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1.
BJU Int ; 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39183466

RESUMO

OBJECTIVE: To quantify the oncological risks of bladder-sparing therapy (BST) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) compared to upfront radical cystectomy (RC). PATIENTS AND METHODS: Pre-specified data elements were collected from retrospective cohorts of patients with BCG-unresponsive NMIBC from 10 international sites. After Institutional Review Board approval, patients were included if they had BCG-unresponsive NMIBC meeting United States Food and Drug Administration criteria. Oncological outcomes were collected following upfront RC or BST. BST regimens included re-resection or surveillance only, repeat BCG, intravesical chemotherapy, systemic immunotherapy, and clinical trials. RESULTS: Among 578 patients, 28% underwent upfront RC and 72% received BST. The median (interquartile range) follow-up was 50 (20-69) months. There were no statistically significant differences in metastasis-free survival, cancer-specific survival, or overall survival between treatment groups. In the BST group, high-grade recurrence rates were 37% and 52% at 12 and 24 months and progression to MIBC was observed in 7% and 13% at 12 and 24 months, respectively. RC was performed in 31.7% in the BST group and nodal disease was found in 13% compared with 4% in upfront RC (P = 0.030). CONCLUSION: In a selected cohort of patients, initial BST offers comparable survival outcomes to upfront RC in the intermediate term. Rates of recurrence and progression increase over time especially in patients treated with additional lines of BST.

2.
BMC Cancer ; 23(1): 320, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024824

RESUMO

BACKGROUND: Bladder cancer is the tenth most common cancer worldwide. For patients with T1 high-grade or T2 bladder cancer, radical cystectomy is recommended. However, radical cystectomy is associated with various complications and has a detrimental impact on the quality of life. Bladder-sparing therapy has been widely explored in patients with muscle-invasive bladder cancer, and whether a combination of transurethral resection of bladder tumour (TURBT) with chemotherapy and immunotherapy shows definite superiority over TURBT plus chemotherapy is still a matter of debate. The aim of this study is to investigate the efficacy and safety of TURBT combined with chemotherapy and immunotherapy in bladder-sparing therapy in patients with T1 high-grade or T2 bladder cancer who are unwilling or unsuitable to undergo radical cystectomy. METHODS: An open-label, multi-institutional, two-armed randomized controlled study will be performed with 86 patients with T1 high-grade or T2 bladder cancer meeting the eligibility criteria. Participants in the experimental group (n = 43) will receive TURBT combined with chemotherapy (GC: gemcitabine 1000 mg/m2 on the 1st day and the 8th day, cisplatin 70 mg/m2 on the 2nd day, repeated every 21 days) and immunotherapy (toripalimab 240 mg on the 5th day, repeated every 21 days), and those in the control group (n = 43) will receive TURBT plus chemotherapy (GC). The primary outcome is pathological response, and the secondary outcomes include progression-free survival, overall survival, toxicities, and quality of life. DISCUSSION: To the best of our knowledge, this is the first study to evaluate the efficacy and safety of TURBT combined with GC regimen and toripalimab in bladder-sparing therapy in patients with T1 high-grade or T2 bladder cancer. The expected benefit is that the combination of TURBT with chemotherapy and immunotherapy would be more effective than TURBT plus chemotherapy without compromising the quality of life and increasing the toxicity. TRIAL REGISTRATION: ChiCTR2200060546, chictr.org.cn, registered on June 14, 2022.


Assuntos
Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Bexiga Urinária/patologia , Qualidade de Vida , Ressecção Transuretral de Bexiga , Resultado do Tratamento , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Cistectomia/métodos , Imunoterapia/efeitos adversos , Invasividade Neoplásica/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Urol Int ; 107(1): 46-57, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34818263

