Renal Malignancy Research Articles

Comparison of clinical manifestation among Australian Indigenous and non-indigenous patients presenting with pleural effusion.

There is sparse evidence in the literature in relation to the nature and causes of pleural effusion among Australian Indigenous population. To investigate the clinical and demographic characteristics of adult indigenous patients presenting with pleural effusion in the Northern Territory of Australia. In this retrospective study, indigenous and non-indigenous adults diagnosed to have pleural effusion over a 2-year study period were included for comparative analysis. Of the 314 patients, 205 (65%) were non-indigenous and 52% were male. In comparison with non-indigenous patients, the indigenous patients were younger (50 years (interquartile range (IQR) 39-60) vs 63 years (IQR 52-72); P < 0.001), female (61% vs 41%; P = 0.001), had a higher prevalence of renal and cardiovascular disease and tended to have exudative effusion (93% vs 76%; P = 0.032). Infections were judged to be the most common cause of effusion in both groups, more so among the indigenous cohort. Effusion secondary to renal disease was higher (13% vs 1%; P < 0.001) among Australian Indigenous patients, but in contrast, malignant effusions were higher (13% vs 4%; P = 0.004) among non-indigenous patients. Length of hospital stay was longer for indigenous patients (P = 0.001), and a greater proportion received renal dialysis (13% vs 1%; P < 0.001). Intensive care unit admission rates were higher with infective aetiology of pleural effusion (82% vs 53% indigenous and 44% vs 39% non-indigenous respectively). Re-presentations to hospital were higher among indigenous patients (46% vs 33%; P = 0.046) and were associated with renal and cardiac disease and malignancy in non-indigenous patients. There are significant differences in the way pleural effusion manifests among Australian Indigenous patients. Understanding these differences might facilitate approaches to management and to implementation of strategies to reduce morbidity and mortality in this population.

Incidental renal neoplasia following simple nephrectomy of the non-functioning kidney. Is it more common than previously reported?

Background: Simple nephrectomy is a technique of removing the kidney from within the gerota’s fascia and is usually for a non-functioning kidney. While for renal tumors, radical nephrectomy is done, which involves the removal of the kidney with gerota’s fascia along with the ureter. Histopathology of patients who undergo simple nephrectomy sometime reveals renal malignancy. Such patients often need further treatment as simple nephrectomy in such cases is mostly suboptimal. The number of studies reporting tumors in simple nephrectomy specimens is limited. We aim to report single-center pathological findings in nephrectomy specimens from patients treated for non-functioning kidneys due to renal stone disease. Methodology: The medical record of patients (n=210) who underwent simple nephrectomy between 2014 and 2021 at the Kidney Centre Postgraduate Training Institute due to renal stone disease was reviewed retrospectively. Results: The total number of patients undergoing simple nephrectomy for non-functioning kidneys due to stone disease was 210. Of those patients, 117 were males, and 93 were females. The mean age was 45.33 ± 17.65 years. The histopathology report of specimens revealed renal malignancy in 10 patients (4.76%), xanthogranulomatous pyelonephritis in 11 patients, tuberculosis of the kidney in 7 patients, and chronic pyelonephritis in 182 patients. Conclusion: In conclusion, the prevalence of renal malignancy in patients undergoing simple nephrectomy is significantly high.

The HLA-G immune checkpoint: a new immuno-stimulatory role for the α1-domain-deleted isoform.

