Renal Malignancy Research Articles

Nurse-led renal cell carcinoma clinic: a single center review.

In 2015 our centre introduced a nurse-led renal cell cancer follow-up protocol and clinic for patients who have undergone partial or radical nephrectomy for organ-confined kidney tumours. The main aims of this clinic were to improve healthcare efficiency and standardize follow-up processes. The primary objective was to assess the effectiveness of a nurse-led renal cell cancer follow up clinic in regard to surveillance protocol compliance and the timely identification and appropriate management of recurrences. A secondary objective was to evaluate this locally developed follow up protocol against the current European Association of Urology (EAU) guidelines surveillance protocol. All patients who underwent a partial or radical nephrectomy between 2015 and 2021 at a single Western Australia institution for a primary renal malignancy were included. Data was collected from local clinical information systems and protocol adherence, recurrence characteristics and management were assessed. The current EAU guidelines were applied to the cohort to assess differences in risk-stratification and theoretical outcomes between the protocols. After a mean follow up period of 31.2 months (range 0-77 months), 75.5% (185/245) of patients had all follow up imaging and reviews within 1 month of the timeframe scheduled on the protocol. 17.1% (42/245) had a delay in their follow up of more than a month at some stage, 5.7% (14/245) did not attend for follow up but had documented attempts to facilitate their compliance, and 0.4% (1/245) were lost to follow up with no evidence of attempted contact. 15.5% (38/245) of patients had recurrence of malignancy detected during follow up and these were all discussed in a multi-disciplinary team (MDT) meeting. The recurrence rate was 2.5% (3/119) for low risk, 17.7% (14/79) for intermediate risk, and 44.7% (21/47) for high risk patients when they were re-stratified according to EAU risk categories. No recurrences were detected through ultrasound (USS) or chest x-ray (CXR) in this cohort and our protocol tended to place patients in higher risk-stratification groups as compared to current EAU guidelines. Nurse-led renal cell cancer follow up is a safe, reliable and effective clinical framework that has significant benefits in regard to resource utilization. USS and CXR are ineffective in detecting recurrence and Computerized tomography (CT) should be considered the imaging modality of choice for this purpose. The EAU surveillance protocol appears superior to our protocol, and we have therefore transitioned to the EAU guideline protocol going forward.

Causal relationship between several autoimmune diseases and renal malignancies: A two-sample mendelian randomization study.

Observational studies have shown an association between systemic autoimmune disease (AD) and multiple malignancies. However, due to the difficulty indetermining the temporal nature of the order, their causal relationship remains elusive. Based on pooled data from a large population-wide genome-wide association study (GWAS), this study explores the genetic causality between systemic autoimmune disease and renal malignancy. We took a series of quality control steps from a large-scale genome-wide association study to select single nucleotide polymorphisms (SNPs) associated with systemic autoimmune disease as instrumental variables(IVs) to analyze genetic causality with renal malignancies. Inverse variance weighting (IVW), MR- Egger, weighted median, simple model and weighted model were used for analysis. The results were mainly based on IVW (Random Effects), followed by sensitivity analysis. Inverse-Variance Weighted(IVW) and MR-Egger were used to test for heterogeneity. MR- Egger is also used for pleiotropic testing. A single SNP analysis was used to identify single nucleotide polymorphisms (SNPs) with potential impact. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate causality, and sensitivity analysis was performed to evaluate pleiotropy and instrumental validity. Acute and subacute iridocylitis (P = 0.006, OR = 1.077), Ankylosing spondylitis (P = 0.002, OR = 1.051), and spondyloarthritis (P = 0.009, OR = 1.073) were positively associated with an increased risk of renal malignancy. Coxarthrosis (P = 0.008, OR = 0.483), Juvenile rheumatism (P = 0.011, OR = 0.897), and Systemic lupus erythematosus (P = 0.014, OR = 0.869) were negatively associated with an increased risk of renal malignancy. The results of sensitivity analysis were consistent without heterogeneity or pleiotropy. Our study suggests a causal relationship between different systemic autoimmune diseases and renal malignancies. These findings prompt health care providers to take seriously the potential risk of systemic autoimmune disease and provide new insights into the genetics of kidney malignancies.

Bone mimetic environments support engineering, propagation, and analysis of therapeutic response of patient-derived cells, ex vivo and in vivo

