RESUMO
INTRODUCTION: Duplication of the urethra is a rare congenital anomaly in females which, if left unidentified, might cause refractory urinary incontinence. This video demonstrates its identification and treatment. PATIENT & METHODS: A 5-year-old female was referred for primary refractory diurnal incontinence without any dry moment since birth. Initial clinical examination showed permanent urine leakage from an opening cranial to the clitoris. Ultrasound did not show any bladder or kidney abnormalities. A diagnostic cystoscopy under anesthesia revealed an accessory meatus located cranially to the orthotopic meatus and to the clitoris. RESULTS: Lying in dorsal decubitus under general anesthesia, catheters were inserted in respectively the orthotopic and accessory meatus. The accessory meatus and urethra were dissected away into the bladder dome from a circumferential skin incision. Defects were closed and bladder drainage per urethram was left in situ for 10 days. P ostoperative recovery was uncomplicated. Complete resolution of the incontinence was immediately achieved at catheter removal. Daytime and night-time continence are observed with 3 years follow-up. CONCLUSION: Urethral duplication is a rare finding in females but should be excluded during the workup of primary incontinence. In girls with isolated urethral duplication, resection of the accessory urethra is the best surgical option.
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Doenças Uretrais , Incontinência Urinária , Humanos , Feminino , Pré-Escolar , Uretra/diagnóstico por imagem , Uretra/cirurgia , Uretra/anormalidades , Bexiga Urinária/cirurgia , Incontinência Urinária/etiologia , Incontinência Urinária/cirurgia , CistoscopiaRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is frequently associated with impaired oral intake and malnutrition, which potentially increases morbidity and mortality. Therefore, nutrition is one of the major challenges in the post-transplant period. METHODS: To document the current clinical approach in nutritional treatment, we designed a questionnaire concerning the current practice in nutrition after alloHSCT and distributed it to German speaking centers performing alloHSCT in Germany, Austria and Switzerland between November 2018 and March 2020. Twenty-eight (39%) of 72 contacted centers completed the survey, 23 from Germany, two from Austria and three from Switzerland, representing 50% of alloHSCT activity within the participating countries in 2018. RESULTS: All centers reported having nutritional guidelines for patients undergoing alloHSCT, whereby 86% (n = 24) provided a low-microbial diet during the neutropenic phase. The criteria to start parenteral nutrition (PN) directly after alloHSCT seemed to be consistent, 75% (n = 21) of the corresponding centers started PN if the oral nutritional intake or the bodyweight dropped below a certain limit. In the setting of intestinal graft-versus-host disease (GvHD) the current practice appeared to be more heterogenous. About 64% (n = 18) of the centers followed a special diet, added food stepwise modulated by GvHD symptoms, while only four centers regularly stopped oral intake completely (intestinal GvHD grade >1). Half of the centers (54%, n = 15) applied a lactose-free diet, followed by 43% (n = 12) which provided fat- and 18% (n = 5) gluten-free food in patients with intestinal GvHD. Supplementation of micronutrients in acute intestinal GvHD patients was performed by 54% (n = 15) of the centers, whereas vitamin D (89%, n = 25) and vitamin B12 (68%, n = 19) was added regularly independently of the presence of GvHD. Only 5 (18%) participating centers ever observed a food-associated infection during hospitalization, whereas food-associated infections were reported to occur more often in the outpatient setting (64%, n = 18). CONCLUSION: The survey documented a general consensus about the need for nutritional guidelines for patients undergoing alloHSCT. However, the nutritional treatment in clinical practice (i.e. lactose-, gluten- or fat-free in intestinal GvHD) as well as the use of food supplements was very heterogeneous. In line with current general recommendations the centers seemed to focus on safe food handling practice rather than providing a strict neutropenic diet. More high-quality data are required to provide evidence-based nutrition to patients during and after alloHSCT.
