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1.
Urol Clin North Am ; 47(1): 83-91, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757303

RESUMO

After Bacillus Calmette-Guerin (BCG) failure, there is likely a 6- to 24-month window whereby salvage intravesical therapy might allow for preservation of the bladder without disease worsening. Combination intravesical, salvage therapy for nonmuscle invasive bladder cancer represents a promising avenue for treatment in patients unfit or unwilling to undergo cystectomy. BCG with concomitant immune stimulating agents or immune checkpoint inhibitors, combination chemotherapy regimens, such as gemcitabine and docetaxol, and novel agents currently in clinical trials provide hope for a bladder-sparing alternative for patients after BCG failure.


Assuntos
Vacina BCG/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel/administração & dosagem , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos , Administração Intravesical , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Desoxicitidina/administração & dosagem , Quimioterapia Combinada , Humanos , Invasividade Neoplásica , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
2.
Urol Clin North Am ; 47(1): 1-4, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757292

RESUMO

High-risk non-muscle invasive bladder cancer is marked by frequent disease recurrences and risk of stage progression, contributing to high surveillance, treatment-related costs, and patient anxiety. Although the mainstay of high-risk non-muscle invasive bladder cancer clinical management remains transurethral resection followed by intravesical bacillus Calmette-Guérin (BCG), patients who develop BCG-unresponsive disease have few salvage options outside of a radical cystectomy with pelvic lymphadenectomy. This article provides a historical context relevant to the development of the BCG-unresponsive definition, an overview of current clinical trial expectations, and an introduction to this issue of Urologic Clinics.


Assuntos
Vacina BCG/administração & dosagem , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Progressão da Doença , Humanos , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/patologia
3.
Urol Clin North Am ; 47(1): 119-128, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757295

RESUMO

Bacillus Calmette-Guerin (BCG)-refractory high-grade non-muscle-invasive bladder cancer remains a challenging problem. Radical cystectomy is standard of care, but carries significant morbidity. Therefore, there is a need for effective treatments. Previous salvage intravesical therapies have had disappointing results with long-term follow-up; however, a wide array of novel agents is currently under investigation. These include novel combinations of existing intravesical agents, novel modes of delivery such as hyperthermia, viral mediated therapies, and immunotherapy. We review the need for novel treatment with existing agents and their long-term results, and discuss novel intravesical therapies and the data currently available on these therapies.


Assuntos
Antineoplásicos/administração & dosagem , Vacina BCG/administração & dosagem , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Quimioterapia Combinada , Humanos , Invasividade Neoplásica , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
4.
Urol Clin North Am ; 47(1): 15-21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757296

RESUMO

Disease progression and recurrence are common among patients on Bacillus Calmette-Guérin (BCG) therapy, and options for bladder-preserving subsequent therapy remain limited. Ongoing efforts to develop better second-line bladder-sparing therapies rely on clinical trials of patients deemed to have failed management with BCG. This article describes historical definitions of BCG failure, as well as recent efforts to better delineate and refine the clinical criteria for identifying individual patients who will not benefit from further intravesical BCG therapy. It also reviews guidance from the most recent expert consensus panels and professional association guidelines regarding which patients should not receive additional BCG therapy.


Assuntos
Vacina BCG/administração & dosagem , Seleção de Pacientes , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Progressão da Doença , Humanos , Invasividade Neoplásica , Falha de Tratamento , Neoplasias da Bexiga Urinária/patologia
5.
Urol Clin North Am ; 47(1): 23-33, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757297

RESUMO

Despite the 40-year reign of bacillus Calmette-Guérin (BCG) as the most effective immunotherapy in urologic cancers, a lack of clinical tools to predict treatment response has hampered progress in the field. Acting as an immunostimulatory agent against a multitude of phenotypically diverse non-muscle-invasive bladder cancers, response to BCG likely depends on both tumor characteristics as well as host factors. With a deeper understanding of the tumor biology as well as the mechanism of action underpinning immunotherapy, newer and more effective clinical tools are being constructed to improve patient selection.


