Clinical Features and Therapeutic Outcomes Comparing Primary Mediastinal Large B-cell Lymphoma to Mediastinal Hodgkin Disease.

Currently, there is limited data available comparing Primary Mediastinal Large B-cell Lymphoma (PMBL) and mediastinal Hodgkin disease, nodular sclerosis type (HDNS). This is a retrospective cohort study that compares the clinical features, histology through immunohistochemistry (IHC) and treatment outcomes of 19 cases of PMBL and 39 cases of HDNS diagnosed over 13 years at a single institution in San Juan, PR. Superior Vena Cava syndrome (SVCS) and elevated Lactate Dehydrogenase (LDH) levels were more frequently seen in the PMBL cohort. At the median follow-up visit, of 74 months, no significant difference was seen in overall survival or progression free survival between PMBL and HDNS. Almost all of the relapses in the PMBL group occurred within 12 months of diagnosis. Our data suggests that PMBL and HDNS differ in their clinical presentation and have a favorable prognosis.

Renal Cell Carcinoma With Tumor Thrombus: A Case Series in Puerto Rico.

INTRODUCTION:  Renal cell carcinoma (RCC) is one of the most common types of kidney cancer. While RCC tends to present as a localized tumor, a notable proportion may present with distant metastasis. In some instances, RCC may also present with intravascular tumor extension, often called tumor thrombus (TT). Its presence confers a worse prognosis and has important implications for the tumor's staging and treatment. Despite extensive documentation of RCC TT in the US, limited data exists regarding its presentation, management, and outcomes in Puerto Rico (PR). This study aims to broaden the available information on RCC TT, emphasizing surgical management and outcomes. We also provide descriptive data on patient demographics and clinical presentation to improve decision-making among clinicians caring for Puerto Rican men and women. METHODS:  In this single-center, retrospective study, we evaluated patients who underwent partial or total nephrectomy at Saint Luke's Episcopal Medical Center between 2018 and 2022. Data was abstracted from electronic health records (EHR). Patients without documented evidence of TT during the peri-operative period were excluded from the study. A total of 220 patient records were evaluated, of which 12 met the inclusion criteria for the study. Cases were categorized using the latest RCC TT guidelines. Central tendency measurements were used to describe the sample distribution. The mean was considered to make assumptions regarding the prevalent observations, and the median was considered to rule out possible outliers. Categorical data were evaluated using proportion analyses, including TT extension level and BMI variables. Fisher's exact test evaluated the association between the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and TT extension level. RESULTS:  Most patients lacked TT-related symptoms. The most severe presenting symptom was a pulmonary embolism (8.3%). Hypertension (83.3%), BMI greater than 25 at the time of diagnosis (75%), and type 2 diabetes mellitus (66.7%) were the most common comorbid conditions within our cohort. Nearly 75% of patients underwent laparoscopic radical nephrectomy with TT resection. One left-sided level III case was managed by laparoscopic-assisted open radical nephrectomy with a right subcostal incision. There were zero intraoperative complications and two postoperative complications. The histopathological reports of all cases were consistent with clear cell carcinoma, and half of the cases (n=6) were WHO/ISUP G4. All patients are alive and free of disease. CONCLUSION:  RCC is a common renal neoplasm in PR that can present with intravascular tumor extension. Our findings do not establish a definitive association between BMI, tumor size, WHO/ISUP grading, and TT extension level. Our study shows that laparoscopic removal of RCC TT is a safe and effective approach. However, the generalizability of our findings is limited by the study's design and sample size. Future research should focus on identifying predictive markers, establishing effective screening protocols, and determining if our hybrid approach has comparable outcomes to the standard open approach.

Identification of Exo-miRNAs: A Summary of the Efforts in Translational Studies Involving Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers (BC) in the US and its diagnosis is associated with poor survival outcomes. A better understanding of the disease etiology is crucial to identify target treatment options to improve patient outcomes. The role of exo-miRNAs in TNBC has been studied for more than two decades. Although some studies have identified exo-miR candidates in TNBC using clinical samples, consensus regarding exo-miR candidates has not been achieved. The purpose of this review is to gather information regarding exo-miR candidates reported in TNBC translational studies along with the techniques used to isolate and validate the potential targets. The techniques suggested in this review are based on the use of commercially available materials for research and clinical laboratories. We expect that the information included in this review can add additional value to the recent efforts in the development of a liquid biopsy to identify TNBC cases and further improve their survival outcomes.

A role for laparoscopy in the age of robotics: a retrospective cohort study of perioperative outcomes between 2D laparoscopic radical prostatectomy vs 3DHD laparoscopic radical prostatectomy.

