Role of MicroRNA-21 in Prostate Cancer Progression and Metastasis: Molecular Mechanisms to Therapeutic Targets.

The role of noncoding RNA has made remarkable progress in understanding progression, metastasis, and metastatic castration-resistant prostate cancer (mCRPC). A better understanding of the miRNAs has enhanced our knowledge of their targeting mainly at the therapy level in solid tumors, such as prostate cancer (PCa). microRNAs (miRNAs) belong to a class of endogenous RNA that deficit encoded proteins. Therefore, the role of miRNAs has been well-coined in the progression and development of PCa. miR-21 has a dual nature in its work both as a tumor suppressor and oncogenic role, but most of the recent studies showed that miR-21 is a tumor promoter and also is involved in castration-resistant prostate cancer (CRPC). Upregulation of miR-21 suppresses programmed cell death and inducing metastasis and castration resistant in PCa. miR-21 is involved in the different stages, such as proliferation, angiogenesis, migration, and invasion, and plays an important role in the progression, metastasis, and advanced stages of PCa. Recently, various studies directly linked the role of high levels of miR-21 with a poor therapeutic response in the patient of PCa. In the present review, we have explained the molecular mechanisms/pathways of miR-21 in PCa progression, metastasis, and castration resistant and summarized the role of miR-21 in diagnosis and therapeutic levels in PCa. In addition, we have spotlighted the recent therapeutic strategies for targeting different stages of PCa.

Intratumoral Heterogeneity, Chemoresistance and Lymph Node Landing Zone Prognosis in Testicular Tumors Based on Histopathological Characteristics.

BACKGROUND: Existing data on the histopathological correlation of testicular tumors with lymph node prognosis have been poorly explored. We aimed to investigate the relationship of the histopathological properties of testicular tumors with lymph nodes and their involvement with chemoresistance and heterogeneity of testicular tumors. METHODS: Patients with non-seminomatous germ cell tumor (NSGCT) were selected for histopathological correlation of testicular tumor with lymph nodes and its relationship with chemoresistance and heterogeneity. Histopathological and radiological parameters associated with the risk of chemoresistance and tumor progression were measured pre- and post-chemotherapy. Binomial logistic regression and Kaplan-Meier analysis were implemented to determine the predictors of progression and adverse overall patient survival. All categorical variables were analyzed using the Chi-square test, while Pearson's R coefficient determined the correlation. RESULTS: Male patients who were diagnosed with NSGCT from March 2017 to December 2018 at Guwahati Medical College, Guwahati, India, were included in this study. Lymph node groups were predominantly incriminated with the EYST or EYS groups and minimally linked with the pure E and YCS groups. Furthermore, the highest number of lymph node stations was associated with pre-chemotherapy. In salvage chemotherapy in the form of VIP, we found exciting outcomes, as approximately 41% of cases responded positively, especially in the EYS group. CONCLUSION: Our study classifies NSGCT according to the most favorable histopathological grouping and explores the tumoral response in different intrinsic and extrinsic variables. Our analysis can serve as a triumphant histopathological nomogram for a sublime management protocol to deal with the onerous histological pairing in NSGCT.

Prospective Assessment of VI-RADS with Muscle Invasion in Urinary Bladder Cancer and Its Implication on Re-Resection/Restaging TURBT Patients.

BACKGROUND: Bladder cancer (BCa) diagnosis relies on distinguishing muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC) forms. Transurethral resection of the bladder tumor (TURBT) is a standard procedure for initial staging and treatment. The Vesical Imaging-Reporting and Data System (VI-RADS) enhances diagnostic accuracy for muscle invasiveness through advanced imaging techniques, potentially reducing reliance on repeat TURBT and improving patient management. OBJECTIVE: We aimed to evaluate the role of VI-RADS in predicting muscle invasiveness in BCa and its potential to predict adverse pathology in high-risk NMIBC to avoid unnecessary repeat TURBT procedures. METHODS: In this prospective study, we included 62 patients over the age of 18 years who underwent TURBT. In a secondary phase, patients selected for restaging TURBT (re-TURBT) were included, but those with T2 tumors or low-risk NMIBC were excluded. Multiparametric magnetic resonance imaging (MRI) examinations were scored by a radiologist using the VI-RADS 5 method, while a pathologist analyzed TURBT and re-TURBT samples for accurate staging. Statistical analysis evaluated the role of VI-RADS in BCa staging. RESULTS: The VI-RADS score was the only predictive factor for muscle invasion in multivariate analysis. Setting the VI-RADS score at >3 resulted in the highest sensitivity, specificity, and diagnostic accuracy, with values of 67.0%, 89.0%, and 78%, respectively. The receiver operating characteristic area under the curve score for VI-RADS for muscle invasion was 85% for stage Ta, 61% for stage T1, and 88% for stage T2, which shows the utility of VI-RADS in the predictiveness of MIBC/NMIBC. CONCLUSION: VI-RADS is effective in stratifying BCa patients by predicting muscle invasiveness and identifying NMIBC cases that may not need repeat TURBT.