Assuntos
Vacina BCG/administração & dosagem , Imunoterapia/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Humanos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
6.
Urol Clin North Am ; 47(1): 35-46, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757298

RESUMO

Non-muscle-invasive bladder cancer (NMIBC) is heterogeneous, but current diagnostic and treatment strategies rely primarily on clinical parameters, lacking individualization to tumor and host genetics and biology. The heterogeneity of NMIBCs is derived from mutations, mutation signatures, chromosomal loss, and disruption of molecular pathways, which ultimately affects tumor progression, recurrence, and responsiveness to intravesical and systemic chemotherapy. Although research is still underway, advances in sequencing technology, insight into differential bacillus Calmette-Guérin responses, and new investigational treatment targets will soon offer clinicians new, precision-based tools to risk stratify and determine treatment regimens for future patients with bladder cancer.


Assuntos
Vacina BCG/administração & dosagem , Biomarcadores Tumorais/genética , DNA de Neoplasias/genética , Genômica/métodos , Imunoterapia/métodos , Mutação , Neoplasias da Bexiga Urinária/genética , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Biomarcadores Tumorais/metabolismo , Análise Mutacional de DNA , Progressão da Doença , Humanos , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia
7.
Urol Clin North Am ; 47(1): 47-54, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757299

RESUMO

Despite therapy with intravesical Bacillus Calmette-Guérin, roughly 50% of patients with high-risk non-muscle-invasive bladder cancer will recur. Although cystectomy is the oncologic gold standard in BCG unresponsive disease, salvage intravesical therapies are valuable treatment options that aim to preserve quality of life while decreasing the risk of cancer recurrence and progression. Single-agent intravesical chemotherapy has been a mainstay salvage treatment and foundational to future trials of combination therapy. Treatment with Bacillus Calmette-Guérin derivative therapies has shown promise with response rates comparable with those of single agent chemotherapy and may warrant further investigation in the continued climate of Bacillus Calmette-Guérin shortages.


Assuntos
Vacina BCG/administração & dosagem , Desoxicitidina/análogos & derivados , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/administração & dosagem , Progressão da Doença , Humanos , Invasividade Neoplásica , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
8.
Urol Clin North Am ; 47(1): 5-13, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757300

RESUMO

The best predictors of response to intravesical immunotherapy are tumor grade and stage, tumor recurrence pattern, nomograms, panels of urinary cytokines, and fluorescent in situ hybridization patterns of urine cytology examinations. Future investigations on predictors of Bacillus Calmette-Guérin efficacy are needed to better select those patients who will really benefit from a conservative treatment. Hardly any of the proposed nomograms were designed to precisely predict the outcome of Bacillus Calmette-Guérin immunotherapy. A new nomogram for NMIBC recurrence and progression based on all non-muscle-invasive bladder cancer subgroups would include factors already proven in cancer prognosis and prediction.


Assuntos
Vacina BCG/administração & dosagem , Imunoterapia/métodos , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Progressão da Doença , Humanos , Invasividade Neoplásica , Nomogramas , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
10.
Medicine (Baltimore) ; 98(36): e16873, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490371