RESUMO

OBJECTIVE: This study aimed to compare the survival outcomes between trimodal therapy (TT) and partial cystectomy (PC) in muscle-invasive bladder cancer (MIBC) patients. METHODS: The data of 13,096 patients with MIBC diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results database. Among them, 4,041 patients underwent TT and 1,670 patients underwent PC. Propensity score matching was performed to balance the characteristics between the 2 treatment groups. A multivariate Cox regression analysis model and a competing risk model were used to evaluate overall survival (OS) and cancer-specific survival. Cumulative incidence survival curves were obtained using the Kaplan-Meier method. RESULTS: Results of multivariate Cox analysis before propensity score matching showed that the TT group had a 31% reduction in cause-specific survival relative to the PC group (HR: 0.69, 95% CI: 0.61-0.78, p < 0.001) and a 28% reduction in OS (HR: 0.72, 95% CI: 0.66-0.79, p < 0.001). After propensity score matching, the 2 groups yielded 972 patients, with 3-year cause-specific survival rates of 54.1% and 68.5% in the TT group and the PC group, respectively. CONCLUSIONS: Patients who underwent PC had a better prognosis than those who received TT. In addition, for MIBC patients who required bladder-sparing therapy, advanced age (≥80 years), pathological type of squamous cell carcinoma, and tumor stage of T3-4, N2-3, and M1 were independent poor prognostic factors.


Assuntos
Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Idoso de 80 Anos ou mais , Bexiga Urinária/patologia , Cistectomia/métodos , Quimiorradioterapia , Neoplasias da Bexiga Urinária/cirurgia , Prognóstico , Músculos/patologia , Invasividade Neoplásica , Resultado do Tratamento
4.
Arch Gynecol Obstet ; 307(2): 583-590, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35674831

RESUMO

PURPOSE: This study aims to evaluate the efficacy of hysteroscopic curettage combined with progestin therapy in young patients with early-stage endometrial cancer (EC) and endometrial atypical hyperplasia (EAH) who wished to preserve their fertility. METHODS: This prospective cohort study included 16 patients with early-stage EC and 25 patients with EAH in Dalian Maternal and Child Health Hospital from August 2014 to October 2018. All patients received fertility-sparing therapy with hysteroscopic evaluation every 3 months until achieving complete response (CR). Demographic, clinical, and pathological data follow-up information as well as fertility outcomes was analyzed. RESULTS: There were 92.6% (37/41) patients who achieved CR. The mean treatment duration to CR was 7.47 ± 2.91 months. BMI ≤ 30 kg/m2 was associated with shorter treatment duration to achieve CR (P = 0.003). Among the patients who attempted to conceive, 30.3% (10/33) had successful pregnancy, and 18.2% (6/33) delivered live births. The implementation of assisted reproductive technology (ART) is closely associated with pregnancy (P = 0.001). CONCLUSION: The fertility-sparing therapy, hysteroscopic curettage combined with progestin therapy, of early young EC and EAH patients is safe and effective. BMI is the main factor affecting the duration of CR. After achieving CR, ART can significantly improve the pregnancy rate of these patients.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Lesões Pré-Cancerosas , Gravidez , Feminino , Criança , Humanos , Progestinas/uso terapêutico , Resultado da Gravidez , Hiperplasia/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/cirurgia , Estudos Prospectivos , Histeroscopia , Estudos Retrospectivos , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/cirurgia , Hiperplasia Endometrial/patologia , Esteroides/uso terapêutico , Resultado do Tratamento
5.
Arch Gynecol Obstet ; 308(5): 1629-1634, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37310452

RESUMO

PURPOSE: Although many patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) achieve complete remission (CR) after high-dose medroxyprogesterone acetate (MPA) treatment, no consensus has been reached on management after CR. Currently, patients receive estrogen-progestin maintenance therapy, but no recommendations exist regarding the duration of maintenance therapy or whether hysterectomy should be considered. This study aimed to provide insights into the management of EC/AEH after achieving CR. METHODS: We retrospectively investigated the prognosis of 50 patients with EC or AEH who achieved CR after MPA therapy. We assessed the association between disease recurrence and clinicopathological features and the pre- and post-operative histological diagnoses of patients who underwent hysterectomy. RESULTS: The median follow-up duration was 34 months (range: 1-179 months). Recurrence was observed in 17 patients. Among the clinical characteristics investigated, only the primary disease was significantly associated with disease recurrence; patients with EC had a higher risk of recurrence than those with AEH (p = 0.037). During the observation period, 27 patients attempted pregnancy, and 14 pregnancies resulted in delivery. Patients who gave birth had significantly longer relapse-free survivals than those who did not (p = 0.031). Further, 16 patients underwent hysterectomies, and AEH was detected postoperatively in 4 of 11 patients (36.4%) with no preoperative abnormalities. CONCLUSIONS: We identified several clinical features of patients with EC and AEH after CR. Given the high probability of endometrial abnormalities detected postoperatively, hysterectomy may be considered for patients who no longer want children.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Gravidez , Feminino , Criança , Humanos , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/cirurgia , Hiperplasia Endometrial/patologia , Estudos Retrospectivos , Preservação da Fertilidade/métodos , Resultado do Tratamento , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/patologia , Acetato de Medroxiprogesterona/uso terapêutico , Prognóstico
6.
Reprod Biol Endocrinol ; 19(1): 118, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344384