Bone metastases are the most common milestone in the lethal progression of prostate cancer and prominent in a substantial portion of renal malignancies. Interactions between cancer and bone host cells have emerged as drivers of both disease progression and therapeutic resistance. To best understand these central host-epithelial cell interactions, biologically relevant preclinical models are required. To achieve this goal, we here established and characterized tissue-engineered bone mimetic environments (BME) capable of supporting the growth of patient-derived xenograft (PDX) cells, ex vivo and in vivo. The BME consisted of a polycaprolactone (PCL) scaffold colonized by human mesenchymal stem cells (hMSCs) differentiated into osteoblasts. PDX-derived cells were isolated from bone metastatic prostate or renal tumors, engineered to express GFP or luciferase and seeded onto the BMEs. BMEs supported the growth and therapy response of PDX-derived cells, ex vivo. Additionally, BMEs survived after in vivo implantation and further sustained the growth of PDX-derived cells, their serial transplant, and their application to study the response to treatment. Taken together, this demonstrates the utility of BMEs in combination with patient-derived cells, both ex vivo and in vivo. Statement of significanceOur tissue-engineered BME supported the growth of patient-derived cells and proved useful to monitor the therapy response, both ex vivo and in vivo. This approach has the potential to enable co-clinical strategies to monitor bone metastatic tumor progression and therapy response, including identification and prioritization of new targets for patient treatment.

Prevalence and risk factors for cirrhotic cardiomyopathy: a prospective cross-sectional study.

This study aimed to assess cardiac structure and function in patients with cirrhosis, to investigate the prevalence of cirrhotic cardiomyopathy (CCM) in patients with cirrhosis of different etiologies and to analyze the risk factors for the development of CCM. This study selected cirrhotic patients aged 18-75 years who were hospitalized in Qilu Hospital of Shandong University. Patients with known heart disease, chronic lung disease, severe renal insufficiency, malignancy, thyroid disease, hypertension, diabetes or pregnancy were excluded. A total of 131 patients with cirrhosis were finally included. Based on the results of echocardiography, patients who met the diagnostic definition of CCM were included in the CCM group, otherwise, they were classified as the non-CCM group. The demographic and clinical data of the two groups were compared, and the clinical characteristics and risk factors of CCM were evaluated. The overall prevalence of CCM was 24.4%, and the occurrence of CCM was not related to the etiology of liver cirrhosis. The prevalence of CCM was significantly higher among cirrhotic patients complicated with ascites (31.4% vs. 16.4%; P = 0.046) or with portal vein thrombosis (PVT) (42.9% vs. 17.1%; P = 0.003). Older age [odds ratio (OR) = 1.058; 95% confidence interval (CI), 1.005-1.113; P = 0.032] and PVT (OR = 2.999; 95% CI, 1.194-7.533; P = 0.019) were independent risk factors for the development of CCM. The prevalence of CCM in cirrhotic patients was 24.4%, and the occurrence of CCM was not related to the etiology of cirrhosis. The prevalence of CCM was higher in cirrhotic patients with ascites or PVT. Older age and PVT are independent risk factors for CCM, but validation in larger sample studies is still needed.

Prevalence and outcomes of chronic comorbid conditions in patients with sepsis in Korea: a nationwide cohort study from 2011 to 2016

BackgroundChronic comorbid conditions are common in patients with sepsis and may affect the outcomes. This study aimed to evaluate the prevalence and outcomes of common comorbidities in patients with sepsis.MethodsWe conducted a nationwide retrospective cohort study. Using data from the National Health Insurance Service of Korea. Adult patients (age ≥ 18 years) who were hospitalized in tertiary or general hospitals with a diagnosis of sepsis between 2011 and 2016 were analyzed. After screening of all International Classification of Diseases 10th revision codes for comorbidities, we identified hypertension, diabetes mellitus (DM), liver cirrhosis (LC), chronic kidney disease (CKD), and malignancy as prevalent comorbidities.ResultsOverall, 373,539 patients diagnosed with sepsis were hospitalized in Korea between 2011 and 2016. Among them, 46.7% had hypertension, 23.6% had DM, 7.4% had LC, 13.7% had CKD, and 30.7% had malignancy. In-hospital mortality rates for patients with hypertension, DM, LC, CKD, and malignancy were 25.5%, 25.2%, 34.5%, 28.0%, and 33.3%, respectively, showing a decreasing trend over time (P < 0.001). After adjusting for baseline characteristics, male sex, older age, use of mechanical ventilation, and continuous renal replacement therapy, LC, CKD, and malignancy were significantly associated with in-hospital mortality.ConclusionsHypertension is the most prevalent comorbidity in patients with sepsis, and it is associated with an increased survival rate. Additionally, liver cirrhosis, chronic kidney disease, and malignancy result in higher mortality rates than hypertension and DM, and are significant risk factors for in-hospital mortality in patients with sepsis.

