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1.
BMC Med Genomics ; 17(1): 150, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822402

ABSTRACT

Long non-coding RNAs (lncRNAs) and cancer stem cells (CSCs) are crucial for the growth, migration, recurrence, and medication resistance of tumors. However, the impact of lncRNAs related to stemness on the outcome and tumor immune microenvironment (TIME) in clear cell renal cell carcinoma (ccRCC) is still unclear. In this study, we aimed to predict the outcome and TIME of ccRCC by constructing a stem related lncRNAs (SRlncRNAs) signature. We firstly downloaded ccRCC patients' clinical data and RNA sequencing data from UCSC and TCGA databases, and abtained the differentially expressed lncRNAs highly correlated with stem index in ccRCC through gene expression differential analysis and Pearson correlation analysis. Then, we selected suitable SRlncRNAs for constructing a prognostic signature of ccRCC patients by LASSO Cox regression. Further, we used nomogram and Kaplan Meier curves to evaluate the SRlncRNA signature for the prognose in ccRCC. At last, we used ssGSEA and GSVA to evaluate the correlation between the SRlncRNAs signature and TIME in ccRCC. Finally, We obtained a signtaure based on six SRlncRNAs, which are correlated with TIME and can effectively predict the ccRCC patients' prognosis. The SRlncRNAs signature may be a noval prognostic indicator in ccRCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplastic Stem Cells , RNA, Long Noncoding , Tumor Microenvironment , Humans , RNA, Long Noncoding/genetics , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/immunology , Prognosis , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/immunology , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/metabolism , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Female , Male , Kaplan-Meier Estimate , Gene Expression Profiling
2.
Rinsho Ketsueki ; 65(5): 335-339, 2024.
Article in Japanese | MEDLINE | ID: mdl-38825510

ABSTRACT

A 69-year-old woman was previously treated with antibiotics for suspected pyelonephritis due to fever but showed limited improvement. Contrast-enhanced CT revealed heterogeneous areas of decreased contrast enhancement in both kidneys, along with an elevated soluble level of the IL-2 receptor (5,090 U/ml), and thus the patient was referred to our department for further evaluation. A percutaneous renal biopsy performed due to suspected malignant lymphoma confirmed lymphoma cell infiltration into the renal interstitium. Immunohistochemical staining was positive for MYC/BCL2/BCL6, leading to the diagnosis of stage IVB primary renal triple expressor diffuse large B cell lymphoma (DLBCL). Due to acute kidney injury, continuous hemodiafiltration (CHDF) was initiated, followed by rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. The patient's renal function improved rapidly, and complete response was achieved after six cycles of R-CHOP. Although DLBCL is a common lymphoma, the primary renal subtype is extremely rare and poses both diagnostic and therapeutic challenges. This case highlights the potential clinical implications of combining CHDF with chemotherapy to achieve complete response despite an initial poor prognosis based on the patient's overall clinical condition and pathology.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Doxorubicin , Kidney Neoplasms , Lymphoma, Large B-Cell, Diffuse , Prednisone , Vincristine , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Female , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Doxorubicin/administration & dosage , Vincristine/administration & dosage , Vincristine/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Prednisone/administration & dosage , Prednisone/therapeutic use , Cyclophosphamide/administration & dosage , Rituximab/administration & dosage , Rituximab/therapeutic use , Renal Dialysis , Treatment Outcome , Hemodiafiltration
3.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 605-609, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38825907

ABSTRACT

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.


Subject(s)
Hepatoblastoma , Kidney Neoplasms , Liver Neoplasms , Neoplasms, Multiple Primary , Rhabdoid Tumor , Stomach Neoplasms , Humans , Male , Child , Female , Child, Preschool , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Infant , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Rhabdoid Tumor/genetics , Rhabdoid Tumor/pathology , Hepatoblastoma/genetics , Hepatoblastoma/pathology , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/diagnosis , Choroid Plexus Neoplasms/genetics , Choroid Plexus Neoplasms/pathology , Choroid Plexus Neoplasms/diagnosis , Adrenocortical Carcinoma/genetics , Adrenocortical Carcinoma/pathology , Adrenal Cortex Neoplasms/pathology , Adrenal Cortex Neoplasms/genetics , Teratoma/pathology , Teratoma/genetics , Teratoma/surgery , Brain Neoplasms/genetics , Brain Neoplasms/pathology , SMARCB1 Protein/genetics , MutL Protein Homolog 1/genetics , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/genetics , High-Throughput Nucleotide Sequencing , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/pathology
5.
Cancer Med ; 13(11): e7247, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38826126

ABSTRACT

OBJECTIVES: To examine real-world characteristics, journey, and outcomes among patients with locoregional, nonmetastatic renal cell carcinoma (RCC). METHODS: A retrospective analysis of medical records from the ConcertAI Oncology Dataset was performed on adults in the United States with newly diagnosed nonmetastatic RCC between January 2012-December 2017 who received surgical treatment, and were followed until August 2021. Patients were stratified based on the risk of recurrence after nephrectomy. Recurrence rate and survival outcomes were assessed. RESULTS: The cohort (n = 439) had a median age of 64 years, 66.1% were male, and 76.5% had clear-cell histology. The median follow-up time from nephrectomy was 39.3 months overall, 41.0 months for intermediate-high-risk patients (n = 377; 85.9%) and 24.1 months for high-risk patients (n = 62; 14.1%). For intermediate-high- and high-risk patients, respectively, 68.4% and 56.5% had ≥1 medical oncologist visit after nephrectomy. Of 260 patients with documentation of postoperative imaging assessments, 72% were ordered by medical oncologists, and the median time from initial nephrectomy to the first scan was 110 days (intermediate-high-risk) and 51 days (high-risk). Provider-documented recurrence occurred in 223 (50.8%) patients, of whom 41.7% had ≥1 medical oncologist visit before the recurrence. Three-year disease-free survival (DFS), and overall survival rates were 49.4% and 80.8% (all patients): 27.7% and 64.7% (high-risk); and 52.9% and 83.3% (intermediate-high-risk). CONCLUSIONS: Our study reports low DFS after nephrectomy for patients with intermediate-high- and high-risk RCC. Subsequent approval and use of new and newly approved adjuvant therapeutic options could potentially delay or prevent recurrence.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplasm Recurrence, Local , Nephrectomy , Humans , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Nephrectomy/methods , Male , Female , Middle Aged , Kidney Neoplasms/surgery , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Retrospective Studies , Aged , Neoplasm Staging , Risk Factors , Treatment Outcome , United States/epidemiology , Adult
6.
Can Vet J ; 65(6): 544-546, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38827601

ABSTRACT

Lymphoma represents up to 30% of neoplasms diagnosed in cats. Diagnosis of lymphoma in the urinary system by examination of urine sediment has been described in a dog, but apparently not previously in cats. Concurrent samples of serum, EDTA whole blood, and urine were submitted from a 15-year-old spayed female domestic shorthair cat exhibiting weight loss, polyuria, and polydipsia. Hematology and biochemical abnormalities included a mild normocytic, normochromic, non-regenerative anemia; an inflammatory leukogram; and azotemia. Urinalysis evaluation revealed inadequate urine concentration and marked proteinuria. Wet-mount urine sediment examination revealed moderate numbers of leukocytes and erythrocytes. A uniform population of intermediate-to-large lymphocytes was observed on a fresh, Wright-Giemsa-stained preparation from cytocentrifuged urine. The cat was euthanized and necropsy was completed. Bilateral renomegaly was identified and characterized by multifocal, pale-yellow, coalescing, poorly defined, homogenous nodules. Microscopically, these nodules were composed of dense sheets of CD3-positive round cells, consistent with T-cell renal lymphoma. Key clinical message: Lymphoma is a common neoplasm in cats that can affect many organ systems, including the upper urinary tract. This case represents an uncommon method of identifying neoplastic lymphocytes via evaluation of cytocentrifuged urine, and emphasizes the benefits of examining Romanowsky-stained urine sediment in animals.


Diagnostic du lymphome rénal chez un chat par évaluation d'urine cytocentrifugée avec coloration Wright-Giemsa. Le lymphome représente jusqu'à 30 % des néoplasmes diagnostiqués chez le chat. Le diagnostic d'un lymphome du système urinaire par examen des sédiments urinaires a été décrit chez un chien, mais apparemment pas à ce jour chez le chat. Des échantillons simultanés de sérum, de sang total dans un tube avec EDTA et d'urine ont été soumis provenant d'une chatte domestique à poils courts stérilisée de 15 ans présentant une perte de poids, une polyurie et une polydipsie. Les anomalies hématologiques et biochimiques comprenaient une légère anémie normocytaire, normochrome et non régénérative; une formule leucocytaire inflammatoire; et une azotémie. L'analyse d'urine a révélé une concentration urinaire insuffisante et une protéinurie marquée. L'examen microscopique des sédiments urinaires a révélé un nombre modéré de leucocytes et d'érythrocytes. Une population uniforme de lymphocytes de taille intermédiaire à grande a été observée sur une préparation fraîche colorée au Wright-Giemsa à partir d'urine cytocentrifugée. Le chat a été euthanasié et une autopsie a été réalisée. Une rénomégalie bilatérale a été identifiée et caractérisée par des nodules multifocaux, jaune pâle, coalescents, mal définis et homogènes. Au microscope, ces nodules étaient composés de feuilles denses de cellules rondes CD3-positives, compatibles avec un lymphome rénal à cellules T.Message clinique clé :Le lymphome est une tumeur courante chez le chat qui peut affecter de nombreux systèmes organiques, y compris les voies urinaires supérieures. Ce cas représente une méthode rare d'identification des lymphocytes néoplasiques via l'évaluation de l'urine cytocentrifugée et met l'emphase sur les avantages de l'examen des sédiments urinaires avec coloration de Romanowsky chez les animaux.(Traduit par Dr Serge Messier).


Subject(s)
Cat Diseases , Kidney Neoplasms , Animals , Cats , Female , Cat Diseases/urine , Cat Diseases/diagnosis , Cat Diseases/pathology , Kidney Neoplasms/veterinary , Kidney Neoplasms/urine , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Urinalysis/veterinary , Lymphoma/veterinary , Lymphoma/urine , Lymphoma/diagnosis , Lymphoma, T-Cell/veterinary , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/urine , Lymphoma, T-Cell/pathology
7.
J Transl Med ; 22(1): 533, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831470

ABSTRACT

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common disease in the urinary system, with a high incidence and poor prognosis in advanced stages. Although γ-interferon-inducible protein 16 (IFI16) has been reported to play a role in various tumors, its involvement in ccRCC remains poorly documented, and the molecular mechanisms are not yet clear. METHODS: We conducted bioinformatics analysis to study the expression of IFI16 in ccRCC using public databases. Additionally, we analyzed and validated clinical specimens that we collected. Subsequently, we explored the impact of IFI16 on ccRCC cell proliferation, migration, and invasion through in vitro and in vivo experiments. Furthermore, we predicted downstream molecules and pathways using transcriptome analysis and confirmed them through follow-up experimental validation. RESULTS: IFI16 was significantly upregulated in ccRCC tissue and correlated with poor patient prognosis. In vitro, IFI16 promoted ccRCC cell proliferation, migration, and invasion, while in vivo, it facilitated subcutaneous tumor growth and the formation of lung metastatic foci. Knocking down IFI16 suppressed its oncogenic function. At the molecular level, IFI16 promoted the transcription and translation of IL6, subsequently activating the PI3K/AKT signaling pathway and inducing epithelial-mesenchymal transition (EMT). CONCLUSION: IFI16 induced EMT through the IL6/PI3K/AKT axis, promoting the progression of ccRCC.


Subject(s)
Carcinoma, Renal Cell , Cell Movement , Cell Proliferation , Disease Progression , Epithelial-Mesenchymal Transition , Interleukin-6 , Kidney Neoplasms , Nuclear Proteins , Phosphatidylinositol 3-Kinases , Phosphoproteins , Proto-Oncogene Proteins c-akt , Signal Transduction , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Cell Line, Tumor , Interleukin-6/metabolism , Phosphoproteins/metabolism , Phosphoproteins/genetics , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Animals , Cell Movement/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Mice, Nude , Neoplasm Invasiveness , Male , Female , Prognosis
8.
Cell Adh Migr ; 18(1): 1-12, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38831518

ABSTRACT

In this research, we investigated the role of PIK3R6, a regulatory subunit of PI3Kγ, known for its tumor-promoting properties, in clear cell renal cell carcinoma (CCRCC). Utilizing the UALCAN website, we found PIK3R6 upregulated in CCRCC, correlating with lower survival rates. We compared PIK3R6 expression in CCRCC tumor tissues and adjacent normal tissues using immunohistochemistry. Post RNA interference-induced knockdown of PIK3R6 in 786-O and ACHN cell lines, we performed CCK-8, colony formation, Edu staining, flow cytometry, wound healing, and transwell assays. Results showed that PIK3R6 silencing reduced cell proliferation, migration, and invasion, and induced G0/G1 phase arrest and apoptosis. Molecular analysis revealed decreased CDK4, Cyclin D1, N-cadherin, Vimentin, Bcl-2, p-PI3K and p-AKT, with increased cleaved caspase-3, Bax, and E-cadherin levels in CCRCC cells. Moreover, inhibiting PIK3R6 hindered tumor growth. These findings suggest a significant role for PIK3R6 in CCRCC cell proliferation and metastasis, presenting it as a potential therapeutic target.


Subject(s)
Apoptosis , Carcinoma, Renal Cell , Cell Movement , Cell Proliferation , Kidney Neoplasms , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Cell Proliferation/genetics , Cell Line, Tumor , Apoptosis/genetics , Cell Movement/genetics , Animals , Gene Expression Regulation, Neoplastic , Mice , Mice, Nude , Gene Knockdown Techniques , Female , Male
9.
Cancer Immunol Immunother ; 73(8): 142, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832989

ABSTRACT

BACKGROUND: There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. METHOD: This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. RESULTS: A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008). CONCLUSIONS: Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Female , Male , Middle Aged , Kidney Neoplasms/mortality , Kidney Neoplasms/immunology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Adult , Aged , Young Adult , Adolescent , Sex Factors , Immune Checkpoint Inhibitors/therapeutic use , Prognosis , Immunotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Survival Rate , Aged, 80 and over
10.
J Robot Surg ; 18(1): 241, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833079

ABSTRACT

While partial nephrectomy offers oncologic efficacy and preserves renal function for T1 renal tumors, renal artery pseudoaneurysm (RAP) remains a rare but potentially life-threatening complication. This study compared RAP incidence across robotic-assisted (RAPN), laparoscopic (LPN), and open (OPN) partial nephrectomies in a large tertiary oncological center. This retrospective study analyzed 785 patients undergoing partial nephrectomy between 2012 and 2022 (398 RAPN, 122 LPN, 265 OPN). Data included demographics, tumor size/location, surgical type, clinical presentation, treatment, and post-operative outcomes. The primary outcome was RAP incidence, with secondary outcomes including presentation, treatment efficacy, and renal function. Seventeen patients (2.1%) developed RAP, presenting with massive hematuria (100%), hemorrhagic shock (5.8%), and clot retention (23%). The median onset was 12 days postoperatively. RAP occurred in 4 (1%), 4 (3.3%), and 9 (3.4%) patients following RAPN, LPN, and OPN, respectively (p = 0.04). Only operative length and surgical approach were independently associated with RAP. Selective embolization achieved immediate bleeding control in 94%, with one patient requiring a second embolization. No additional surgery or nephrectomy was needed. Estimated GFR at one year was similar across both groups (p = 0.53). RAPN demonstrated a significantly lower RAP incidence compared to LPN and OPN (p = 0.04). Emergency angiographic embolization proved effective, with no long-term renal function impact. This retrospective study lacked randomization and long-term follow-up. Further research with larger datasets and longer follow-ups is warranted. This study suggests that robotic-assisted partial nephrectomy is associated with a significantly lower risk of RAP compared to traditional approaches. Emergency embolization effectively treats RAP without compromising long-term renal function.