RESUMO

At present, intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is recommended for prophylaxis purposes after transurethral resection of bladder tumor, but has chances of recurrence. Radical cystectomy reduces the risk of recurrence in bladder cancer patients, but may have chances of postoperative complications. The objective of the study was to test the hypothesis that radical cystectomy has overtreatment and definitive BCG immunotherapy has undertreatment in intermediate or high-risk nonmuscle invasive bladder cancer patients. Data regarding biopsies, ultrasound, the computed tomography scan, adopted treatment strategy, treatment-emergent adverse effect, and a follow-up period of 312 patients with confirmed nonmuscle invasive bladder cancer (pTa, pTis, or pT1 stage; intermediate or high-risk cancer) were reviewed. Patients who had received definitive intravesical BCG immunotherapy were included in BCG group (n = 210) and those who underwent radical cystectomy were included in RXC group (n = 87). Clinical decision-making for treatment strategies was evaluated for both groups. Cystitis was frequently observed in all patients who received BCG immunotherapy. In RXC group, ileus was frequently observed in all patients in early days after the operation. During 2 years of the follow-up period, biopsies, ultrasound, and the computed tomography scan reported that BCG group had fewer numbers of negative cancer patients after treatment than the RXC group after surgery (P < .0001). Total expenditure for BCG immunotherapy was higher than radical cystectomy (22,945 ±â€Š945 ¥/patient vs 17,985 ±â€Š545 ¥/patient; P < .0001). Definitive BCG immunotherapy had undertreatment and radical cystectomy had overtreatment for intermediate or high-risk invasive bladder cancer patients (level of evidence III).


Assuntos
Vacina BCG/uso terapêutico , Cistectomia/estatística & dados numéricos , Imunoterapia/métodos , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Adolescente , Adulto , Idoso , Vacina BCG/efeitos adversos , Vacina BCG/economia , Análise Custo-Benefício , Cistectomia/efeitos adversos , Cistectomia/economia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Imunoterapia/economia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores Socioeconômicos , Neoplasias da Bexiga Urinária/patologia , Adulto Jovem
11.
BMC Infect Dis ; 19(1): 682, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375068

RESUMO

BACKGROUND: Adolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations. METHODS: Adolescents aged 12-18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 h for reading. A TST of ≥10 mm if HIV negative or ≥ 5 mm if HIV positive, was considered positive. RESULTS: Of 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1, 95% CI 29.2-35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2-3.1). Risk factors for a positive TST included being male (OR 1.3, 95% CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95% CI 1.2,1.8), having a BCG scar (OR 1.5,95% CI 1.2,1.8), living in a rural area (OR 1.4, 95% CI 1.1,1.9), and being out of school (OR 1.8, 95% CI 1.4,2.3). CONCLUSION: We conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.


Assuntos
Tuberculose/epidemiologia , Adolescente , Vacina BCG/uso terapêutico , Criança , Feminino , Humanos , Quênia/epidemiologia , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Masculino , Mycobacterium tuberculosis/patogenicidade , Prevalência , Fatores de Risco , Instituições Acadêmicas , Teste Tuberculínico , Tuberculose/diagnóstico
12.
Medicine (Baltimore) ; 98(33): e16771, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415377

RESUMO

The cell wall skeleton of Bacillus Calmette-Guérin (BCG-CWS) is a bioactive component that is a strong immune adjuvant for cancer immunotherapy. BCG-CWS activates the innate immune system through various pattern recognition receptors and is expected to elicit antigen-specific cellular immune responses when co-administered with tumor antigens. To determine the recommended dose (RD) of BCG-CWS based on its safety profile, we conducted a phase I dose-escalation study of BCG-CWS in combination with WT1 peptide for patients with advanced cancer.The primary endpoint was the proportion of treatment-related adverse events (AEs) at each BCG-CWS dose. The secondary endpoints were immune responses and clinical effects. A BCG-CWS dose of 50, 100, or 200 µg/body was administered intradermally on days 0, 7, 21, and 42, followed by 2 mg of WT1 peptide on the next day. For the escalation of a dose level, 3 + 3 design was used.Study subjects were 18 patients with advanced WT1-expressing cancers refractory to standard anti-cancer therapies (7 melanoma, 5 colorectal, 4 hepatobiliary, 1 ovarian, and 1 lung). Dose-limiting toxicity occurred in the form of local skin reactions in 2 patients at a dose of 200 µg although no serious treatment-related systemic AEs were observed. Neutrophils and monocytes transiently increased in response to BCG-CWS. Some patients demonstrated the induction of the CD4 T cell subset and its differentiation from the naïve to memory phenotype, resulting in a tumor response.The RD of BCG-CWS was determined to be 100 µg/body. This dose was well tolerated and showed promising clinical effects with the induction of an appropriate immune response.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Esqueleto da Parede Celular/uso terapêutico , Mycobacterium bovis , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Vacina BCG/administração & dosagem , Contagem de Linfócito CD4 , Esqueleto da Parede Celular/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
13.
Vet Immunol Immunopathol ; 215: 109884, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31420066

