MiR-15b-5p Promotes Growth and Metastasis of Renal Clear Cell Carcinoma / MiR-15b-5p Promueve el Crecimiento y la Metástasis del Carcinoma Renal de Células Claras

SUMMARY: We investigated the expression and clinical significance of miR-15b-5p in clear cell renal cell carcinoma (RCC) through bioinformatics analysis and experimental verification. The differentially expressed miRNAs were screened in the GEO database. Venn diagram showed that there were 5 up-regulated miRNAs (has-miR-210, has-miR-142-3p, has-miR-142-5p, has-miR-15b-5p, and has-miR-193a-3p) and only 1 down-regulated miRNA (has-miR-532-3p) that were commonly expressed between GSE189331 and GSE16441 datasets. This was further confirmed in TCGA. Further analysis showed that the has-miR-193a-3p, has-miR-142-3p, has- miR-142-5p, and has-miR-15b-5p were closely related to tumor invasion, distant metastasis and survival probability. The expression of miR-15b-5p in ccRCC tissues was significantly higher than that in adjacent normal kidney tissues (P0.05). Following inhibition of miR-15b-5p expression, RCC cells had attenuated proliferation, increased apoptosis, and attenuated migration and invasion. has-miR-15b-5p-WEE1, has-miR-15b-5p-EIF4E, has-miR-15b-5p-PPP2R1B may be three potential regulatory pathways in ccRCC. miR-15b-5p is highly expressed in cancer tissues of ccRCC patients. It may promote proliferation, inhibit apoptosis and enhance cell migration and invasion of RCC cells. The has-miR-15b-5p-WEE1, has-miR-15b-5p-EIF4E, and has-miR-15b-5p-PPP2R1B may be three potential regulatory pathways in ccRCC.

Investigamos la expresión y la importancia clínica de miR-15b-5p en el carcinoma de células renales (CCR) de células claras mediante análisis bioinformático y verificación experimental. Los miARN expresados diferencialmente se examinaron en la base de datos GEO. El diagrama de Venn mostró que había 5 miARN regulados positivamente (has-miR-210, has-miR-142-3p, has-miR-142-5p, has-miR-15b-5p y has-miR-193a-3p). ) y solo 1 miARN regulado negativamente (has-miR-532-3p) que se expresaron comúnmente entre los conjuntos de datos GSE189331 y GSE16441. Esto fue confirmado aún más en TCGA. Un análisis más detallado mostró que has-miR-193a-3p, has-miR-142-3p, has- miR-142-5p y has-miR-15b-5p estaban estrechamente relacionados con la invasión tumoral, la metástasis a distancia y la probabilidad de supervivencia. La expresión de miR-15b-5p en tejidos ccRCC fue significativamente mayor que la de los tejidos renales normales adyacentes (P 0,05). Tras la inhibición de la expresión de miR-15b-5p, las células RCC tuvieron una proliferación atenuada, un aumento de la apoptosis y una migración e invasión atenuadas. has-miR-15b-5p-WEE1, has- miR-15b-5p-EIF4E, has-miR-15b-5p-PPP2R1B pueden ser tres posibles vías reguladoras en ccRCC. miR-15b-5p se expresa altamente en tejidos cancerosos de pacientes con ccRCC. Puede promover la proliferación, inhibir la apoptosis y mejorar la migración celular y la invasión de células RCC. has-miR-15b-5p-WEE1, has- miR-15b-5p-EIF4E y has-miR-15b-5p-PPP2R1B pueden ser tres posibles vías reguladoras en ccRCC.

Metastatic clear-cell renal carcinoma: an exceptional cause of ileocolonic intussusception in adults

Introduction: Intussusceptions in adults are rare, representing 1% to 5% of intestinal obstructions in this age group. This condition can be caused by benign and malignant lesions acting as lead points, the latter being the most frequent. Furthermore, the diagnosis is challenging due to the non-specific symptoms with variable duration. Case Presentation: A 43-year-old man, with a history of localized clear-cell renal carcinoma (ccRCC) treated 9 years earlier with a right radical nephrectomy, presented with bowel obstruction symptoms. An abdominal computed tomography scan showed an ileocolonic intussusception. Hence, the patient required a right hemicolectomy with ileotransverse anastomosis. The histopathological analysis showed a metastatic ccRC to the terminal ileum causing the intussusception. Discussion: Adult intussusceptions are rare. However, they should be considered in the differential diagnosis of patients with abdominal pain and symptoms of bowel obstruction. Metastases of renal cancer to the small bowel are uncommon and even more so in the form of intussusception. Definitive treatment must be tailored to the patient's condition and underlying cause. (AU)

