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ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.
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Abstract Objective: To evaluate the impact of preoperative body composition in patients with renal cell carcinoma (RCC) undergoing surgical treatment. Materials and Methods: This was a retrospective study of 52 patients with RCC undergoing total or partial nephrectomy. Body composition assessment was performed using the body mass index, together with computed tomography analysis at the level of the third lumbar vertebra to measure the area of visceral adipose tissue, as well as the area and density of skeletal muscle mass. Results: Malnutrition, obesity and inadequate skeletal muscle gauge (SMG) were associated with higher hospital length of stay (p = 0.028, p = 0.02 and p = 0.012, respectively). Although the rates of postoperative symptoms and readmissions were low, survival was better among the patients with an adequate SMG than among those with an inadequate SMG (p = 0.003). Conclusion: Among patients with RCC undergoing surgical treatment, preoperative body composition does not seem to be associated with the rates of perioperative complications, although an inadequate SMG seems to be associated with worse overall survival.
Resumo Objetivo Avaliar o impacto da composição corporal pré-operatória em pacientes portadores de carcinoma de células renais (CCR) submetidos a tratamento cirúrgico. Materiais e Métodos: Foi realizado estudo retrospectivo de 52 pacientes portadores de CCR submetidos a tratamento cirúrgico. A avaliação da composição corporal foi realizada por meio do índice de massa corporal e análise da L3 obtida pela tomografia computadorizada para mensurar a área do tecido adiposo visceral, área e densidade da massa muscular esquelética. Resultados: Os pacientes desnutridos, obesos e que apresentaram produto muscular esquelético (PME) inadequado permaneceram mais tempo internados (p = 0,028, p = 0,02 e p = 0,012, respectivamente). As taxas de sintomas e reinternações no pósoperatório foram baixas em toda a amostra, no entanto, observou-se que pacientes com PME inadequado apresentaram uma pior sobrevida em relação aos pacientes com PME adequado (p = 0,003). Conclusão: A análise da composição corporal pré-operatória não mostrou associação com as taxas de complicações periope-ratórias em pacientes portadores de CCR submetidos a nefrectomia total ou parcial, no entanto, a inadequação do PME está associada a uma pior sobrevida.
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El carcinoma de células renales (CCR) a nivel mundial presenta una incidencia de 431.288 casos anuales, causando 179.368 muertes en 2020. Sin embargo, a pesar de su incidencia, el desarrollo de metástasis pancreática (MP) de un RCC es un hecho inusual. El objetivo de este manuscrito fue reportar el caso de una paciente con una MP metacrónica de un CCR. Se trata de una paciente de 56 años, sexo femenino, nefrectomizada derecha hace 132 meses por un CCR, en adyuvancia con inmunoterapia. En un control imagenológico de rutina, se le pesquisó una lesión de aspecto tumoral en el cuerpo y cola del páncreas. Se intervino quirúrgicamente, realizándose una pancreatectomía córporo-caudal con preservación esplénica. Evolucionó de forma satisfactoria, sin complicaciones, siendo dada de alta al 4º día de su cirugía. El informe del estudio de la pieza operatoria con estudio inmunohistoquímico concluyó que se trataba de una MP de CCR. La paciente se encuentra en buenas condiciones generales y reinició quimioterapia con anticuerpos monoclonales. El seguimiento frecuente y prolongado de pacientes con antecedentes de CCR, facilita un diagnóstico y tratamiento oportuno de MP facilitando el mejor pronóstico de los pacientes, con tasas más altas de supervivencia.
SUMMARY: Renal cell carcinoma (RCC) worldwide has an incidence of 431,288 cases per year, causing 179,368 deaths in 2020. However, despite its incidence, the development of pancreatic metastasis (MP) from RCC is unusual. The aim of this manuscript was to report the case of a patient with a PM of a RCC. This is a 56-year-old female patient, underwent right nephrectomy 132 months earlier for RCC. While she was in adjuvant immunotherapy, in a routine imaging control, it was found a tumor lesion in the body and the tail of the pancreas. So, she underwent surgery, performing a corpora-caudal pancreatectomy with splenic preservation. Postoperative evolution was correct, without complications, and she was discharged on the 4th day after surgery. The report of the study of the surgical piece with an immunohistochemical study included, conclusive of PM of RCC. Currently, the patient is in good general condition and restarted chemotherapy with monoclonal antibodies. Frequent and prolonged follow-up of patients with a history of RCC facilitates timely diag- nosis and treatment of PM, facilitating the best prognosis for patients, with higher survival rates.