RESUMO

Many vaccines against childhood diseases are administered early after birth, but vaccine development studies frequently test efficacy in adult rather than in neonatal animal models. In countries with endemic tuberculosis (TB), Bacillus Calmette-Guerin (BCG) is administered as part of the neonatal vaccine regimen because it prevents against the disseminated form of TB in children, although it has variable efficacy against pulmonary TB. Several promising new vaccines against TB are currently being tested in adult animal models. Here we evaluated neonatal piglets as an animal model to test vaccine efficacy. For this purpose, minipigs were vaccinated or not with BCG 48 h after birth and their immune response followed longitudinally until adolescence. We characterized the memory and activation phenotype of T cells, cytokine profile, and monocyte activation in response to BCG stimulation from 4 weeks of age into adolescence- age of 24 weeks. Immunological responses in vaccinated and non-vaccinated animals were further monitored upon infection with a low dose exposure to Mycobacterium tuberculosis strain HN878 via the aerosol route. Comparing the immunological response elicited by BCG vaccination in minipigs vs similar studies in infants, suggest that minipigs have the potential to serve as an effective neonatal animal model for vaccine development.


Assuntos
Vacina BCG/imunologia , Modelos Animais de Doenças , Mycobacterium tuberculosis/imunologia , Porco Miniatura/imunologia , Tuberculose Pulmonar/imunologia , Animais , Animais Recém-Nascidos , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Imunogenicidade da Vacina , Memória Imunológica , Imunofenotipagem , Estudos Longitudinais , Ativação Linfocitária , Masculino , Monócitos/imunologia , Suínos , Tuberculose/imunologia , Tuberculose Pulmonar/prevenção & controle
14.
Expert Opin Investig Drugs ; 28(9): 757-770, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31412742

RESUMO

Introduction: The current first line therapy for high grade (HG) non-muscle invasive bladder cancer (NMIBC) is intravesical Bacillus Calmette-Guerin (BCG). Patients who recur or progress despite BCG are recommended to undergo radical cystectomy or participate in clinical trials. There is an urgent need for alternative therapies in the BCG-unresponsive NMIBC realm. Areas covered: We queried clinicaltrials.gov and pubmed.gov for current and recently completed early clinical trials pertaining to investigational agents used for the treatment of BCG-unresponsive NMIBC. These included intravesical chemotherapy, immunotherapy, vaccines, gene therapy, viruses, and agents used with novel drug delivery methods. In this article, we discuss the treatment guidelines for non-muscle invasive bladder cancer and therapeutic approaches under investigation in clinical trials. Expert opinion: The FDA is currently allowing single-arm studies as a pathway for approval in BCG-refractory patients with CIS. Although many agents are currently undergoing testing, none have been approved since Valrubicin. Hopefully, we will identify therapies sufficiently effective and durable to achieve FDA approval. Other considerations in this realm include the use of biomarkers in NMIBC to identify patients who will most likely respond to specific interventions. In addition, as systemic agents such as checkpoint inhibitors, are studied further, a multidisciplinary approach may be needed to treat this subset of patients.


