Tumor neuroectodérmico maligno del tracto gastrointestinal: a propósito de un caso / Malignant neuroectodermal tumor of the gastrointestinal tract: case report

El tumor neuroectodérmico maligno del tracto gastrointestinal es una neoplasia rara con pocos casos reportados en la literatura, especialmente en América Latina. Descrito por primera vez en 2003, se trata de una entidad sin tratamiento estandarizado y de pobre pronóstico. Se presenta el caso de una paciente de 22 años de edad que acude a la consulta por dolor abdominal, anemia y masa abdominal palpable. Luego de estudios pertinentes se decide la conducta resectiva y el posterior tratamiento oncológico. (AU)

Malignant gastrointestinal neuroectodermal tumor (GNET), formerly known as clear cell sarcoma of the gastrointestinal tract, is an extremely rare tumor of mesenchymal origin, which presents great microscopic and molecular similarity to clear cell sarcoma found in other parts of the body, such as tendons and aponeurosis. It is characterized by its rapid evolution, high recurrence rate and frequent diagnosis as metastatic disease.1,2 (AU)

Analysis of prognostic factors for clear cell adenocarcinoma of the uterine cervix based on the Surveillance, Epidemiology and End Results database / 肿瘤研究与临床

Objective:To explore the prognostic factors associated with clear cell adenocarcinoma (CCAC) of the uterine cervix based on data in the Surveillance, Epidemiology and End Results (SEER) database.Methods:Clinical data were collected from 431 patients with confirmed CCAC in the SEER database from 1976 to 2017. Survival analysis was performed using the Kaplan-Meier method with log-rank test for comparison between subgroups. Cox proportional hazards model was used to analyze the influencing factors of overall survival (OS).Results:The median age [ M ( Q1, Q3)] of 431 patients was 54 years old (40 years old, 71 years old); there were 333 cases (77.3%) of whit. The median OS time of 431 patients was 93 months (95% CI: 47-148 months), and the 1-, 2-, and 5-year OS rates were 80.1%, 65.8% and 54.2%, respectively. The median OS time was not reached in patients with American Joint Committee on Cancer (AJCC) stage Ⅰ, 83 months (95% CI: 21-144 months) for stage Ⅱ, 32 months (95% CI: 16-47 months) for stage Ⅲ, and 9 months (95% CI: 5-13 months) for stage Ⅳ ( P < 0.001). Median OS time was not reached in patients with SEER stage of localized lesions, 46 months (95% CI: 8-83 months) for regional lesions stage, and 9 months (95% CI: 5-12 months) for distant metastases stage ( P < 0.001). Of the patients with clear AJCC staging and some with unspecified AJCC staging, 118 received surgical treatment alone and 119 received postoperative radiotherapy, the median OS time of the two groups was 443 months (95% CI: 162-723 months) and 102 months (95% CI: 75-129 months), and the difference in OS between the two groups was statistically significant ( P < 0.001). Among the patients with AJCC stage Ⅰ, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 82.5% and 78.5%, the stage Ⅱ were 80.0% and 52.3%, and the stage Ⅲ were 27.8% and 63.3%, respectively; the differences in OS between different stages were not statistically significant (all P>0.05). Among the patients with SEER localized lesions stage, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 88.9% and 73.1%, and the difference was statistically significant ( P = 0.012); the regional lesions stage were 45.5% and 60.0%, and the difference was not statistically significant ( P = 0.568). The results of multivariate Cox regression analysis showed that AJCC staging (stage Ⅰ vs. stage Ⅳ, HR = 0.281, 95% CI: 0.178-0.543, P < 0.001; stage Ⅱ vs. stage Ⅳ, HR = 0.347, 95% CI: 0.113-0.439, P < 0.001; stage Ⅲ vs. stage Ⅳ, HR = 0.399, 95% CI: 0.030-0.145, P < 0.001), SEER staging (localized lesions stage vs. distant metastases stage, HR = 0.104, 95% CI: 0.059-0.182, P < 0.001; regional lesions stage vs. distant metastases stage, HR = 0.301, 95% CI: 0.195-0.463, P < 0.001) and whether or not receive surgery (yes vs. no, HR = 0.359, 95% CI: 0.241-0.535, P < 0.001) were independent influencing factors of OS in CCAC patients. Conclusions:AJCC staging, SEER staging and surgery are independent influence factors for OS in patients with CCAC, and postoperative radiotherapy may not provide more survival benefit.

Clinicopathological features and prognosis of non-clear cell renal cell carcinoma in young patients aged 18-40 years / 现代泌尿外科杂志

