Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Glioblastoma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Procedimentos Neurocirúrgicos/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
CD40 is a central costimulatory receptor implicated in productive antitumor immune responses across multiple cancers, including bladder cancer. Despite strong preclinical rationale, systemic administration of therapeutic agonistic antibodies targeting the CD40 pathway has demonstrated dose-limiting toxicities with minimal clinical activity, emphasizing an important need for optimized CD40-targeted approaches, including rational combination therapy strategies. Here, we describe a role for the endogenous IL-15 pathway in contributing to the therapeutic activity of CD40 agonism in orthotopic bladder tumors, with upregulation of transpresented IL-15/IL-15Rα surface complexes, particularly by cross-presenting conventional type 1 DCs (Dendritic Cells), and associated enrichment of activated CD8 T cells. In bladder cancer patient samples, we identify DCs as the primary source of IL-15, although they lack high levels of IL-15Rα at baseline. Using humanized immunocompetent orthotopic bladder tumor models, we demonstrate the ability to therapeutically augment this interaction through combined treatment with anti-CD40 agonist antibodies and exogenous IL-15, including the fully-human Fc-optimized antibody 2141-V11 currently in clinical development for the treatment of bladder cancer. Collectively, these data reveal an important role for IL-15 in mediating antitumor CD40 agonist responses in bladder cancer and provide key proof-of-concept for combined use of Fc-optimized anti-CD40 agonist antibodies and agents targeting the IL-15 pathway. These data support expansion of ongoing clinical studies evaluating anti-CD40 agonist antibodies and IL-15-based approaches to develop combinations of these promising therapeutics for the treatment of patients with bladder cancer.
Assuntos
Interleucina-15 , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Terapia Combinada , Antígenos CD40 , Fragmentos Fc das ImunoglobulinasRESUMO
CD40 is a central co-stimulatory receptor implicated in the development of productive anti-tumor immune responses across multiple cancers, including bladder cancer. Despite strong preclinical rationale, systemic administration of therapeutic agonistic antibodies targeting the CD40 pathway have demonstrated dose limiting toxicities with minimal clinical activity to date, emphasizing an important need for optimized CD40-targeted approaches, including rational combination therapy strategies. Here, we describe an important role for the endogenous IL-15 pathway in contributing to the therapeutic activity of CD40 agonism in orthotopic bladder tumors, with upregulation of trans-presented IL-15/IL-15Rα surface complexes, particularly by cross-presenting cDC1s, and associated enrichment of activated CD8 T cells within the bladder tumor microenvironment. In bladder cancer patient samples, we identify DCs as the primary source of IL-15, however, they lack high levels of IL-15Rα at baseline. Using humanized immunocompetent orthotopic bladder tumor models, we demonstrate the ability to therapeutically augment this interaction through combined treatment with anti-CD40 agonist antibodies and exogenous IL-15, including the fully-human Fc-optimized antibody 2141-V11 currently in clinical development for the treatment of bladder cancer. Combination therapy enhances the crosstalk between Batf3-dependent cDC1s and CD8 T cells, driving robust primary anti-tumor activity and further stimulating long-term systemic anti-tumor memory responses associated with circulating memory-phenotype T and NK cell populations. Collectively, these data reveal an important role for IL-15 in mediating anti-tumor CD40 agonist responses in bladder cancer and provide key proof-of-concept for combined use of Fc-optimized anti-CD40 agonist antibodies and agents targeting the IL-15 pathway. These data support expansion of ongoing clinical studies evaluating anti-CD40 agonist antibodies and IL-15-based approaches to evaluate combinations of these promising therapeutics for the treatment of patients with bladder cancer.