Assuntos
Antineoplásicos/farmacologia , Drogas em Investigação/farmacologia , Neoplasias da Bexiga Urinária/terapia , Animais , Antineoplásicos/administração & dosagem , Vacina BCG/administração & dosagem , Biomarcadores Tumorais/metabolismo , Cistectomia/métodos , Sistemas de Liberação de Medicamentos , Drogas em Investigação/administração & dosagem , Humanos , Imunoterapia/métodos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/patologia
15.
J Med Microbiol ; 68(9): 1314-1319, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31274404

RESUMO

Introduction. Current intradermal tuberculin skin tests for latent tuberculosis infection (LTBI) based on purified protein derivative (PPD) have poor specificity.Aims. Developing a better skin test antigen as well as a simple skin patch test may improve and facilitate diagnostic performance.Methodology. Defined recombinant antigens that were unique to Mycobacterium tuberculosis (MTB), including two potential latency-associated antigens (ESAT-6 and Rv2653c) and five DosR-encoded latency proteins (Rv1996, Rv2031c, Rv2032, DevR and Rv3716c), were used as diagnostic skin test reagents in comparison with a standard PPD. The performance of the skin tests based on the detection of delayed-type hypersensitivity (DTH) reaction in guinea pigs sensitized to MTB and M. bovis bacille Calmette-Guérin (BCG) vaccine was evaluated.Results. The latency antigens Rv1996, Rv2031c, Rv2032 and Rv2653c and the ESAT-6 protein elicited less reactive DTH skin responses in MTB-sensitized guinea pigs than those resulting from PPD, but elicited no response in BCG-vaccinated guinea pigs. The remaining two latency antigens (DevR and Rv3716c) elicited DTH responses in both groups of animals, as did PPD. The reactivity of PPD in BCG-vaccinated guinea pigs was greater than that of any of the selected skin test reagents. Using stronger concentrations of selected skin test reagents in the patch test led to increased DTH responses that were comparable to those elicited by PPD in guinea pigs sensitized with MTB.Conclusion. Transdermal application of defined purified antigens might be a promising method for LTBI screening.


Assuntos
Hipersensibilidade Tardia/imunologia , Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/imunologia , Testes Cutâneos/métodos , Adesivo Transdérmico , Animais , Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Feminino , Cobaias , Indicadores e Reagentes , Mycobacterium tuberculosis/isolamento & purificação , Testes Cutâneos/normas , Tuberculina/imunologia
16.
BMC Infect Dis ; 19(1): 568, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262260

RESUMO

BACKGROUND: With the aim of preparing a more effective, safe and economical vaccine for tuberculosis, inhalable live mycobacterium formulations were evaluated. METHODS: Alginate particles in the size range of 2-4 µm were prepared by encapsulating live Bacille Calmette-Guérin (BCG) and "Mycobacterium indicus pranii" (MIP). These particles were characterized for their size, stability and release profile. Mice were immunized with liquid aerosol or dry powder aerosol (DPA) alginate encapsulated mycobacterium particles and their in-vitro recall response and infection with mycobacterium H37Rv were investigated. RESULTS: It was found that the DPA of alginate encapsulated mycobacterium particles invoked superior immune response and provided higher protection in mice than the liquid aerosol. The BCG encapsulated in alginate particles (BEAP) and MIP encapsulated in alginate particles (MEAP) were engulfed by bone marrow dendritic cells (BMDCs) and co-localized with lysosome. The MEAP/BEAP activated BMDCs exhibited higher chemotaxis movement and had enhanced ability of antigen presentation to T cells. The in-vitro recall response of BEAP/MEAP immunized mice when compared in terms of proliferation index and Interferon gamma (IFN-gamma) released by splenocytes and mediastinal lymph node cells was found to be higher than mice immunized by liquid aerosol of BCG/MIP. Finally, different groups of immunized mice were infected with M. tb H37Rv and after 16 weeks the Colony forming units (CFUs) in lung and spleen estimated. The bacilli burden in the BEAP/MEAP immunized mice was significantly less than the respective liquid aerosol immunized mice and the histopathology of BEAP/MEAP immunized mice lungs showed very little damage. CONCLUSIONS: These inhale-able vaccines formulation of alginate coated live mycobacterium are more immunogenic as compared to the aerosol of bacilli and they provide better protection in mice when infected with H37Rv.