Assuntos
Dieta/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Desnutrição/prevenção & controle , Neutropenia/dietoterapia , Política Nutricional , Áustria , Peso Corporal , Consenso , Dieta/normas , Suplementos Nutricionais , Ingestão de Alimentos , Alemanha , Pesquisas sobre Atenção à Saúde , Humanos , Desnutrição/etiologia , Neutropenia/etiologia , Nutrição Parenteral/normas , Padrões de Prática Médica , SuíçaRESUMO
Refractory skin ulcers due to severe chronic graft-versus-host disease (cGVHD) remain to be associated with significant morbidity and mortality.We performed an allogeneic donor skin transplantation in seven adult patients after allogeneic hematopoietic stem cell transplantation for cGVHD-associated refractory skin ulcers. While four patients received a split skin graft (SSG), in one patient, a full thickness skin graft for two small refractory ulcers of the ankle was performed, and one patient received in vitro expanded donor keratinocyte grafts derived from hair roots of the original unrelated donor. In one additional patient, a large deep fascial defect of the lower leg was covered with an autologous greater omentum free graft before coverage with an allogeneic SSG. An additional patient was treated with an autologous scrotal skin graft for a refractory ulcer associated with deep sclerosis of cGVHD after unrelated donor transplantation.All skin grafts engrafted and resulted in permanent coverage of the grafted ulcers without any signs of immunological mediated damage. In the patient receiving in vitro expanded keratinocyte grafts, two localized ulcers were permanently covered by donor skin while this approach failed to cover extensive circular ulcers of the lower legs.Allogeneic donor skin grafts are a valuable treatment option in refractory ulcers due to cGVHD but are restricted mainly to related donors while keratinocyte grafts from unrelated donors remain experimental. In male patients lacking a related donor, autologous scrotal skin graft may be an alternative option.
Assuntos
Procedimentos Cirúrgicos Dermatológicos/métodos , Doença Enxerto-Hospedeiro/cirurgia , Transplante de Células-Tronco Hematopoéticas , Queratinócitos/transplante , Úlcera Cutânea/cirurgia , Condicionamento Pré-Transplante/métodos , Adulto , Doença Crônica , Ciclofosfamida/uso terapêutico , Feminino , Sobrevivência de Enxerto/fisiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Imunossupressores/uso terapêutico , Queratinócitos/citologia , Queratinócitos/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Irmãos , Pele/imunologia , Pele/patologia , Úlcera Cutânea/imunologia , Úlcera Cutânea/patologia , Úlcera Cutânea/terapia , Transplante Autólogo , Transplante Homólogo , Doadores não Relacionados , Irradiação Corporal TotalRESUMO
We analyzed lymphocyte subpopulations and cytokines 3 months after allogeneic hematopoietic stem cell transplantation aiming to identify predictive cellular and serum markers for chronic graft-versus-host disease (cGVHD). Samples of 49 patients (pts) (no cGVHD (n = 14), subsequent quiescent onset (n = 16), de novo onset of cGVHD (n = 19)) were analyzed in the absence of active GVHD by flow cytometry and enzyme-linked immunosorbent assay. All mean absolute cell counts are presented as cells per microliter; relative cell counts are presented as percentage of lymphocytes. Pts with subsequent de novo cGVHD had significantly higher relative and absolute counts of CD4+ T cells including higher absolute counts of CD4+ memory T cells (22.36%; 206.55/µl; 136/µl, respectively) compared to pts with subsequent quiescent onset of cGVHD (12.41%; 83.42/µl; 54.3/µl) and pts without cGVHD (10.55%) with regard to relative counts of CD4+ T cells. Similarly, significantly more relative and absolute regulatory T cell numbers (CD4+FOXP3+) were detected in pts with de novo onset of cGVHD (3.08% and 24.63/µl) compared to those in pts without (1.25% and 9.06/µl) or with quiescent onset of cGVHD (1.15% and 6.91/µl). Finally, relative B cell counts, including naïve and memory B cells, were also significantly decreased in pts developing quiescent cGVHD (0.85, 0.73, 0.12% resp.) when compared to pts with de novo onset (5.61, 5.24, 0.38%). The results demonstrate that alterations in immune reconstitution are already present before onset of clinical symptoms and differ between de novo and quiescent onset of disease.