The heterogeneity of cancer cells, in part maintained via the expression of multiple isoforms, introduces significant challenges in designing effective therapeutic approaches. In this regard, isoforms of the immune checkpoint HLA-G have been found in most of the tumors analyzed, such as ccRCC, the most common human renal malignancy. In particular, HLA-G∆α1, which is the only HLA-G isoform described that lacks the α1 extracellular domain, has been newly identified in ccRCC and now here in trophoblasts. Using a cellular model expressing HLA-G∆α1, we have uncovered its specific and overlapping functional roles, relative to the main HLA-G isoform, i.e., the full-length HLA-G1. We found that HLA-G∆α1 has several particular features: (i) although possessing the α3 domain, it does not associate with β2-microglobulin; (ii) it may not present peptides to T cells due to absence of the peptide-binding groove; and (iii) it exerts immune-stimulatory activity towards peripheral blood NK and T cells, while all known isoforms of HLA-G are immune-inhibitory checkpoint molecules. Such immune-stimulatory properties of HLA-G∆α1 on the cytotoxic function of peripheral blood NK cells are individual dependent and are not exerted through the interaction with the known HLA-G receptor, ILT2. Importantly, we are faced here with a potential antitumor effect of an HLA-G isoform, opposed to the pro-tumor properties described for all other HLA-G isoforms, which should be taken into account in future therapeutic designs aimed at blocking this immune checkpoint.

Unexpected Huge Prevalence of Intracardiac Extension of Wilms Tumor-A Single Center Experience from a Ugandan Hospital.

Wilms tumor (WT) is the most common primary renal malignancy in young children. WT vascular extension to the inferior vena cava (IVC) occurs in 4–10% of cases and can reach the right atrium (RA) in 1%. Data on WT clinical presentation and outcome in developing countries are limited. The aim of the present study is to describe the prevalence of intracardiac extension in a consecutive population of WT patients observed in a large non-profit Ugandan hospital. A total of 16 patients with a histological diagnosis of 29 WT were screened in a 6-month period. Patient n°2, a 3 y/o child, presented with a 3-week history of abdominal distension, difficulty in breathing, and swelling of the lower limbs. A cardiovascular system exam showed rhythmic heart sounds, a heart rate of 110 beats per minute, and a pansystolic murmur on the tricuspid area; the abdomen was grossly distended with a palpable mass in the right flank, hepatomegaly, and splenomegaly. An abdomen ultrasound showed an intra-abdominal tumor, involving the right kidney and the liver and extended to the IVC. An ultrasound guided biopsy showed a picture consistent with WT. Cardiac echo showed a huge, mobile, cardiac mass attached to the right side of the interatrial septum, involving the tricuspid valve annulus, causing a “functional” tricuspid stenosis. The patient died of cardiogenic shock 7 days after admission. Patient n°3, a 3 y/o child, presented with analogue symptoms and the same diagnosis. The cardiac echo showed a round mass in the RA. Thirteen more patients were screened with cardiac echo, showing a normal heart picture. In our limited series, we found WT cardiac extension in three patients over 16 (19%). Cardiac echo performed routinely can lead to a better staging, prognostic, and therapeutic assessment. In our setting, the intra-cardiac extension could be more frequent than previously reported and might have prognostic implications.

PARG suppresses tumorigenesis and downregulates genes controlling angiogenesis, inflammatory response, and immune cell recruitment

Chemokines are highly expressed in tumor microenvironment and play a critical role in all aspects of tumorigenesis, including the recruitment of tumor-promoting immune cells, activation of cancer-associated fibroblasts, angiogenesis, metastasis, and growth. Poly (ADP-ribose) polymerase (PARP) is a multi-target transcription regulator with high levels of poly(ADP-ribose) (pADPr) being reported in a variety of cancers. Furthermore, poly (ADP-ribose) glycohydrolase (PARG), an enzyme that degrades pADPr, has been reported to be downregulated in tumor tissues with abnormally high levels of pADPr. In conjunction to this, we have recently reported that the reduction of pADPr, by either pharmacological inhibition of PARP or PARG’s overexpression, disrupts renal carcinoma cell malignancy in vitro. Here, we use 3 T3 mouse embryonic fibroblasts, a universal model for malignant transformation, to follow the effect of PARG upregulation on cells’ tumorigenicity in vivo. We found that the overexpression of PARG in mouse allografts produces significantly smaller tumors with a delay in tumor onset. As downregulation of PARG has also been implicated in promoting the activation of pro-inflammatory genes, we also followed the gene expression profile of PARG-overexpressing 3 T3 cells using RNA-seq approach and observed that chemokine transcripts are significantly reduced in those cells. Our data suggest that the upregulation of PARG may be potentially useful for the tumor growth inhibition in cancer treatment and as anti-inflammatory intervention.