Assuntos
Aerossóis/administração & dosagem , Pulmão/imunologia , Vacinas contra a Tuberculose/farmacologia , Tuberculose/prevenção & controle , Alginatos/química , Animais , Vacina BCG/imunologia , Sistemas de Liberação de Medicamentos/métodos , Interferon gama/imunologia , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Complexo Mycobacterium avium/química , Complexo Mycobacterium avium/imunologia , Mycobacterium bovis/química , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Baço/microbiologia , Linfócitos T/imunologia , Linfócitos T/microbiologia , Tuberculose/imunologia , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/imunologia , Vacinação/métodos
17.
Rev. méd. Urug ; 35(2): 155-164, jun. 2019. fig
Artigo em Espanhol | LILACS | ID: biblio-999629

RESUMO

La tuberculosis cutánea es una enfermedad infecciosa crónica y poco frecuente ocasionada por Mycobacteriun tuberculosis. Existen varias formas de la infección cutánea, siendo el lupus vulgar la más frecuente y común en los países industrializados. Las variantes clínicas dependerán de la vía de llegada del bacilo a la piel, del estado inmunológico del paciente y del medio ambiente. En el lupus vulgar, además de M. tuberculosis puede estar implicado M. bovis y menos frecuentemente el bacilo de Calmette y Guérin. Esta entidad presenta una evolución crónica, es de carácter progresivo y es rara de ver en niños. Se presenta el caso de una niña en la cual se diagnosticó una forma de tuberculosis cutánea denominada lupus vulgar provocada por el bacilo de Calmette y Guérin. Caso clínico: niña de 10 años que presentaba lesiones cutáneas de diferentes características, de evolución tórpida y asintomáticas; la de mayor tamaño se localizaba en la cara externa del deltoides derecho en forma de placa eritematosa de 20 por 10 cm con bordes sobreelevados presentando en su centro micropápulas que coalescen dejando una zona de atrofia central. Esta había comenzado en etapa neonatal luego de la vacunación por el bacilo de Calmette y Guérin. Desde hacía tres años presentaba una segunda lesión más pequeña en cara externa de muslo derecho de similares características y otras de carácter múltiple en dorso con forma de micropápulas rojo vinosas. Los exámenes de valoración general fueron normales, al igual que la radiografía de tórax y de los miembros. El test de la tuberculina mostró una induración de 15 mm y las baciloscopias fueron negativas. La biopsia de la lesión de piel del deltoides mostró granulomas caseosos y las técnicas moleculares diagnosticaron Mycobacterium bovis atenuado. Con ese diagnóstico, recibió tratamiento antituberculoso por diez meses con buena tolerancia y con mejoría de las lesiones.


Cutaneous TB is a rather unusual chronic infectious disease caused by Mycobacteriun tuberculosis. There are several forms of cutaneous infection, lupus vulgaris being the most frequent and ordinary one in developed countries. Clinical variations will depend on the site of infiltration of the skin by the bacillus, the patient's immune condition and the environment. In the case of lupus vulgaris, apart from Mycobacteriun tuberculosis, M. bovis may be involved, and the Bacille Calmette Guérin involvement is less frequent. The latter presents a chronic evolution, being progressive and unusual in children. The study presents the case of a girl who was diagnosed with a form of cutaneous tuberculosis called lupus vulgaris caused by the Bacille Calmette-Guérin vaccine. Clinical case: a 10 year old girl who evidenced skin lesions of different kinds, of slow evolution and asymptomatic: the largest one was in the external part of the right deltoid muscle as an erythematous plaque of 20 by 10 cm with higher borders evidencing micro papules in the center that coalesce leaving a central atrophy zone. The latter had started in the neonatal stage after the Bacille Calmette-Guérin vaccine. For three years she had evidenced a second smaller lesion in the outer face of the right thigh of similar characteristics and other multiple lesions in the back with the shape of vinous red micro papules. Assessment tests were generally normal, as well as the chest and limbs X-ray. The tuberculin test evidenced a 15 mm induration and smears were negative. The deltoid muscle skin lesion biopsy showed caseous granulomas and molecular techniques diagnosed attenuated Mycobacteriumbovis. Given that diagnose the patient received anti-TB treatment during 10 months, tolerance being good and the lesions improved.


