Haassteele5039
Background Systemic metastasis is the main cause of death in patients with prostate cancer. It is necessary to establish a more accurate model to distinguish and predict patients with a high risk of metastasis to optimize individualized treatment. Methods In this study, it was determined that hypoxia could affect the metastasis-free survival of patients with prostate cancer, and a hypoxia-related gene signature composed of seven genes for predicting metastasis was established and verified in different cohorts. The study further evaluated the effects of ALDOB expression on the proliferation and invasion of the LNCaP and DU145 cell lines under hypoxia and finally constructed a nomogram containing specific clinical characteristics of prostate cancer combined with the hypoxia gene signature to quantify the metastasis risk of individual patients. Results The hypoxia-related gene signature was identified as an independent risk factor for metastasis-free survival in patients with prostate cancer. The expression of ALDOB increased under hypoxia and promoted the proliferation and invasion of LNCaP and DU145 cells. In addition, patients with a high risk score showed therapeutic resistance and immunosuppression. Compared with other parameters, the nomogram had the strongest predictive power and net clinical benefit. Conclusion The study established a hypoxia-related gene signature and a nomogram to distinguish and predict patients with a high risk of prostate cancer metastasis, which may help to optimize individualized treatment and explore possible therapeutic targets.Lymph node metastasis indicates a poor prognosis in colorectal cancer. To better understand the underlying mechanisms of lymph node metastasis, we analyzed transcriptome characteristics of the pre-metastatic lymph node, a putative microenvironment favorable for the seeding and proliferation of cancer cells. Thus, we tried to compare and elucidate the transcriptional and immune characteristics of sentinel lymph nodes (SNs) with matched non-sentinel lymph nodes (NSNs) in colorectal cancer patients. In this study, a total of 38 pairs of SNs and NSNs were collected, in which 26 pairs of non-metastatic lymph nodes were subjected to RNA-seq and bioinformatics analysis for the gene expression profiles. There were 16 differentially expressed genes between SNs and NSNs being identified, including 9 upregulated and 7 downregulated genes in SN. Gene Ontology (GO) classification analysis revealed that the differentially expressed genes were mainly involved in leukocyte differentiation, chemokine secretion, and immune sys can enhance the anti-tumor function of T cells, as indicated by cytokine release analysis. In conclusion, we presented here a first report on the gene expression profiling of the pre-metastatic lymph node in colorectal cancer. The findings in this study suggest that SIGLEC15 plays an important role in SN immunosuppression. SEGLEC15 silencing could be a therapeutic strategy for restoring T cell function in tumor SNs.
The aim of this study was to demonstrate the role of carbon fiducial markers (fiducials) for guiding radiotherapy in the management of uveal melanoma (UM).
This is a retrospective interventional case series at a single-center ocular oncology practice. The medical records were reviewed retrospectively for all patients with UM treated with stereotactic radiosurgery using episcleral fiducials. We report our short-term experience with surgical placement of fiducials, UM localization, treatment outcomes, and optimization approaches.
We evaluated 11 cases of UM (mean age 65 years; 64% female). The placed fiducials were numbered from 2 to 4, each secured to the sclera with a surgical microscope or surgical loupes and either 5-0 or 8-0 nylon sutures at 50% scleral depth and 3 mm beyond the tumor margin. Over a median follow-up of 11 months (range 4.2-43.2 months), no recurrences of intraocular UM were observed. One case of enucleation after stereotactic radiosurgery developed because of radiation-related surfacresult in clinically important radiation dose attenuation at the tumor margins. Anteriorly placed fiducials may cause discomfort, yet they are easily removed in the outpatient setting.
This study aimed to explore factors for refusing treatment in patients diagnosed with uveal melanoma and their subsequent clinical course.
This study included patients with uveal melanoma who refused standard of care treatment. Patient-reported reasons and pre-existing mental health diagnoses were assessed. The sociodemographic profile was compared with the controls. Ocular survival, metastasis-free survival (MFS), and overall survival (OS) were calculated.
Nine patients with uveal melanoma declined ocular treatment (plaque brachytherapy,
= 7 [78%]; enucleation,
= 2 [22%]). The choroidal melanomas were small (
= 1 [11%]), medium (
= 5 [56%]), and large (
= 3 [33%]) in size (COMS criteria). The sociodemographic profile of the study patients was not different from those that accepted treatment. One patient (11%) had pre-existing mental health diagnosis. JAK activation Five patients (56%) eventually accepted treatment following an average delay of 19 months (range 4-55 months) due to neovascular glaucoma or severe vision loss. MFS could not be ascertained, and OS was 67% (6/9) at 4.2 years of follow-up (mean).
Refusal of initial recommended treatment is associated with poor ocular survival. The small sample size did not allow for an evaluation of the impact on survival.
Refusal of initial recommended treatment is associated with poor ocular survival. The small sample size did not allow for an evaluation of the impact on survival.
To evaluate the histopathological characteristics of clinically advanced retinoblastoma (RB) and its relationship with tumor differentiation.