ColorNephroNet: Kidney tumor malignancy prediction using medical image colorization

Renal tumor malignancy classification is one of the crucial tasks in urology, being a primary factor included in the decision of whether to perform kidney removal surgery (nephrectomy) or not. Currently, tumor malignancy prediction is determined by the radiological diagnosis based on computed tomography (CT) images. However, it is estimated that up to 16% of nephrectomies could have been avoided because the tumor that had been diagnosed as malignant, was found to be benign in the postoperative histopathological examination. The excess of false-positive diagnoses results in unnecessarily performed nephrectomies that carry the risk of periprocedural complications. In this paper, we present a machine-aided diagnosis system that predicts the tumor malignancy based on a CT image. The prediction is performed after radiological diagnosis and is used to capture false-positive diagnoses. Our solution is able to achieve a 0.84 F1-score in this task. We also propose a novel approach to knowledge transfer in the medical domain in terms of colorization based pre-processing that is able to increase the F1-score by up to 1.8pp.

Clinical and Genetic Comparison of Birt-Hogg-Dubé Syndrome (Hornstein-Knickenberg Syndrome) in Chinese: A Systemic Review of Reported Cases.

BackgroundBirt–Hogg–Dubé syndrome (BHD), also named Hornstein–Knickenberg syndrome, is a rare autosomal dominant disease characterized by lung cysts, recurrent pneumothoraxes, renal cell carcinoma and skin fibrofolliculomas.PurposeThis study summarizes the clinical and genetic information of Chinese BHD patients from all available reported cases and explores the relationship between the clinical and genetic spectrum in the hope of improving the prognosis of Chinese BHD patients.MethodsRelative studies were collected by searching PubMed, Cochrane Library, Embase, OVID medicine, SinoMed, Web of Science, China National Knowledge Infrastructure, Wanfang Data and China Hospital Knowledge Database from January 1, 1977 to December 31, 2021. The search strategy included the following term keys: (Birt–Hogg–Dubé syndrome OR Hornstein-Kinckenberg syndrome OR familial pulmonary cysts OR familial spontaneous pneumothorax OR fibrofolliculomas OR trichodiscomas OR inherited renal cancer syndromes OR FLCN) AND (Chinese OR China).ResultsIn total, 287 Chinese patients from 143 families described in 31 references were included in this article. Chinese BHD patients tended to present more pulmonary symptoms but fewer skin lesions and renal malignancies, which appeared to be atypical when compared with Caucasian patients. The FLCN mutation spectrum among Chinese BHD patients was established with the mutational hot spot c.1285depC/delC as the most frequent mutation. In addition, this mutation spectrum also showed some differences from other races, with a relatively frequent large deletion c.872–429_1740+1763del (exon 9–14 deletion) reported only in Chinese individuals but no observation of the two mutational hot spots found in Japanese individuals. We also attempted to establish potential pheno-genotype correlations in Chinese BHD patients, but the results were negative.ConclusionTo improve the prognosis of BHD patients, physicians need to increase their awareness of BHD by focusing on the family history of pneumothorax as well as skin lesions in patients with lung cysts and promptly advising patients on genetic sequencing.

Tumor Suppressive Role of MUC6 in Wilms Tumor via Autophagy-Dependent β-Catenin Degradation.