Read-through circular RNA rt-circ-HS promotes hypoxia inducible factor 1α expression and renal carcinoma cell proliferation, migration and invasiveness / 北京大学学报(医学版)

OBJECTIVE@#To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α.@*METHODS@#Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays.@*RESULTS@#We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α.@*CONCLUSION@#The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.

Expression of GPNMB in renal eosinophilic tumors and its value in differential diagnosis / 中华病理学杂志

Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.

Risk factors for massive hemorrhage after radical nephrectomy and removal of venous tumor thrombus / 北京大学学报(医学版)

OBJECTIVE@#To investigate and analyze the risk factors of massive hemorrhage in patients with renal cell carcinoma and venous tumor thrombus undergoing radical nephrectomy and removal of venous tumor thrombus.@*METHODS@#From January 2014 to June 2020, 241 patients with renal cancer and tumor thrombus in a single center of urology at Peking University Third Hospital were retrospectively analyzed. All patients underwent radical nephrectomy and removal of venous tumor thrombus. The relevant preoperative indicators, intraoperative conditions, and postoperative data were statistically analyzed by using statistical software of SPSS 18.0. The main end point of the study was intraoperative bleeding volume greater than 2 000 mL. Logistic regression analysis was used to determine the relevant influencing factors. First, single factor Logistic regression was used for preliminary screening of influencing factors, and variables with single factor Logistic regression analysis P < 0.05 were included in multivariate Logistic regression. In all statistical analyses, P < 0.05 is considered statistically significant.@*RESULTS@#Among the 241 patients included, there were 60 cases of massive hemorrhage, 48 males and 12 females, with a median age of 62 years. The number of non-massive hemorrhage was 181. There were 136 males and 45 females, with a median age of 59 years. Univariate analysis showed that the clinical symptoms (both systemic and local symptoms, OR 2.794, 95%CI 1.087-7.181, P=0.033), surgical approach (open surgery, OR 9.365, 95%CI 4.447-19.72, P < 0.001), Mayo grade (Mayo 3-4, OR 5.257, 95%CI 2.806-10.886, P < 0.001), American Society of Anesthesiologists (ASA) score (ASA level 3, OR 2.842, 95%CI 1.338-6.036, P=0.007), preoperative hemoglobin (OR 0.978, 95%CI 0.965-0.991, P=0.001), preoperative platelet count (OR 0.996, 95%CI 0.992-1.000, P=0.037), maximum tumor thrombus width (OR 1.061, 95%CI 1.033-1.091, P < 0.001), Complicated with bland thrombus (OR 4.493, 95%CI 2.264-8.915, P < 0.001), adrenalectomy (OR 3.101, 95%CI 1.614-5.958, P=0.001), segmental resection of the inferior vena cava (OR 2.857, 95%CI 1.395-5.852, P=0.004). There was a statistically significant difference in these aspects(P < 0.05). Multivariate Logistic regression analysis showed that there was a statistically significant difference in surgical approach (open surgery, OR 6.730, 95%CI 2.947-15.368;P < 0.001), Mayo grade (Mayo 3-4, OR 2.294, 95%CI 1.064-4.948, P=0.034), Complicated with bland thrombus (OR 3.236, 95%CI 1.492-7.020, P=0.003).@*CONCLUSION@#Combining the results of univariate and multivariate Logistic regression analysis, the surgical approach, Mayo grade, and tumor thrombus combined with conventional thrombus were associated risk factors for massive hemorrhage during surgery for renal cell carcinoma with tumor thrombus. Patients who undergo open surgery, high Mayo grade, and tumor thrombus combined with conventional thrombus are at a relatively higher risk of massive hemorrhage.

Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation / 中华病理学杂志

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma / 中华病理学杂志

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34βE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34βE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

Lesiones metastásicas a glándula tiroides. Una serie de casos / Metastatic lesions to the thyroid gland. Case series

Las lesiones metastásicas representan hasta un 3 % de los tumores malignos de la glándula tiroides. La mayoría de los casos se originan de tumores de células renales y de pulmón. El abordaje diagnóstico implica una alta sospecha clínica en pacientes con primarios conocidos, sin embargo, puede ser la manifestación inicial de una enfermedad maligna extensa no diagnosticada hasta en un 20 % a 40 % de los pacientes. La biopsia por aguja fina ha demostrado buen rendimiento para el diagnóstico de los nódulos metastásicos. El pronóstico y la opción del tratamiento quirúrgico dependen del control local del primario y del estado de la enfermedad sistémica asociada, por lo tanto, debe ser individualizado. Por lo general, hasta un 80 % de los pacientes con compromiso de la tiroides tienen enfermedad metastásica multiorgánica, y la intención del tratamiento quirúrgico es con fines paliativos para prevenir las complicaciones derivadas de la extensión local de la enfermedad a las estructuras del tracto aerodigestivo superior en el cuello. Se presenta a continuación, una serie de seis casos de pacientes con lesiones metastásicas a glándula tiroides con primarios en riñón, mama y de melanomas

Metastatic lesions represent up to 3% of malignant tumors of the thyroid gland. Most cases originate from lung and renal cell tumors. The diagnostic approach implies a high clinical suspicion in patients with known primaries, however, it can be the initial manifestation of an extensive undiagnosed malignant disease in up to 20% to 40% of patients. Fine-needle biopsy has shown good performance for the diagnosis of metastatic nodules. The prognosis and the option of surgical treatment depend on the local control of the primary condition and the state of the associated systemic disease, therefore it must be individualized. In general, up to 80% of patients with thyroid involvement have multi-organ metastatic disease and surgical treatment is intended to be palliative to prevent complications resulting from local extension of the disease to structures of the upper aerodigestive tract in the neck. A case series of six patients with metastatic lesions to the thyroid gland with primaries in the kidney, breast and melanomas is presented below

IMP-1 inhibits renal cell carcinoma 786-O cell growth by targeting EphrinB2 signaling pathway

Abstract EphrinB2 plays a critical role in tumor growth. In this study, we studied the antitumor activity of imperatorin derivative IMP-1 in renal cell carcinoma (RCC) by regulating EphrinB2 pathway.. Results showed that IMP-1 inhibited the proliferation of 786-O cells in a dose- and time-dependent manner. More importantly, knockdown and transfection of EphrinB2 altered the inhibitory effect of IMP-1 on the activity of 786-O cells. IMP-1 arrested 786-O cell cycle at G0/G1 phase by decreasing the expression of cyclin D1 and cyclin E. Moreover, IMP-1 regulated Bcl-2 family proteins' expression, thus inducing apoptosis of 786-O cells. IMP-1 down-regulated the expression of EphrinB2, Syntenin1 and PICK1. Then, IMP-1 decreased the phosphorylation of Erk1/2 and AKT. In all, IMP-1 could regulate the EphrinB2 pathway in order to inhibit 786-O cell growth by arresting the cell cycle at G0/G1 phase and inducing cell apoptosis. Thus, IMP-1 may present as a potential strategy for RCC treatment.

Metástasis de cáncer de células claras renal en cuerdas vocales. Reporte de un caso / Metastasis of renal clear cell carcinoma in vocal cords. A Case report

Introducción: Las metástasis a distancia de tumores primarios a cuerdas vocales son poco frecuentes. Las metástasis a laringe con mayor frecuencia corresponden a melanomas y carcinomas, afectando principalmente a la región supraglótica. Las metástasis a cabeza y cuello de los carcinomas de células renales (CCR) tienen una incidencia de 14-16%. Se presenta el caso de un paciente con metástasis de carcinoma de células claras renal a cuerdas vocales, cuya importancia recae en que es un caso poco frecuente y no existen reportes similares en el país. Paciente masculino, 57 años, con disfonía de 3 meses de evolución. Nasofibroscopía evidencia lesión polipoídea en cuerda vocal y ventrículo izquierdo. Se realiza microcirugía laríngea, enviando muestra a biopsia diferida, resultando lesión metastásica de CCR células claras. Evaluado por nefrología, se pesquisa tumor renal izquierdo sugerente de CCR. Las metástasis de neoplasias remotas a laringe son infrecuentes. Se considera al CCR el tercero en frecuencia respecto a neoplasias infraclaviculares. Éstas se pueden presentar hasta 10 años después del tratamiento del primario. Se recomienda seguimiento a largo plazo y énfasis a nuevos síntomas en región de cabeza y cuello, teniendo en consideración antecedente de CCR en pacientes con disfonía y lesiones polipoídeas en cuerdas vocales.

Introduction: The metastasis of distant site primary tumors to the vocal cords is infrequent. The most frequent source of metastasis to the larynx is melanomas and carcinomas, mainly affecting the supraglottic region. The metastasis to the head and neck of renal cell carcinomas (RCC) has an incidence of 14-16%. To present a case of metastasis of clear renal cell carcinoma to the vocal cords, since it is very infrequent, and there are no similar reports in the country. A male patient, 57 years old, presenting dysphonia for a duration of 3 months. Nasofibroscopy showed a polypoid lesion in the left vocal cord and ventricle. Larynx microsurgery was performed, and a sample was sent for biopsy, which reported a metastatic lesion of RCC clear cells. When assessed by nephrology, a left renal tumor is found, suggesting RCC. The metastasis of distant site neoplasias are infrequent. RCC is considered the third in frequency concerning to infraclavicular neoplasias. These can present up to 10 years after the treatment of the primary. Long term follow-up is recommended, and an emphasis on new symptoms in the head and neck region, considering the history of RCC in patients with dysphonia and polypoid lesions in vocal cords.

Nefrectomía radical con trombectomía de vena cava: 20 años de cirugías por tumor renal / Vena cava thrombectomy in kidney cancer. Report of 32 nephrectomies

BACKGROUND: Vena cava (VC) involvement in kidney tumors occurs in 4 to 10% of cases, and is associated with a higher mortality. Nephrectomy with thrombectomy of the VC, performed by a multidisciplinary team, improves survival. Aim: To report a series of consecutive nephrectomies with caval thrombectomy performed in an academic center. PATIENTS AND METHODS: We report 32 patients with cT3b and 3c renal tumors, who underwent radical nephrectomy with VC thrombectomy between 2001 and 2021. A descriptive analysis of clinical, surgical and pathological variables was performed. Overall survival (OS) and cancer-specific survival (CSS) was calculated using Kaplan-Meier curves. Results: The mean tumor size was 9.7 cm. According to Mayo classification 3/32 (9%) patients had a type I thrombus, 10/32 (31%) had a type II thrombus, 8/32 (25%) had a type III thrombus, and 5/32 (16%) had a type IV thrombus. The mean bleeding was 2000 cc. There was one intraoperative death. Nineteen percent of patients had complications >= 3 according to Clavien-Dindo classification. Reoperations occurred in 9%. Pre and postoperative creatinine levels were 1.17 and 1.91 mg/dl respectively (p < 0.01). Pre and postoperative Hematocrit levels were 47.9 and 31% respectively (p = 0.02). Sixty six percent of tumors were clear cell renal cancer, 9% were papillary and 3% were chromophobic. Mean OS was 10 months. Two-year SCE was 40%. CONCLUSIONS: Our results are similar to those reported elsewhere. Despite being an unusual pathology, the surgical technique has been improving, thanks to the multidisciplinary work of urologists and surgeons.

Eosinophilic vacuolated tumor of the kidney: clinicopathological and molecular characteristics / 中华病理学杂志