RESUMO

BACKGROUND: Fertility-sparing therapy is an alternative conservative treatment for patients with early stage endometrioid cancer or atypical endometrial hyperplasia. In this study, we investigated pregnancy outcomes and pregnancy-associated factors in young patients receiving hormonal therapy. METHODS: We retrospectively analyzed 68 patients who attempted to conceive after fertility-sparing therapy and achieving complete remission (CR). They were divided into a pregnancy group and a non-pregnancy group. A Cox proportional hazard regression model was applied for univariate and multivariate analysis to determine factors associated with pregnancy. Kaplan-Meier analysis, combined with the log-rank test, was used to calculate a patient's pregnancy probability and the distribution of recurrence-free survival (RFS). RESULTS: A total of 36 patients became pregnant with 47 pregnancies. Univariate and multivariate Cox analysis revealed that several factors were associated with pregnancy, including BMI at the time of pregnancy permission, the time to CR, prolonged treatment time, the number of hysteroscopy procedures, the endometrium thickness after CR, and relapse before pregnancy. The mean RFS of patients who achieved pregnancy, and those who did not, was 27.6 months and 14.8 months, respectively (P = 0.002). No significant difference was detected in terms of cumulative RFS when compared between assisted reproductive technology (ART) cases and those involving natural conception (NC) (P = 0.707). CONCLUSIONS: Normal BMI, a shorter time to CR, a prolonged three-month treatment, fewer hysteroscopy procedures, and a thicker endometrium may be positive indicators for successful pregnancies, while relapse before pregnancy may have a negative effect on conception. Moreover, a successful pregnancy protects the endometrium while ART does not increase the risk of recurrence.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Carcinoma Endometrioide/tratamento farmacológico , Hiperplasia Endometrial/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Taxa de Gravidez , Progestinas/uso terapêutico , Adulto , Índice de Massa Corporal , Carcinoma Endometrioide/patologia , Intervalo Livre de Doença , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Feminino , Preservação da Fertilidade , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Gravidez , Resultado da Gravidez , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão , Técnicas de Reprodução Assistida/estatística & dados numéricos , Estudos Retrospectivos , Útero
7.
BMC Gastroenterol ; 20(1): 65, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164573

RESUMO

BACKGROUND: Ineffective antibiotic therapy increases mortality of acute cholangitis. The choice of antibiotics should reflect local resistance patterns and avoid the overuse of broad-spectrum agents. In this study, we analysed how results of bile and blood cultures and patient data can be used for selection of empirical antibiotic therapy in acute cholangits. METHODS: Pathogen frequencies and susceptibility rates were determined in 423 positive bile duct cultures and 197 corresponding blood cultures obtained from 348 consecutive patients with acute cholangitis. Patient data were retrieved from the medical records. Associations of patient and microbiological data were assessed using the Chi-2 test and multivariate binary logistic regression. RESULTS: In bile cultures, enterobacterales and enterococci were isolated with equal frequencies of approximately 30% whereas in blood cultures, enterobacterales predominated (56% compared to 21% enterococci). Antibiotic resistance rates of enterobacterales were > 20% for fluorochinolones, cephalosporines and acylureidopenicillins but not for carbapenems (< 2%). The efficacy of empirical therapy was poor with a coverage of bacterial bile and blood culture isolates in 51 and 69%, respectively. By multivariate analysis, predictors for pathogen species, antibiotic susceptibility and expected antibiotic coverage were identified. CONCLUSIONS: In unselected patients treated for acute cholangitis in a large tertiary refferential center, use of carbapenems seems necessary to achieve a high antibiotic coverage. However, by analysis of patient and microbiological data, subgroups for highly effective carbapenem-sparing therapy can be defined. For patients with community-acquired cholangitis without biliary prosthesis who do not need intensive care, piperacillin/tazobactam represents a regimen with an expected excellent antibiotic coverage.