A tuberculose cutânea é uma doença infecciosa crônica e pouco frequente causada pelo Mycobacteriun tuberculosis. Existem várias formas de infecção cutânea, sendo o lúpus vulgar a mais frequente e comum nos países industrializados. As variantes clínicas dependerão da via de entrada do bacilo à pele, do estado imunológico do paciente e do ambiente. No lúpus vulgar, além do M. tuberculosis podem estar implicados o M. bovis e mais raramente o bacilo de Calmette-Guérin. Esta entidade apresenta uma evolução crônica, é progressiva e é rara em crianças. Apresenta-se o caso de uma paciente de sexo feminino com 10 anos que foi diagnosticada com uma forma de tuberculose cutânea denominada lúpus vulgar provocada pelo bacilo de Calmette-Guérin. Caso clínico: paciente de sexo feminino com 10 anos que apresentava lesões cutâneas de diferentes características, com evolução letárgica e assintomática; a maior lesão estava localizada na face externa do deltoide direito sob a forma de placa eritematosa de 20 x 10 cm com bordes sobrelevados apresentando no centro micropápulas que coalescem deixando una zona de atrofia central. Esta lesão começou na etapa neonatal depois da vacinação com o bacilo de Calmette-Guérin. Desde 3 anos apresentava uma segunda lesão menor na face externa da coxa direita com características similares e outras múltiplas no dorso com forma de micropápulas com coloração de manchas em vinho do Porto. Os exames de avaliação geral foram normais, bem como as radiografias de tórax e de membros. O teste da tuberculina mostrou uma induración de 15 mm e as baciloscopias foram negativas. A biopsia da lesão de pele dos deltoides mostrou granulomas caseosos e as técnicas moleculares diagnosticaram Mycobacterium bovis atenuado. Com esse diagnóstico recebeu tratamento antituberculoso por 10 meses com boa tolerância e melhoria das lesões.


Assuntos
Criança , Tuberculose Cutânea/diagnóstico , Lúpus Vulgar/diagnóstico , Vacina BCG/efeitos adversos , Criança
18.
BMC Infect Dis ; 19(1): 520, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196008

RESUMO

BACKGROUND: Leprosy is is still considered a public health issue and in Colombia 7-10% of new cases are found in children, indicating both active transmission and social inequality. We hypothesized that circulating antibodies against Natural Octyl Disaccharide-Leprosy IDRI Diagnostic (NDO-LID) (a combination of Mycobacterium leprae antigens) could reveal the social and environmental aspects associated with higher frequencies of M. leprae infection among children and adolescents in Colombia. METHODS: An observational cross-sectional study was conducted involving sampling from 82 children and adolescents (younger than 18 years of age) who had household contact with index leprosy patients diagnosed in the last 5 years. Data were analyzed through bivariate analysis made by applying a Pearson x2 test for qualitative variables, while quantitative variables, depending on their distribution, were analyzed using either a Student's t-test or Mann-Whitney U test. Multivariate analysis was performed using a multiple regression and binomial logistic approach. RESULTS: A bivariate analysis demonstrated that antibody titers against NDO-LID were significantly greater in children and adolescents with a low socioeconomic status that had: lived in vulnerable areas of the UAChR shared region; eaten armadillo meat; exposure of over 10 years to an index case and; not received BCG immunization. Moreover, a multivariate analysis showed that residing in the UAChR region has a strong association with a greater possibility of M. leprae infection. CONCLUSIONS: M. leprae transmission persists among young Colombians, and this is associated with social and environmental conditions. An intensification of efforts to identify new leprosy cases in vulnerable and forgotten populations where M. leprae transmission continues therefore appears necessary.