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Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/tendências , Adolescente , Adulto , Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Citocinas/sangue , Citocinas/imunologia , Feminino , Doença Enxerto-Hospedeiro/sangue , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo/efeitos adversos , Transplante Homólogo/tendências , Adulto JovemRESUMO
The EBMT risk score is an established tool successfully used in the prognosis of survival post-HSCT and is applicable for a range of haematological disorders. One of its main advantages is that score generation involves summation of clinical parameters that are available pretransplant. However, the EBMT risk score is recognized as not being optimal. Previous analyses, involving patients with various diagnoses, have shown that non-HLA gene polymorphisms influence outcome after allogeneic HSCT. This study is novel as it focuses only on patients having acute leukaemia (N = 458) and attempts to demonstrate how non-HLA gene polymorphisms can be added to the EBMT risk score in a Cox regression model to improve prognostic ability for overall survival. The results of the study found that three genetic factors improved EBMT risk score. The presence of MAL (rs8177374) allele T in the patient, absence of glucocorticoid receptor haplotype (consisting of rs6198, rs33389 and rs33388) ACT in the patient and absence of heat-shock protein 70-hom (+2437) (rs2227956) allele C in the patient were associated with decreased survival time. When compared to the EBMT risk score, the scores combining EBMT risk score with the genetic factors had an improved correlation with clinical outcome and better separation of risk groups. A bootstrapping technique, involving repeated testing of a model using multiple validation sets, also revealed that the newly proposed model had improved predictive value when compared to the EBMT risk score alone. Results support the view that non-HLA polymorphisms could be useful for pretransplant clinical assessment and provide evidence that polymorphisms in the recipient genotype may influence incoming donor cells, suppressing the initiation of the graft versus leukaemia effect and reducing survival.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/genética , Leucemia/imunologia , Adulto , Feminino , Genômica , Genótipo , Proteínas de Choque Térmico HSP70/genética , Haplótipos/genética , Teste de Histocompatibilidade , Humanos , Leucemia/patologia , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Transplante Homólogo/efeitos adversosRESUMO
Intestinal dysbiosis has been associated with acute gastrointestinal GvHD and poor outcome following allogeneic stem cell transplantation (ASCT). To assess the effect of a switch in 2012 from ciprofloxacin/metronidazole to rifaximin for gut decontamination on intestinal microbiota composition and ASCT outcome, we retrospectively analyzed 394 patients receiving ASCT from September 2008 through June 2015. In 131 and 90 patients, respectively, urinary 3-indoxyl sulfate levels and intestinal enterococcal load were measured before conditioning and weekly within the first 28 days after ASCT. The use of rifaximin correlated with lower enterococcal positivity (6.9 vs 21.9%, P=0.05) and higher urinary 3-indoxyl sulfate concentrations (10.5 vs 4.6 µmoL/mmoL crea, P<0.001) after ASCT. Patients on rifaximin showed lower 1-year transplant-related mortality (P=0.04) and higher overall survival (P=0.008). Treatment of infectious complications with systemic antibiotics did not abrogate the beneficial effects of rifaximin on intestinal microbiota composition in the early course of ASCT and outcome. The data underscore the importance of maintaining a diverse population of symbiotic and mutualistic bacteria in the gut on ASCT outcome.
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Microbioma Gastrointestinal/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/métodos , Rifamicinas/administração & dosagem , Adulto , Enterococcus/efeitos dos fármacos , Feminino , Gastroenteropatias/prevenção & controle , Doença Enxerto-Hospedeiro/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Indicã/análise , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rifamicinas/farmacologia , Rifaximina , Análise de Sobrevida , Transplante HomólogoRESUMO
Previous studies of non-histocompatibility leukocyte antigen (HLA) gene single-nucleotide polymorphisms (SNPs) on subgroups of patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) revealed an association with transplant outcome. This study further evaluated the association of non-HLA polymorphisms with overall survival in a cohort of 762 HSCT patients using data on 26 polymorphisms in 16 non-HLA genes. When viewed in addition to an already established clinical risk score (EBMT-score), three polymorphisms: rs8177374 in the gene for MyD88-adapter-like (MAL; P=0.026), rs9340799 in the oestrogen receptor gene (ESR; P=0.003) and rs1800795 in interleukin-6 (IL-6; P=0.007) were found to be associated with reduced overall survival, whereas the haplo-genotype (ACC/ACC) in IL-10 was protective (P=0.02). The addition of these non-HLA polymorphisms in a Cox regression model alongside the EBMT-score improved discrimination between risk groups and increased the level of prediction compared with the EBMT-score alone (gain in prediction capability for EBMT-genetic-score 10.8%). Results also demonstrated how changes in clinical practice through time have altered the effects of non-HLA analysis. The study illustrates the significance of non-HLA genotyping prior to HSCT and the importance of further investigation into non-HLA gene polymorphisms in risk prediction.