Contemporary approaches in the management of uterine leiomyomas.

BACKGROUND: Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The current management of uterine leiomyomas mainly includes surgical interventions such as hysterectomy and myomectomy, either by laparoscopy or laparotomy, which have several complications and are not ideal for preserving fertility. Therefore, there is a need to develop or repurpose medical treatments that do not require surgical intervention. OBJECTIVE: Many drugs are used to treat the symptoms associated with uterine fibroids. The main objective of this systematic review is to give an up-to-date account of potential pharmacological agents (non-surgical methods) for the management of uterine leiomyomas. SEARCH STRATEGY: PubMed was searched for scientific and clinical literature using the keyword 'uterine fibroids' along with the drug names described in each section. For example, 'uterine fibroids' and 'ulipristal acetate' were the keywords used to search for literature on ulipristal acetate (UPA). RESULTS: Various preclinical and clinical studies have shown that some drugs and herbal formulations exhibit activity in the management of uterine leiomyomas. Recent studies found that drugs such as UPA, elagolix, EC313, asoprisnol, nutritional supplements and herbal preparations were helpful in treating the symptoms associated with uterine leiomyomas. CONCLUSION: Many drugs show efficacy in patients with symptomatic uterine fibroids. UPA is one of the most studied and prescribed medicines for uterine fibroids; however, its usage has been restricted due to a few recent incidences of hepatic toxicity. Herbal drugs and natural supplements have also shown promising effects on uterine fibroids. The synergistic effects of nutritional and herbal supplements have been reported in certain cases, and should be studied in detail. Further research is warranted to identify the mode of action of the drugs, and to determine the precise conditions that would explain the causes of toxicity in some patients.

Skeletal-Related Events in Renal Cell Carcinoma: Prediction With Alkaline Phosphatase (ALP), C-reactive Protein (CRP), Haemoglobin (Hb) and Erythrocyte Sedimentation Rate (ESR) (A.C.H.E.) Score for Risk Stratification.

Introduction  Skeletal metastasis is catastrophic in patients with renal cell carcinoma (RCC), leading to skeletal-related events (SRE) such as nerve entrapment, hypercalcemia and even pathological fractures, which may require surgical intervention. The nature of the bone metastasis in advanced RCC is large, destructive, hyper-vascular and mostly lytic. The present retrospective analysis aims to identify potential risk factors for predicting SREs in advanced RCC with bone metastasis. Methods The clinical data of 42 patients with RCC and bone metastasis and at least one episode of SRE were reviewed, and the correlations between erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), C-reactive protein (CRP), haemoglobin (Hb), carcinoembryonic antigen (CEA) and bone metastases were analysed. Risk factors were identified by multivariate logistic regression analysis. Bone metastasis was diagnosed on a bone scan. The receiver operating characteristic (ROC) curve calculated the cut-off value of the independent correlation factors. Results The areas under the ROC curve for ALP, Hb, CRP, and ESR were 0.84, 0.76, 0.86 and 0.88, respectively, suggesting excellent discriminatory capability of ALP, CRP, ESR and sufficient discriminative ability of Hb in predicting bone metastasis. Multivariate logistic regression analysis showed ALP, CRP, Hb and ESR associated with SRE and skeletal metastasis. Conclusion We propose that an A.C.H.E. score encompassing ALP, CRP, Hb, and ESR are potential risk factors for developing SRE and concomitant bone metastasis in advanced RCC patients. For new RCC patients, if values of ALP >128 U/L, CRP ≥74 mg/L, Hb <11.5 g/L, and ESR ≥55 mm/hr are detected, intensive monitoring and bone scanning are warranted as these cases are at a higher risk of skeletal events.

Predictors of Progression-Free Survival and Overall Survival in Metastatic Non-Clear Cell Renal Cell Carcinoma: A Single-Center Experience.

BACKGROUND: Due to the infrequency of non-clear cell renal cell carcinoma (RCC), there is currently a paucity of high-quality literature to help guide the effective treatment of these tumors. Recently, biomarkers such as platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic immune inflammation (SII) index and C-reactive protein to albumin ratio (CAR) have been demonstrated to be closely related to poor prognosis of patients with RCC. The objective of this study was to evaluate these biomarkers for determining the progression-free survival (PFS) and overall survival (OS) in patients with metastatic non-clear cell cancer. METHODS: We retrospectively reviewed 31 cases diagnosed with metastatic non-clear cell RCC from January 2012 to December 2017. We assessed the prognostic value (OS and PFS) of pretreatment PLR, LMR, SII index and CAR based on multivariate analysis and Kaplan-Meier survival curve. RESULTS: Median time of OS and PFS were 15.5 months (95% confidence interval (CI): 13.7 - 15.2) and 10.9 months (95% CI: 8.9 - 12.8), respectively. The median PFS (0.001) and OS (P = 0.01) was shorter in patients with PLR > 171, LMR < 2.61. Moreover, median PFS but not OS was significantly lower in SII index > 883 (P = 0.064) and CAR > 0.11 (P = 0.229). Scan to surgery time (3.91 weeks, P = 0.001) was also significantly related to progression. CONCLUSIONS: Elevated pretreatment inflammatory biomarkers such as PLR, LMR, SII index and CAR are significant determinants of shorter PFS and OS (PLR and LMR only) in patients with metastatic non-clear cell RCC treated with cytoreductive nephrectomy.

