's syndrome in 5 (16.7%), and Wegener's granulomatosis in 3 (10%). When 2 or more locations were involved, the condition was regarded as multifocal fibrosclerosis (33.3%). Localized forms were revealed in 20 (66.7%) patients. Among them, the largest number of patients was those who had orbital pseudotumor, Mikulicz's disease, or retroperitoneal fibrosclerosis. The most common sites of involvement were orbits (66.7%), salivary glands (70%) and lymph nodes (36.7%). Comparison of serum IgG4 levels in 28 patients with IgG4-RD, 22 patients with Sjögren's disease, salivary and lacrimal gland lymphomas, and 10 healthy controls showed that the concentration of IgG4 was significantly higher in Group 1 (median 2.6 g/I; IQR 1.22-4.65 (p < 0.001). Tissue IgG4/IgG ratio varied from 25 to 50% and averaged 38%. A moiré-like pattern of varying fibrosis was noted in 83% of cases. Analysis of laboratory data revealed elevated C-reactive protein concentrations (46.7% with a mean of 39.5 mg/l; normal values < 5.0 mg/l), increased erythrocyte sedimentation rate (60% with a mean of 37.6 mm/h), hypergammaglobulinemia (30% with a mean of 29.4%; normal range 13-22%), and rheumatoid factor (23.3%). After rituximab therapy, all the patients showed a decrease of IgG4 levels to the normal levels and positive changes evidenced by visualization techniques (computed tomography, magnetic resonance imaging). CONCLUSION: IgG4-RD is a novel problem in modern medicine, which requires a multidisciplinary approach and further study. Rituximab therapy is a promising treatment.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/fisiopatología , Inmunoglobulina G/sangre , Factores Inmunológicos/uso terapéutico , Adulto , Enfermedades Autoinmunes/etiología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rituximab , Resultado del TratamientoRESUMEN
Estrogens play the most important role in breast cancer oncogenesis. There are different methods used to decrease estrogen production and serum concentration: surgery, irradiation and drug-based method. In the current study 500 patients with localized surgically resectable breast cancer (infiltrative-edematous form included) or disseminated breast cancer with indication for ovarial function inhibition. The patients were divided into 3 groups. The first group consisted of 400 patients with prior endoscopic bilateral ovariectomy. The second group included 50 patients with prior ovarian irradiation, the third one included 50 patients after laparotomic ovarian resection. The results obtained show 100% effect of endoscopic ovariectomy resulted in disabled ovarian function, which is more effective, than ovarian irradiation (92%). Besides, the endoscopic method doesn't have negative effects characteristic for irradiation, such as involvement of non-target organs or restoration of hormone production. Endoscopic surgery was characterized by 10-fold decrease in complications rate compared to laparotomic operation (2.2% vs 24%). Besides, endoscopic intervention leads to much shorter inpatient treatment duration and demand for anesthetics and antibiotic treatment making it less costly, than more traditional methods of castration. Therefore, endoscopic ovarian resection is a safe and effective castration method in breast cancer patients.
Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/terapia , Estrógenos/biosíntesis , Neoplasias Hormono-Dependientes/metabolismo , Neoplasias Hormono-Dependientes/terapia , Ovariectomía , Ovario/efectos de la radiación , Adulto , Neoplasias de la Mama/sangre , Neoplasias de la Mama/radioterapia , Endoscopía , Estrógenos/sangre , Femenino , Humanos , Laparotomía , Persona de Mediana Edad , Neoplasias Hormono-Dependientes/sangre , Neoplasias Hormono-Dependientes/radioterapia , Ovariectomía/métodos , Ovario/metabolismo , Premenopausia , Estudios RetrospectivosRESUMEN
Whether the DNA index (DNAI) of tumor cells and serum carcinoembryonic antigen (CEA) may be used to make prognosis in 78 patients with epidermoid lung cancer at the stage of T1-3 N(o) Mo was studied. There was a direct correlation between tumor ploidy and CEA levels. The two-year relapse- free survival among the operated-on patients at the stage T1-2 N(o) Mo was not shown to be associated with DNAI. At the same time in the T1-3 M1-2 Mo patients radically operated on, the two-year survival correlates with DNAI: it is significantly (p < 0,05) higher in patients with diploid tumors (DNAI = 1.0) than in those with aneuploid cancer (DNAI > 1.05). The patients with low preoperative CEA levels ( < 10 micrograms/l) have a more favourable prognosis after radical surgical treatment.