PURPOSE: Our study compares perioperative outcomes between two-dimensional (2D) laparoscopic radical prostatectomy (LRP) and the 4th generation three-dimensional/high definition (3DHD) LRP. METHODS: Retrospectively acquired data from patients that underwent 2D LRP (n = 75) and 3DHD LRP (n = 75) from March 2013 to October 2015 were evaluated. Procedures were performed by a single surgeon. The extra-peritoneal approach with 5 trocars was utilized. Perioperative outcomes, potency, and continence were compared between groups. RESULTS: Patient characteristics were similar between the two groups in terms of age (p = 0.44), prostate-specific antigen (PSA) levels (p = 0.34), and Gleason scores (p = 0.14). Body mass index (BMI) was significantly higher in the 3DHD group (p = 0.0036). Postoperatively, no significant differences were observed in Hgb loss (p = 0.50), positive surgical margins (p = 1.00), and post-op Gleason scores (p = 0.30). Significant differences were observed for length of hospital stay (p < 0.001) and Jackson-Pratt (JP) drainage (p < 0.001). Regarding potency, 73.7% and 51.6% of the patients in the 3DHD and 2D groups regained potency at 6 months, respectively (p = 0.0025). Almost 43% of the patients in the 3DHD group regained continence at 1 month while for the 2D groups it was only 17.3% (p = 0.0008). CONCLUSION: 3DHD and 2D LRP have resulted in good outcomes in the perioperative periods. Our results show decreased JP drainage, shorter length of hospital stay, earlier return of urinary control, and earlier return of sexual function in the 3DHD LRP group. In lower volume centers where robotics equipment is not feasible due to economic barriers 3DHD can be safely performed as a minimally invasive alternative.

Reduced DNA Repair Capacity in Prostate Cancer Patients: A Phenotypic Approach Using the CometChip.

Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic men in the US. Among Hispanics, Puerto Rican (PR) men show the highest PCa-specific mortality. Epidemiological studies using functional assays in lymphocytes have demonstrated that having low DRC is a significant risk factor for cancer development. The aim of this study was to evaluate variations in DRC in PR men with PCa. Lymphocytes were isolated from blood samples from PCa cases (n = 41) and controls (n = 14) recruited at a hospital setting. DRC levels through the nucleotide excision repair (NER) pathway were measured with the CometChip using UVC as a NER inductor. The mean DRC for controls and PCa cases were 20.66% (±7.96) and 8.41 (±4.88), respectively (p < 0.001). The relationship between DRC and tumor aggressiveness was also evaluated. Additional comparisons were performed to evaluate the contributions of age, anthropometric measurements, and prostate-specific antigen levels to the DRC. This is the first study to apply the CometChip in a clinical cancer study. Our results represent an innovative step in the development of a blood-based screening test for PCa based on DRC levels. Our data also suggest that DRC levels may have the potential to discriminate between aggressive and indolent cases.

Differential DNA Methylation in Prostate Tumors from Puerto Rican Men.

In 2020, approximately 191,930 new prostate cancer (PCa) cases are estimated in the United States (US). Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. This study aims to assess methylation patterns between aggressive and indolent PCa including DNA repair genes along with ancestry proportions. Prostate tumors classified as aggressive (n = 11) and indolent (n = 13) on the basis of the Gleason score were collected. Tumor and adjacent normal tissue were annotated on H&E (Haemotoxylin and Eosin) slides and extracted by macro-dissection. Methylation patterns were assessed using the Illumina 850K DNA methylation platform. Raw data were processed using the Bioconductor package. Global ancestry proportions were estimated using ADMIXTURE (k = 3). One hundred eight genes including AOX1 were differentially methylated in tumor samples. Regarding the PCa aggressiveness, six hypermethylated genes (RREB1, FAM71F2, JMJD1C, COL5A3, RAE1, and GABRQ) and 11 hypomethylated genes (COL9A2, FAM179A, SLC17A2, PDE10A, PLEKHS1, TNNI2, OR51A4, RNF169, SPNS2, ADAMTSL5, and CYP4F12) were identified. Two significant differentially methylated DNA repair genes, JMJD1C and RNF169, were found. Ancestry proportion results for African, European, and Indigenous American were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation patterns related to PCa in H/L men along with specific patterns related to aggressiveness and DNA repair constitutes a pivotal effort for the understanding of PCa in this population.

Dysregulation of DNA Methylation and Epigenetic Clocks in Prostate Cancer among Puerto Rican Men.