Subject(s)
Aneurysm, False , Kidney Neoplasms , Laparoscopy , Nephrectomy , Postoperative Complications , Renal Artery , Robotic Surgical Procedures , Humans , Nephrectomy/methods , Nephrectomy/adverse effects , Aneurysm, False/surgery , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/adverse effects , Male , Female , Middle Aged , Laparoscopy/methods , Laparoscopy/statistics & numerical data , Retrospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Aged , Renal Artery/surgery , Kidney Neoplasms/surgery , Incidence , Treatment Outcome , Embolization, Therapeutic/methods
12.
Asian J Endosc Surg ; 17(3): e13317, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38692582

ABSTRACT

INTRODUCTION: Robot-assisted nephroureterectomy (RANU) for upper urinary tract urothelial carcinoma is typically performed via the transperitoneal approach because of limited surgical space. However, a retroperitoneal approach may be preferable in patients with a history of abdominal surgery or in those in whom pelvic lymph node dissection is unnecessary. MATERIALS AND SURGICAL TECHNIQUES: RANU via the retroperitoneal approach was selected for two patients diagnosed with high-grade upper urothelial carcinoma with a history of abdominal surgery. Nephrectomy was performed in the 90° flank position, and the bed was tilted at 20°. The retroperitoneal space was extended, and the robot trocar was subsequently repositioned in the left lower quadrant. After redocking the robot, the distal ureter was dissected, and the bladder cuff was resected en bloc along with the kidney and the ureter. Neither patient had any complications within 3 months postoperatively. DISCUSSION: By devising a new technique for trocar placement, total retroperitoneal RANU without repositioning was possible, even in a small patient.


Subject(s)
Nephroureterectomy , Robotic Surgical Procedures , Humans , Robotic Surgical Procedures/methods , Retroperitoneal Space/surgery , Nephroureterectomy/methods , Male , Aged , Ureteral Neoplasms/surgery , Carcinoma, Transitional Cell/surgery , Carcinoma, Transitional Cell/pathology , Urinary Bladder/surgery , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Middle Aged , Female
15.
Lancet Oncol ; 25(5): e193-e204, 2024 May.
Article in English | MEDLINE | ID: mdl-38697165

ABSTRACT

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.


Subject(s)
Carcinoma, Renal Cell , Consensus , Delphi Technique , Kidney Neoplasms , Radiosurgery , Humans , Carcinoma, Renal Cell/radiotherapy , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/pathology , Radiosurgery/standards , Kidney Neoplasms/pathology , Kidney Neoplasms/radiotherapy , Europe , Disease Progression , Urology/standards , Male , Neoplasm Metastasis
16.
J Cell Mol Med ; 28(9): e18329, 2024 May.
Article in English | MEDLINE | ID: mdl-38693863

ABSTRACT

Therapy failure with the tyrosine kinase inhibitor (TKI) sunitinib remains a great challenge in metastatic renal cell carcinoma (mRCC). Growing evidence indicates that the tumour subpopulation can enter a transient, non-mutagenic drug-tolerant state to endure the treatment underlying the minimal residual disease and tumour relapse. Drug tolerance to sunitinib remains largely unexplored in RCC. Here, we show that sunitinib-tolerant 786-O/S and Caki-2/S cells are induced by prolonged drug treatment showing reduced drug sensitivity, enhanced clonogenicity, and DNA synthesis. Sunitinib-tolerance developed via dynamic processes, including (i) engagement of c-MET and AXL pathways, (ii) alteration of stress-induced p38 kinase and pro-survival BCL-2 signalling, (iii) extensive actin remodelling, which was correlated with activation of focal adhesion proteins. Remarkably, the acute drug response in both sensitive and sunitinib-tolerant cell lines led to dramatic fine-tuning of the actin-cytoskeleton and boosted cellular migration and invasion, indicating that the drug-response might depend on cell state transition rather than pre-existing mutations. The drug-tolerant state was transiently acquired, as the cells resumed initial drug sensitivity after >10 passages under drug withdrawal, reinforcing the concept of dynamic regulation and phenotypic heterogeneity. Our study described molecular events contributing to the reversible switch into sunitinib-tolerance, providing possible novel therapeutic opportunities in RCC.