Subject(s)
Humans , Female , Middle Aged , Pancreatic Neoplasms/secondary , Carcinoma, Renal Cell/secondary , Kidney Neoplasms/pathology , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/diagnostic imaging , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/diagnostic imagingABSTRACT
ABSTRACT Ocular metastases from systemic tumors are uncommon. The choroid is the most frequent target, with a preference for elderly individuals. Lung cancer is the predominant primary tumor that metastasizes to the eyes in males, although other ocular conditions such as uveitis and retinal lesions can mimic secondary tumor implants in ocular tissues. On fundoscopy, choroidal metastasis resembles other infectious processes, especially choroidal tuberculoma. Therefore, patients presenting with choroidal masses should undergo detailed clinical examinations, especially if the mass is the first manifestation of a systemic and severe disease. In this report, we describe a young man with a metastatic choroidal tumor secondary to papillary renal cell carcinoma mimicking a unilateral choroidal tuberculoma.
RESUMO A disseminação metastática ocular de tumores sistêmicos é incomum, ocorrendo principalmente na coroide e em pacientes idosos. O câncer de pulmão é considerado o principal tumor metastático ocular em homens, contudo, outras doenças oculares, como as uveítes e lesões retinianas, podem mimetizar os implantes secundários tumorais nos tecidos oculares. O aspecto fundoscópico das neoplasias da coroide pode apresentar similaridade com outros processos infecciosos, especialmente o tuberculoma de coroide. Dessa forma, a investigação clínica detalhada é de grande importância no diagnóstico de pacientes com massas coroideanas, especialmente quando configuram a primeira manifestação de uma doença sistêmica e grave. Relatamos um caso raro de metástase coroideana como primeira manifestação clínica do carcinoma de células renais em um homem jovem, mimetizando um tuberculoma de coroide.
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Objective:To analyze the expression of targeting protein for Xklp2 (TPX2) in kidney renal clear cell carcinoma (KIRC) and its clinical significance.Methods:The postoperative tissue samples of 54 patients with KIRC admitted to the Department of Urology, the First Affiliated Hospital of Bengbu Medical College from July 2017 to June 2019 were collected. Immunohistochemistry was used to detect the protein expression of TPX2 in renal carcinoma and paracancerous tissues. The difference of TPX2 mRNA expression between KIRC tissues and normal tissues was analyzed by using the TIMER database, which verified the immunohistochemical results. The UALCAN database and the Kaplan-Meier plotter database were used to analyze the relationship between TPX2 mRNA expression and clinical stage, molecular subtypes, lymph node metastasis, and prognosis of patients with KIRC. The protein interaction network was constructed by STRING database to obtain TPX2-related proteins, and the genes corresponding to the related proteins were enriched for the KEGG pathway. The relationship between TPX2 expression and immune cell infiltration and the immune checkpoint was studied by using the TIMER database.Results:Immunohistochemical results showed that the positive expression rate of TPX2 protein was 48.15% (26/54) in cancer tissues, which was higher than that in paracancerous tissues (20.37%, 11/54) ( χ2=9.25, P=0.002). The results of bioinformatics analysis showed that TPX2 mRNA expression was significantly up-regulated in KIRC [cancer tissue: 1.89 (1.49, 2.42), normal tissue: 0.35 (0.24, 0.57), U=2 297.00, P<0.001]. The expression of TPX2 mRNA was related to the clinical stage ( χ2=34.36, P<0.001), molecular subtypes ( χ2=30.15, P<0.001), and lymph node metastasis status ( χ2=27.21, P<0.001) of KIRC patients. The 5-year survival rate (53.80%) in patients with high TPX2 expression was lower than that in patients with low TPX2 expression (74.40%, χ2=18.87, P<0.001). STRING database protein interaction network construction obtained 20 TPX2-related proteins, and the genes corresponding to the related proteins were enriched in the cell cycle. The expression of TPX2 was positively correlated with B cells ( r=0.30, P<0.001), CD8 + T cells ( r=0.23, P<0.001), CD4 + T cells ( r=0.18, P<0.001), macrophages ( r=0.20, P<0.001), neutrophils ( r=0.31, P<0.001), dendritic cells ( r=0.39, P<0.001) infiltration and most of its biomarkers (all P<0.05). It was positively correlated with immune checkpoint PD-1 ( r=0.31, P<0.001) and CTLA-4 ( r=0.27, P<0.001), but not correlated with PD-L1 ( r=0.07, P=0.146) . Conclusion:TPX2 is highly expressed in KIRC and is closely associated with poor prognosis. It is expected to be a new therapeutic target for KIRC.
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Renal cell carcinoma is a malignant tumor originating from renal tubular epithelial cells. Its pathogenesis is complicated, with no typical early clinical symptoms. Most patients are already in the advanced stage at the time of diagnosis and have a high mortality rate. The development mechanism and treatment strategy of renal cell carcinoma are the current research focus. In recent years, non-coding RNA has been proved to play a crucial role in regulating tumor progression. Among them, circular RNA plays a unique role in tumor development due to its nonlinear structure. The dysregulation of circular RNA is closely related to the progression of a series of diseases including metabolic diseases and cancer. Similarly, circular RNA plays a key role in the progression, treatment, and prognosis prediction of renal cell carcinoma. This article briefly reviews role of circular RNA in renal cell carcinoma, hoping to bring new research directions for the diagnosis and treatment of renal cell carcinoma.
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Objective:To explore the value of quantitative parameters of enhanced MRI in predicting the establishment of inferior vena cava collateral circulation in patients with renal cell carcinoma and inferior vena cava tumor thrombus.Methods:Sixty-seven patients with renal cell carcinoma and inferior vena cava tumor thrombus who underwent radical resection and inferior vena cava venography in First Medical Center, PLA General Hospital from May 2006 to January 2021 were included retrospectively. According to the results of inferior vena cava venography, the patients were divided into two groups: the well-established collateral circulation group ( n=41) and the poor-established collateral circulation group ( n=26). Quantitative parameters were measured on preoperative enhanced MRI images, including tumor size, the maximum diameter of bilateral lumbar veins, the length of tumor thrombus, and the long and short diameters of tumor thrombus. Student′s t test or Mann-Whitney U test was used for comparison between the two groups. The independent risk factors related to the establishment of collateral circulation were obtained by binary logistic regression analysis and the model was established. The receiver operating characteristic curve was employed to evaluate MRI quantitative parameters and the logistic model, and the area under the curve (AUC) was compared by the DeLong test. Results:Between the well-established collateral circulation group and the poor-established collateral circulation group, the maximum diameter of the right lumbar vein, the maximum diameter of the left lumbar vein, the length of the tumor thrombus, the long diameter of the tumor thrombus, and the short diameter of the tumor thrombus were different significantly ( P<0.05). There was no significant difference in the tumor size between the two groups ( t=0.30, P=0.766). The AUC of the maximum diameters of the right lumbar veins and left lumbar veins, length of tumor thrombus, long and short diameters of tumor thrombus in predicting the collateral circulation were 0.917 (95%CI 0.824-0.971), 0.869 (95%CI 0.764-0.939), 0.756 (95%CI 0.636-0.853), 0.886 (95%CI 0.785-0.951), and 0.906 (95%CI 0.809-0.963). The AUC of the maximum diameter of the right lumbar vein and the short diameter of the tumor thrombus were larger than those of the length of the tumor thrombus, and the differences were statistically significant ( Z=2.25, 2.04, P=0.025, 0.041), but the AUC between other parameters had no significant difference ( P>0.05). The maximum diameter of the right lumbar vein (OR 24.210, 95%CI 2.845-205.998), the maximum diameter of the left lumbar vein (OR 20.973, 95%CI 2.359-186.490), and the length of the tumor thrombus (OR 23.006, 95%CI 2.952-179.309) were independent risk factors for predicting the establishment of inferior vena cava collateral circulation. The AUC of logistic model was 0.969 (95%CI 0.931-1.000). Conclusion:Quantitative parameters of tumor thrombus and lumbar vein based on enhanced MRI have a good ability in predicting the establishment of inferior vena cava collateral circulation in patients with renal cell carcinoma and inferior vena cava tumor thrombus. The maximum diameter of bilateral lumbar veins and the length of the tumor thrombus were independent risk factors for inferior vena cava collateral circulation.
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Objectives:To investigate the effect of fat suppression (FS) T 2WI on the interobserver agreement and diagnostic performance of clear cell likelihood score version 2.0 (ccLS v2.0) for clear cell renal cell carcinoma (ccRCC). Methods:In this retrospective study, the MR images of 111 patients with pathologically confirmed small renal masses (SRM) from January to December 2021 were analyzed in the First Medical Centre, Chinese PLA General Hospital. Of the 111 SRM, 82 cases were ccRCC and 29 cases were non-ccRCC. Two radiologists independently assessed ccLS scores based on T 2WI signal intensity (hypointense, isointense, hyperintense) and other MRI features (ccLS-T 2WI). After a one-month interval, the ccLS scores were independently evaluated utilizing the frequency-selective saturation FS-T 2WI and other MRI features (ccLS-FS-T 2WI). Fisher′s exact test was used to compare the difference in SRM signal intensity on T 2WI and FS-T 2WI. The weighted Kappa test was performed to assess the interobserver agreement of the two radiologists, and differences in the weighted Kappa coefficients were compared using the Gwet consistency coefficient. Receiver operating characteristic curves were drawn to evaluate the diagnostic performance of ccLS-T 2WI and ccLS-FS-T 2WI in diagnosing ccRCC, and the area under the curve (AUC) was compared utilizing the DeLong test. Results:The signal intensity of 111 SRM on T 2WI and FS-T 2WI had statistically significant difference (χ 2=126.33, P<0.001), consistent in 88 cases (79.3%) and varied in 23 cases (20.7%). The weighted Kappa coefficient of ccLS-T 2WI was 0.57 (95%CI 0.45-0.69) between the two radiologists, and the weighted Kappa coefficient of ccLS-FS-T 2WI was 0.55 (95%CI 0.42-0.67), and the difference was not statistically significant ( t=-0.65, P=0.520). The AUC of ccLS-T 2WI for ccRCC diagnosis was 0.92 (95%CI 0.86-0.97), while the AUC of ccLS-FS-T 2WI for ccRCC diagnosis was 0.91 (95%CI 0.85-0.96), and the difference was not statistically significant ( Z=1.50, P=0.133). Conclusions:The interobserver agreement and diagnostic performance of ccLS v2.0 based on T 2WI and FS-T 2WI sequences for ccRCC are comparable, and FS-T 2WI is applicable for the clinical application of ccLS v2.0.