In 2021, approximately 248,530 new prostate cancer (PCa) cases are estimated in the United States. Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. The objective of this study was to assess DNA methylation patterns between aggressive and indolent PCa along with ancestry proportions in 49 H/L men from Puerto Rico (PR). Prostate tumors were classified as aggressive (n = 17) and indolent (n = 32) based on the Gleason score. Genomic DNA samples were extracted by macro-dissection. DNA methylation patterns were assessed using the Illumina EPIC DNA methylation platform. We used ADMIXTURE to estimate global ancestry proportions. We identified 892 differentially methylated genes in prostate tumor tissues as compared with normal tissues. Based on an epigenetic clock model, we observed that the total number of stem cell divisions (TNSC) and stem cell division rate (SCDR) were significantly higher in tumor than adjacent normal tissues. Regarding PCa aggressiveness, 141 differentially methylated genes were identified. Ancestry proportions of PR men were estimated as African, European, and Indigenous American; these were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation profiles associated with risk and aggressiveness of PCa in PR H/L men will shed light on potential mechanisms contributing to PCa disparities in PR population.

Circulating Vitamin D Levels and DNA Repair Capacity in Four Molecular Subtypes of Women with Breast Cancer.

Vitamin D regulates estrogen synthesis among other mechanisms involved in breast cancer (BC) development; however, no evidence has been found regarding its relationship with DNA repair capacity (DRC). Therefore, the objective of this study was to elucidate whether DRC levels are linked with plasma 25(OH)D levels. BC cases and controls were selected from our BC cohort. DRC levels were assessed in lymphocytes through the host-cell reactivation assay. 25(OH)D levels were measured using the UniCel DxI 600 Access Immunoassay System. BC cases (n = 91) showed higher 25(OH)D levels than the controls (n = 92) (p = 0.001). When stratifying BC cases and controls into low and high DRC categories, BC cases with low DRC (n = 74) had the highest 25(OH)D levels (p = 0.0001). A positive correlation between 25(OH)D and DRC levels was found for the controls (r = 0.215, p = 0.043) while a negative correlation was found for BC cases (r = -0.236, p = 0.026). Significant differences in 25(OH)D levels were observed when stratifying by molecular subtypes (p = 0.0025). Our study provides evidence of a link between 25(OH)D and DRC in BC along with a description of to how 25(OH)D levels vary across subtypes. The positive correlation observed in the control group suggests that 25(OH)D contributes differently to DRC levels once the malignancy is developed.

Norepinephrine-Induced DNA Damage in Ovarian Cancer Cells.

Multiple studies have shown that psychological distress in epithelial ovarian cancer (EOC) patients is associated with worse quality of life and poor treatment adherence. This may influence chemotherapy response and prognosis. Moreover, although stress hormones can reduce cisplatin efficacy in EOC treatment, their effect on the integrity of DNA remains poorly understood. In this study, we investigated whether norepinephrine and epinephrine can induce DNA damage and modulate cisplatin-induced DNA damage in three EOC cell lines. Our data show that norepinephrine and epinephrine exposure led to increased nuclear γ-H2AX foci formation in EOC cells, a marker of double-strand DNA breaks. We further characterized norepinephrine-induced DNA damage by subjecting EOC cells to alkaline and neutral comet assays. Norepinephrine exposure caused DNA double-strand breaks, but not single-strand breaks. Interestingly, pre-treatment with propranolol abrogated norepinephrine-induced DNA damage indicating that its effects may be mediated by ß-adrenergic receptors. Lastly, we determined the effects of norepinephrine on cisplatin-induced DNA damage. Our data suggest that norepinephrine reduced cisplatin-induced DNA damage in EOC cells and that this effect may be mediated independently of ß-adrenergic receptors. Taken together, these results suggest that stress hormones can affect DNA integrity and modulate cisplatin resistance in EOC cells.

Selective Interactions of Valeriana officinalis Extracts and Valerenic Acid with [H]Glutamate Binding to Rat Synaptic Membranes.

Although GABA neurotransmission has been suggested as a mechanism for Valeriana officinalis effects, CNS depression can also be evoked by inhibition of ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). In this study, we examined if aqueous valerian extract interacted with glutamatergic receptors. Freshly prepared aqueous valerian extract was incubated with rat cortical synaptic membranes in presence of 20 nM [(3)H]Glutamate. Aqueous valerian extract increased [(3)H]Glutamate binding from 1 × 10(-7) to 1 × 10(-3) mg/mL. In the presence of (2S,1'S,2'S)-2-(Carboxycyclopropyl)glycine (LCCG-I) and (2S,2'R,3'R)-2-(2',3'-Dicarboxycyclopropyl)glycine (DCG-IV), Group II mGluR agents, valerian extract markedly decreased [(3)H]Glutamate binding, while (2S)-2-amino-3-(3,5-dioxo-1,2,4-oxadiazolidin-2-yl) propanoic acid) (quisqualic acid, QA), Group I mGluR agonist, increased [(3)H]Glutamate binding. At 0.05 mg/mL aqueous valerian extract specifically interacted with kainic acid NMDA and AMPA receptors. Valerenic acid, a marker compound for Valeriana officinalis, increased the [(3)H]Glutamate binding after 1.6 × 10(-2) mg/mL, and at 0.008 mg/mL it interacted only with QA (Group I mGluR). The selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant.