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1.
Crit Rev Oncol Hematol ; 169: 103574, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34958916

RESUMO

Radiotherapy plays a key role in breast cancer treatment, and recent technical advances have been made to improve the therapeutic window by limiting the risk of radiation-induced toxicity or by increasing tumor control. Hadrontherapy is a form a radiotherapy relying on particle beams; compared with photon beams, particle beams have specific physical, radiobiological and immunological properties, which can be valuable in diverse clinical situations. To date, available hadrontherapy techniques for breast cancer irradiation include proton therapy, carbon ion radiation therapy, fast neutron therapy and boron neutron capture therapy. This review analyzes the current rationale and level of evidence for each hadrontherapy technique for breast cancer.

3.
Front Cell Dev Biol ; 9: 778677, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901024

RESUMO

Background: Psoriatic disease is a multifactorial inflammatory condition spanning from skin and nail psoriasis (Pso) to spine and joint involvement characterizing psoriatic arthritis (PsA). Monozygotic twins provide a model to investigate genetic, early life environmental exposure and stochastic influences to complex diseases, mainly mediated by epigenetics. Methods: We performed a genome-wide DNA methylation study on whole blood of monozygotic twins from 7 pairs discordant for Pso/PsA using the Infinium Methylation EPIC array (Illumina). MeDiP-qPCR was used to confirm specific signals. Data were replicated in an independent cohort of seven patients with Pso/PsA and 3 healthy controls. Transcriptomic profiling was performed by RNAsequence on the same 7 monozygotic twin pairs. Results: We identified 2,564 differentially methylated positions between psoriatic disease and controls, corresponding to 1,703 genes, 59% within gene bodies. There were 19 regions with at least two DMPs within 1 kb of distance and significant within-pair Δß-values (p < 0.005), among them SNX25, BRG1 and SMAD3 genes, all involved in TGF-ß signaling pathway, were identified. Co-expression analyses on transcriptome data identified IL-6/JAK/STAT3 and TNF-α pathways as important signaling axes involved in the disease, and they also suggested an altered glucose metabolism in patients' immune cells, characteristic of pro-inflammatory T lymphocytes. Conclusion: The study suggests the presence of an epigenetic signature in affected individuals, pointing to genes involved in immunological and inflammatory responses. This result is also supported by transcriptome data, that altogether suggest a higher activation state of the immune system, that could promote the disease status.

5.
J Rheumatol ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782448

RESUMO

OBJECTIVE: There is still a great deal to learn about the influence of gender in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying gender differences in disease expressions, with a special focus on demographic, clinical and serological characteristics. METHODS: A multicenter SSc cohort of 2,281 patients, 247 men, was recruited in the Italian SPRING (Systemic Sclerosis PRogression INvestiGation) registry. Demographic data, disease manifestations, serological profile and internal organ involvement were compared. RESULTS: The overall female/male ratio was 8.2/1. Female/male ratios for limited SSc, diffuse SSc and sine SSc subsets were 8.7/1, 4.9/1, and 10.7/1 respectively. A shorter Raynaud's onset to SSc diagnosis, an increased prevalence of diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, while a significant higher percentage of sicca syndrome, serum ANA, anti-ENA, anti-La/SSB, and anti-CENP-1 was detected in the female group. Males exhibited lower left ventricular ejection fraction, higher prevalence of conduction blocks, arrhythmias, ground glass and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. CONCLUSION: Our study further supports the presence of several gender-related differences in SSc patients. These differences were pronounced as regards the severity of cutaneous, peripheral vascular and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterize the female gender.