RESUMO
Background There is a clear association between testicular cancer and microlithiasis when there are predisposing risk factors such as the history of germ cell tumors in first-degree relatives, testicular atrophy, Klinefelter's syndrome, and cryptorchidism. This study aimed to establish an association between microlithiasis and the histological subtype of testicular cancer by analyzing data on Hispanic population. Methods A retrospective cohort, longitudinal, comparative, and analytic study was conducted on patients with a confirmed diagnosis of primary testicular cancer. The testicular ultrasounds were checked before any surgical treatment to find microlithiasis. We performed a binary logistic regression to establish an association between microlithiasis and the type of testicular cancer. Results A total of 130 clinical files were analyzed. Binary logistic regression showed no association between testicular microlithiasis and the subtype of testicular cancer (p = 0.438, 95% CI: 0.80-1.64). The result of the Pearson chi-square test showed no association (p = 0.184). We also analyzed the association between age and microlithiasis using the one-way ANOVA test (p = 0.82) and the association between age and the dichotomic subtype of testicular cancer (seminomatous and non-seminomatous) using the ANOVA one-way test, which showed no significant association in age and testicular cancer subtype (p = 0.178). Conclusions There was no association between testicular microlithiasis and the histological subtype of testicular cancer in our study. As mentioned before, we recommend conducting a more extensive study to provide further scientific evidence to establish a reliable association between microlithiasis and the subtype of testicular cancer since there is a discrepancy in the results of our study with the information previously reported. We encourage the study of characterization of risk factors among ethnic groups as this field has not been explored yet.
RESUMO
OBJECTIVES: To establish the level of access to healthcare, education, social and geographical factors predisposing a negative surgical outcome and higher mortality rate in patients with penile cancer. METHODS: This is a retrospective, longitudinal and analytical study. Ninety-three medical records of adult male patients diagnosed with penile cancer were reviewed. Fisher's exact test was performed to determine the association between the level of healthcare, social and geographical factors, and the outcomes for penile cancer. RESULTS: Patients without primary care access had a higher chance of having lymphovascular invasion at the time of diagnosis (OR=37.5, P<0.0001), a higher mortality rate at 24 months after diagnosis (OR=19.2, P=0.005), a lack of high school diploma or equivalent (OR=3.8, P=0.049) and a higher likelihood of referral from a provincial hospital (OR=10.1, P<0.0001). Patients without a favorable surgical outcome (radical penectomy) were more likely to have been referred from a provincial hospital (OR=6.8, P<0.0001) and not have access to a primary care center (OR=149.5, P<0.0001), a tertiary care center (OR=20.7, P=0.003), and a high school diploma (OR=7.9, P=0.004). Conclusions: The lack of access to primary care is strongly associated with vascular invasion at diagnosis, lower educational level, a referral from provincial zones, and a higher mortality rate at 24 months. Patients who did not have access to primary and tertiary care, a high school diploma, and were referred from the province were more likely to have a radical penectomy.
RESUMO
Stingray injuries usually happen when a person steps into one, resulting in the attack of the fish introducing a sting into the feet or leg in a defensive manner, causing significant pain and inflammation due to the venom. Retained stingray barb occurs in a low percentage of these accidents and may be difficult to diagnose, for this reason, it is always recommended to use imaging studies. In this case report, we present a 42-year-old man who presented to the orthopedic consult one week after a stingray injury with the diagnosis of retained stingray barb. The aim of this case report is to present a new surgical approach for stingray barb removal with a minimally invasive technique using arthroscopic equipment using the stingray barb entry site as the port to introduce the endoscopic tools.
RESUMO
Urothelial bladder cancer (UBC) is an exceptionally rare condition in adolescents between 15 and 19 years of age. Typically, adolescents and pediatric patients with UBC are more likely to have a favorable histological report. The aim of the paper is to report our experience in the management of a 16-year-old patient with UBC with no risk factors that came to the office because of a history of painless gross hematuria.