Objective: To study the clinicopathological features, immunophenotype, molecular changes, differential diagnosis and prognosis of eosinophilic vacuolated tumor (EVT) of the kidney. Methods: Four cases were collected retrospectively from 2014 to 2020 at Ningbo Diagnostic Pathology Center. The clinicopathologic features and immunophenotypic profile were studied by light microscopy and immunohistochemistry. Targeted next-generation sequencing (NGS) panel was used to detect cancer-associated mutation. Follow-up and literature review were also performed. Results: Among the 4 patients studied,2 were males and 2 were females. The age of the patients ranged from 44 to 63 years (the mean age: 51 years).Tumor size ranged from 1.5 to 4.2 cm (mean: 2.3 cm). Microscopically, tumors were well-circumscribed, unencapsulated. Thick-walled vessels and entrapped renal tubules were found within or at the periphery of the tumors. The tumors were predominantly composed of nest pattern, and focal tubular pattern. The tumor cells exhibited abundant, eosinophilic, granular cytoplasm and conspicuous, large nucleoli. Prominent intracytoplasmic vacuoles were seen. These cytoplasmic vacuoles varied in size and frequently coalesced into a large space. Loose fibromatous or hyaline stroma was focally noted. Immunohistochemically, the tumor cells in all cases exhibited a CD117+/CK7-phenotype. All cases were positive for CD10 and p504s. MTOR, S6 and cathepsin K were positive in 4 cases. TFE3, CA9, Melan A and HMB45 were negative in all cases. SDHB retained expression. NGS demonstrated MTOR mutations in all cases, and TSC2 mutation in 2 cases. Conclusions: EVT is a rarely oncocytic renal tumor with unique morphology, immunohistochemical phenotype, molecular profile and an indolent behavior. Recognition of the characteristics of this novel but rare entity will allow for better classification of renal tumors.

Curcumin Inhibits Viability of Clear Cell Renal Cell Carcinoma by Down-Regulating ADAMTS18 Gene Methylation though NF-κ B and AKT Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of curcumin on viability of clear cell renal cell carcinoma (ccRCC) and analyze its possible mechanism.@*METHODS@#In cell lines of A498 and 786-O, the effects of curcumin (1.25, 2.5, 5 and 10 μ mol/L) on the viability of ccRCC were analyzed at 24, 48 and 72 h by MTT assay. The protein expression levels of ADAMTS18 gene, p65, phosphorylation p65 (pp65), AKT, phosphorylation AKT (pAKT) and matrix metallopeptidase 2 (MMP-2) before and after curcumin (10 μ mol/L) treatment were examined by Western blotting. Real-time PCR and methylation specific PCR (MSP) were applied to analyze the expression and methylation level of ADAMTS18 gene before and after curcumin treatment (10 μ mol/L).@*RESULTS@#Curcumin significantly inhibited the viability of A498 and 786-O cell lines in a dose- and time-dependent manner (P<0.01). Up-regulation of ADAMTS18 gene expression with down-regulation of ADAMTS18 gene methylation was reflected after curcumin treatment, accompanied by down-regulation of nuclear factor κ B (NF-κ kB) related protein (p65 and pp65), AKT related protein (AKT and pAKT), and NF-κ B/AKT common related protein MMP-2. With ADAMTS18 gene overexpressed, the expression levels of p65, AKT and MMP2 were downregulated, of which were conversely up-regulated in silenced ADAMTS18 (sh-ADAMTS18). The expression of pp65, pAKT and MMP2 in sh-ADAMTS18 was down-regulated after being treated with PDTC (NF-κ B inhibitor) and LY294002 (AKT inhibitor).@*CONCLUSIONS@#Curcumin could inhibit the viability of ccRCC by down-regulating ADAMTS18 gene methylation though NF-κ B and AKT signaling pathway.

Metástasis oral de carcinoma de células renales. A propósito de un caso y revisión de la literatura / Oral metastasis of renal cell carcinoma. A Case report and literature review / Metástase oral de carcinoma de células renais. Relato de um caso e revisão da literatura

Los tumores metastásicos en cavidad oral son pocos frecuentes, representan el 1% de las neoplasias malignas orales, son relativamente más frecuentes en los maxilares, respecto a aquellos localizados en los tejidos blandos orales. Se describe el caso de una paciente de 75 años de edad, con antecedentes de carcinoma renal de células claras, que consulta por la aparición repentina de una lesión tumoral en reborde alveolar superior izquierdo. Se realizó la biopsia exéresis con diagnóstico presuntivo de tumor metastásico o posible lesión reactiva. El informe anátomo - patológico confirma el diagnóstico de metástasis de un carcinoma renal. Las metástasis orales tienen un pronóstico generalmente malo, compromete la sobrevida, por lo que es importante realizar un exhaustivo estudio del paciente y considerar sus antecedentes, ya que en ocasiones son diagnosticadas tardíamentete.