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Objective:To investigate the clinical and MRI features of the mixed epithelial and stromal tumor family (MESTF) of the kidney.Methods:From January 2009 to September 2021, 42 patients with pathologically-proven MESTF from the First Medical Center of Chinese PLA General Hospital were collected in this retrospective study. Clinical information, MRI features, and pathological results were documented. According to the Bosniak classification (BC) version 2019, all MESTFs were divided into cystic MESTFs (36 cases) and solid-cystic MESTFs (6 cases). The R.E.N.A.L. nephrometry score (RNS), lesion size, laterality, location, margin, shape, growth pattern, presence of protruding into renal sinus, hemorrhage, and enhancement pattern were evaluated and documented. Based on BC versions 2005 and 2019, all the cystic MESTFs were assessed and divided into low (Ⅰ, Ⅱ, ⅡF) and high (Ⅲ, Ⅳ) grades. The independent sample t test or Mann-Whitney U test were performed to compare age, RNS, and lesion size between cystic MESTFs and solid-cystic MESTFs. Pearson χ 2 test, continuity-adjusted χ 2 test or Fisher exact probability test were utilized to evaluated the differences of clinical and MRI features and the distribution of low or high grades in two versions of BC. Results:Forty-two MESTFs were unilateral and solitary masses, 25 males and 17 females, with a mean age of (41±13) years old. Compared to solid-cystic MESTFs, cystic MESTFs were prone to demonstrate endophytic growth pattern (χ 2=17.77, P<0.001), and no significant differences in other clinical and MRI features were observed between cystic and solid-cystic MESTFs (all P>0.05). There were 7 low-grade and 29 high-grade tumors in the BC version 2005, respectively. Meanwhile, 24 low-grade and 12 high-grade tumors in the BC version 2019, respectively. The distribution of low or high-grade tumors in the two versions of BC had a statistically significant difference (χ 2=16.37, P<0.001). Conclusion:MESTFs demonstrated middle-age onset and no gender predilection. Cystic MESTFs are more likely to exhibit endophytic growth pattern with low-grade classification in BC system version 2019.
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Objective:To investigate the efficacy of different treatment modes for locoregional recurrence after nephrectomy in patients with renal cell carcinoma.Methods:A total of 106 patients with locoregional recurrence after nephrectomy without distant metastasis (77 males and 29 females) admitted to Sun Yat-sen University Cancer Center from October 2001 to July 2020 were retrospectively analyzed. The median age was 51 (40, 60) years old. Radical nephrectomy was performed in 90 patients with primary tumor and partial nephrectomy was performed in 16 patients. Pathological diagnosis showed that 54 cases were clear cell carcinoma and 52 cases were non-clear cell carcinoma. 53 cases were in stage T 1-2 and 53 cases in stage T 3-4. The median diameter of recurrent lesions was 3.2 (2.0, 6.3) cm, and the median number was 2 (1, 4). The recurrence sites were divided into renal fossa recurrence (33 cases), renal fossa±retroperitoneal lymph node recurrence (38 cases), and intra-abdominal spread (35 cases). The median duration from primary surgery to local recurrence was 14.8 (7.3, 35.8) months. Two treatment groups were identified as systemic therapy alone (Group A) and local therapy with or without systemic therapy (Group B). The Kaplan-Meier method was used to compare the progression free survival (PFS) and overall survival (OS) between Group A and Group B. The Cox model was used to perform univariate and multivariate analysis. Results:Of all the 106 patients, 33 patients were in Group A and 73 patients were in Group B. In Group A, 29 patients (87.9%) received targeted therapy, and 4 patients (12.1%) received targeted therapy combined with immunotherapy. In Group B, 34 patients (46.6%) received surgery or ablation and 39 patients (53.4%) received SBRT, of which 62 patients (84.9%) received concurrent systemic therapy. Among them, 58 patients (93.5%) received targeted therapy, and 4 patients (6.5%) received targeted therapy combined with immunotherapy. The median follow-up period was 29.0 (15.4, 45.9) months, 64 patients progressed on tumor including 28 patients died. The median PFS and OS were 15.6 (7.1, 35.2) months and 66.9 (37.8, not reached) months. The median PFS of Group A and Group B were 7.6(5.0, 17.2)months and 22.2(9.6, 63.9)months respectively ( P=0.001), median OS of Group A and Group B were 45.7 (23.4, 62.8)months and 71.0(50.6, not reached)months respectively, and the 2-year OS were 70.6% and 85.5% in Group A and Group B respectively ( P=0.023). The univariate analysis showed local therapy with or without systemic therapy was significantly reduced 56% risk of tumor progression ( HR=0.44, P=0.003) and reduced 60% risk of death ( HR=0.40, P=0.028). The multivariate analysis showed that the OS was associated with ECOG score( HR=10.20, 95% CI 4.13-25.30, P<0.001)and local therapy( HR=0.23, 95% CI 0.09-0.58, P=0.002). Conclusion:Compared with systemic therapy alone, local therapy with or without systemic therapy can effectively improve the PFS and OS of patients with locoregional recurrence after nephrectomy.