Assuntos
Antibacterianos/uso terapêutico , Colangite/tratamento farmacológico , Colangite/microbiologia , Tomada de Decisão Clínica , Testes de Sensibilidade Microbiana , Doença Aguda , Bile/microbiologia , Hemocultura , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
Dermatol Ther ; 32(2): e12792, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30515931

RESUMO

The rifampicin (RF)-clindamycin (CL) combination is recommended as first line therapy in moderate to severe Hidradenitis Suppurativa (HS) by European S1 guidelines. Although prolonged use of RF should be discouraged, there are currently few alternatives to this combination therapy. The aim of the present study was to assess retrospectively the efficacy of oral CL monotherapy in patients diagnosed with HS. In the period January 2017-May 2018, 31 HS patients who received a 300 mg b.i.d. oral dose of CL were studied retrospectively. Efficacy of the treatment was evaluated by comparing the main HS severity scores (Sartorius score modified by Revuz, Hidradenitis Suppurativa Physician Global Assessment [HS-PGA] and International Hidradenitis Suppurativa Severity Score System [IHS4]) before (W0) and after (W12) CL oral therapy. CL efficacy was demonstrated by the extreme and significant reduction of all three disease severity parameters during the 12-week period (p ≤ .01). There was also a statistically significant change in the mean visual analogue scale for pain. The present study demonstrates the efficacy of oral CL monotherapy as RF-sparing regimen alternative to RF-CL combination in a selected group of patients.


Assuntos
Antibacterianos/administração & dosagem , Clindamicina/administração & dosagem , Hidradenite Supurativa/tratamento farmacológico , Dor/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
9.
J Obstet Gynaecol Res ; 44(1): 151-156, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29121428

RESUMO

AIM: Medroxyprogesterone acetate (MPA) is used to preserve fertility in patients with Grade 1 endometrial cancer without myometrial invasion (G1EA) and those with atypical endometrial hyperplasia (AEH). However, the efficacy of retreatment with MPA has not been sufficiently established for patients who experience recurrence but wish to retain their fertility. This study aimed to show the effectiveness of MPA treatment and retreatment for AEH and G1EA. METHODS: A total of 39 patients received MPA treatment between 2005 and 2015, including nine with G1EA and 30 with AEH. The patients received high-dose (600 mg/day) MPA for 26 weeks. If a complete response was not achieved, MPA treatment was continued. After complete remission, if there was a recurrence, the patient was offered a choice of a hysterectomy or retreatment with MPA. The gynecologic and obstetric outcomes were retrospectively analyzed. RESULTS: The median age was 34 years, and the median body mass index was 23.3 kg/m2 . The median follow-up period was 52 months. Complete response rates for the initial treatment were 89% for G1EA and 93% for AEH. Recurrence occurred in 88% of patients with G1EA (7/8) and 50% of those with AEH (14/28). Seven patients with G1EA and 11 with AEH received MPA retreatment, and 100% and 92% of these achieved a complete response. During the study period, a total of 14 pregnancies were recorded with 10 live births. CONCLUSION: MPA can be effective for G1EA and AEH treatment even when they recur.


Assuntos
Antineoplásicos Hormonais/farmacologia , Hiperplasia Endometrial/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Acetato de Medroxiprogesterona/farmacologia , Recidiva Local de Neoplasia/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Adulto , Antineoplásicos Hormonais/administração & dosagem , Feminino , Humanos , Acetato de Medroxiprogesterona/administração & dosagem , Recidiva
10.
BMC Pulm Med ; 17(1): 114, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28810909

RESUMO

BACKGROUND: The most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids. However, this treatment has not been shown to reduce mortality and can potentially have serious side effects. Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone. By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome. METHODS: This is an ongoing prospective multicenter randomized controlled open label trial comprising 320 patients with AECOPD recruited from four hospitals in Denmark. The patients are randomized 1:1 to either standard care or eosinophil-guided corticosteroid-sparing therapy where prednisolone is not administered if the daily blood sampling reveals an eosinophil level below 0.3 × 109 cells/L. The primary endpoint is length of hospital stay within 14 days after recruitment. The secondary endpoints are treatment failure, 30-day mortality rate, COPD related re-admission rate, change in FEV1, and a number of adverse effect measures obtained within 3 months after the index hospitalisation date related to corticosteroid usage. DISCUSSION: This will be a very large RCT providing knowledge about the effectiveness of individualized biomarker-guided corticosteroid therapy in hospitalised patients with AECOPD. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02857842 , 02-august-2016. Clinicaltrialregister.eu: Classification Code: 10,010,953, 02-marts-2016.