Asunto(s)
Antígeno Carcinoembrionario/sangre , Carcinoma de Células Escamosas/diagnóstico , ADN de Neoplasias/genética , Neoplasias Pulmonares/diagnóstico , Ploidias , Aneuploidia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Diploidia , Supervivencia sin Enfermedad , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Pronóstico , Radioinmunoensayo , Factores de TiempoRESUMEN
Conservative treatment was carried out in 119 cases of hepatic malignancy (primary cancer--36 and metastatic tumors--83). Radiation therapy using a Rokus-M installation or a Saturn linear accelerator was performed in 26 cases, chemoradiation treatment--14 and cytostatic therapy alone--in 79 patients. Single focal dose used was 2 Gy, while total dose was as high as 51-70 Gy in cases receiving radiation alone and 35-40 Gy in the combined therapy group. Various combinations of carminomycin, bleomycin, cisplatinum, adriamycin, 5-fluorouracil, allopurinol and cyclophosphamide were employed. Radiation and chemoradiation treatment proved effective in 67.5% of cases. Mean survival time for patients suffering primary cancer was 15.8 +/- 4.3 months, and for those with metastatic tumor--8.3 +/- 1.6 months. Remission was registered in 14, while stabilization--in 31 out of 79 patients who had received chemotherapy. The symptomatic effect was observed in 38%.
Asunto(s)
Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/radioterapia , Adulto , Anciano , Terapia Combinada , Femenino , Fluorouracilo/uso terapéutico , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Aceleradores de Partículas , Dosificación Radioterapéutica , Tegafur/uso terapéuticoRESUMEN
The paper is concerned with the analysis of the results of surgical and drug therapy of 225 cases of primary hepatic tumor treated at the Center clinic within 1957-1981. 86 patients were operated on: radical surgery was performed in 20 cases. Postoperative lethality rate in radical surgery group was 10%, mean survival time-26.7 months. Systemic chemotherapy was given to 111, and regional one-to 12 patients. New schemes of drug treatment (carminomycin + bleomycin; preparations of platinum + other cytostatic drugs) were used in 30 cases. This was followed by a higher effectiveness of treatment and a longer survival, the latter being 9.0 +/- 1.3 months, as compared with 4.0 +/- 0.5 months in controls.
Asunto(s)
Adenoma de los Conductos Biliares/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Adenoma de los Conductos Biliares/tratamiento farmacológico , Adenoma de los Conductos Biliares/mortalidad , Adolescente , Adulto , Anciano , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Terapia Combinada , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana EdadRESUMEN
The investigation involved 30 patients with locally advanced breast cancer (T3-4N1-2M0). Combination therapy comprised two courses: carboplatin 300 mg/m2, i.v., dropwise, on day 1; doxorubicin 30 mg/m2, i.v., bolus-flow, on days 1 and 8; 5-fluorouracil 350 mg/m2, i.v., bolus-flow, on days 1 and 8, and irradiation of the breast and regional metastasis area (single target dose--2 Gy, total target dose--40 Gy). Overall clinical response was 96.7% (29/30), mammography-wise--83.3% (25/30). All patients were found operable and radical mastectomy was performed in 25. Therapeutic effect stage III-IV was histologically confirmed in 40% (25/30), stage I-II--60% (15/25). Median overall and recurrence-free survival was not reached within 36 months in 24/30, relapse-free survival was been reported in 16/24 (66.6%), tumor progression--8/24 (33.4%). Three-year; host-mastectomy recurrence-free survival--68.8 +/- 16.0%.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/terapia , Adulto , Antibióticos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Carboplatino/administración & dosificación , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/mortalidad , Carcinoma Lobular/radioterapia , Carcinoma Lobular/cirugía , Terapia Combinada , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Mamografía , Mastectomía Radical , Persona de Mediana Edad , Dosificación Radioterapéutica , Análisis de Supervivencia , Factores de TiempoRESUMEN
Functional activity of multidrug resistance (MDR) markers (total activity of ABC-transporters, P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) activities) in human colon adenocarcinoma and normal mucosa was examined. Functional activity of ABC-transporters was revealed in all colon tumors and in 70% of normal mucosa samples investigated. Expression of Pgp and MRP functional activity was determined in about 50% and 70% of colon tumors respectively. Pgp+MRP+ phenotype was determined in 36% of normal mucosa and adenocarcinoma samples. Expression of Pgp+MRP- phenotype was practically the same in normal mucosa and tumors (in 10 and 18% of samples respectively). Pgp-MRP+ phenotype was revealed two times more often in tumors than in mucosa--in 36 and 18% respectively. On the contrary, Pgp-MRP- phenotype was detected more rarely in tumors than in mucosa (in 10 and 36% of samples respectively). Transporters different from Pgp and MRP were also determined in some tumors and normal mucosa. At the patients with expression of Pgp function in normal mucosa the activity of the transporter was revealed in 25% of tumor samples only. On the contrary, at the patients with expression of MRP function in normal mucosa the activity of the transporter was revealed in 70% of tumor samples. At the patients with no expression of Pgp or MRP activity in normal mucosa the function of the transporters in tumors was determined in 60% and 70% of samples respectively. It is concluded that functional activity of various ABC-transporters (Pgp, MRP and other different from Pgp and MRP) is expressed in human colon adenocarcinoma; expression of ABC-transporters functional activity in normal mucosa does not predict MDR phenotype of the tumor.