Cross-sectional analysis of cardiovascular disease and risk factors in patients with spondyloarthritis: a real-life evidence from biostar nationwide registry

The association between spondyloarthritis and cardiovascular (CV) diseases is complex with variable outcomes. This study aimed to assess the prevalence rates of CV diseases and to analyze the impact of CV risk factors on CV disease in patients with spondyloarthritis. A multi-center cross-sectional study using the BioSTAR (Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs Registry) database was performed on patients with spondyloarthritis. Socio-demographic, laboratory, and clinical data were collected. Patients with and without major adverse cardiovascular events (MACE) were grouped as Group 1 and Group 2. The primary outcome was the overall group’s prevalence rates of CV disease and CV risk factors. The secondary outcome was the difference in socio-demographic and clinical characteristics between the groups and predictive risk factors for CV disease. There were 1457 patients with a mean age of 45.7 ± 10.9 years. The prevalence rate for CV disease was 3% (n = 44). The distribution of these diseases was coronary artery disease (n = 42), congestive heart failure (n = 4), peripheral vascular disorders (n = 6), and cerebrovascular events (n = 4). Patients in Group 1 were significantly male (p = 0.014) and older than those in Group 2 (p < 0.001). There were significantly more patients with hypertension, diabetes mellitus, chronic renal failure, dyslipidemia, and malignancy in Group 1 than in Group 2 (p < 0.05). Smoking (36.7%), obesity (24.4%), and hypertension (13.8%) were the most prevalent traditional CV risk factors. Hypertension (HR = 3.147, 95% CI 1.461–6.778, p = 0.003), dyslipidemia (HR = 3.476, 95% CI 1.631–7.406, p = 0.001), and cancer history (HR = 5.852, 95% CI 1.189–28.810, p = 0.030) were the independent predictors for CV disease. A multi-center cross-sectional study using the BioSTAR (Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs Registry) database was performed on patients with spondyloarthritis. Socio-demographic, laboratory, and clinical data were collected. Patients with and without major adverse cardiovascular events (MACE) were grouped as Group 1 and Group 2. The primary outcome was the overall group’s prevalence rates of CV disease and CV risk factors. The secondary outcome was the difference in socio-demographic and clinical characteristics between the groups and predictive risk factors for CV disease. There were 1457 patients with a mean age of 45.7 ± 10.9 years. The prevalence rate for CV disease was 3% (n = 44). The distribution of these diseases was coronary artery disease (n = 42), congestive heart failure (n = 4), peripheral vascular disorders (n = 6), and cerebrovascular events (n = 4). Patients in Group 1 were significantly male (p = 0.014) and older than those in Group 2 (p < 0.001). There were significantly more patients with hypertension, diabetes mellitus, chronic renal failure, dyslipidemia, and malignancy in Group 1 than in Group 2 (p < 0.05). Smoking (36.7%), obesity (24.4%), and hypertension (13.8%) were the most prevalent traditional CV risk factors. Hypertension (HR = 3.147, 95% CI 1.461–6.778, p = 0.003), dyslipidemia (HR = 3.476, 95% CI 1.631–7.406, p = 0.001), and cancer history (HR = 5.852, 95% CI 1.189–28.810, p = 0.030) were the independent predictors for CV disease. The prevalence rate of CV disease was 3.0% in patients with spondyloarthritis. Hypertension, dyslipidemia, and cancer history were the independent CV risk factors for CV disease in patients with spondyloarthritis.

Ultrasound-guided continuous erector spinae plane block versus thoracic epidural analgesia in open nephrectomy for renal malignancy: a randomized controlled study

Background &amp; objective: Pain during nephrectomy has been reported to be extremely intense and may trigger complex biochemical and physiological stress response if managed inadequately. Erector spinae plane block (ESPB) and thoracic epidural analgesia (TEA) both have been advocated for pain management in adult patients undergoing open nephrectomy under general anesthesia. We compared the efficacy and the dynamics of both of these procedures. Methodology: This was a randomized, double-blinded, controlled trial involving 54 patients were undergoing open nephrectomy for malignant kidney tumors. All patients were ASA class II, had a BMI 20-40 kg/m2, and were between the ages of 18-65 y. Through random assignment, people were divided into two identical, equivalent groups: Group A (n = 27) received TEA, whereas Group B (n = 27) received US-guided continuous ESPB. Mean arterial pressure (MAP) and intraoperative heart rate (HR) were recorded before and after incision, and at 30 min, 1 h, and 1.5 h. Postoperative HR, MAP were recorded at 6 h and 12 h, both at rest and when moving. Numerical rating scale (NRS) score was used to compare the intensity of postoperative pain. Results: Postoperative HR, MAP, at 6 h and 12 h, at rest and when moving, were substantially reduced in the TEA group than those in the ESPB group. The NRS score of the ESPB group was substantially greater than that of the TEA group. In contrast to the TEA group, much more total amount of morphine was consumed in the ESPB group. The time to first rescue analgesia was substantially shorter in ESPB group than that of the TEA group. Conclusions: The results of our study prove that US guided erector spinae plane block is effective in providing postoperative analgesia, decreasing use of intraoperative and postoperative opioids in patients having open nephrectomy. However, it is still inferior to thoracic epidural analgesia in terms of pain control after 6 h postoperatively. Otherwise, erector spinae plane block has fewer side effects compared to thoracic epidural analgesia. So, it may be used as an alternative to thoracic epidural analgesia. Key words: Erector Spinae Plane Block; Epidural Analgesia; Open Nephrectomy; Pain, Postoperative; Ultrasound Citation: Wadood MA, Abdelrahman MA, Mostafe MM, Abdelghafar EM. Ultrasound-guided continuous erector spinae plane block versus thoracic epidural analgesia in open nephrectomy for renal malignancy: a randomized controlled study, Anaesth. pain intensive care 2024;28(1):26-32; DOI: 10.35975/apic.v28i1.2377 Received July 24, 2023; Revised: September 08, 2023; Accepted: October 03, 2023

Can non-contrast magnetic resonance imaging replace contrast-enhanced computerized tomography in the local staging of pediatric renal tumors?