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The metastasis of contralateral adrenal gland and gallbladder following radical nephrectomy is extremely uncommon in clinical practice. We presented one such case. The patient underwent laparoscopic radical right nephrectomy. Postoperative pathology revealed clear cell carcinoma of the right kidney. Five years after operation, CT revealed occupying lesions in the left adrenal gland and gallbladder. Transperitoneal laparoscopic left adrenalectomy and cholecystectomy were performed. Pathological examination showed that the left adrenal tumor and gallbladder tumor were clear cell carcinoma. The patient received targeted therapy and tumor-free survived for 10 months.
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Objective:To investigate the effect of tumor-associated macrophage(TAM) on proliferation of renal carcinoma cells and its related mechanism.Methods:The model of TAM was established by stimulating human monocytic leukemia cell line THP-1 with phorbol myristate acetate (PMA), bacterial endotoxin (LPS) and interferon-γ (IFN- γ). Then the TAM model was co-cultured with carcinoma cell lines ACHN and 786-O in vitro .The cytokines IL-6, TNF-α and IL-1β in TAM supernatant were detected by enzyme-linked immunosorbent assay (ELISA). MTT method was used to detect the proliferation of ACHN and 786-O cells treated with supernatant of TAM or TAM/Tocilizumab. Western blot was used to detect lactate dehydrogenase A (LDHA) expression of both renal cancer cells co-cultured with TAM or TAM/Tocilizumab. The ACHN and 786-O cells with LDHA-overexpression and LDHA-knockdown were cultured in TAM supernatant in vitro. The cell proliferation was detected by MTT and the relative proliferation rate was calculated.Results:THP-1 cells was differentiated into TAM through the treatment of 80 ng/ml PMA combined with 20 ng/ml LPS and 20 ng/ml IFN- γ.The expression rate of CD68, a cell surface marker on TAM, was (36.2 ±4.5)%. When TAM was co-cultured with ACHN cells, the results of ELISA showed that the secretion of IL-6 in the supernatant was significantly elevated compared with that in the supernatant when ACHN cells cultured alone [(138.0 ±12.4) pg/ml and (19.7±4.9) pg/ml], and the secretion of TNF- α [(122.5 ±14.2) pg/ml and (12.6 ±2.3) pg/ml] and IL-1 β [(89.2 ±6.4) pg/ml and (69.2 ±3.5) pg/ml] were also significantly increased. The secretion of IL-6 [(119.2 ±14.8) pg/ml and (17.1 ±3.3) pg/ml], TNF- α [(122.6 ±14.4) pg/ml and (45.7 ±7.2) pg/ml] and IL-1 β [(95.1 ±11.8) pg/ml and (88.2 ±12.7) pg/ml] in the supernatant were also significantly elevated when 786-O cells co-cultured with TAM compared with 786-O cells cultured alone. After treated with the supernatant of TAM for 72 hours, the relative proliferation rates of ACHN and 786-O cells [(128.6 ±21.4)% and (124.2 ±19.7)%] were significantly higher than that of the control group (100.0%). At the same time, the expression of LDHA in ACHN and 786-O cells increased significantly. After 72 hours of treatment with the supernatant of TAM combined with tocilizumab, the relative proliferation rates of ACHN and 786-O cells [(76.5±13.7)% and (74.8±12.5)%] were significantly lower than that of the control group(100.0%), and the expression of LDHA was also significantly decreased at the same time. The relative proliferation rates of ACHN and 786-O cells in LDHA overexpression group [(121.5 ±17.2)% and (122.7±21.6)%]were significantly higher than that in blank-vector-transfection group[(93.3±10.7)% and (89.8±11.2)%], while the relative proliferation rates in LDHA-knockdown group [(61.4±11.2)% and (58.0 ±10.6)% ]were significantly lower than that in blank-vector-transfection group.Conclusions:By secreting IL-6, TAM can up-regulate the expression of LDHA and promote the proliferation of renal cancer cells.