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Adenocarcinoma/metabolismo , Colon/metabolismo , Neoplasias del Colon/metabolismo , Resistencia a Múltiples Medicamentos , Mucosa Intestinal/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Antineoplásicos/farmacología , Doxorrubicina/farmacología , Humanos , Técnicas In Vitro , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/antagonistas & inhibidores , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , FenotipoRESUMEN
With an account of the literature data that platinum drugs react with many cellular targets, including ATP and proteins, the authors suggested that disturbance of the function of energy-dependent ABC-transporters (markers of multidrug resistance, MDR) under the effect of platinum drugs could be a cause of increased efficacy of MDR agents (agents, MDR to which is developed by the classical mechanism) when used in combination with platinum drugs even in the treatment of multidrug resistant lung cancer. The cisplatin and carboplatin effect on accumulation of MDR doxorubicin in cells of non-small cell cancer was studied by flow cytometry with the use of biopsy specimens. The MDR phenotype of the tumors was determined by a change in doxorubicin intracellular accumulation under the action of the ABC-transporter(s)' inhibitors: verapamil and genistein (specific inhibitors of Pgp and MRP respectively) and sodium azide (an inhibitor of all energy-dependent ABC-transporters). The MDR phenotypes, i.e. Pgp-MRP+ or Pgp+MRP+, were detected in all the tumors investigated. Two types of changes in doxorubicin intracellular accumulation under the action of the inhibitors and the platinum drugs were shown: (a) an increase in doxorubicin cytoplasmic accumulation and (b) a change in subcellular distribution of the anthracycline (increased accumulation of doxorubicin in the cell nucleus and its higher binding to DNA). Cisplatin and carboplatin had an inhibitory effect on ABC-transporter(s) in all the tumors investigated but the effect of carboplatin was less pronounced. It was concluded that cisplatin and carboplatin stimulation of doxorubicin intracellular accumulation, as well as a change in subcellular distribution of the anthracycline under the action of the platinum drugs (increased doxorubicin accumulation in the cell nucleus) in multidrug resistant lung tumors could be at least partly explained by inhibition of the MDR transporter(s)' function. The results could provide a basis for the use of the sequential combination cisplatin (or carboplatin)-->doxorubicin in the treatment of multidrug resistant lung cancer.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Antineoplásicos/farmacología , Carboplatino/farmacología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Cisplatino/farmacología , Doxorrubicina/metabolismo , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Neoplasias Pulmonares/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Transportadoras de Casetes de Unión a ATP/metabolismo , Antineoplásicos/uso terapéutico , Biopsia , Línea Celular Tumoral/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Citoplasma/efectos de los fármacos , Citoplasma/metabolismo , Doxorrubicina/análisis , Combinación de Medicamentos , Quimioterapia Combinada , Inhibidores Enzimáticos/farmacología , Citometría de Flujo , Genisteína/farmacología , Humanos , Verapamilo/farmacologíaRESUMEN
Radioimmunoassay was employed to measure serum levels of neuron-specific enolase (NSE) in 38 lung cancer patients, 20 patients with noncancer pulmonary lesions and 10 healthy donors. An average NSE level (92.8 +/- 18.7 micrograms/l) in small cell carcinoma (10 patients) was significantly higher (p less than 0.01) than in control, nonmalignant pulmonary diseases, squamous cell and adenocarcinoma. Sensitivity and specificity of the tumor marker to small cell carcinoma reached 80 and 95%, respectively. NSE serum test may serve an additional tool in differential diagnosis of small cell carcinoma of the lung.
Asunto(s)
Biomarcadores de Tumor/sangre , Bronquitis/enzimología , Enfermedades Pulmonares/enzimología , Neoplasias Pulmonares/enzimología , Fosfopiruvato Hidratasa/sangre , Neumonía/enzimología , Sarcoidosis/enzimología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , RadioinmunoensayoRESUMEN
The work is based on the experience with treatment of 86 patients with Raynaud's disease. 41 patients were treated conservatively, in 45 patients thoracic sympathectomy was performed. All 45 patients subjected to thoracic sympathectomy showed excellent and good immediate results. Late results were favourable in 20 out of 23 operated patients, examined within the terms from 5 to 15 years postoperatively. Thus, thoracic sympathectomy is an effective method of treatment for Raynaud's disease.