Subject(s)
Carcinoma, Renal Cell , Cell Movement , Drug Resistance, Neoplasm , Kidney Neoplasms , Sunitinib , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Sunitinib/pharmacology , Sunitinib/therapeutic use , Cell Line, Tumor , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Cell Movement/drug effects , Receptor Protein-Tyrosine Kinases/metabolism , Receptor Protein-Tyrosine Kinases/genetics , Signal Transduction/drug effects , Proto-Oncogene Proteins c-met/metabolism , Proto-Oncogene Proteins c-met/genetics , Antineoplastic Agents/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Axl Receptor Tyrosine Kinase , Pyrroles/pharmacology , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , Cell Proliferation/drug effects , Indoles/pharmacology
17.
PLoS One ; 19(5): e0300367, 2024.
Article in English | MEDLINE | ID: mdl-38696458

ABSTRACT

The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or RN in a retrospective cohort of patients with moderate-to-severe CKD (RN-CKD and PN-CKD) or SK (PN-SK). All surgical procedures conducted between 2013 and 2018 in our institution in patients with pre-operative estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2 or with SK were included. The primary outcome was a composite criterion including CKD progression or major adverse cardio-vascular events (MACE) or death, assessed one year after surgery. Predictors of the primary outcome were determined using multivariate analyses. A total of 173 procedures were included (67 RN, and 106 PN including 27 SK patients). Patients undergoing RN were older, with larger tumors. Preoperative eGFR was not significantly different between the groups. One year after surgery, PN-CKD was associated with lower rate of the primary outcome compared to RN-CKD (43% vs 71% p = 0.007). In multivariate analysis, independent risk factors for the primary outcome were postoperative AKI (stage 1 to stage 3 ranging from OR = 8.68, 95% CI 3.23-23.33, to OR = 28.87, 95% CI 4.77-167.61), larger tumor size (OR = 1.21 per cm, 95% CI 1.02-1.45), while preoperative eGFR, age, sex, diabetes mellitus, and hypertension were not. Postoperative AKI after PN or RN was the major independent determinant of worse outcomes (CKD progression, MACE, or death) one year after surgery.


Subject(s)
Glomerular Filtration Rate , Nephrectomy , Renal Insufficiency, Chronic , Humans , Nephrectomy/adverse effects , Nephrectomy/methods , Male , Female , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/surgery , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Middle Aged , Aged , Risk Factors , Kidney Neoplasms/surgery , Kidney Neoplasms/complications , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Treatment Outcome , Kidney/surgery , Kidney/physiopathology , Solitary Kidney/surgery , Solitary Kidney/complications
18.
Pediatr Surg Int ; 40(1): 122, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704513

ABSTRACT

BACKGROUND: Wilm's tumor (WT) is one of the most common childhood urological tumors, ranking second in the incidence of pediatric abdominal tumors. The development of WT is associated with various factors, and the correlation with autophagy is currently unclear. PURPOSE: To develop a new prognostic model of autophagy-related genes (ATG) for WT. METHODS: Using the Therapeutically applicable research to generate effective treatments (TARGET) database to screen for differentially expressed ATGs in WT and normal tissues. ATGs were screened for prognostic relevance to WT using one-way and multifactorial Cox regression analyses and prognostic models were constructed. The risk score was calculated according to the model, and the predictive ability of the constructed model was analyzed using the ROC (receiver operating characteristic) curve to verify the significance of the model for the prognosis of WT. RESULTS: Sixty-eight differentially expressed ATGs were identified by univariate Cox regression analysis, and two critical prognostic ATGs (CXCR4 and ERBB2) were identified by multivariate Cox regression analysis. Patients were divided into high-risk and low-risk groups according to the differential expression of these two ATGs. Kaplan-Meier (KM) curves showed a significant difference in survival time between the two groups. The critical prognostic ATGs were combined with race, age, and stage in a multifactorial regression analysis, and the final prognostic model was produced as a line graph. CONCLUSION: The prognostic model of autophagy-related genes composed of the CXCR4 gene and ERBB2 gene has a specific predictive value for the prognosis of WT, and the present study provides a clear basis for future research on biomarkers and therapeutic targets.