Metastatic tumors to the oral cavity are rare, representing only 1% of malignant oral neoplasms. These metastatic tumors occur more frequently in the jaws than in soft oral tissues. This article describes the case of a 75-year-old patient with a history of clear cell renal carcinoma who seeks care because of the sudden appearance of a tumor lesion in the upper left alveolar ridge. An excision biopsy was performed with a presumptive diagnosis of a metastatic tumor or potential reactive lesion. The pathology report confirmed the diagnosis of renal cell carcinoma metastasis. Oral metastatic tumors usually present a bad prognosis with a low survival rate. It is important to examine patients thoroughly and consider their medical records, as they are sometimes diagnosed late.

Os tumores metastásicos na cavidade oral são raros, representam 1% das neoplasias malignas orais, sendo relativamente mais frequentes nos ossos maxilares enquanto aos localizados nos tecidos moles orais. Descreve-se o caso de uma mulher de 75 anos com história de carcinoma renal de células claras, que consultou com queixa de lesão tumoral localizada na crista alveolar superior esquerda. Uma biópsia foi feita com diagnóstico clínico presuntivo de tumor metastático ou possível lesão reativa. O laudo anátomopatológico confirmou o diagnóstico de metástase de carcinoma renal. As metástases orais geralmente têm um prognóstico ruim, com baixa sobrevivência, portanto é importante fazer um estudo exaustivo do paciente e tomar em conta sua história, já que às vezes o diagnóstico é tardio.

Vertebral metastasis of renal carcinoma at diagnosis: mechanical and clinical evaluation: surgical management / Metástasis vertebral de carcinoma renal en el momento del diagnóstico: evaluación mecánica y clínica: manejo quirúrgico

Renal cell carcinoma accounts for 2-3% of all malignant neoplasms. Metastatic disease of the spine is common and 50% of bone metastases are already present at the time of primary diagnosis. Bone metastases from renal cell carcinoma are difficult to manage, especially vertebral localization.A 48-year-old woman was diagnosed with renal cell carcinoma in the context of low back pain. The patient presented two skeleton metastases at diagnosis (T11 and 5th rib). The patient received neoadjuvant treatment with cabozantinib, followed by removal of the renal tumor. Radiotherapy was administered for the lumbar lesion. In spite of the radiotherapy treatment, increased low back pain limiting mobility and ambulation. MRI showed an occupation of the spinal canal, without neurological lesion. The SINS scale revealed a score of 14 (vertebral instability). The patient's prognosis was greater than 12 months according to the Tokuhashi score. Based on clinical and mechanical criteria, surgical treatment of the vertebral lesion was decided. T11 vertebrectomy was performed, the reconstruction was made with an expandable cage, and T8 a L2 posterior spinal arthrodesis. A partial resection of the fifth rib was performed in order to remove the whole macroscopic tumor. After 3 months, she was diagnosed with a local infection, treated by irrigation, debridement and antibiotherapy, with good evolution. At 1-year follow-up, she has no low back pain or functional limitation. Follow-up chest-abdomen-pelvis computed CT scan showed absence of disease progression, furthermore, the vertebral arthrodesis shows fusion signs. At the time of this report, there are no clinical or radiological data of infection