BackgroundRenal tumors account for approximately 6–7% of the total incidence of pediatric cancers. Wilms tumor (WT) is the most common renal malignancy observed in the pediatric population under 5 years old. Computed tomography (CT) is used for staging of the renal tumors. Magnetic resonance imaging (MRI) offers enhanced soft tissue resolution and provides more comprehensive insights into tumor extension through the capsule, including tumor infiltration into the renal vein or IVC. MRI is a noninvasive imaging modality that does not involve any radiation hazards, making it safe for children. In addition, MRI can be performed without the administration of contrast agents in patients with impaired renal function. Therefore, MRI plays a vital role in screening, staging, preoperative evaluation, and follow-up. Diffusion-weighted imaging (DWI) is a functional tool that aids in locating the most receptive tumoral region to guide confirmatory biopsies. In this study, we aim to evaluate the potential value of non-contrast MRI in staging pediatric renal tumors compared to contrast-enhanced CT.ResultsThis study included 50 patients presented with renal mass, with ages ranging from 1 to 8 years and a mean age of 4.27 ± 1.27 (mean ± SD). The final diagnosis was Wilm’s tumor at 86%, clear cell sarcoma at 4%, rhabdoid tumor at 4%, rhabdomyosarcoma at 2%, and nephroblastomatosis with no malignant transformation at 4%. CT accurately diagnosed stages 4 and 5 in agreement with pathological findings while upstaging the other cases, with a CT sensitivity of 90.91%, specificity of 82.35%, PPV of 92%, and NPV of 84%. MRI is superior to CT in stages 1 and 3, accurately diagnosing stages 2, 4, and 5, with a sensitivity of 93.30%, specificity of 95.65%, PPV of 95%, and NPV of 97%.ConclusionsNon-contrast MRI could be considered the optimal radiation-free imaging modality in staging pediatric renal tumors mainly Wilm’s tumor as it offers high sensitivity and specificity of capsular and vascular infiltration, compared to contrast-enhanced CT especially in cases with impaired renal functions.

The general population&amp;apos;s knowledge and awareness of smoking as a risk factor for urological diseases in the Western Region of Saudi Arabia

Background: In Saudi Arabia, smoking is a significant public health concern. Cigarette smoking is the leading preventable cause of urinary bladder cancer and increases the risk of prostatic and renal malignancies. There have been a limited number of studies conducted on this topic in Saudi Arabia, especially in the Western Region. Objectives: The current study aims to assess the knowledge and awareness of the general population in the Western Region of Saudi Arabia regarding smoking as a risk factor for urological diseases. Methods: A cross-sectional study was conducted between February and October 2023, employing an online survey self-administered and disseminated through social media platforms. A method of sampling by convenience was utilized to enlist the participants for the study. Following approval from an Institutional Review Board, information was gathered from Saudi Arabian citizens and residents aged 18 or older residing in the western region. Results: The study included a total of 850 individuals. Based on the gender distribution, 67% of the individuals were male, while 33% were female. The participants were surveyed regarding their smoking habits; out of the total, 70% identified as non-smokers, 18% identified as smokers, and 12% identified as ex-smokers. 37% of respondents acknowledged that smoking posed a risk for bladder cancer, while 36.8% acknowledged that smoking posed a risk for kidney cancer. Gender exhibited a notable correlation with kidney cancer and erectile dysfunction (p &amp;lt; 0.05). Moreover, there was a strong correlation between smoking status and erectile dysfunction (p &amp;lt; 0.05). Conclusion: The study revealed that only a small proportion of participants have sufficient knowledge of the association between smoking and the heightened susceptibility to kidney and bladder cancer. Therefore, it is necessary to increase awareness through the implementation of campaigns and the utilization of social media channels.