6.
Int J Cancer ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648657

RESUMO

In randomized clinical trials, the androgen-receptor inhibitor enzalutamide has demonstrated efficacy and safety in metastatic castration-resistant prostate cancer (mCRPC). This study captured efficacy, safety and patient-reported outcomes (PROs) of enzalutamide in mCRPC patients in a real-world European setting. PREMISE (NCT0249574) was a European, long-term, prospective, observational study in mCRPC patients prescribed enzalutamide as part of standard clinical practice. Patients were categorized based on prior docetaxel and/or abiraterone use. The primary endpoint was time to treatment failure (TTF), defined as time from enzalutamide initiation to permanent treatment discontinuation for any reason. Secondary endpoints included prostate-specific antigen (PSA) response, time to PSA progression, time to disease progression and safety. PROs included EuroQol 5-Dimension, 5-Level questionnaire, Functional Assessment of Cancer Therapy-Prostate and Brief Pain Inventory-Short Form. Overall, 1732 men were enrolled. Median TTF with enzalutamide was 12.9 months in the chemotherapy- and abiraterone-naïve cohort (Cohort 1) and 8.4 months in the postchemotherapy and abiraterone-naïve cohort (Cohort 2). Clinical outcomes based on secondary endpoints also varied between cohorts. Cohorts 1 and 2 showed small improvements in health-related quality of life and pain status. The proportions of patients reporting treatment-emergent adverse events (TEAEs) were 51.0% and 62.2% in Cohorts 1 and 2, respectively; enzalutamide-related TEAEs were similar in both cohorts. The most frequent TEAE across cohorts was fatigue. These data from unselected mCRPC patients in European, real-world, clinical-practice settings confirmed the benefits of enzalutamide previously shown in clinical trial outcomes, with safety results consistent with enzalutamide's known safety profile.

8.
Front Immunol ; 12: 714174, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566970

RESUMO

Background: Antineutrophil cytoplasmic antibodies (ANCA) are primarily involved in the pathogenesis of ANCA-associated vasculitides (AAV). However, ANCA may also be present in healthy subjects and in patients with autoimmune disorders different from AAV. We hypothesized that serum ANCA are associated with a worse prognosis in disorders other than AAV. Objective: We investigated the association between the overall survival and the presence of serum ANCA in 1,024 Italian subjects with various testing indications in a 10-year interval. Methods: In this retrospective cohort study, a population of 6,285 patients (many of whom were subsequently excluded due to our criteria) who tested for ANCA at a single center in 10 years was considered, and life status and comorbidities of subjects were collected. We compared the overall survival of ANCA-positive and ANCA-negative patients by means of Kaplan-Meier curves, while a multivariable adjusted Cox regression was used to evaluate the association between the ANCA status and the outcome (death) in terms of hazard ratios (HR) with 95% confidence intervals (CI). Results: The positivity of perinuclear ANCA (pANCA) increased significantly mortality (HR, 1.60; 95% CI, 1.10-2.32), while cytoplasmic ANCA (cANCA) positivity failed to show a significant association (HR, 1.43; 95% CI, 0.77-2.68). The increased mortality rate was observed for both pANCA and cANCA in patients suffering from rheumatic disorders. No association was found between mortality and anti-MPO (HR, 0.63; 95% CI, 0.20-2.00) or anti-PR3 (HR, 0.98; 95% CI, 0.24-3.96) after adjusting for confounders. Conclusions: Serum pANCA and cANCA are independent negative prognostic factors in patients with concurrent autoimmune diseases.

9.
Curr Pharm Des ; 27(41): 4245-4252, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34477509

RESUMO

BACKGROUND: The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations. OBJECTIVE: This study aims to investigate the prevalence of symptomatic Covid-19 and its correlations with both organ involvement and ongoing treatments in a large series of Italian ASD patients during the first wave of pandemic. METHODS: Our multicenter telephone 6-week survey included 3,029 unselected ASD patients enrolled at 36 tertiary referral centers of northern, central, and southern Italian macro-areas with different diffusion of the pandemic. Symptomatic SARS-CoV-2 infection was classified as definite Covid-19 (presence of symptoms plus positive oral/nasopharyngeal swabs) or highly suspected Covid-19 (highly suggestive symptoms, in the absence of a swab testing). RESULTS: A significantly higher prevalence of definite plus highly suspected Covid-19 compared to the Italian general population was detected in the whole ASD series (p=.000), as well as in patients from the three macro-areas (p=.000 in all). Statistically higher prevalence of Covid-19 was also found in connective tissue diseases compared to chronic arthritis subgroup (p=.000) and in ASD patients with pre-existing interstitial lung involvement (p=.000). Patients treated with either conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or biological DMARDs showed a significantly lower prevalence of Covid-19 (p=.000 in both). Finally, scleroderma patients undergoing low-dose aspirin showed a significantly lower rate of Covid-19 compared to those without (p=0.003). CONCLUSION: The higher prevalence of Covid-19 in ASD patients, along with the significant correlations with important clinical features and therapeutic regimens, suggests the need to develop targeted prevention/management strategies during the current pandemic wave.


Assuntos
Doenças Autoimunes , COVID-19 , Doenças Reumáticas , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/epidemiologia , Humanos , Pulmão , Pandemias , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , SARS-CoV-2
10.
Curr Opin Rheumatol ; 33(6): 514-521, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506341

RESUMO

PURPOSE OF REVIEW: The aim of the present review is to analyze the link between autoimmune diseases and environmental factors, in particular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) as it shares numerous features with the interstitial lung disease associated with connective tissue diseases positive for rare autoantibodies directed at highly specific autoantigens (i.e., MDA5 and RIG1) among the intracellular sensors of SARS-CoV-2 in the innate response against viruses. RECENT FINDINGS: As shown in recent publications and in our original data, specific autoantibodies may be functionally relevant to COVID-19 infection. We evaluated sera from 35 hospitalized patients with COVID-19 to identify antinuclear antibodies and autoantibodies directed against specific antigenic targets, and we identified anti-nuclear antibodies (ANA) in 20/35 of patients with COVID-19 (57%), in patients with need for supplemental oxygen (90% vs. 20% in ANA-negative cases; P < 0.0001). In 7/35 COVID-19 sera, we detected anti-MJ/NXP2 (n = 3), anti-RIG1 (n = 2), anti-Scl-70/TOPO1 (n = 1), and anti-MDA5 (n = 1), overall associated with a significantly worse pulmonary involvement at lung computerized tomography scans. Eleven (31%) patients were positive for antibodies against the E2/E3 subunits of mitochondrial pyruvate dehydrogenase complex. SUMMARY: Viral infections such as COVID-19 are associated with ANA and autoantibodies directed toward antiviral signaling antigens in particular in patients with worse pulmonary involvement.


Assuntos
COVID-19 , Doenças do Tecido Conjuntivo , Dermatomiosite , Anticorpos Antinucleares , Autoanticorpos , Dermatomiosite/complicações , Humanos , SARS-CoV-2
11.
Med Oncol ; 38(9): 107, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342725

RESUMO

The purpose of this study was to evaluate the impact of breast size on acute and late side effects in breast cancer (BC) patients treated with hypofractionated radiotherapy (Hypo-RT). In this study we analyzed patients over 50 years with a diagnosis of early BC, candidate for Hypo-RT after conservative surgery. Acute and late skin toxicities were evaluated in accordance with the RTOG scale. Multivariable logistic analysis was performed using dosimetric/anatomical factors resulted associated with toxicity outcome in univariable analysis. Among patients treated between 2009 and 2015, 425 had at least 5 years of follow-up. At RT end, acute skin toxicity ≥ G2 and edema ≥ G2 occurred in 88 (20.7%) and 4 (0.9%) patients, respectively. The multivariable analysis showed association of skin toxicity with boost administration (p < 0.01), treated skin area (TSA) receiving more than 20 Gy (p = 0.027) and breast volume receiving 105% of the prescription dose (V105%) (p = 0.016), but not breast size. At 5 years after RT, fibrosis ≥ G1 occurred in 89 (20.9%) patients and edema ≥ G1 in 36 (8.5%) patients. Fibrosis resulted associated with breast volume ≥ 1000 cm3 (p = 0.04) and hypertension (p = 0.04). As for edema, multivariable logistic analysis showed a correlation with hypertension and logarithm of age, but not with boost administration. Breast volume had an unclear impact (p = 0.055). A recurrent association was found between acute and late toxicities and breast V105%, which is correlated with breast size. This may suggest that a more homogenous RT technique may be preferred for patients with larger breast size.

12.
Comput Biol Med ; 135: 104624, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34247131

RESUMO

The prediction by classification of side effects incidence in a given medical treatment is a common challenge in medical research. Machine Learning (ML) methods are widely used in the areas of risk prediction and classification. The primary objective of such algorithms is to use several features to predict dichotomous responses (e.g., disease positive/negative). Similar to statistical inference modelling, ML modelling is subject to the class imbalance problem and is affected by the majority class, increasing the false-negative rate. In this study, seventy-nine ML models were built and evaluated to classify approximately 2000 participants from 26 hospitals in eight different countries into two groups of radiotherapy (RT) side effects incidence based on recorded observations from the international study of RT related toxicity "REQUITE". We also examined the effect of sampling techniques and cost-sensitive learning methods on the models when dealing with class imbalance. The combinations of such techniques used had a significant impact on the classification. They resulted in an improvement in incidence status prediction by shifting classifiers' attention to the minority group. The best classification model for RT acute toxicity prediction was identified based on domain experts' success criteria. The Area Under Receiver Operator Characteristic curve of the models tested with an isolated dataset ranged from 0.50 to 0.77. The scale of improved results is promising and will guide further development of models to predict RT acute toxicities. One model was optimised and found to be beneficial to identify patients who are at risk of developing acute RT early-stage toxicities as a result of undergoing breast RT ensuring relevant treatment interventions can be appropriately targeted. The design of the approach presented in this paper resulted in producing a preclinical-valid prediction model. The study was developed by a multi-disciplinary collaboration of data scientists, medical physicists, oncologists and surgeons in the UK Radiotherapy Machine Learning Network.


Assuntos
Ciência de Dados , Aprendizado de Máquina , Algoritmos , Humanos , Modelos Estatísticos
14.
Radiol Med ; 126(10): 1366-1373, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34268681

RESUMO

AIM: To explore breast cancer patient's perspective on future genetic testing for prediction of toxicity after breast radiotherapy (RT). MATERIALS AND METHODS: The study involved patient enrolled in the Italian branch of the REQUITE project conducted at the National Cancer Institute in Milan. Semi-structured interviews were conducted within one month from the end of radiotherapy treatment by two radiation oncologists and a radiotherapy technician previously trained by a clinical psychologist with experience in the oncology field. Semi-structured interviews are characterized by a set of pre-defined questions and developed ad hoc by researchers in Leicester within the REQUITE project. The interview questions investigated interest in undergoing the genetic test and expectations on its usefulness and disadvantages. RESULTS: Eighteen interviews were conducted and analysed. Forty-five initial codes were combined into nine themes which were then clustered in two main macro-areas (i) Opportunities and (ii) Challenges. Overall, all patients understand the aim of the genetic test and considered its intrinsic opportunity to make the physician more confident with the treatment. Regarding side effects, most of patients felt prepared to RT but not without fear. Many women considered important to have the largest and reliable information, also about negative experiences. Prevailing emotions were anxiety and fear but not connected to genetic test's result. CONCLUSIONS: A genetic test could be an opportunity because generate knowledge and give patients a dynamic role in the decision-making approach. Prediction of single patient radiosensitivity before RT could prompt suggestion to entail a more and more tailored radiation treatment in the era of personalized approach.


Assuntos
Neoplasias da Mama/radioterapia , Testes Genéticos/métodos , Pacientes/psicologia , Tolerância a Radiação/genética , Adulto , Idoso , Feminino , Humanos , Entrevistas como Assunto , Itália , Pessoa de Meia-Idade , Pacientes/estatística & dados numéricos , Valor Preditivo dos Testes , Inquéritos e Questionários
15.
Curr Rheumatol Rep ; 23(8): 59, 2021 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-34216293

RESUMO

PURPOSE OF REVIEW: To highlight the recent discoveries and lines of evidence on the role of microRNAs in ankylosing spondylitis (AS) and psoriatic arthritis (PsA), focusing on their expression profiling and mechanisms of action. RECENT FINDINGS: AS and PsA are chronic inflammatory musculoskeletal diseases with axial manifestations and represent an excellent model for studying microRNAs contribution to the disease pathogenesis, particularly through immunomodulation, inflammation, and bone remodelling, or their value as candidate diagnostic and prognostic biomarkers. MicroRNAs are single-stranded nucleotides able to regulate gene expression. They are a key component of the epigenetic machinery, involved in physiological and pathological processes. The contribution of microRNAs in AS and PsA (such as miR-29a in regulating bone metabolism) is highlighted by several works in the field but their utility as possible markers must be still confirmed, particularly in larger patients' cohorts.


Assuntos
Artrite Psoriásica , MicroRNAs , Espondilartrite , Espondilite Anquilosante , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/genética , Biomarcadores , Humanos , MicroRNAs/genética , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/genética
16.
Cancer Treat Rev ; 99: 102236, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34126314

RESUMO

Breast conserving surgery (BCS) plus radiation therapy (RT) or mastectomy have shown comparable oncological outcomes in early-stage breast cancer and are considered standard of care treatments. Postmastectomy radiation therapy (PMRT) targeted to both the chest wall and regional lymph nodes is recommended in high-risk patients. Oncoplastic breast conserving surgery (OBCS) represents a significant recent improvement in breast surgery. Nevertheless, it represents a challenge for radiation oncologists as it triggers different decision-making strategies related to treatment volume definition and target delineation. Hence, the choice of the best combination and timing when offering RT to breast cancer patients who underwent or are planned to undergo reconstruction procedures should be carefully evaluated and based on individual considerations. We present an Italian expert Delphi Consensus statements and critical review, led by a core group of all the professional profiles involved in the management of breast cancer patients undergoing reconstructive procedures and RT. The report was structured as to consider the main recommendations on breast reconstruction and RT and analyse the current open issues deserving investigation and consensus. We used a three key-phases and a Delphi process. The final expert panel of 40 colleagues selected key topics as identified by the core group of the project. A final consensus on 26 key statements on RT and breast reconstruction after three rounds of the Delphi voting process and harmonisation was reached. An accompanying critical review of available literature was summarized. A clear communication and cooperation between surgeon and radiation oncologist is of paramount relevance both in the setting of breast reconstruction following mastectomy when PMRT is planned and when extensive glandular rearrangements as OBCS is performed. A shared-decision making, relying on outcome-based and patient-centred considerations, is essential, while waiting for higher level-of-evidence data.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Consenso , Técnica Delfos , Feminino , Humanos , Mamoplastia/normas , Mastectomia Segmentar/métodos , Mastectomia Segmentar/normas , Guias de Prática Clínica como Assunto , Radioterapia (Especialidade)/normas , Ensaios Clínicos Controlados Aleatórios como Assunto , Oncologia Cirúrgica/normas
17.
Eur Urol Focus ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34147405

RESUMO

CONTEXT: Surgical techniques aimed at preserving the neurovascular bundles during radical prostatectomy (RP) have been proposed to improve functional outcomes. However, it remains unclear if nerve-sparing (NS) surgery adversely affects oncological metrics. OBJECTIVE: To explore the oncological safety of NS versus non-NS (NNS) surgery and to identify factors affecting the oncological outcomes of NS surgery. EVIDENCE ACQUISITION: Relevant databases were searched for English language articles published between January 1, 1990 and May 8, 2020. Comparative studies for patients with nonmetastatic prostate cancer (PCa) treated with primary RP were included. NS and NNS techniques were compared. The main outcomes were side-specific positive surgical margins (ssPSM) and biochemical recurrence (BCR). Risk of bias (RoB) and confounding assessments were performed. EVIDENCE SYNTHESIS: Out of 1573 articles identified, 18 studies recruiting a total of 21 654 patients were included. The overall RoB and confounding were high across all domains. The most common selection criteria for NS RP identified were characteristic of low-risk disease, including low core-biopsy involvement. Seven studies evaluated the link with ssPSM and showed an increase in ssPSM after adjustment for side-specific confounders, with the relative risk for NS RP ranging from 1.50 to 1.53. Thirteen papers assessing BCR showed no difference in outcomes with at least 12 mo of follow-up. Lack of data prevented any subgroup analysis for potentially important variables. The definitions of NS were heterogeneous and poorly described in most studies. CONCLUSIONS: Current data revealed an association between NS surgery and an increase in the risk of ssPSM. This did not translate into a negative impact on BCR, although follow-up was short and many men harbored low-risk PCa. There are significant knowledge gaps in terms of how various patient, disease, and surgical factors affect outcomes. Adequately powered and well-designed prospective trials and cohort studies accounting for these issues with long-term follow-up are recommended. PATIENT SUMMARY: Neurovascular bundles (NVBs) are structures containing nerves and blood vessels. The NVBs close to the prostate are responsible for erections. We reviewed the literature to determine if a technique to preserve the NVBs during removal of the prostate causes worse cancer outcomes. We found that NVB preservation was poorly defined but, if applied, was associated with a higher risk of cancer at the margins of the tissue removed, even in patients with low-risk prostate cancer. The long-term importance of this finding for patients is unclear. More data are needed to provide recommendations.