Wilms tumor is the most common renal malignancy in children. Known gene mutations account for about 40% of all wilms tumor cases, but the full map of genetic mutations in wilms tumor is far from clear. Whole genome sequencing and RNA sequencing were performed in 5 pairs of wilms tumor tissues and adjacent normal tissues to figure out important genetic mutations. Gene knock-down, CRISPR-induced mutations were used to investigate their potential effects in cell lines and in-vivo xenografted model. Mutations in seven novel genes (MUC6, GOLGA6L2, GPRIN2, MDN1, MUC4, OR4L1 and PDE4DIP) occurred in more than one patient. The most prevalent mutation was found in MUC6, which had 7 somatic exonic variants in 4 patients. In addition, TaqMan assay and immunoblot confirmed that MUC6 expression was reduced in WT tissues when compared with control tissues. Moreover, the results of MUC6 knock-down assay and CRISPR-induced MUC6 mutations showed that MUC6 inhibited tumor aggression via autophagy-dependent β-catenin degradation while its mutations attenuated tumor-suppressive effects of MUC6. Seven novel mutated genes (MUC6, GOLGA6L2, GPRIN2, MDN1, MUC4, OR4L1 and PDE4DIP) were found in WT, among which MUC6 was the most prevalent one. MUC6 acted as a tumor suppressive gene through autophagy dependent β-catenin pathway.

Clinical features and upper airway symptoms in association with severity and outcome in patients with COVID-19

Objectives: To assess the relationship between the early occurrence of upper respiratory tract symptoms and the severity of SARS-COV-2 infection.Methods: A cohort observational study had been conducted on a total of 140 patients [60 mild, 40 moderate, 40 severe], diagnosed with SARS-CoV-2 between 4th of August and 31 of October 2020. Patients diagnosed by PCR or chest CT scan or both of them. A full history was taken from the patients and data including the age of the patient, gender, occupation, residence, height, weight, history of previous comorbidities {cardiovascular, Diabetes mellitus, Hypertension, chronic respiratory disease, chronic renal disease, malignancy, and other diseases}. Smoking and alcoholic history were also taken, clinical features {loss of smell/taste, sore throat, rhinorrhea, fever, cough, shortness of breath, headache, fatigue, myalgia, arthralgia, diarrhea, and vomiting} and temperature, SPO2, investigations, the need for respiratory support {O2, non-invasive ventilation, invasive ventilation} and any complications developed during illness.&#x0D; Results: Mean age of the patients was 51(range:17-82) Males were dominant; (57.1%) with male to female ratio of 1.33 to one, out of the 140 COVID-19 patients, 63 (45%) had upper respiratory symptoms. Regarding biomarkers of severity only S.LDH was significantly lower in cases who did have compared to those who did not have upper respiratory symptoms, 1.3 ± 1.4 vs. 1.7 ± 1.3, respectively. The mean SPO2% was significantly higher in patients with upper respiratory symptoms compared to those without. Percent of Pulmonary damage was significantly lower in patients with upper Respiratory symptom compared to those without. Mortalities were significantly lower in patients with upper respiratory symptoms compared to those without; among the 113 patients with upper respiratory symptom compared only 7(6.2%) died compared to 7 out of 27 (25.9%) patients with no upper respiratory symptom.Conclusion: Early occurrence of upper respiratory tract symptoms predicts less severe form of the disease.

Radiogenomics in Clear Cell Renal Cell Carcinoma: A Review of the Current Status and Future Directions.