Identification and Validation of Cytotoxicity-Related Features to Predict Prognostic and Immunotherapy Response in Patients with Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a renal cortical malignancy with a complex pathogenesis. Identifying ideal biomarkers to establish more accurate promising prognostic models is crucial for the survival of kidney cancer patients. Seurat R package was used for single-cell RNA-sequencing (scRNA-seq) data filtering, dimensionality reduction, clustering, and differentially expressed genes analysis. Gene coexpression network analysis (WGCNA) was performed to identify the cytotoxicity-related module. The independent cytotoxicity-related risk model was established by the survival R package, and Kaplan-Meier (KM) survival analysis and timeROC with area under the curve (AUC) were employed to confirm the prognosis and effectiveness of the risk model. The risk and prognosis in patients suffering from ccRCC were predicted by establishing a nomogram. A comparison of the level of immune infiltration in different risk groups and subtypes using the CIBERSORT, MCP-counter, and TIMER methods, as well as assessment of drug sensitivity to conventional chemotherapeutic agents in risk groups using the pRRophetic package, was made. Eleven ccRCC subpopulations were identified by single-cell sequencing data from the GSE224630 dataset. The identified cytotoxicity-related T-cell cluster and module genes defined three cytotoxicity-related molecular subtypes. Six key genes (SOWAHB, SLC16A12, IL20RB, SLC12A8, PLG, and HHLA2) affecting prognosis risk genes were selected for developing a risk model. A nomogram containing the RiskScore and stage revealed that the RiskScore contributed the most and exhibited excellent predicted performance for prognosis in the calibration plots and decision curve analysis (DCA). Notably, high-risk patients with ccRCC demonstrate a poorer prognosis with higher immune infiltration characteristics and TIDE scores, whereas low-risk patients are more likely to benefit from immunotherapy. A ccRCC survival prognostic model was produced based on the cytotoxicity-related signature, which had important clinical significance and may provide guidance for ccRCC treatment.

Early-Stage Renal Cell Carcinoma Locoregional Therapies: Current Approaches and Future Directions.

Renal cell carcinoma (RCC) is the most common primary renal malignancy. Prevalence of RCC in developed countries has slowly increased. Although partial or total nephrectomy has been the first-line treatment for early-stage RCC, improved or similar safety and treatment outcomes with locoregional therapies have challenged this paradigm. In this review, we explore locoregional techniques for early-stage RCC, including radiofrequency ablation, cryoablation, and microwave ablation with a focus on procedural technique, patient selection, and safety/treatment outcomes. Furthermore, we discuss future advances and novel techniques, including radiomics, combination therapy, high-intensity focused ultrasound, and catheter-directed techniques.

An inflammatory Renal Pseudotumour Mimicking Urothelial Carcinoma

Abstract Although the incidence of renal malignancies has been on the rise, a broad spectrum of lesions, including hyperplastic, metaplastic, inflammatory, infectious and reactive, may occur in the urinary tract, which can mimic cancer and causing erroneous diagnoses. We present a rare case of chronic pyelonephritis with an inflammatory mass which mimicked urothelial carcinoma, which almost ended up in nephrectomy.

Renal cell carcinoma metastasizing to salivary glands: Systematic review.

Distant metastasis to salivary glands is a very rare event. Renal cell carcinoma (RCC) has been known for its high propensity of metastasis to unusual locations and salivary glands are one among those sites. Approximately 0.1% of all salivary gland metastatic neoplasms originate from renal malignancies Literature has reported several studies analysing the metastatic tumors to the oral region. However, very little research work has been published to date to analyse solely the RCC metastasizing to the salivary glands. Thus, this review was conducted to examine the published cases of RCC metastasizing to salivary glands in the literature to date and to learn about their characteristics. An electronic search of the published literature was performed without publication year limitation in PubMed/ Medline, Scopus, Google Scholar, Web of Science, Science Direct, Embase, and Research Gate databases, using mesh keywords like ('Renal cancer', OR 'Renal carcinoma' OR 'Renal cell cancer' OR 'Renal cell carcinoma'), AND ('Metastasis' OR 'Metastases'), And ('Salivary glands' OR 'Parotid gland' OR 'Submandibular gland' OR 'Sublingual gland'). We also searched all related journals manually. The reference list of all articles was also checked. Our research revealed a total of 83 relevant papers (1965-2022) with 100 patients. Parotid was the most predominant gland affected. 8% of patients died with a mean survival time of 1.3 yr. From this research, it can be concluded that RCC metastasizing to salivary glands is a rare occurrence. Careful evaluation of these cases is needed in order to raise awareness of these lesions and gain a better understanding of their characteristics for clinical as well as global implications.

Undifferentiated Renal Cell Carcinoma Presenting As Wunderlich Syndrome: A Case Report

Wunderlich syndrome is a spontaneous, non-traumatic, sub-capsular perinephric hematoma described by a triad of acute flank pain, the presence of flank mass, and hypovolemic shock. This acute syndrome is mostly caused by renal malignancies, particularly renal angiomyolipoma and renal cell carcinoma. Computed tomography (CT) scan is the preferred diagnostic modality for Wunderlich syndrome and its treatment depends on the cause. Herein, we present a 41- year-old male admitted with flank pain, who was subsequently found to have thrombocytosis, hematuria, and hypotension. A computed tomographic scan revealed a kidney mass and hematoma, which was removed. Biopsy of the mass revealed undifferentiated renal cell carcinoma and the mass caused malignant pleural effusion. This case report demonstrates increasing platelet counts, which raised concern for advanced malignancy and the triad of features may not always be present. It also highlights the etiology, clinical manifestation, and management of this syndrome.