El carcinoma de células renales representa el 2-3% de todas las neoplasias malignas. La enfermedad metastásica de la columna vertebral es frecuente y el 50% de las metástasis óseas ya están presentes en el momento del diagnóstico. Las metástasis óseas del carcinoma de células renales son difíciles de manejar, especialmente en localización vertebral.Una mujer de 48 años fue diagnosticada de carcinoma de células renales en el contexto de un dolor lumbar. La paciente presentaba dos metástasis óseas en el momento del diagnóstico (T11 y 5ª costilla). Inicialmente recibió tratamiento neoadyuvante con cabozantinib, seguido de la extirpación quirúrgica del tumor renal. Se administró radioterapia para la lesión lumbar. A pesar del tratamiento radioterápico, aumentó el dolor lumbar con limitación para la movilidad y la deambulación. La RM mostró una ocupación del canal espinal, sin lesión neurológica. La escala SINS reveló una puntuación de 14 (inestabilidad vertebral). El pronóstico de la paciente era superior a 12 meses según la puntuación de Tokuhashi. Basándose en criterios clínicos y mecánicos, se decidió el tratamiento quirúrgico de la lesión vertebral. Se realizó una vertebrectomía de T11, para la reconstrucción se usó una caja extensible, junto con una artrodesis vertebral T8-L2. Se realizó una resección parcial de la quinta costilla para eliminar todo el tumor macroscópico. A los 3 meses de la cirugía la paciente fue diagnosticada de infección local, tratada mediante irrigación, desbridamiento y antibioterapia, con buena evolución. Al año de seguimiento, no presenta dolor lumbar ni limitación funcional. La tomografía computarizada de tórax-abdomen-pelvis de seguimiento mostró ausencia de progresión de la enfermedad, además, la artrodesis vertebral muestra signos de fusión. En el momento de este informe, no hay datos clínicos ni radiológicos de infección.

A comparison of oncologic and functional outcomes in patients with pt3a renal cell carcinoma treated with partial and radical nephrectomy

ABSTRACT Hypothesis: Partial Nephrectomy is oncological safe in patients with pT3a RCC. Purpose: To compare the oncological and functional outcomes of patients with pT3a RCC scheduled for PN and RN. Materials and Methods: We retrospectively reviewed patients with pT3a N0 M0 RCC who underwent partial or radical nephrectomy from 2005 to 2016. Perioperative characteristics, including estimated glomerular filtration rate, tumor size, pathological histology, and RENAL nephrometry score, were compared between patients scheduled for partial or radical nephrectomy. We used multivariable Cox proportional hazards regression models to compare overall survival, cancer-specific survival, and recurrence-free survival between planned procedure type. Results: Of the 589 patients, 369 (63%) and 220 (37%) were scheduled for radical and partial nephrectomy, respectively; 26 (12%) of the scheduled partial nephrectomy cases were intraoperatively converted to radical nephrectomy. After adjusting for tumor size and histology, there were no statistically significant differences in overall survival (hazard ratio 0.66; 95% CI, 0.38-1.13), cancer-specific survival (hazard ratio 0.53; 95% CI, 0.16-1.75), or recurrence-free survival (hazard ratio 0.66; 95% CI, 0.34-1.28) between patients scheduled for partial or radical nephrectomy. Fewer patients scheduled for partial nephrectomy had estimated glomerular filtration rate reductions 3 to 9 months after surgery than patients scheduled for radical nephrectomy. Conclusion: We found no evidence that patients scheduled to undergo partial nephrectomy had poorer oncologic outcomes than patients scheduled to undergo radical nephrectomy. In select patients with pT3a renal cell carcinoma in whom partial nephrectomy is deemed feasible by the surgeon, partial nephrectomy should not be discouraged.

Bellini duct carcinoma

The modern era has brought an appreciation that renal cell carcinoma (RCC) includes diverse subtypes derived from the various parts of the nephron, each with its distinctive genetic basis and tumor biology. Carcinoma of the collecting ducts of Bellini (CDC) is a rare subtype of RCC, with a predictably poor prognosis. This rare subtype represents less than 1% of all kidney carcinomas. It derives from presumably numerous chromosomal losses. It is of chief importance to differentiate CDC from other types of renal cell cancer. Typically, it is characterized by a firm, centrally located tumor with infiltrative borders. Regarding the histopathologic characteristics, we can find complex, highly infiltrative cords with inflamed (desmoplastic) stroma, with high-grade nuclei and mitoses. Most reported cases of CDC had been high grade, advanced stage, and unresponsive to conventional therapies. This rare form of disease highlights the importance of multidisciplinary teams in the management of cancer patients.