Simple SummaryClear renal cell carcinoma (ccRCC) is the most common type of renal cancer. As with other malignancies, knowledge of the genetic makeup of ccRCC tumors may provide insights for tumor management and outcomes. However, this normally requires obtaining tissue specimens from the tumor by invasive interventions—surgery or biopsy. Radiogenomics is a field that aims to non-invasively predict the genetic makeup of the tumor based on the tumor’s appearance on conventional imaging, such as CT scans. To achieve this, radiogenomics uses complex machine learning (artificial intelligence) algorithms to process imaging data and build predictive models that can infer a tumor’s genetic makeup and clinical outcomes from its features on conventional imaging. In this article, we searched scientific literature databases for radiogenomic studies in ccRCC, offering a review and critical analysis of these studies. More research and validation are needed before applying radiogenomics in clinical practice.Radiogenomics is a field of translational radiology that aims to associate a disease’s radiologic phenotype with its underlying genotype, thus offering a novel class of non-invasive biomarkers with diagnostic, prognostic, and therapeutic potential. We herein review current radiogenomics literature in clear cell renal cell carcinoma (ccRCC), the most common renal malignancy. A literature review was performed by querying PubMed, Medline, Cochrane Library, Google Scholar, and Web of Science databases, identifying all relevant articles using the following search terms: “radiogenomics”, “renal cell carcinoma”, and “clear cell renal cell carcinoma”. Articles included were limited to the English language and published between 2009–2021. Of 141 retrieved articles, 16 fit our inclusion criteria. Most studies used computed tomography (CT) images from open-source and institutional databases to extract radiomic features that were then modeled against common genomic mutations in ccRCC using a variety of machine learning algorithms. In more recent studies, we noted a shift towards the prediction of transcriptomic and/or epigenetic disease profiles, as well as downstream clinical outcomes. Radiogenomics offers a platform for the development of non-invasive biomarkers for ccRCC, with promising results in small-scale retrospective studies. However, more research is needed to identify and validate robust radiogenomic biomarkers before integration into clinical practice.

ДИАГНОСТИЧЕСКАЯ ЭФФЕКТИВНОСТЬ НОВОГО МЕТОДА ОПРЕДЕЛЕНИЯ ПОВРЕЖДЕНИЯ ПОЧЕК ПРИ ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ

Objectives. To evaluate diagnostic effectiveness of a complex ultrasound method for determining kidney damage in patients with chronic heart failure (CHF). Material and methods. In 2017-2021 on the basis of the Healthcare Institution «1st City Clinical Hospital» in Minsk, a clinical and instrumental study was performed on 203 patients aged 66 (59; 75) years, of which 111 (54.7%) were women and 92 (45.3%) men. Dynamic ultrasound investigation of the kidneys was carried out in 80 patients with CHF after ≥3 months. Inclusion criteria: sinus rhythm in patients; essential (primary) arterial hypertension; chronic ischemic heart disease; congestive heart failure; informed voluntary consent of the patient to participate in the study. Exclusion criteria: glomerular, tubulointerstitial kidney disease, obstructive uropathy, renal artery stenosis, congenital kidney diseases, history of renal malignancy. Results. The method for determining kidney damage in CHF is based on the concept of establishing a complex of ultrasound signs. It includes an assessment of the total volume of the kidneys, parenchymal thickness, end diastolic blood flow velocity, pulsation index, resistance index in segmental renal arteries, and characterizes kidney damage in patients with normal or slightly reduced glomerular filtration rate (GFR) (categories C1 - C2), chronic kidney disease (CKD) with categories of GFR C3A - C4 and CHF. Conclusions. The method has a high accuracy - 98.3%, which makes it possible to recommend its use when establishing CKD in patients with CHF.

Incidence, management and treatment outcomes of renal malignancy in a post-transplant recipient at a tertiary care centre: A 16-year experience

Introduction and Objective: Although the incidence of malignancy in renal transplant recipients is on the rise owing to boom in the post-transplant immunosuppressive therapy, there is paucity of literature regarding their reporting and management. In this study, we report the incidence of de novo renal malignancies, post-renal transplantation at our centre over a 16-year period and discuss their management. Methods: All patients who underwent renal transplantation at our department between March 2004 and February 2020 were included and retrospectively reviewed. We analysed the incidence of renal malignancy both in the native kidney and the graft, histological subtype, time to and type of treatment. Results: A total of 376 patients underwent renal transplantation. Mean age of recipients was 48.2 and 52.15 years among those who developed cancer. 13 (2.93%) of 376 recipients developed urogenital malignancy, of whom 8 had renal cell carcinoma (RCC) in their native kidneys and 1 in the allograft. Transitional cell carcinoma (TCC) of renal pelvis was noted in three patients with one concomitant TCC of bladder. No treatment-related graft losses occurred in the native kidney malignancy. Patients with RCC underwent nephrectomy while TCC of renal pelvis underwent nephroureterectomy with bladder cuff excision. Transurethral resection was done for bladder tumour. All patients were followed up as per standard protocol. Conclusion: A rise in urological post-transplant malignancies mandates regular surveillance after renal transplantation to ensure early detection of de novo malignancies and early initiation of treatment. Goal should be to minimise adverse graft outcomes with no compromise on oncological outcomes. Level of evidence: Not applicable

Construction and validation of a prognostic model for kidney renal clear cell carcinoma based on podocyte-associated genes.