Assuntos
Hanseníase/diagnóstico , Mycobacterium leprae/isolamento & purificação , Adolescente , Animais , Anticorpos Antibacterianos/sangue , Tatus , Vacina BCG/imunologia , Criança , Pré-Escolar , Colômbia/epidemiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Hanseníase/epidemiologia , Hanseníase/transmissão , Modelos Logísticos , Masculino , Carne/análise , Carne/microbiologia , Mycobacterium leprae/imunologia , Classe Social , Estatísticas não Paramétricas
19.
J Cancer Res Clin Oncol ; 145(8): 2131-2140, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31227894

RESUMO

PURPOSE: This study aimed at determining the relationship between classification according to the papillary tumor pattern of carcinoma in situ (CIS) of the bladder and prognosis, as this has not yet been well established. METHODS: This study comprised a consecutive cohort of 254 patients (primary CIS: 66 patients, stage Ta-CIS: 52 patients, and stage T1-CIS: 136 patients) with CIS-associated bladder cancer. We classified CIS according to the pathological pattern of papillary tumors and analyzed prognostic factors, including CIS classification, for progression. We evaluated progression using two endpoints: infiltrative tumors detected at stage T1 or higher or at stage T2 or higher. Bacillus Calmette-Guerin (BCG) immunotherapy response was defined as no recurrence within 6 months. RESULTS: Both the BCG immunotherapy response and CIS classification were significant prognostic factors for both the endpoints. Patients with CIS-associated stage Ta urinary bladder cancer had better prognosis for both the endpoints than those with stage T1 cancer or those with primary CIS. BCG immunotherapy response (p < 0.001) and age (p = 0.007) were also significant prognostic factors for the progression of stage T2 or higher infiltrative tumors. The prognosis of patients with recurrent primary CIS (12/26, 46.2%) and T1-CIS (25/45, 55.6%) was poor for progression; distant metastasis occurred in approximately 40% of these patients. CONCLUSIONS: Clinicians should consider radical surgery for poor prognosis in patients with recurrent CIS-associated T1 cancer or primary CIS. The CIS classification according to the tumor pattern reflects the prognosis.


Assuntos
Vacina BCG/uso terapêutico , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/tratamento farmacológico , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/tratamento farmacológico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Carcinoma Papilar/patologia , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Progressão da Doença , Feminino , Humanos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia
20.
Minerva Urol Nefrol ; 71(4): 406-412, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144485

RESUMO

BACKGROUND: The aim of this study was to identify the predictive factors for progression defined as any event that shifted the management of the disease from a bladder sparing approach, by comparing patients with pure versus non-pure carcinoma in situ (CIS) of the bladder. METHODS: A retrospective analysis was carried out in consecutive patients affected by newly-diagnosed pure CIS and non-pure CIS (excluding cases with concomitant muscle invasive cancer). All patients were enrolled a in our institution from 1998 to 2010. Data was prospectively collected. Main end point was progression-free survival. RESULTS: Overall, 149 patients with CIS were identified for the analysis. A total of 98 patients had pure CIS (66%). Median follow-up was 103 months (range: 40-206 months). Progression occurred in 29 patients (19%). A total of 30 patients died during the follow-up (20%). In 13 cases (9%), the death was cancer specific. Progression-free survival estimate was 181 months (95% CI: 169-193 months) and 154 months (95% CI: 133-176 months) respectively for pure and non-pure CIS population (P=0.03). Among examined variables (age, gender, symptoms, smoking habit, ASA score, number of bacillus Calmette-Guérin [BCG] instillations), multivariate analysis disclosed that only CIS type was an independent predictor of progression (P=0.03) with a relative risk of 0.37 in favor of pure CIS. CONCLUSIONS: Pure and non-pure CIS are efficiently treated by BCG therapy combined with trans-urethral resection and/or radical cystectomy, with relatively low rate of progression. CIS type was the only significant predictor of progression.


Assuntos
Carcinoma in Situ/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/uso terapêutico , Carcinoma in Situ/mortalidade , Terapia Combinada , Cistectomia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Bexiga Urinária/mortalidade , Procedimentos Cirúrgicos Urológicos
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