18.
Blood ; 138(21): 2093-2105, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34125889

RESUMO

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of cancers and inflammation-related diseases. This phenomenon becomes common in persons aged ≥80 years, in whom the implications of CHIP are not well defined. We performed a mutational screening in 1794 persons aged ≥80 years and investigated the relationships between CHIP and associated pathologies. Mutations were observed in one-third of persons aged ≥80 years and were associated with reduced survival. Mutations in JAK2 and splicing genes, multiple mutations (DNMT3A, TET2, and ASXL1 with additional genetic lesions), and variant allele frequency ≥0.096 had positive predictive value for myeloid neoplasms. Combining mutation profiles with abnormalities in red blood cell indices improved the ability of myeloid neoplasm prediction. On this basis, we defined a predictive model that identifies 3 risk groups with different probabilities of developing myeloid neoplasms. Mutations in DNMT3A, TET2, ASXL1, or JAK2 were associated with coronary heart disease and rheumatoid arthritis. Cytopenia was common in persons aged ≥80 years, with the underlying cause remaining unexplained in 30% of cases. Among individuals with unexplained cytopenia, the presence of highly specific mutation patterns was associated with myelodysplastic-like phenotype and a probability of survival comparable to that of myeloid neoplasms. Accordingly, 7.5% of subjects aged ≥80 years with cytopenia had presumptive evidence of myeloid neoplasm. In summary, specific mutational patterns define different risk of developing myeloid neoplasms vs inflammatory-associated diseases in persons aged ≥80 years. In individuals with unexplained cytopenia, mutational status may identify those subjects with presumptive evidence of myeloid neoplasms.

20.
Eur Urol ; 80(5): 531-545, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33962808

RESUMO

CONTEXT: The impact of surgeon and hospital volume on outcomes after radical prostatectomy (RP) for localised prostate cancer (PCa) remains unknown. OBJECTIVE: To perform a systematic review on the association between surgeon or hospital volume and oncological and nononcological outcomes following RP for PCa. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. All comparative studies for nonmetastatic PCa patients treated with RP published between January 1990 and May 2020 were included. For inclusion, studies had to compare hospital or surgeon volume, defined as caseload per unit time. Main outcomes included oncological (including prostate-specific antigen persistence, positive surgical margin [PSM], biochemical recurrence, local and distant recurrence, and cancer-specific and overall survival) and nononcological (perioperative complications including need for blood transfusion, conversion to open procedure and within 90-d death, and continence and erectile function) outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Both a narrative and a quantitative synthesis were planned if the data allowed. EVIDENCE SYNTHESIS: Sixty retrospective comparative studies were included. Generally, increasing surgeon and hospital volumes were associated with lower rates of mortality, PSM, adjuvant or salvage therapies, and perioperative complications. Combining group size cut-offs as used in the included studies, the median threshold for hospital volume at which outcomes start to diverge is 86 (interquartile range [IQR] 35-100) cases per year. In addition, above this threshold, the higher the caseload, the better the outcomes, especially for PSM. RoB and confounding were high for most domains. CONCLUSIONS: Higher surgeon and hospital volumes for RP are associated with lower rates of PSMs, adjuvant or salvage therapies, and perioperative complications. This association becomes apparent from a caseload of >86 (IQR 35-100) per year and may further improve hereafter. Both high- and low-volume centres should measure their outcomes, make them publicly available, and improve their quality of care if needed. PATIENT SUMMARY: We reviewed the literature to determine whether the number of prostate cancer operations (radical prostatectomy) performed in a hospital affects the outcomes of surgery. We found that, overall, hospitals with a higher number of operations per year have better outcomes in terms of cancer recurrence and complications during or after hospitalisation. However, it must be noted that surgeons working in hospitals with lower annual operations can still achieve similar or even better outcomes. Therefore, making hospital's outcome data publicly available should be promoted internationally, so that patients can make an informed decision where they want to be treated.

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