BackgroundAs the most common renal malignancy, kidney renal clear cell carcinoma (KIRC) has a high prevalence and death rate as well as a poor response to treatment. Developing an efficient prognostic model is essential for accurately predicting the outcome and therapeutic benefit of KIRC patients.MethodsGene expression profiles of podocyte‐associated genes (PAGs) were obtained from The Cancer Genome Atlas and GEO datasets. Cox regression and Lasso regression analyses were then used for filtering prognosis‐associated PAGs. Risk score (RS) was computed from these genetic characteristics. Kaplan–Meier analysis and receiver operating characteristic (ROC) curves were applied for ascertaining the prognostic value. Stratified analysis was used to sufficiently validate model performance. Concordance index was used to compare the predictive ability of different models. Immuno‐infiltration analysis and immunophenoscore were utilized for the prediction of patient reaction to immune checkpoint inhibitors (ICIs).ResultsWT1, ANLN, CUBN, OSGEP, and RHOA were significantly associated with KIRC prognosis. Prognostic analysis indicated that high‐RS patients have a significantly poorer outcome. Cox regression analysis demonstrated a potential for RS to be an independent prognostic factor. Pathway enrichment results indicated a lower enrichment of cancer‐related biological pathways in the low‐RS subgroup. Immune infiltration analysis and IPS demonstrated greater responsiveness to ICIs in the high RS group.ConclusionsThis podocyte‐associated KIRC prognostic model can effectively predict KIRC prognosis and immunotherapy response, which may help to provide clinicians with more effective treatment strategies.

Tumor-to-Tumor Metastasis of Renal Cell Carcinoma to a Follicular Variant of Papillary Thyroid Carcinoma: A Case Report and Literature Review

Renal cell carcinoma (RCC) is the most common renal malignancy. It has a variable clinical course with metastasis to unusual sites occurring months to years after the initial diagnosis. However, metastasis can also be the first presentation of RCC. Although relatively uncommon, the thyroid gland is the most common location for RCC metastasis in the head and neck region. Tumor-to-tumor metastasis is an exceedingly rare occurrence. Only 10 cases were reported of RCC metastasis to primary thyroid neoplasms.We present a case of clear cell RCC metastasizing to a follicular of variant papillary thyroid carcinoma (FVPTC) 14 years after the initial diagnosis of RCC. A review of similar reported cases revealed that the most common primary thyroid recipient of tumor-to-tumor metastasis of RCC was FVPTC. The rich lymphovascular network in FVPTC compared to other thyroid tumors, which may promote the deposition of metastatic tumor cells, might explain this predilection.Careful review of the clinical and radiological findings and checking for any history of malignancy when examining thyroid nodules is important for guiding further studies. Performing a targeted panel of immunohistochemical stains for any suspicious areas is also essential for the diagnosis of such unusual cases.

Pediatric genitourinary tumors: Distribution, demographics, and outcomes.