Assuntos
Eosinofilia/sangue , Glucocorticoides/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Prednisolona/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Progressão da Doença , Eosinofilia/complicações , Eosinófilos , Hospitalização , Humanos , Contagem de Leucócitos , Mortalidade , Planejamento de Assistência ao Paciente , Readmissão do Paciente , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/mortalidade , Falha de Tratamento , Resultado do Tratamento
11.
Cancer ; 122(6): 842-51, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26773572

RESUMO

There is uncertainty regarding the use of bladder-sparing alternatives to standard radical cystectomy, optimal lymph node dissection techniques, and optimal chemotherapeutic regimens. This study was conducted to systematically review the benefits and harms of bladder-sparing therapies, lymph node dissection, and systemic chemotherapy for patients with clinically localized muscle-invasive bladder cancer. Systematic literature searches of MEDLINE (from 1990 through October 2014), the Cochrane databases, reference lists, and the ClinicalTrials.gov Web site were performed. A total of 41 articles were selected for review. Bladder-sparing therapies were found to be associated with worse survival compared with radical cystectomy, although the studies had serious methodological shortcomings, findings were inconsistent, and only a few studies evaluated currently recommended techniques. More extensive lymph node dissection might be more effective than less extensive dissection at improving survival and decreasing local disease recurrence, but there were methodological shortcomings and some inconsistency. Six randomized trials found cisplatin-based combination neoadjuvant chemotherapy to be associated with a decreased mortality risk versus cystectomy alone. Four randomized trials found adjuvant chemotherapy to be associated with decreased mortality versus cystectomy alone, but none of these trials reported a statistically significant effect. There was insufficient evidence to determine optimal chemotherapeutic regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistectomia , Excisão de Linfonodo , Terapia Neoadjuvante/métodos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cistectomia/métodos , Medicina Baseada em Evidências , Humanos , Invasividade Neoplásica , Tratamentos com Preservação do Órgão/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade
12.
BJU Int ; 114(5): 719-26, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24325202

RESUMO

OBJECTIVE: To evaluate the association between patterns of care and patient survival for the treatment of muscle-invasive bladder cancer (MIBC) using a large, national database. PATIENTS AND METHODS: We identified a cohort of 36,469 patients with MIBC (stage II) from 1998 to 2010 from the National Cancer Data Base. Patients were stratified into four treatment groups: radical cystectomy, chemo-radiation, other therapy, or no treatment. Overall survival (OS) among the groups was evaluated using Kaplan-Meier analysis and the log rank test. A multivariable Cox proportional hazards model was fit to evaluate the association between treatment groups and OS. RESULTS: In all, 27% of patients received radical cystectomy, 10% chemo-radiation, 61% other therapy and 2% no treatment. Unadjusted Kaplan-Meier analysis showed significant differences by treatment group, with cystectomy having the greatest median OS (48 months) followed by chemo-radiation (28 months), other therapy (20 months), and no treatment (5 months). When controlling for multiple covariates, the OS for cystectomy was similar to that for chemo-radiation (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.98, 1.12), but superior to other therapy (HR 1.42; 95% CI 1.35, 1.48), and no treatment (HR 2.40; 95% CI 2.12, 2.72). The OS time for chemo-radiation was superior to other therapy and no treatment. CONCLUSIONS: Radical cystectomy and chemo-radiation are significantly underused despite a substantial survival benefit compared with other therapies or no treatment. Future studies are needed to optimise care delivery and improve outcomes for patients with MIBC.


Assuntos
Cistectomia/mortalidade , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Cistectomia/métodos , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Tratamentos com Preservação do Órgão/mortalidade , Sistema de Registros , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia
13.
Clin Genitourin Cancer ; 22(3): 102085, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636170

RESUMO

PURPOSE: To evaluate the efficacy and safety of a novel humanized anti-HER2 antibody, RC48-ADC (Disitamab vedotin, DV), the combination of RC48-ADC with PD-1 inhibitors was used to treat muscle-invasive bladder cancer (MIBC). This combination therapy has potential applications in both bladder preservation and neoadjuvant therapy for MIBC. METHODS: Patients with MIBC underwent transurethral resection of bladder tumors followed by RC48-ADC alone or in combination with PD-1 inhibitors. Radiological and endoscopic evaluations were conducted 3 months later. The primary endpoint was objective response rate (ORR), with secondary endpoints including complete response rate (CR), partial response rate (PR), and bladder preservation rate. Treatment safety was assessed according to RECIST v1.1 criteria. RESULTS: Eleven patients were enrolled, with a median follow-up of 19.0 months. Nine patients achieved objective response, including 6 CR and 3 PR cases. The pathological ORR was 81.8%. Eight patients continued combined treatment after 3 months, maintaining a 72.7% bladder preservation rate at 16 months. One elderly patient progressed from ypT2N0M0 to ypT3N0M0 and underwent radical cystectomy but had no recurrence or metastasis 12 months postoperation. All patients reported varying degrees of treatment-related adverse reactions, which were largely manageable. CONCLUSION: The combination of RC48-ADC and PD-1 inhibitors proves to be a viable and safe option for bladder-sparing therapy, particularly for T2-stage MIBC patients who are ineligible for surgery and chemotherapy. This approach offers a promising new direction for bladder preservation or neoadjuvant therapy in MIBC patients.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Terapia Neoadjuvante/métodos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Cistectomia , Tratamentos com Preservação do Órgão/métodos , Invasividade Neoplásica , Idoso de 80 Anos ou mais
14.
Curr Rheumatol Rev ; 20(3): 296-303, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38173068

RESUMO

OBJECTIVE: We aim to establish the utility of a trial of low-dose systemic glucocorticoid therapy in the assessment of new clinically suspected inflammatory arthritis patients. METHODS: We retrospectively identified patients from a private rheumatology practice in Melbourne, Australia between January 1st, 2019, and December 31st, 2021, who presented with clinically suspected inflammatory arthritis and subsequently underwent a trial of low-dose prednisolone (15 mg daily weaned over three weeks in 5 mg increments). We excluded patients with known autoimmune/ inflammatory disorders or concurrent immunosuppression at presentation. We collected basic participant demographic details and clinical details of their presentation, glucocorticoid response, investigations, and treatment. RESULTS: We recruited 177 participants with a median age of 52, and 69.5% were female gender. The median symptom time to presentation was 12 months. Hands were the most affected joint in 63.3% and 85% had bilateral disease. Among the participants, 29.4% had synovitis on clinical review and 75.7% had imaging performed as part of the initial assessment. At presentation, the median CRP was 11 and the median ESR was 16. 79.7% of the cohort experienced significant improvement in their arthritis symptoms from low-dose glucocorticoids and 83.6% of the cohort required long-term immunosuppression for an underlying inflammatory condition. Of those who responded to glucocorticoids, 92.1% were diagnosed with an inflammatory condition. Rheumatoid arthritis was the most common overall diagnosis in 28%. CONCLUSION: An initial trial of low-dose glucocorticoids in undifferentiated arthritis patients is useful in predicting the diagnosis of inflammatory arthritis. It is also a predictor of further long-term steroid-sparing therapy.


Assuntos
Glucocorticoides , Prednisolona , Humanos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Adulto , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Idoso , Artrite/tratamento farmacológico , Artrite/diagnóstico , Artrite/sangue
15.
J Neuroimmunol ; 388: 578294, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38306927