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Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Polimorfismo de Nucleotídeo Único , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Aloenxertos , Causas de Morte , Criança , Receptor alfa de Estrogênio/genética , Feminino , Seguimentos , Genótipo , Doença Enxerto-Hospedeiro/mortalidade , Haplótipos , Neoplasias Hematológicas/mortalidade , Histocompatibilidade , Humanos , Infecções/mortalidade , Interleucina-10/genética , Interleucina-6/genética , Estimativa de Kaplan-Meier , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Receptores de Interleucina-1/genética , Condicionamento Pré-Transplante/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Histopathological diagnosis including selection of lesions, the determination of the best point of time for biopsy and workup is not trivial in cutaneous graft-versus-host disease (GvHD). OBJECTIVES: To develop interdisciplinary recommendations on performing, the laboratory work up and reporting of the results of skin biopsies in patients with suspected cutaneous GvHD. METHODS: A working group consisting of dermatopathologists, dermatologists, transplant-physicians and transplant-pathologists prepared recommendations for performing skin biopsies, laboratory workup and evaluation of tissue samples, and reporting of the results in patients with cutaneous GvHD. After achieving a consensus within the working group, a survey that comprised the core issues of the recommendations was electronically sent out to 72 alloHSCT centres within Germany, Austria, and Switzerland and their Departments of Pathology. The answers were discussed in a Consensus Conference and final recommendations were established. RESULTS: Twenty-five centres responded to the clinical and 17 centres to the histopathological survey. Questions addressed to the clinicians comprised the indication for skin biopsy in chronic GvHD (cGvHD) and acute GvHD (aGvHD) and the appropriate point of time for skin biopsy. Eighty-eight per cent agreed that the skin biopsy is generally indicated in patients with suspected cGvHD lacking diagnostic features. In contrast, with suspected aGvHD, only 62% of respondents felt that skin biopsy was necessary even if GvHD had not been confirmed in another organ. Although restricted due to the fact that immunosuppression is often applied in an emergency setting most centres supported skin biopsies before initiation of topical or systemic immunosuppression. The majority of pathologists agreed that in non-sclerotic GvHD a punch biopsy is adequate, whereas in sclerotic GvHD a scalpel biopsy is preferred. CONCLUSION: While a consensus on the need for biopsies in cGvHD was reached the value of skin biopsies in aGvHD and subsequent biopsies during therapy requires further evaluation.
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Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Dermatopatias/patologia , Pele/patologia , Doença Aguda , Biópsia/métodos , Doença Crônica , Consenso , Técnicas Histológicas , Humanos , Dermatopatias/etiologia , Inquéritos e Questionários , Transplante HomólogoRESUMO
Despite similarities relevant age- and gender-specific issues exist in the care of patients after allogeneic hematopoietic SCT (HSCT). Female genital chronic GVHD (cGVHD) has been markedly underreported in the past but has a significant impact on the patients' health and quality of life. Data on prevention and treatment of this complication are still limited. Here we present a comprehensive review summarizing the current knowledge, which was discussed during several meetings of the German, Austrian and Swiss Consensus Project on clinical practice in cGVHD. In this report, we provide recommendations for post-transplant gynecological care of cGVHD manifestations agreed upon by all participants. This includes guidelines for diagnosis, prevention, and therapeutic options and topical treatments in female patients with genital cGVHD and hormonal replacement treatment of premature ovarian failure for adult and pediatric patients and underlines the necessity for regular gynecological care and screening programs for women after HSCT.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Insuficiência Ovariana Primária , Serviços de Saúde da Mulher , Adulto , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Terapia de Reposição Hormonal , Humanos , Guias de Prática Clínica como Assunto , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/prevenção & controleRESUMO
Chronic GVHD (cGVHD) remains the most important cause of late non-relapse mortality post allogeneic hematopoietic SCT (HSCT). Although first-line treatment of cGVHD with steroids is well established, evidence for second-line treatment remains limited. Here, we report a dual center retrospective analysis of the off-label salvage treatment of steroid-refractory cGVHD with everolimus. Out of 80 patients with a median age of 50 (17-70) years, 14 (17%) suffered from mild, 39 (49%) from moderate and 27 (34%) from severe cGVHD. At the final analysis, median follow-up after introduction of everolimus was 724 (14-2205) days. Thirty-four patients (43%) required the addition of further immunosuppression during everolimus-based therapy. Global NIH Severity Score improved in 34 patients (43%), remained stable in 37 patients (46%) and worsened in 9 patients (11%). The total sum of Global NIH Severity Scores in all patients assessable was significantly reduced after treatment with everolimus (P<0.0001). Most frequent grade 3/4 toxicities included infections (n=30) and thrombocytopenia (n=15). There was a single case of relapse. Everolimus-based salvage treatment of refractory cGVHD results in significant improvement of the NIH Severity Score without impairing control of the malignant disease. Finally, these preliminary results demand further verification in prospective trials.