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Succinate dehydrogenase (SDH) defective renal cell carcinoma (RCC) is a new subtype of renal carcinoma newly identified by WHO(2016). Until now, only a few samples and a few cases have been reported retrospectively. This article reported a young female patient who was found to have a small tumor in the left kidney by physical examination and underwent left partial nephrectomy. The postoperative pathological result was SDH-RCC. There was no recurrence and metastasis of the tumor 3 months after operation.
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The ASCO-GU 23 conference was held offline as scheduled after the pandemic. A total of 167 abstracts in the field of renal cell carcinoma has been posted during the conference, covering the first PET/CT diagnostic technology targeting tumors in renal cell carcinoma, risk stratified interpretation of the previous clinical trial results, and exploring the value of tumor and serum biomarkers for precise classification therapy, as well as providing evidence for the therapeutic scheme sequencing.
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Objective:To investigate the risk factors of massive intraoperative bleeding in patients with renal cell carcinoma and tumor thrombus.Methods:Data of 177 patients with renal cell carcinoma and tumor thrombus in Peking University Third Hospital from January 2017 to July 2020 were retrospectively analyzed, including 129 males and 48 females. The average age was (59.3±10.6) years. The tumors were located on the left in 66 cases and on the right in 111 cases. The tumor size was less than 7 cm in 52 cases, 7-10 cm in 63 cases and >10 cm in 62 cases. There were 45 cases with tumor thrombus of Mayo grade 0, 101 cases of grade Ⅰ-Ⅱ and 31 cases of grade Ⅲ-Ⅳ. There were 93 cases undergoing laparoscopic surgery and 84 cases undergoing open surgery. Segmental resection of vena cava was performed in 30 cases. Massive intraoperative bleeding was defined as the total of bleeding ≥ 1 500 ml. The difference of clinical data between massive bleeding group and non-massive bleeding group was compared. Logistic multivariate regression was used to analyze the independent risk factors of massive intraoperative bleeding.Result:The median intraoperative bleeding of 177 cases was 600 (200, 1 500) ml. There were 50 cases (28.2%) in massive bleeding group and 127 cases(71.8%) in non-massive bleeding group. Comparing massive bleeding group and non-massive bleeding group, the preoperative ASA scores of 1-2 scores were 38 cases (76.0%) and 114 cases (89.8%) respectively, and the 3 scores were 12 cases (24.0%) and 13 cases (10.2%) respectively ( P=0.029); Hemoglobin was (116.8±23.1) g/L and (127.6±23.6) g/L respectively ( P=0.006); The tumor size less than 7 cm in 10 cases (20.0%) and 42 cases (33.1%), 7-10 cm in 15 cases (30.0%) and 48 cases (37.8%), and >10 cm in 25 cases (50.0%) and 37 cases (29.1%)( P=0.024); Tumor thrombus of Mayo grade 0 were 3 cases (6.0%) and 42 cases (33.1%), grade Ⅰ-Ⅱ were 27 cases (54.0%) and 74 cases (58.3%), grade Ⅲ-Ⅳ were 20 cases (40.0%) and 11 cases (8.6%) respectively ( P<0.01); Open surgery were performed in 42 (84.0%) and 42 (33.1%) cases ( P<0.01); Segmental resection of vena cava was performed in 19 cases (38.0%) and 11 cases (8.7%) respectively ( P<0.01). Multivariate analysis showed that Mayo grade Ⅲ-Ⅳ tumor thrombus ( OR=10.261, P=0.006), tumor size > 10 cm ( OR=3.223, P=0.030), open surgery ( OR=5.454, P<0.01) and segmental resection of vena cava ( OR=4.441, P<0.01) were independent risk factors for massive intraoperative bleeding. The median bleeding of Mayo grade Ⅲ-Ⅳ tumor thrombus, tumor size >10cm, open surgery and segmental resection of vena cava were 2000, 750, 1 450 and 1 650 ml respectively. Conclusions:Renal cell carcinoma with tumor thrombus has a high risk of bleeding. Mayo grade Ⅲ-Ⅳ tumor thrombus, tumor size >10 cm, open surgery and segmental resection of vena cava are independent risk factors for massive intraoperative bleeding.
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MiT family translocation renal cell carcinoma mainly includes Xp11.2/TFE3 gene fusion-related renal cell carcinoma (TFE3 RCC)and t(6; 11)/TFEB gene fusion-related renal cell carcinoma(TFEB RCC), which is rare and there is no standard treatment plan yet, and the prognosis is still controversial. For localized lesions, surgery is the first choice for treatment, and systemic treatment such as targeted drugs and immune checkpoint inhibitors can be combined when there is metastasis. The application of gene testing provides the basis for personalized treatment. TFE3 RCC is highly invasive and has a poor prognosis, while TFEB RCC usually has a biological behavior of inertia and a better prognosis.