ABSTRACTImportanceThe diversity of pediatric genitourinary malignancies requires a timely resource detailing tumor characteristics and survival.ObjectiveTo determine the incidence, demographics, and outcomes of all pediatric genitourinary tumors within the United States.MethodsA population‐based search for patients diagnosed with genitourinary cancers under age 15 was performed using the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 registry. Information on primary tumor location, histologic type, patient age, sex, year of diagnosis, race, treatment, cause of death, and survival months was extracted. Descriptive epidemiological and survival statistics were calculated for all variables.ResultsA total of 4576 cases from 1973 through 2015 were identified. The most common primary tumor sites were the kidney (80.3%), testis (12.3%), bladder (2.8%), and vagina (1.5%). Nephroblastoma (87.9%) and sarcoma (3.4%) were the most common renal malignancies. Rhabdomyosarcoma was common in the vagina, bladder, and testis at rates of 66.2%, 61.2%, and 24.6%, respectively. Germ cell tumors (71.0%) were the most common primary tumor of the testis. Ten‐year overall survival (OS) for renal nephroblastoma and sarcoma was 88% and 82%, respectively. Ten‐year OS for RMS of the testis was 91%, the bladder was 79%, the vagina was 79%, and the prostate was 56%. Germ cell tumor 10‐year OS were 96% in the testis and 100% in the vagina.InterpretationA better understanding of the overall distribution and outcomes associated with pediatric genitourinary cancers allows physicians to best understand the patient's disease in the context of current frequency in a genitourinary setting and reported outcomes.

Determinants of label non-adherence to non-vitamin K oral anticoagulants in patients with newly diagnosed atrial fibrillation.

AimsTo evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients.Methods and resultsIn the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01–1.02], lower renal function (OR: 0.96 per ml/min/1.73 m2, 0.92–0.98), lower weight (OR: 0.98 per kg, 0.97–1.00), active malignancy (OR: 2.46, 1.19–5.09), anaemia (OR: 1.73, 1.08–2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57–9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88–0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m2, 0.96–1.00).ConclusionIn newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.

Multi-detector computed tomography (MDCT) evaluation of synchronous renal cell carcinoma and other solid malignancies

BackgroundMultiple primary malignant neoplasms (MPMNs) became more prevalent as the population aged and medical technology progressed. The purpose of this research was to review the findings of multidetector computed tomography (MDCT) in synchronous renal cell carcinoma and other solid tumors.Results31 individuals with synchronous renal cell carcinoma and additional solid cancers were included in this retrospective analysis. CT scanning was carried out using 64 MDCT scanners. All sixty-two malignancies were undergoing pathological assessment. Out of 685 patients with renal cell carcinoma, 31 individuals were identified with another primary solid cancer that occurred concurrently. All of our instances were pathologically verified. In all 31 individuals, clear renal cell carcinoma was found. The most frequent extra-renal malignancies were hepatocellular carcinoma (10/31), followed by breast carcinoma (4/31), non-Hodgkin lymphoma (4/31), bronchogenic carcinoma (3/31), colonic carcinoma (3/31), prostatic carcinoma (2/31), urinary bladder carcinoma (1/31), periampullary carcinoma (1/31), mucoepidermoid carcinoma (1/31) and skin squamous cell carcinoma (1/31) as well as malignant hemangioendothelioma (1/31).ConclusionMDCT scanning was an accurate imaging method for diagnosing synchronous renal cell carcinoma and other solid tumors. Even in the face of numerous cancers, the goal of therapy in cancer patients must always be curative. During the pretreatment examination, the potential of synchronous double malignancies with renal cell carcinoma should be explored.

Second Primary Malignancies in Patients With Melanoma Subtypes: Analysis of 120,299 Patients From the SEER Database (2000-2016).