Embolization of renal tumor bone metastasis: case report / Embolização de metástase óssea de tumor renal: relato de caso

Abstract Primary or secondary bone tumors can manifest in different ways, from simple bone pain to possible pathological fractures. Hypervascularized tumors are of greatest concern, with increased incidence of complications. Preoperative embolization of the bone tumor is an effective measure for reducing blood loss during open surgery to excise the tumor. With appropriate experience, the risks of the procedure are minimal and final outcomes are highly satisfactory. The purpose of this paper is to describe the case of a 43-year-old male patient with a metastatic renal cell tumor in the left proximal femur (seen on lower limb computed tomography) who underwent selective preoperative embolization. The procedure resulted in a remarkable absence of bleeding and successful response to subsequent onco-orthopedic surgery.

Resumo Os tumores ósseos, primários ou secundários, podem se manifestar de várias formas, desde dor óssea até fraturas patológicas. A preocupação maior repousa sobre tumores hipervascularizados, com maior incidência de complicações. A embolização pré-operatória do tumor ósseo é uma medida eficaz para reduzir a perda sanguínea durante a exérese tumoral em cirurgia aberta. Com uma experiência apropriada, os riscos do procedimento são mínimos, com resultados finais bastante satisfatórios. O presente artigo tem por finalidade descrever o caso de um paciente do sexo masculino, de 43 anos, com tumor metastático de células renais em fêmur proximal esquerdo (visualizado por angiotomografia de membro inferior), submetido à embolização arterial seletiva pré-operatória. O procedimento resultou em ausência de sangramento e ótima resposta à cirurgia onco-ortopédica realizada.

Diagnostic accuracy of contrast-enhanced ultrasound for detecting bland thrombus from inferior vena cava tumor thrombus in patients with renal cell carcinoma

ABSTRACT Purpose: To evaluate the role of contrast-enhanced ultrasound (CEUS) in differentiating bland thrombus from tumor thrombus of the inferior vena cava (IVC) in patients with renal cell carcinoma (RCC). Materials and Methods: We retrospectively investigated 30 consecutive patients who underwent robot-assisted radical nephrectomy with IVC thrombectomy and had pathologically confirmed RCC. All patients underwent US and CEUS examination. Two off-line readers observed and recorded thrombus imaging information and enhancement patterns. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value for bland thrombus were assessed. Results: Of the 30 patients, no adverse events occurred during administration of the contrast agent. Early enhancement of the mass within the IVC lumen on CEUS was an indicator of tumor thrombus. Bland thrombus showed no intraluminal flow on CEUS. There were eight (26.7%) patients with bland thrombus, including three level II, two level III, and three level IV. There were three cases with cephalic bland thrombus and five cases with caudal bland thrombus. Three caudal bland thrombi extended to the iliac vein and underwent surgical IVC interruption. Based on no intraluminal flow, for bland thrombus, CEUS had 87.5% sensitivity, 100% specificity, 96.7% accuracy, 100% positive predictive value and 95.6% negative predictive value. Conclusion: Our study demonstrates the potential of CEUS in the differentiation of bland and tumor thrombus of the IVC in patients with RCC. Since CEUS is an effective, inexpensive, and non-invasive method, it could be a reliable tool in the evaluation of IVC thrombus in patients with RCC.

Computed tomography imaging characteristics of clear cell papillary renal cell carcinoma

ABSTRACT Purpose: Clear cell papillary (CCP) renal cell carcinoma (RCC) is a new subtype of RCC that was formally recognized by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia in 2013. Subsequently, CCP RCC was added to the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. In this study, we retrospectively investigated the computed tomography (CT) findings of pathologically diagnosed CCP RCC. Materials and Methods: This study included 12 patients pathologically diagnosed with CCP RCC at our institution between 2015 and 2017. We reviewed the patient's CT data and analyzed the characteristics. Results: Nine solid masses and 3 cystic masses with a mean tumor size of 22.7±9.2mm were included. Solid masses exhibited slight hyper-density on unenhanced CT with a mean value of 34±6 Hounsfield units (HU), good enhancement in the corticomedullary phase with a mean of 195±34HU, and washout in the nephrogenic phase with a mean of 133±29HU. The walls of cystic masses enhanced gradually during the corticomedullary and nephrogenic phases. Solid and cystic masses were preoperatively diagnosed as clear cell RCC and cystic RCC, respectively. Conclusions: The CT imaging characteristics of CCP RCCs could be categorized into either the solid or cystic type. These masses were diagnosed radiologically as clear cell RCC and cystic RCC, respectively.