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Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.
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Objective:To Explore the diagnosis, treatment and prognosis of FH-deficient renal cell carcinoma (FH-deficient RCC) with tumor thrombus, and share surgical experience.Methods:From August 2019 to October 2022, 6 cases of FH-deficient RCC with tumor thrombus were diagnosed and treated in our center, including 4 males and 2 females. The patients were aged 22 to 57 years, with 2 cases younger than 40 years, icluding 5 cases on the left and 1 case on the right. The median maximum diameter of the tumor is 8 (4.8, 14.0) cm. Operations were performed after complete examination (enhanced CT and other related examinations). One case underwent open surgery and palliative resection of the left kidney was performed because of severe adhesion of the inferior vena cava. Among the remaining 5 cases, 1 case underwent retroperitoneal laparoscopic right radical nephrectomy with inferior vena cava thrombectomy, 1 case underwent transabdominal laparoscopic left radical nephrectomy with inferior vena cava thrombectomy, and 3 cases underwent robot assisted laparoscopic left radical nephrectomy with inferior vena cava thrombectomy.Results:The median surgical time was 293 (185, 366) min, with blockage of the vena cava for 13 min and 28 min in 2 of 6 cases, respectively. The pathological report of renal tumor and tumor thrombus was FH-deficient renal carcinoma. The pathological features were as follows: the gross section of the specimen was gray yellow solid, often accompanied by necrosis, and the cystic cavity could be seen locally. Microscopically, the tumor extensively involved the renal parenchyma, with papillary, cribriform and tubular cystic structures. Immunohistochemistry showed FH (-), 2SC (+ ). The median postoperative hospital stay was 8 (4, 15) days. The median follow-up time was 13 (4, 27) months. One patient undergoing palliative resection of the left kidney underwent targeted therapy and radiotherapy after surgery (died 15 months after surgery due to gastrointestinal perforation). During the follow-up process, 4 cases experienced metastasis and received systematic treatment, with 1 death 27 months after surgery. Uterine leiomyomas were found in the remaining 1 case during follow-up.Conclusions:FH-deficient RCC with tumor thrombus is very rare. This disease is highly invasive, difficult to be diagnosed preoperatively and poor clinically prognostic. Operation combined with systemic therapy is an effective way to treat FH-deficient RCC with tumor thrombus.
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Objective:To investigate the safety and prognosis of partial nephrectomy (PN) in the treatment of highly malignant non-clear renal cell carcinoma (nccRCC).Methods:Clinical data of 47 patients with cT 1N 0M 0 high malignant nccRCC treated in Changhai Hospital from March 2016 to March 2022 were retrospectively analyzed. All patients received PN. There were 34(72.3%) males and 13(27.7%) females. The mean age was (53.5±15.0) years, and average BMI, was(23.7±3.4)kg/m 2.The maximum tumor diameter was (29.8±12.6) mm, and R. E.N.A.L. score was 7(5-9), with 37(78.7%) cases of T 1a and 10(21.3%) cases of T 1b. The mean estimated glomerular filtration rate (eGFR) before surgery was (96.3±25.5) ml/ (min·1.73m 2). All patients underwent PN, including 1 patient (2.1%) undergoing open surgery, 29 patients (61.7%) undergoing laparoscopic surgery, and 17 patients (36.2%) undergoing robotic surgery. There were a total of 22(46.8%) cases of papillary cell carcinoma(pRCC)type Ⅱ, 4(8.5%) cases of collecting duct carcinoma (cdRCC), 9(19.1%) cases of MiT family translocated renal cell carcinoma (tRCC), 5(10.6%) cases of mucoid tubular and spindle cell carcinoma (mtSCC)and 7(14.9%) cases of unclassified renal cell carcinoma (uRCC). The surgical conversion rate, positive margin rate, operative time, intraoperative blood loss, complications, and postoperative hospital stay were analyzed. Preoperative and postoperative eGFR were analyzed, and overall survival (OS) and cancer specific survival (CSS) were calculated. Results:All the operations were successfully completed. No radical operation or open operation was performed, with operation time of(100±60) min and intraoperative blood loss of(100±59) ml. There were no intraoperative complication and 1 case (2.1%) suffered from postoperative complication. Postoperative hospital stay were 5 (4-6) days. The mean eGFR after surgery was (86.5±27.1) ml/(min·1.73m 2), and the difference was statistically significant ( P=0.041). In this study, the mean follow-up time was (45.7±20.9)months, and no adjuvant therapy was used after surgery. During the follow-up period, 2 patients died, who all of them were kidney cancer-related death, and both OS and CSS were 95.7% (45/47). Conclusions:PN is safe, feasible and has a good prognosis in the treatment of high malignant T 1 nccRCC. For tumors with clear imaging boundaries and complete envelope, complete tumor resection is more likely, postoperative follow-up should be strict, and no remedial radical or systemic treatment was required.