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) can cause HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Current treatment options for HAM/TSP are limited. We present a woman with rapidly-progressive HAM/TSP with significant, sustained clinical improvement following initiation of mycophenolate mofetil (MMA). Peripheral blood mononuclear cells from the patient, her asymptomatic carrier husband and eight healthy controls were isolated. Frequencies of T-cell populations upon exposure to low and high MMA concentrations and differences in proliferation were analyzed using flow cytometry and a CSFE-proliferation assay. Characterization of T-cell function and proliferation showed higher levels of GranzymeB in HTLV-1+ donors. The improvement and stability of symptoms in this patient with HAM/TSP following MMA initiation requires further study as a potential treatment for HAM/TSP.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Feminino , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Ácido Micofenólico/uso terapêutico , Leucócitos Mononucleares , Paraparesia Espástica Tropical/tratamento farmacológico , Paraparesia Espástica Tropical/diagnóstico
16.
Eur Urol ; 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39183090

RESUMO

BACKGROUND AND OBJECTIVE: There has been a recent surge in the development of agents for bacillus Calmette-Guérin-unresponsive (BCG-U) non-muscle-invasive bladder cancer (NMIBC). Critical assessment of these agents and practical recommendations for optimal selection of patients and therapies are urgently needed, especially in the absence of randomized trials on bladder-sparing treatment (BST) options. METHODS: A global committee of bladder cancer experts was assembled to develop recommendations on BST for BCG-U NMIBC. Working groups reviewed the literature and developed draft recommendations, which were then voted on by International Bladder Cancer Group (IBCG) members using a modified Delphi process. During a live meeting in August 2023, voting results and supporting evidence were presented, and recommendations were refined on the basis of meeting discussions. Final recommendations achieved >75% agreement during the meeting, and some were further refined via web conferences and e-mail discussions. KEY FINDINGS AND LIMITATIONS: There is currently no single optimal agent for patients with BCG-U disease who seek to avoid radical cystectomy (RC). BST selection should be personalized, taking into account individual patient characteristics and preferences, tumor attributes, and efficacy/toxicity data for the agents available. For patients with BCG-U carcinoma in situ (CIS), gemcitabine/docetaxel (GEM/DOCE), nadofaragene firadenovec (NFF), and nogapendekin alfa inbakicept-pmln (NAI) + BCG are recommended; because of its systemic toxicity, pembrolizumab should only be offered after other options are exhausted. For patients with BCG-U papillary-only tumors, GEM/DOCE, NFF, NAI + BCG, single-agent chemotherapy, hyperthermic mitomycin C, and pembrolizumab are recommended. Given the modest efficacy of available options, clinical trial participation is encouraged. For unapproved agents with reported data, IBCG recommendations await the final results of pivotal trials. CONCLUSIONS AND CLINICAL IMPLICATIONS: The IBCG consensus recommendations provide practical guidance on BST for BCG-U NMIBC.

17.
Oncol Res Treat ; 46(7-8): 330-335, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37364543

RESUMO

INTRODUCTION: As the numbers of young patients diagnosed with early-stage endometrial carcinoma continue to rise, the question regarding fertility-preserving therapeutic options will increasingly gain significance in the future. CASE PRESENTATION: Here, we present the case of a 21-year-old patient diagnosed with symptomatic atypical endometrial hyperplasia. After 4 months of treatment with medroxyprogesterone acetate, a follow-up dilatation and curettage revealed early-stage, well-differentiated endometrioid endometrial carcinoma. Despite national guidelines recommending hysterectomy, the nulliparous patient expressed a desire to preserve her fertility. Subsequently, she underwent polyendocrine therapy with letrozole, everolimus, metformin, and Zoladex. Forty-three months after diagnosis, the patient successfully gave birth to a healthy child, and there have been no indications of recurrence thus far. DISCUSSION: This case suggests that triple endocrine therapy may be an option for selected patients with early endometrial cancer and a desire for fertility-sparing therapy.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Feminino , Humanos , Adulto Jovem , Antineoplásicos Hormonais/uso terapêutico , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Acetato de Medroxiprogesterona/uso terapêutico , Estudos Retrospectivos
18.
Ocul Immunol Inflamm ; 31(8): 1579-1586, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34406900