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Doença Enxerto-Hospedeiro/tratamento farmacológico , Imunossupressores/administração & dosagem , Terapia de Salvação/métodos , Sirolimo/análogos & derivados , Adolescente , Adulto , Idoso , Doença Crônica , Estudos Transversais , Everolimo , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Sirolimo/administração & dosagemRESUMO
With increased survival after pediatric allogeneic hematopoietic SCT health-related quality of life (HRQL) has emerged as an essential health outcome. The impact of transplant and chronic GVHD (cGVHD)-associated morbidity remains a major obstacle. In 2005, the National Institutes of Health (NIH) Consensus Conference on Criteria for Clinical Trials in cGVHD recommended HRQL tools as an independent measure of the impact of disease burden. The NIH recommendations did not provide a cGVHD-specific tool for HRQOL measures in children. This report focuses on the development of an SCT-specific instrument to assess HRQL in children and adolescents. For the assessment of generic HRQL we chose the PedsQL (Pediatric Quality of Life Inventory) Generic Cores Scales, which have been used in a large number of healthy, acutely ill and chronically ill children and adolescents. To capture SCT- and, specifically, cGVHD-related problems, we developed the PedsQL Stem Cell Transplant module by reviewing the literature, taking over some items/scales of other PedsQL modules, interviewing patients, parents and members of the health-care team, and applying the PedsQL measurement methods. The final PedsQL Stem Cell Transplant module consists of the HRQL domains: pain and hurt, fatigue/sleeping problems/weakness, nausea, worry/anxiety about disease/treatment, nutritional problems, neurocognitive problems, communication about disease/treatment, loneliness, physical functioning and additional somatic complaints (pruritus, skin inflammation, oral problems, eyes or breathing) including patients' and parents' assessment. It was tested in 35 pediatric patients, who were referred to our SCT Outpatient Clinic about 100 days post SCT. Both the generic PedsQL and the SCT-specific scales showed high internal consistency, with Cronbach alpha levels of ⩾0.70 in almost all scales. Most problems were detected within the HRQL domains of physical functioning and pain. The summary scores of the generic PedsQL and the PedsQL Stem Cell Transplant module showed high correlations (r=0.89 in patients' and r=0.81 in parents' assessments). Moreover, both tools discriminated between patients with and without cGVHD. The PedsQL Stem Cell Transplant module is practical for use and suitable across a broad age range (2-18 years) both in patients with and without cGVHD. However, it is still a pilot instrument and needs further development and testing in a larger patient population.
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Doença Enxerto-Hospedeiro/psicologia , Doença Enxerto-Hospedeiro/terapia , Qualidade de Vida/psicologia , Transplante de Células-Tronco , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Doença Crônica , Conferências para Desenvolvimento de Consenso de NIH como Assunto , Feminino , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Masculino , Projetos Piloto , Estados UnidosAssuntos
Oftalmopatias/etiologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Doença Crônica , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Recidiva , Transplante HomólogoRESUMO
PURPOSE: On the basis of correct Hounsfield unit to electron density calibration, cone-beam computed tomography (CBCT) data provide the opportunity for retrospective dose recalculation in the patient. Therefore, the consequences of translational positioning corrections and of morphological changes in the patient anatomy can be quantified for prostate cancer patients. MATERIALS AND METHODS: The organs at risk were newly contoured on the CBCT data sets of 7 patients so as to evaluate the actual applied dose. The daily dose to the planning target volume (PTV) was recalculated with and without the translation data, which result from the real patient repositioning. RESULTS: A CBCT-based dose recalculation with uncertainties less than 3 % is possible. The deviations between the planning CT and the CBCT without the translational positioning correction vector show an average dose difference of - 8 % inside the PTV. An inverse proportional relation between the mean bladder dose and the actual volume of the bladder could be established. The daily applied dose to the rectum is about 1-54 % higher than predicted by the planning CT. CONCLUSION: A dose calculation based on CBCT data is possible. The daily positioning correction of the patient is necessary to avoid an underdosage in the PTV. The new contouring of the organs at risk - the bladder and rectum - allows a better appraisal to be made of the total applied dose to these organs.
Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Fracionamento da Dose de Radiação , Órgãos em Risco , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Reto/efeitos da radiação , Bexiga Urinária/efeitos da radiação , Calibragem , Tomografia Computadorizada de Feixe Cônico/instrumentação , Humanos , Masculino , Posicionamento do Paciente/instrumentação , Posicionamento do Paciente/métodos , Imagens de Fantasmas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/instrumentação , Radioterapia Guiada por Imagem/instrumentação , Estudos RetrospectivosRESUMO
Allogeneic hematopoietic stem cell transplantation is one curative treatment for hematological malignancies, but is compromised by life-threatening complications, such as severe acute graft-versus-host disease (aGvHD). Prediction of severe aGvHD as early as possible is crucial to allow timely initiation of treatment. Here we report on a multicentre validation of an aGvHD-specific urinary proteomic classifier (aGvHD_MS17) in 423 patients. Samples (n=1106) were collected prospectively between day +7 and day +130 and analyzed using capillary electrophoresis coupled on-line to mass spectrometry. Integration of aGvHD_MS17 analysis with demographic and clinical variables using a logistic regression model led to correct classification of patients developing severe aGvHD 14 days before any clinical signs with 82.4% sensitivity and 77.3% specificity. Multivariate regression analysis showed that aGvHD_MS17 positivity was the only strong predictor for aGvHD grade III or IV (P<0.0001). The classifier consists of 17 peptides derived from albumin, ß2-microglobulin, CD99, fibronectin and various collagen α-chains, indicating inflammation, activation of T cells and changes in the extracellular matrix as early signs of GvHD-induced organ damage. This study is currently the largest demonstration of accurate and investigator-independent prediction of patients at risk for severe aGvHD, thus allowing preemptive therapy based on proteomic profiling.
Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Proteômica , Doença Aguda , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/urina , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Albumina Sérica/análise , Transplante HomólogoRESUMO
BACKGROUND: Histopathology is an important tool in diagnosing cutaneous graft-versus-host disease (GvHD). Minimum diagnostic criteria for active chronic GvHD have recently been defined. However, they are not specific and their interpretation is dependent on observer judgement. AIMS OF THE STUDY: i) to explore interobserver variability in the interpretation of histopathological changes in GvHD, and ii) to analyse the impact of detailed clinical data on histopathological diagnosis of GvHD. METHODS: Histopathological slides from 15 skin biopsies of GvHD and from dermatoses with histopathologically similar appearance were sent in two phases to four dermatopathologists experienced in cutaneous GvHD in France, Germany, Italy and Switzerland (first round of 'blind' review followed by a second round with complete clinical information provided). RESULTS: Interface dermatitis, especially vacuolar alteration, was the most inconsistently evaluated, particularly in cases with minor alterations. Interestingly, for vacuolar alteration and apoptotic keratinocytes, interobserver variability was lower in the adnexal epithelia than in the interfollicular epidermis. Complete clinical information resulted in increased diagnostic confidence and greater concordance on the final diagnosis, rising from 53% (first round, k = 0.345, fair agreement) to 80% (second round, k = 0.529, moderate agreement). The percentage of correct diagnoses increased from 33.3% to 80%. CONCLUSION: For the diagnosis of GvHD, histopathological analysis is of importance, but, for correct diagnosis, the correlation of pathological findings with clinical results is crucial. In cases of minor alteration, histopathologists should focus on the interpretation of vacuolar changes and apoptotic keratinocytes, possibly on the adnexal epithelia.