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Objective:A single-center analysis was performed to assess the significant clinical features and prognostic factors of TFE3-rearranged renal cell carcinoma (TFE3 rRCC).Methods:The clinical data of 85 confirmed cases of TFE3 rRCC patients at the Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2007 to February 2023 were analyzed retrospectively. Among these patients, there were 39 males and 46 females, with a median age of 32 (26, 45) years. All patients underwent preoperative CT scans, 21/85 cases (24.7%) of TFE3 rRCC exhibited the characteristic feature of "circular calcification" with plain CT imaging, and enhanced CT scan showed that the tumor enhancement during the arterial phase was lower than the adjacent renal cortex. Among the 85 patients in this cohort, the median tumor diameter was 4.8(3.2, 6.5). Thirty-two patients underwent partial nephrectomy (NSS), while 51 patients underwent radical nephrectomy (RN). Two patients with distant metastasis at the time of diagnosis received only sunitinib therapy. Forty-three patients received adjuvant treatment, including 14 patients who received targeted therapy. There were 29 patients in AJCC stage Ⅲ/Ⅳ, with 10 patients presenting with venous tumor thrombus and 14 patients with lymph node metastasis. Histopathology, TFE3 immunohistochemistry, and break-apart TFE3 FISH probe detection were performed on all 85 cases, while 52 patients underwent RT-PCR and/or DNA sequencing. By combining the clinical and pathological data, we summarized the diagnostic Methods for TFE3 rRCC, evaluated the impact of surgical approaches (RN and NSS) on the survival outcomes of cT 1a/b patients, and assessed the influence of genetic subtypes (ASPL, NONO, PRCC, SFPQ, and others) on the survival outcomes of all patients. Furthermore, we analyzed the risk factors for disease progression. Results:TFE3 rRCC exhibited variable histopathological features, and the presence of acinar-like structures with psammoma bodies may be a relatively typical characteristic. All 85 patients showed positive TFE3 immunohistochemical staining. In 6 cases of TFE3 rRCC, break-apart TFE3 FISH probe yielded negative results. However, final confirmation was achieved through genetic sequence, with 5 cases diagnosed as NONO-TFE3 subtype and 1 case as RBM10-TFE3 subtype. Among the 85 patients, 52 underwent RT-PCR and/or DNA sequencing, revealing a total of 8 TFE3 fusion subtypes, including 11 cases of ASPL-TFE3, 8 cases of PRCC-TFE3, 10 cases of NONO-TFE3, 15 cases of SFPQ-TFE3, 1 case of CLTC-TFE3, 2 cases of LUC7L3-TFE3, 4 cases of MED15-TFE3, and 1 case of RBM10-TFE3. The survival analysis results revealed that among the 12 patients with cT 1b stage tumors who underwent radical nephrectomy (RN), the progression-free survival (PFS) was 35 (14, 109) months, which was significantly better than the NSS group ( P=0.041). However, for the 14 patients with cT 1a stage tumors who underwent RN, there was no statistically significant difference in overall survival (OS) and PFS compared to the NSS group, with OS being 55(27, 134) months and PFS being 71(41, 134) months. Stratifying according to TFE3 fusion subtypes, it was found that patients with ASPL-TFE3 fusion had a significantly lower PFS compared to those with non-ASPL-TFE3 fusion subtypes ( P=0.029). Survival analysis revealed that tumor diameter, surgical approach, adjuvant therapy, AJCC staging, venous tumor thrombus, and lymph node metastasis were associated with OS and PFS( P<0.05). The results of the multivariate Cox regression analysis showed that AJCC stage Ⅲ/Ⅳ( HR=2.393, 95% CI 1.418-4.039, P=0.001) and venous tumor thrombus ( HR=3.543, 95% CI 1.159-10.827, P=0.026) were independent risk factors for progression-free survival (PFS). Conclusions:During the non-enhanced phase of CT scan, TFE3 rRCC tumors can exhibit a circular calcification. TFE3 immunohistochemistry is an important screening method for TFE3 rRCC.Break-apart TFE3 FISH probe detection is considered the diagnostic gold standard, and gene sequencing, if feasible, can provide the subtype diagnosis of TFE3 rRCC. For cT 1a stage TFE3 rRCC, partial nephrectomy (NSS) is a viable option, while caution should be taken in selecting NSS for cT1b stage patients. Patients with ASPL-TFE3 fusion subtype have a worse prognosis. AJCC stage Ⅲ/Ⅳ and venous tumor thrombus indicate poor prognosis in TFE3 rRCC.