This challenging procedure has successful outcomes: Laparoscopic nephrectomy in inflammatory renal diseases.

In prospective study from November 2011- November 2013, we performed 44 laparoscopic nephrectomies for benign non-functioning kidney diseases. Twenty eight patients underwent laparoscopic transperitoneal nephrectomies (63.6%), ten were laparoscopic assisted (22.7%) and six (13.6%) were converted to open. Patient's age, gender, laterality and etiology of renal failure were noted. Outcomes were measured as operative time, intraoperative and post operative complications, blood loss, pain score and hospital stay. Patients were followed up at one, three and 12 weeks and 6 monthly thereafter. Of the 44, ten (22.7%) were 15-24 years old, 32 (72%) between 25-50 years and two were more than 50 years old. Females were 54.6%. 22 patients had either right or left nephrectomy. Pelviureteric-junction (PUJ) obstruction was the commonest cause, 26 cases (59.0%). Operative time: less than two hours in 30 (68.2%) patients, more than two hours in 14 cases. Blood loss: less than 100 ml in 12 (27.3%), 100-200 ml in 20 (45.4%) and more than 200 ml in 12 (27.3%) patients. All four major complications were converted to open, two had injury to mesocolic veins and two had vascular stapler malfunction. Post-operative complications: surgical site infection (SSI), paralytic ileus and mild grade fever in six cases each and non infected benign intra abdominal collection in two cases. Maximum pain score on POD-1: four in 20 cases (45.7%), two in 24 (54%). Two had pain score between 3-4 three weeks after surgery. Oral intake started by POD-2 in 30 (68.2%) and by POD-4 in 100% cases. 22 (50%) patients were ambulating by POD-2, 16 (36.7%) by POD-4. Our study and randomized and non-randomized published literature report acceptables complication and conversion rates. In conclusion, laparoscopic nephrectomy for benign non functional kidney is a better alternative to open nephrectomy.

Role of Diffusion-Weighted Magnetic Resonance Imaging (DWMRI) in Assessment of Primary Penile Tumor Characteristics and Its Correlations With Inguinal Lymph Node Metastasis: A Prospective Study.

BACKGROUND: Penile cancer is a rare malignancy. The extent of lymph node (LN) metastasis is the most important prognostic factor in penile cancer. However, preoperative prediction of LN involvement in clinically non-palpable LN is still a challenge. In absence of a reliable biomarker, attempts are being made to validate imaging characteristics as a predictive tool. The aim of the present study is to assess the primary penile tumor characteristics with diffusion-weighted magnetic resonance imaging (DWMRI) and its correlations with inguinal LN status and tumor positivity in LN dissection specimen within normal sized LNs. METHODS: Twenty-six patients with carcinoma penis underwent DWMRI of penis and pelvis. The apparent diffusion coefficient (ADC) values of primary tumor were compared with histological characteristics. Inclusion criteria encompassed all cases of clinically non-palpable inguinal LN and normal sized LN on imaging. All palpable inguinal nodes with pelvic lymphadenopathies were excluded from this study. RESULTS: The primary tumor ADC ranged from 0.65 × 10-3 - 1.2 × 10-3 mm2/s (mean: 0.87 × 10-3 ± 0.11 × 10-3 mm2/s). In pT1 and pT3 tumors, mean ADC values were 0.86 × 10-3 ± 0.10 × 10-3 and 0.81 × 103 ± 0.09 × 103 mm2/s, respectively. The mean ADC values for grade 1, grade 2 and grade 3 were 0.89 × 10-3, 0.82 × 10-3 and 0.80 × 10-3 mm2/s, respectively. The ADC value of < 0.95 × 10-3 mm2/s was positively correlated with pathological LN presence within normal sized LN. With mean ADC value of 0.87 × 10-3 ± 0.11 × 10-3 mm2/s, sensitivity and positive predictive values for primary penile cancer were 100% and 84.61%, respectively. The mean ADC value for higher-grade and -stage tumor was low. The sensitivity and specificity of predicting LN metastasis by DWMRI were 87.22% and 80.90%, respectively. CONCLUSION: ADC value of primary tumor can help in prediction of LN metastasis in carcinoma penis with clinically and radiologically normal groin.