Inpatient Outcomes of Cirrhosis-related Cachexia in the United States

Background and AimsCachexia is a metabolic syndrome defined by a loss of more than 5% of body weight in patients with chronic diseases. The goal of this study was to investigate the link between cirrhotic cachexia and hospital mortality and the 30-day risk of all-cause readmission. MethodsThe study utilized Nationwide Readmission Database for the years 2016-2019 in which all patients older than 18 years old with a primary diagnosis of cirrhosis were included. We excluded patients with a concurrent diagnosis of Human Immunodeficiency Virus (HIV), chronic lung disease, end-stage renal disease, malignancy, heart failure, and certain neurological diseases. We compared baseline characteristics and outcomes between those who were cachectic and those who were not. Survey multivariate logistic regression was used to analyze the independent impact of cachexia on categorical outcomes. ResultsThe study cohort was 342,030 cases. Cachexia was identified in approximately 17% of the study population (58,509 discharges). The mean age was 56 years. Slightly more female patients noted in cachexia group (41% vs. 38%). Inpatient mortality during index hospitalization were higher in patients with cirrhotic cachexia (6.7% versus 3%, p<0.01). Inpatient mortality during first all-cause readmission within 30 days of index discharge was also higher in cachexia group (8.6% versus 6.5%, p<0.01). ConclusionsCachexia is an adverse prognosticator for inpatient outcomes in patients with cirrhosis. It is associated with greater readmission rates, inpatient mortality, and prolonged hospital admissions.

Minimal Residual Disease-Guided Combination of Ibrutinib and Venetoclax Compared to FCR in Untreated Patients with CLL of Intermediate Risk : Interim Results of MRD Kinetics in the Eradic Trial from the Filo Group

With the emergence of targeted therapies, defining the best strategy for first-line treatment in chronic lymphocytic leukemia (CLL) patients has become challenging. The aim of the ERADIC phase 2 study was to compare the efficacy of a standard FCR regimen to that of an MRD-guided combination of ibrutinib and venetoclax (IV), in fit patients with CLL of intermediate risk defined by either unmutated IGHV status, 11q deletion or complex karyotype in the absence of TP53 alteration. MRD was assessed in bone marrow (BM) or peripheral blood (PB) by flow cytometry. After a lead-in phase of ibrutinib as a single agent from month (M)1 to M3, the total duration of treatment with the IV combination was based on BM M9 MRD. If it was &amp;lt;0.01% (uMRD) at that time, treatment was continued for 6 additional months (M15) then stopped. If M9 BM-MRD was ≥0.01%, IV treatment was continued for 18 additional months (M27). BM-MRD was reassessed at that time-point in both arms. Additionally, PB-MRD evaluation was performed every 6 months.The primary endpoint will be the percentage of patients with BM uMRD at M27. Here, intermediate safety data and MRD kinetics (M9 to M21) are presented. Between September 2019 and February 2021, 120 patients were randomized 1:1 between the two treatment arms. The median age was 59 [34-72] and 61 [34-74] year-old in the FCR and IV arms, respectively. Patient characteristics were well balanced between the 2 arms in terms of gender (male 72% FCR, 74% IV), PS ECOG 0-1 (59% FCR, 68% IV) and Binet stage (A, B and C 15%, 64%, 21% for FCR ; 8.5%, 59% and 32% for IV). An11q deletion was found in 20% and 24% of the cases in the FCR and IV arms, respectively and all patients but one had unmutated IGHV. At the time of data cut-off for this analysis, the median follow-up was 29.7 months [range: 25.3- 32.8]. Sixty-three serious adverse events (SAE) have been reported so far, 32 in the FCR arm and 31 in the IV arm. In the FCR arm, the most frequent SAE were infections (N=12 including 4 COVID-19), febrile neutropenia (N=5) biological tumour lysis syndrome (N=3), and secondary malignancies (N=2, including 1 myelodysplastic syndrome and 1 acute myeloid leukemia). In the IV arm, the most frequently reported SAE were infections (N=8 including 4 COVID-19), cardiovascular events (N=7), biological tumour lysis syndrome (N=5), acute renal failure (N=2) and secondary malignancies (N=2, including 1 colorectal cancer and 1 skin basal cell carcinoma). Four grade 5 adverse events were reported, respectively 2 in the FCR arm (1 septic shock and 1 AML) and 3 in the IV arm (2 sudden deaths and one death COVID-19-related). In the FCR arm (intention to treat [ITT] n=57), 59.6% of the patients had BM-uMRD at M9. The kinetics of PB-uMRD was 68% at M9, 65% at M15 and 52% at M21. In the IV arm (ITT n=54), the rate of BM-uMRD at M9 was much lower at 33%. PB-MRD kinetics showed levels of uMRD of 52%,70% and 67% at M9, M15 and M21 respectively. In terms of response, CR/CRi rates were 56% for the FCR arm and 66% for the IV arm. Three patients progressed in the FCR arm (1 at M9 and 2 at M15) and 2 in the IV arm, at respectively M13 and M39. Among the 13 patients who achieved BM-uMRD at M9 in the IV arm, 10 have indeed stopped according to the protocol and only 1 has progressed at M39. In conclusion, monitoring MRD kinetics in this trial showed a stable level of PB-uMRD in the FCR arm yet a clear increase in the IV arm between M9 and M15. Toxicity remains an important parameter in both treatment arms that will have to be taken into account when determining whether treatment should be continued because of detectable BM-MRD at M9 (IV arm). Upcoming data of the primary enpoint analysis at M27 will be of great interest to try to determine the best strategy.

Late Effects of Allogeneic Stem Cell Transplantation for Non-Hodgkin Lymphoma. Swiss Cohort Analysis 1997-2021

Background: despite rapid development of new highly efficient targeted and cellular-therapies, allogeneic stem cell transplantation (allo-HSCT) represents so far the only potentially curable treatment according to a longest follow-up in a setting of relapse/refractory Non-Hodgkin lymphoma (rrNHL). However, late effect (LE) issues of allo-HSCT in rrNHL seem to be underexplored. Here, we present the first analysis of a retrospective, multicenter, registry-based analysis (Swiss Blood Stem Cell Transplantation and Cellular Therapy, SBST) of LE in patients who underwent allo-HSCT for rrNHL in Switzerland. Methods: We retrospectively collected data from 109 patients with all types of rrNHL who underwent allo-HSCT in 3 University Hospitals of Switzerland (Zurich, Basel and Geneva) between May 1997 and November 2021. The inclusion criteria was 2 years survival after allo-HSCT. The primary endpoint was the cumulative incidence (CI) of LE and secondary endpoint were overall survival (OS), relapse incidence (RI) and type of LE according to organ/systems involved. Results: median of follow-up was 6.5 years. Patients who survived 2 years after allo-HSCT presented 5 and 10 years OS of 94% [95% CI 86.3 - 97.5] and 86% [95% CI 75 - 92.4] respectively. RI and CI of LE were 18.3% and 44% at 5 years and 34.4% and 58% at 10 years post allo-HSCT. A total of 79/109 (72%) of patients experienced any type of LE during the follow-up period. Renal dysfunction (21%), secondary malignancies (18%), cardiovascular disease (18%), osteoporosis (18%) and thyroid dysfunction (17%) were the most frequently observed. CI of secondary malignancies was 6.1% and 20% at 5 and 10 years respectively. Conclusions: Our analysis of a mixed-type rrNHL cohort confirms the efficacy of allo-HSCT in heavily pretreated/refractory patients, showing excellent OS at 5 and 10 years for those who survived 2 years. Both RI and LE present a competitive risk for survival benefit beyond 2 years after allo-HSCT. Secondary malignancies, renal and cardiovascular disease appear to be the most frequent types of LE, revealing the toxicity accumulated prior to allo-HSCT in the setting of rrNHL. These results should be interpreted with caution due to a retrospective nature of the analysis, the heterogeneity of the conditioning regimen and the NHL cohort. Figure 1. a) Overall survival (KM-estimate) b) cumulative incidence of late effects

Downregulation of RNA binding protein 47 predicts low survival in patients and promotes the development of renal cell malignancies through RNA stability modification

RNA binding proteins (RBPs) are crucial for cell function, tissue growth, and disease development in disease or normal physiological processes. RNA binding motif protein 47 (RBM47) has been proven to have anti-tumor effects on many cancers, but its effect is not yet clear in renal cancer. Here, we demonstrated the expression and the prognostic role of RBM47 in public databases and clinical samples of clear cell renal carcinoma (ccRCC) with bioinformatics analysis. The possible mechanism of RBM47 in renal cancer was verified by gene function prediction and in vitro experiments. The results showed that RBM47 was downregulated in renal cancers when compared with control groups. Low RBM47 expression indicated poor prognosis in ccRCC. RBM47 expression in renal cancer cell lines was reduced significantly when compared to normal renal tubular epithelial cells. Epithelial-mesenchymal transition (EMT) and transforming growth factor-β signaling pathway was associated with RBM47 in ccRCC by Gene set enrichment analysis. RBM47 expression had a positive correlation with e-cadherin, but a negative correlation with snail and vimentin. RBM47 overexpression could repress the migration, invasion activity, and proliferation capacity of renal cancer cells, while RBM47 inhibition could promote the development of the malignant features through EMT signaling by RNA stability modification. Therefore, our results suggest that RBM47, as a new molecular biomarker, may play a key role in the cancer development of ccRCC.