PurposeEvaluate incidence of second primary malignancies (SPM) after non-acral cutaneous melanoma (NACM), acral lentiginous melanoma (ALM), mucosal melanoma (MM), and uveal melanoma (UM).Patients and MethodsFirst primary NACM, ALM, MM, and UM cases diagnosed 2000-2016 were extracted from SEER. Seer*Stat was used to calculate excess absolute risks (EAR) and standardized incidence ratios (SIR) of SPMs relative to a matched cohort from the general population. P-value of 0.05 determined significance.ResultsInclusion criteria was met by 109,385 patients with NACM, 2166 with ALM, 2498 with MM, and 6250 with UM. Increased incidence of malignancies occurred after NACM (SIR 1.51; 95%CI, 1.49-1.54), ALM (SIR 1.59; 95%CI, 1.40-1.81), MM (SIR 2.14; 95%CI, 1.85-2.45), and UM (SIR 1.24; 95%CI, 1.14-1.34) relative to the general population. Cutaneous melanoma occurred more frequently after NACM (SIR 9.54; 95%CI, 9.27-9.83), ALM (SIR 12.19; 95%CI, 9.70-15.14), MM (SIR 10.05; 95%CI, 7.18-13.68), and UM (SIR 2.91; 95%CI, 2.27-3.66). Patients with initial NACM (SIR 2.44; 95%CI, 1.64-3.51) and UM (SIR 44.34; 95%CI, 29.91-63.29) demonstrated increased incidence of eye and orbit melanoma. Renal malignancies occurred more frequently after NACM (SIR 1.24; 95%CI, 1.11-1.38), MM (SIR 3.54; 95%CI, 1.62-6.72) and UM (SIR 1.68; 95%CI, 1.09-2.48). Increased incidence of thyroid malignancies was observed after NACM (SIR 1.83; 95%CI, 1.61-2.06), ALM (SIR 3.74; 95%CI, 1.71-7.11), MM (SIR 4.40; 95%CI, 1.77-9.06), and UM (SIR 3.79; 95%CI, 2.52-5.47). Increased incidence of lymphoma was observed after NACM (SIR 1.20; 95%CI, 1.09-1.31) and ALM (SIR 2.06; 95%CI, 1.13-3.46).ConclusionPatients with NACM, ALM, MM, and UM have increased incidence of SPMs compared to that expected from the general population. Each of these melanoma subtypes had increased occurrence of cutaneous melanoma and thyroid cancer; some, but not all, had increased occurrence of renal malignancies, eye and orbit melanoma, and lymphoma.

Application of Mass Spectrometry Imaging in Uro-Oncology: Discovering Potential Biomarkers.

A growing need is emerging worldwide for new molecular markers which could enhance the accuracy of diagnostic and therapeutic methods for detecting urogenital cancers. Mass spectrometry imaging (MSI) is a very promising tool in this regard. In this review, we attempt to provide a subjective summary of the latest publications on potential biomarkers of renal, bladder, prostate, and testicular malignancies detected with MSI through the eyes of a clinical urologist.

PDGF-BB/PDGFRβ promotes epithelial-mesenchymal transition by affecting PI3K/AKT/mTOR-driven aerobic glycolysis in Wilms' tumor G401 cells.

Wilms' tumor (WT) is the most common pediatric renal malignancy. PDGFRβ belongs to the type III receptor tyrosine kinase family and is known to be involved in tumor metastasis and angiogenesis. Here, we studied the effect and underlying mechanism of PDGFRβ on WT G401 cells. Transwell assay and wound-healing assay were used to detect the effect of PDGFRβ on G401 cells invasion and migration. Western blot and immunofluorescence were used to detect the expression of EMT-related genes. The expression of PI3K/AKT/mTOR pathway proteins was detected by Western blot. The relationship between PDGFRβ and aerobic glycolysis was studied by assessing the expression of glycolysis-related enzymes detected by qRT-PCR and Western blot. The activity of HK, PK, and LDH was detected by corresponding enzyme activity kits. The concentration of lactic acid and glucose was detected by Lactic Acid Assay Kit and Glucose Assay Kit-glucose oxidase method separately. To investigate the mechanism of PDGFRβ in the development of WT, the changes of glucose and lactic acid were analyzed after blocking PI3K pathway, aerobic glycolysis, or PDGFRβ. The key enzyme was screened by Western blot and glucose metabolism experiment after HK2, PKM2, and PDK1 were inhibited. The results showed that PDGFRβ promoted the EMT process by modulating aerobic glycolysis through PI3K/AKT/mTOR pathway in which PKM2 plays a key role. Therefore, our study of the mechanism of PDGFRβ in G401 cells provides a new target for the treatment of WT.