Subject(s)
Autophagy , Kidney Neoplasms , Humans , Autophagy/genetics , Prognosis , Male , Female , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Receptors, CXCR4/genetics , Receptors, CXCR4/metabolism , Child, Preschool , Infant , Biomarkers, Tumor/genetics
19.
Ther Drug Monit ; 46(3): 321-331, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38723115

ABSTRACT

BACKGROUND: Pazopanib, an anti-angiogenic multitarget tyrosine kinase inhibitor, has been approved for the treatment of metastatic renal cell carcinoma and soft tissue sarcoma. However, its recommended dose does not always produce consistent outcomes, with some patients experiencing adverse effects or toxicity. This variability is due to differences in the systemic exposure to pazopanib. This review aimed to establish whether sufficient evidence exists for the routine or selective therapeutic drug monitoring of pazopanib in adult patients with approved indications. METHODS: A systematic search of the PubMed and Web of Science databases using search terms related to pazopanib and therapeutic drug monitoring yielded 186 and 275 articles, respectively. Ten articles associated with treatment outcomes or toxicity due to drug exposure were selected for review. RESULTS: The included studies were evaluated to determine the significance of the relationship between drug exposure/Ctrough and treatment outcomes and between drug exposure and toxicity. A relationship between exposure and treatment outcomes was observed in 5 studies, whereas the trend was nonsignificant in 4 studies. A relationship between exposure and toxicity was observed in 6 studies, whereas 2 studies did not find a significant relationship; significance was not reported in 3 studies. CONCLUSIONS: Sufficient evidence supports the therapeutic drug monitoring of pazopanib in adult patients to improve its efficacy and/or safety in the approved indications.


Subject(s)
Angiogenesis Inhibitors , Carcinoma, Renal Cell , Drug Monitoring , Indazoles , Kidney Neoplasms , Pyrimidines , Sarcoma , Sulfonamides , Indazoles/therapeutic use , Humans , Sulfonamides/therapeutic use , Sulfonamides/pharmacokinetics , Pyrimidines/therapeutic use , Pyrimidines/pharmacokinetics , Drug Monitoring/methods , Carcinoma, Renal Cell/drug therapy , Sarcoma/drug therapy , Kidney Neoplasms/drug therapy , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/pharmacokinetics
20.
Aging Male ; 27(1): 2346308, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38709235

ABSTRACT

OBJECTIVE: To assess various management options for renal angiomyolipoma (AML) to guide clinical practice. METHODS: A single center retrospectively reviewed an AML series from 2002 to 2022. The image reports and chart reviews of patients who received two abdominal scans at least 6 months between the first and last scans were assessed. RESULTS: A total of 203 patients with 209 tumors were identified and followed up for a median of 42.6 months. Active surveillance (AS) was the most frequently selected option (70.9% of cases). Interventions were required for 59 AMLs, of which 20 were treated with embolization, 29 with partial nephrectomy, 9 with radical nephrectomy, and 1 with radiofrequency (RF) ablation. The median size of the lesions at intervention was 5 cm. The average growth rate of the lesions was 0.12 cm/year, and there was a significant difference in the average growth rate of lesions ≤4 cm and those >4 cm (0.11 vs. 0.24 cm/year; p = 0.0046). CONCLUSION: This series on AMLs confirms that lesions >4 cm do not require early intervention based on size alone. Appropriately selected cases of renal AML can be managed by AS.KEYWORDS: Angiomyolipoma; active surveillance; embolization; nephrectomy; nephron-sparing surgery.


Subject(s)
Angiomyolipoma , Embolization, Therapeutic , Kidney Neoplasms , Nephrectomy , Watchful Waiting , Humans , Angiomyolipoma/therapy , Angiomyolipoma/pathology , Kidney Neoplasms/therapy , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Retrospective Studies , Nephrectomy/methods , Middle Aged , Female , Male , Adult , Embolization, Therapeutic/methods , Aged , Radiofrequency Ablation/methods
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