Abstract 18215: The Silent Intruder Unveiled: A Case of Renal Malignancy Presenting as Cardiac Mass

Background: Cardiac mass is a space-occupying lesion within the cardiac cavity. Its differential diagnosis includes thrombus, vegetation or tumor. Diagnosis is on imaging. Primary cardiac tumors are benign, solitary masses attached by a stalk in the atria. Carcinomas are metastatic from direct invasion or hematogenous spread. Right-sided cardiac masses present with shortness of breath, fatigue, syncope, and night sweats. We discuss a patient with a right atrial (RA) mass as the presenting sign of renal malignancy. Case: A middle-aged female with no prior cardiac history presented to the hospital with complaints of shortness of breath. On presentation, the patient was hemodynamically stable. Echocardiogram showed a 4.9 x 2.9cm mobile RA mass heterogeneous in texture and attached to the interatrial septum with a narrow stalk. Further views showed that the RA mass continued into the inferior vena cava (IVC) and filled it entirely. A CT scan abdomen demonstrated a heterogeneous mass involving the left kidney extending from the left renal vein into the IVC and ultimately extending up to the RA. Given the high suspicion of renal cell carcinoma (RCC), a biopsy was offered however the patient declined further workup. Discussion: RCC can invade through the renal vein into the IVC and involve the right heart. Cavoatrial tumor thrombus extension is seen in 1% of RCC. In this case, the RA mass was the first step in the diagnosis of renal malignancy. It is imperative to assess for the extension of a RA mass into the IVC as it has diagnostic implications. Treatment is resection performed on cardiopulmonary bypass for intracardiac exploration and preventing embolization.

Alterations of Plasma Metabolomics Profile in Thalassemia Patients with Low Bone Mineral Density

Background: Osteoporosis is commonly found in thalassemia patients; however, its pathogenesis is not thoroughly understood. Metabolomics is the study of metabolites in biofluids, which help to elucidate the underlying mechanism of several metabolic diseases. Nevertheless, plasma metabolomics profiling has not been carefully investigated in thalassemia patients with low bone mineral density (BMD). Objective: To investigate the alterations of plasma targeted metabolomics in adult thalassemia patients with low BMD. Methods: We conducted a cross-sectional study from February 2022 to January 2023 at Outpatient Hematology Clinic, Chiang Mai University. Thalassemia patients, confirmed by HPLC hemoglobin typing, who aged 19-50 years (male) or more than 19 years (premenopausal female) were eligible. Exclusion criteria were (1) current use or history of any bone modifying agent use within 1 year, (2) severe hepatic or renal impairment, (3) active malignancy or infection. Age- and sex-matched with normal body mass index were also recruited as controls. Two-point BMD, plasma targeted metabolomics by using liquid chromatography coupled with mass spectrometry (LC/MS), and serum bone turnover markers, including bone resorption using CTX, and bone formation using P1NP, were assessed. Interested metabolomes included 19 amino acids, 7 free fatty acids, 20 acylcarnitine intermediates of branched-chain amino acids and fatty acids, 37 phospholipid derivatives, and 4 Krebs' cycle metabolomes. Low BMD was defined as a Z-score of less than -2.0 at any site. Outcomes were the alterations of plasma levels of metabolomes among control, thalassemia with normal BMD, and thalassemia with low BMD. Results: There were a total of 80 thalassemia patients and 40 controls recruited. The mean age of patients was 34.8 years (SD 8.7). Twenty-six patients (32.5%) were male. Forty-seven patients (58.8%) were transfusion-dependent thalassemia. Low BMD was detected in 37 patients (47.5%). We found several plasma metabolomes that were significantly changed between controls and thalassemia and further altered when compared between thalassemia with normal BMD and low BMD (Figure 1). Considering plasma amino acids, glutamate level was significantly increased while glutamine level was decreased. Regarding fatty acid-related metabolomes, arachidonic acid level was increased in thalassemia with low BMD. In addition, several fatty acid-derived medium- and long-chain acylcarnitine levels were higher in plasma of thalassemia with low BMD, particularly C14:0 carnitine. Among plasma phospholipid derivatives, phosphatidylinositol (PI) and lysoPI levels were significantly increased in thalassemia with low BMD. Four plasma Krebs' cycle metabolites were not different among groups. Surprisingly, two serum bone turnover markers (CTX and P1NP) were not sensitive for detecting low bone mineral density in thalassemia (Control vs Thalassemia with normal BMD vs Thalassemia with low BMD: CTX 0.27±0.17 vs 0.36±0.20 vs 0.34±0.19 ng/mL, p=0.079 and P1NP 57.2±25.0 vs 57.2±34.0 vs 53.7±26.4 ng/mL, p=0.824). Conclusion: There were several changes in plasma metabolome levels among thalassemia with low BMD, including altered glutamate-glutamine metabolism, impaired fatty acid oxidation, and increased plasma phosphatidylinositol. Interestingly, these changes were found in patients with normal BMD and further increased in patients with low BMD. Our findings suggest the role of plasma metabolomics as non-invasive biomarkers for osteoporotic condition in thalassemia patients.