RESUMO

PURPOSE: To study the efficacy and safety of suprachoroidal CLS-TA (proprietary suspension of triamcinolone acetonide) in uveitic macular edema (UME) with and without concurrent systemic corticosteroid or steroid-sparing therapy (ST). METHODS: Post hoc analysis of the PEACHTREE phase 3 randomized trial. RESULTS: Among UME patients receiving no ST, at week 24, mean BCVA change was +15.6 letters in 68 CLS-TA patients versus +4.9 letters in 49 sham-control patients (p < .001), while mean CST change was -169.8 µm versus -10.3 µm, respectively (p < .001). Among patients receiving ST, at week 24, mean BCVA change was +9.4 letters in 28 CLS-TA patients versus -3.2 letters in 15 sham-control patients (p = .019), while mean CST change was -108.3 µm versus -43.5 µm, respectively (p = .190). No SAEs related to treatment were reported. CONCLUSIONS: A clinically meaningful benefit of CLS-TA was noted in UME patients, regardless of concurrent ST usage.Abbreviation and AcronymsCST = central subfield thickness; BCVA = best corrected visual acuity; ME = macular edemaI; IVT = intravitreal; AE = adverse event; FA = fluocinolone acetonide; SD-OCT = spectral-domain optical coherence tomography; NIU = noninfectious uveitis; SAE = serious adverse event; TEAE = treatment emergent adverse event; ITT = intent to treat; CI = confidence interval.


Assuntos
Edema Macular , Uveíte , Humanos , Glucocorticoides/uso terapêutico , Resultado do Tratamento , Injeções Intravítreas , Triancinolona Acetonida/uso terapêutico , Uveíte/tratamento farmacológico , Corticosteroides/uso terapêutico , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Tomografia de Coerência Óptica/métodos
19.
Bull Cancer ; 2023 May 09.
Artigo em Francês | MEDLINE | ID: mdl-37169604

RESUMO

Managing a malignant renal tumor requires, first of all, a reflection on the necessity of its treatment. It must consider the renal function, altered at the time of diagnosis in 50% of cases. The treatment method chosen depends on many factors, in particular, the predicted residual renal function, the risk of chronic kidney disease, the need for temporary or long-term dialysis, and overall long-term survival. Other factors include the size, position, and number of tumors and a hereditary tumor background. When a renal-sparing management alternative is available, total nephrectomy should no longer be performed in patients with small malignant renal masses (cT1a). This may consist of surgery (partial nephrectomy or lumpectomy), percutaneous thermo-ablation (by radiofrequency, microwave, or cryotherapy). In patients with limited life expectancy, imaging-based surveillance may be proposed to suggest treatment in case of local progression. Good coordination between urologist, radiologist, nephrologist, and sometimes radiotherapist should allow optimal management of patients with a malignant renal tumor with or without underlying renal failure.

20.
J Neurol ; 269(4): 1834-1850, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34652505

RESUMO

BACKGROUND: The best choice between levodopa alone and levodopa sparing medications for early Parkinson's disease (PD) remains controversial. We aimed to evaluate the effect and safety of levodopa alone and levodopa sparing therapy in symptom relief, neuroimage results and complications. METHODS: A systematic search was performed in PubMed, The Cochrane Library, EMBASE, and Web of Science for randomized controlled trials of early PD patients comparing levodopa-alone with levodopa-sparing therapy. The mean difference (MD) and the risk ratio (RR) were meta-analyzed. RESULTS: Twenty-three articles with 4913 patients were included. Significantly greater benefit was detected for the levodopa group in the changes of Unified Parkinson's Disease Rating Scale part II (p < 0.00001), III (p < 0.00001), and total (p < 0.00001) scores, and the between-group MD in part III score increased over time. The loss of the radioligands uptake in levodopa-alone group was also increasingly greater over time. Patients treated with levodopa alone were at higher risk for wearing-off (p < 0.001) and dyskinesia (p < 0.001), but the RR for dyskinesia between the two groups decreased after 2 years of follow-up. CONCLUSION: Levodopa-alone therapy might be superior in motor symptom relief than levodopa-sparing therapy for early PD patients, and the motor advantage of levodopa-alone might grow over time. Sparing therapy might be associated with less risk of wearing-off and dyskinesia, but the events between the two groups might not be different in the long run. Overall, levodopa alone therapy might bring more net benefit to early PD patients compared with levodopa sparing strategies. The clinical and imaging findings are conflicting, which requires further investigation.


Assuntos
Discinesia Induzida por Medicamentos , Doença de Parkinson , Antiparkinsonianos/efeitos adversos , Discinesia Induzida por Medicamentos/etiologia , Humanos , Levodopa/efeitos adversos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico
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