RESUMO
Wünderlich syndrome (WS) is a spontaneous retroperitoneal hemorrhage confined to the subcapsular or perinephric space without a history of trauma. Since it is a rare condition with a significant mortality rate if not treated timely, it is essential to identify its risk factors and early clinical manifestations for a favorable outcome. Various conditions are associated, but the most common causes are benign and malignant renal neoplasms. We present a 26-year-old female with a history of tonic-clonic seizures who presented to the ED with intense abdominal pain located on the right flank with a palpable mass. Management included IV fluids and blood transfusion. She underwent a right total nephrectomy. She was later diagnosed with tuberous sclerosis. A 44-year-old female with a three-year history of right costovertebral pain and recurrent urinary tract infections that presented to the ED with acute right flank pain was diagnosed with WS secondary to an angiomyolipoma and underwent right total nephrectomy. WS is a very rare pathology that represents a diagnostic challenge for the physician. The treatment will depend on the hemodynamic condition of the patient. Active follow-up should be reserved for those who have small tumors, are asymptomatic, and have hemodynamic stability. Surgical or radiology intervention is reserved for those who are hemodynamically unstable or who have a suspicion of renal cell carcinoma.
RESUMO
Background On encountering a self-inflicted foreign body in the urinary tract, it is common that emergency physicians only consult the department of urology, and no further evaluations from other specialties are sought. Psychological conditions can also involve people with psychiatric disorders who perform self-harming or sexual practices. Many case reports of foreign bodies have been reported in the literature. However, there is little information regarding which specialties to consult in this situation within the emergency department (ED). Methodology This case series study gathered information on 10 cases from patients who attended the ED from 2005 to 2020 with the diagnosis of genital or lower urinary tract foreign body. Results In total, 10 patients were analyzed with a mean age of 37.3 (SD: ±14.1) years. Of the 10 patients, seven (70%) were males, and three (30%) were females. Overall, four (40%) patients presented with lower urinary tract symptoms (dysuria, tenesmus, hematuria, urinary frequency), five (50%) patients had a significant psychiatric history, and eight (80%) patients admitted having these practices for sexual gratification. Conclusions Foreign bodies in the lower urinary tract pose a significant challenge to ED physicians and urologists because some patients do not admit or do not recall inserting foreign bodies. Patients should be interrogated for mental illness, medication use, and a history of foreign bodies in the urinary tract or genitals during the initial evaluation. There is no consensus or screening method for such patients presenting to the ED. Hence, the use of complementary imaging studies and cystoscopy is fundamental for diagnosis. Further, it is essential to perform a psychiatric evaluation to diagnose or address any underlying psychiatric conditions that could cause this behavior.
RESUMO
INTRODUCTION: High-grade adenocarcinoma of the prostate tends to have denser glandular structures and a prominent desmoplastic reaction, which could be detected by magnetic resonance imaging (MRI) with a super-high b-value in diffusion-weighted imaging (DWI) sequence, to differentiate it from low-grade carcinomas. OBJECTIVE: To evaluate the diagnostic validity of the diffusion sequence with values ââof b4000 s/mm2 for the diagnosis of high-grade prostate cancer (Gleason score ≥ 7). MATERIALS AND METHODS: It is a retrospective analytical study of male patients who have undergone a prostate biopsy and count with a prostate MRI with a DWI sequence of a super-high b-value (4000 s/mm2). RESULTS: The sensitivity of the diffusion sequence with b4000 s/mm2 values ââto classify as positive for prostate cancer was 57.14% as compared to biopsy. The specificity of the diffusion sequence with b4000 s/mm2 values ââclassifying patients with prostate carcinoma as negative was 84.62%. The probability that the diffusion sequence with b4000 s/mm2 values ââclassifies patients with prostate cancer was 80%. The probability that the diffusion sequence with b4000 s/mm2 values ââdoes not classify patients with prostate cancer was 64.71%. The proportion of patients adequately classified with prostate cancer using the diffusion sequence with b4000 s/mm2 values ââwas 70.37%. CONCLUSIONS: The study shows that using the diffusion sequence with values of b4000 s/mm2 is an optimal value that serves as a tool to be able to decant those high-risk carcinomas with those of low risk; however, it is not a definitive method of diagnosis that could replace the performance of a biopsy. Since the study sample was limited, these results cannot be interpreted as reliable for diagnosing high-grade prostate cancer and should encourage future studies on a larger scale population to obtain significant evidence for a non-invasive diagnostic tool with a better cost-benefit for the patient.