This was a cross-sectional study of primary enucleated group D/E intraocular RB using medical records from 2017 to 2020 in a tertiary referral hospital. Cases with incomplete histopathological results were excluded. Tumors were classified into well, moderately, and poorly differentiated and undifferentiated. High-risk histopathological features were classified as per Thaung and Karaa [
. 2018;31(101)17-3].
This study included 121 patients (129 eyes), of which 32.2% were diagnosed at 25-36 months. High-risk features (HRFs) were found in 100/129 eyes, and of 73 complete histopathological results, the 2 most common HRFs were postlaminar optic nerve invasion and massive choroidal invasion. RB was poorly differentiated in 69.9% and well differentiated in 12.3% of eyes. There was no statistically significant association between any HRFs and tumor differentiation, with age >2 years associated with tumor differentiation (
< 0.05).
The frequency of HRFs is 77.5% of primary enucleated eyes, mainly poorly and undifferentiated cells, particularly in children aged >2 years old.
2 years old.
The aim of this study was to optimize the technique of performing vitrectomy-assisted biopsy of intraocular tumors by comparing the cytohistological findings in specimens obtained with different vitrectomy probes and cut rates.
Vitrectomy-assisted biopsies were taken from a fresh porcine liver. For each sampling, the vacuum level was 300 mm Hg. The following parameters were compared; cut rate (60, 600 and 6,000 cuts per minute [cpm]), probe type (standard and two-dimensional cutting [TDC]), and probe diameter (23-gauge and 25-gauge). The specimens were assessed by automated whole-slide imaging analysis and conventional light microscopy.
Seventy-two biopsies were analyzed for the number of hepatocytes, total area of tissue fragments, and total stained area of each microscope slide. For all probe types, these parameters were significantly and positively correlated with the cut rate. TDC probes led to significantly higher scores than those of standard probes, independent of the cut rate. There were no significant differences in results when using 23-gauge or 25-gauge standard probes. Light microscopic examination demonstrated well-preserved cells sufficient for cytohistological analyses in all investigated cases.
The higher the cut rate, the larger is the amount of aspirated cellular material. There were no significant differences between 23-gauge and 25-gauge biopsies. Cut rates up to 6,000 cpm did not adversely affect the cytohistological features of the samples.
The higher the cut rate, the larger is the amount of aspirated cellular material. There were no significant differences between 23-gauge and 25-gauge biopsies. Cut rates up to 6,000 cpm did not adversely affect the cytohistological features of the samples.Uveal melanoma (UM) and renal cell carcinoma (RCC) can occur sporadically and as a manifestation of BAP1 tumor predisposition syndrome. We aimed to understand the prevalence of germ line BAP1 pathogenic variants in patients with UM and RCC. We reviewed patients managed at Cleveland Clinic between November 2003 and November 2019 who were diagnosed with UM and RCC. Charts were reviewed for demographic and cancer-related characteristics. RCC samples were tested for BAP1 protein expression using immunohistochemical (IHC) staining, and testing for germ line BAP1 pathogenic variants was performed as part of routine clinical care. Thirteen patients were included in the study. The average age at diagnosis of UM was 61.3 years. Seven patients underwent fine-needle aspiration biopsy for prognostic testing of UM (low risk =5, high risk =2). Twelve patients were treated with plaque radiation therapy, and 3 patients developed metastatic disease requiring systemic therapy. The median time to diagnosis of RCC from time of diagnosis of UM was 0 months. RCC samples were available for 7 patients for BAP1 IHC staining (intact =6, loss =1). All patients underwent nephrectomy (total = 3, partial = 8, unknown =2), and 1 received systemic therapy for metastatic RCC. Six patients underwent germ line BAP1 genetic testing. Of these, 1 patient was heterozygous for a pathogenic variant of BAP1 gene c.1781-1782delGG, p.Gly594Valfs*48. The overall prevalence of germ line BAP1 pathogenic variants in our study was high (1/6; 17%; 95% CI 0-46%). Patients with UM and RCC should be referred for genetic counseling to discuss genetic testing.
The purpose of this study is to describe variations in microvasculature before and after treatment of treatment-naive lesions and during consolidation therapy of retinoblastoma lesions using an investigational portable optical coherence tomography angiography (OCTA) system.
This study is a single-center, prospective, observational case series. Recruited subjects were either undergoing surveillance for retinoblastoma or had newly detected retinoblastoma. Nine tumors from 7 eyes in 6 patients were included. During exams under anesthesia, the tumors were imaged with an investigational portable OCTA system. OCTA images were analyzed to assess vascular changes before and after treatment.
In all 6 presented cases, OCTA imaging revealed distinctive vascular patterns, such as dilated feeder arteries and draining veins, disorganized and complex branching patterns, irregular vessel calibers, and dilation and tortuosity of vessels. After treatment, OCTA imaging revealed decreased intrinsic tumor vascularity and reduced dilation of draining and feeder vessels.