Assuntos
Diagnóstico por Imagem/métodos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/patologia , Dermatopatias/diagnóstico , Dermatopatias/patologia , Adulto , Idoso , Apoptose , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Queratinócitos/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Patologia Clínica/métodos , Pele/patologia , Vacúolos/patologiaRESUMO
In 2005, the National Institutes of Health (NIH) consensus conference published a series of papers recommending methods to improve the conduct of clinical trials in chronic GVHD. Although the NIH recommendations were primarily aimed at strengthening research, several papers addressed issues relevant for clinical practice, particularly diagnosis, severity scoring, and ancillary and supportive care practices. We conducted an international survey to assess the uptake of these recommendations, identify barriers to greater use and document the use and perceived effectiveness of available treatments. The response rate for the American survey of 1387 practitioners was 21.8%, and it was 24.6% for 407 centers surveyed in Europe, Asia, Australia and Africa. Most respondents were familiar with the NIH consensus recommendations (94-96%) and used them in practice. Multiple barriers to greater use were reported. Besides lack of time (55-62%), unfamiliarity with the recommendations, scarcity of evidence supporting the impact of recommendations on outcomes, insufficient training/experience in chronic GVHD management and inaccessibility of subspecialists were also endorsed. Systemic corticosteroids were reported to be the most effective treatment for chronic GVHD, but many others were perceived to have moderate or great success. Therapeutic management of steroid-refractory chronic GVHD was identified as the highest priority for research.
Assuntos
Ensaios Clínicos como Assunto/normas , Doença Enxerto-Hospedeiro/terapia , Hematologia/normas , Transplante de Células-Tronco Hematopoéticas/normas , Transplante Homólogo/normas , Doença Crônica , Ensaios Clínicos como Assunto/tendências , Conferências para Desenvolvimento de Consenso de NIH como Assunto , Coleta de Dados , Gerenciamento Clínico , Doença Enxerto-Hospedeiro/diagnóstico , Hematologia/tendências , Humanos , Cooperação Internacional , National Institutes of Health (U.S.) , Guias de Prática Clínica como Assunto , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: The granulocyte colony-stimulating factor (G-CSF) is utilized to reduce neutropenic complications in patients receiving cancer chemotherapy. This study represents a systematic review and evidence summary of the impact of G-CSF support on chemotherapy dose intensity and overall mortality. MATERIALS AND METHODS: All randomized controlled trials (RCTs) comparing chemotherapy with or without G-CSF support and reporting all-cause mortality with at least 2 years of follow-up were sought. Dual-blind data abstraction of disease, treatment, patient and outcome study results with conflict resolution by third party was carried out. RESULTS: The search revealed 61 randomized comparisons of chemotherapy with or without initial G-CSF support. Death was reported in 4251 patients randomized to G-CSFs and in 5188 controls. Relative risk (RR) with G-CSF support for all-cause mortality was 0.93 (95% confidence interval: 0.90-0.96; P < 0.001). RR for mortality varied by intended chemotherapy dose and schedule: same dose and schedule (RR = 0.96; P = 0.060), dose dense (RR = 0.89; P < 0.001), dose escalation (RR = 0.92; P = 0.019) and drug substitution or addition (RR = 0.94; P = 0.003). Greater RR reduction was observed among studies with longer follow-up (P = 0.02), where treatment was for curative intent (RR = 0.91; P < 0.001), and where survival was the primary outcome (RR = 0.91; P < 0.001). CONCLUSIONS: All-cause mortality is reduced in patients receiving chemotherapy with primary G-CSF support. The greatest impact was observed in RCTs in patients receiving dose-dense schedules.
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Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Febre/tratamento farmacológico , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Chronic GVHD (cGVHD) is associated with mortality, disability and impaired quality of life. Understanding the role of comorbidity in patients with cGVHD is important both for prognostication and potentially for tailoring treatments based on mortality risks. In a prospective cohort study of patients with cGVHD (n=239), we examined the performance of two comorbidity scales, the Functional Comorbidity Index (FCI) and the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). Both scales detected a higher number of comorbidities at cGVHD cohort enrollment than pre-hematopoietic cell transplant (HCT) (P<0.001). Higher HCT-CI scores at the time of cGVHD cohort enrollment were associated with higher non-relapse mortality (HR: 1.21:1.04-1.42, P=0.01). For overall mortality, we detected an interaction with platelet count. Higher HCT-CI scores at enrollment were associated with an increased risk of overall mortality when the platelet count was ≤ 100,000/µL (HR: 2.01:1.20-3.35, P=0.01), but not when it was >100,000/µL (HR: 1.05:0.90-1.22, P=0.53). Comorbidity scoring may help better to predict survival outcomes in patients with cGVHD. Further studies to understand vulnerability unrelated to cGVHD activity in this patient population are needed.