【Objective】 To summarize the clinicopathological features and prognosis of young patients (18-40 years old) with non-clear cell renal cell carcinoma (nccRCC) treated in a single center to provide reference for the diagnosis and treatment of similar patients. 【Methods】 Clinical data of 113 nccRCC patients treated during Jan. 2012 and Aug. 2022 were retrospectively analyzed, including 57 males (50.4%) and 56 females (49.6%). The average age of onset was (31.6±5.8) years. Among all patients, 57 had lesions (50.4%) on the left side, and 56 (49.6%) on the right side. Young patients undergoing renal cancer surgery accounted for approximately 12.4% of the total number of renal cancer patients undergoing surgery, and nccRCC accounted for 34.8% of the total number of cases. 【Results】 Minimally invasive surgery (laparoscopic or robot-assisted) was performed in 102 cases (90.3%), and open surgery in 11 cases (9.7%). Fifty-five cases (48.7%) underwent partial nephrectomy and 58 (51.3%) radical nephrectomy. Among them, 11 patients (9.7%) developed tumor thrombi. All surgeries were successful with no serious complications. The pathological types included 32 cases (28.3%) of chromophobe renal cell carcinoma, 25 cases (22.1%) of MiT family translocation renal cell carcinoma, and 20 cases (17.7%) of papillary renal cell carcinoma. The total proportion of the three pathological subtypes reached 68.1%. After 46 (2-115) months of follow-up, 8 cases (7.8%, 8/102) developed tumor metastasis and 2 died. 【Conclusion】 The nccRCC is rare in young patients. The major pathological type is chromophobe, and the major treatment method is minimally invasive surgery. Most pathological types have good long-term prognosis, while patients with tumor thrombi have a high risk of metastasis and poor prognosis.

Construction of a prognostic model and drug prediction for clear cell renal cell carcinoma based on endoplasmic reticulum stress-related lncRNA / 现代泌尿外科杂志

【Objective】 To construct a prognostic model of clear cell renal cell carcinoma (ccRCC) based on endoplasmic reticulum stress (ERS)-related long non-coding ribonucleotides (lncRNA),so as to explore the correlation between immune cell infiltration and prognosis of ccRCC patients,and to search for new drugs for the treatment of ccRCC. 【Methods】 The transcriptome and clinical data of cancerous and paracancerous tissues of ccRCC were obtained from the TCGA database.The ERS-associated gene set was obtained from the MSigDB database.ERS co-expressed lncRNAs were screened with Pearson correlation analysis.ERS-related lncRNA (ERSRL) with prognostic significance were screened with Lasso regression,univariate and multivariate Cox regression analyses,and a prognostic model was constructed.The risk value of each sample was calculated according to the prognostic model formula.The patients were divided into high- risk and low- risk groups for survival difference analysis.The predictive performance of the prognostic model was evaluated with survival curve,receiver operating characteristic (ROC) curve and calibration curve.The infiltration of immune cells in high-and low-risk groups was analyzed with CIBERSORT database.The relationship between ERSRL and drug sensitivity was analyzed with GDSC database to identify drugs with potential efficacy against ccRCC. 【Results】 A total of 9 lncRNAs with independent prognostic significance were screened to construct the prognostic model.Kaplan-Meier analysis showed significant survival differences between the high- and low-risk groups.Univariate and multivariate Cox regression analyses showed that age,grade,stage and risk score could be used as independent prognostic factors.The area under the ROC curve (AUC) of the 1-,3-,and 5-year survival rates of the training set were 0.754 (95%CI:0.659-0.848),0.744 (95%CI:0.667-0.815),and 0.759 (95%CI:0.662-0.820),respectively,and the C-index was 0.777 (95%CI:0.759-0.796).Immune infiltration results showed that plasma cells,activated memory CD4+T cells,regulatory T cells,M0 macrophages,and activated mast cell infiltration levels were higher in the high-risk group than those in the low-risk group.Drug susceptibility analysis identified 12 drugs with potential curative effects on ccRCC,including AZD8055. 【Conclusion】 Based on 9 ERSRLs,a prognostic model for ccRCC patients was constructed,and 12 drugs with potential therapeutic effects were screened,including AZD8055.

Differential value of CT radiomics in papillary renal cell carcinoma and clear cell renal cell carcinoma / 实用放射学杂志

Objective To construct a radiomics nomogram combining clinical and a radiomics signature for distinguishing type Ⅱpapillary renal cell carcinoma(pRCC)from atypical clear cell renal cell carcinoma(ccRCC).Methods Clinical and CT data of patients with pathologically confirmed type Ⅱ pRCC(62 cases)and atypical ccRCC(56 cases)were analyzed.A random sample was divided into a training set(82 cases)and a test set(36 cases)in a ratio of 7∶3.Clinical factors were screened to construct clinical factor models.A total of 1 595 radiomics features of tumors were extracted from the corticomedullary phase CT images and based on the most effective features to construct a radiomics signature and calculate the radiomics score(Rad-score).A radiomics nomogram was constructed by combining the Rad-score and independent clinical factors.Receiver operating characteristic(ROC)curve was used to assess the clini-cal usefulness of the models.Decision curve analysis(DCA)was used to assess the difference between the models.Results The radiomics signature showed good discrimination in training set area under the curve(AUC)0.894[95％confidence interval(CI)0.834-0.947]and test set AUC 0.879(95％CI 0.774-0.963).The AUC of the clinical factors model in training set and test set were 0.725(95％CI 0.646-0.804)and 0.698(95％CI 0.567-0.819).The AUC of the radiomics nomogram in training set and test set were 0.901(95％CI 0.840-0.953)and 0.901(95％CI 0.809-0.975).DCA demonstrated the radiomics nomogram outmatched the clinical factors model and radiomics signature in the aspects of clinical usefulness.Conclusion Radiomics nomogram based on enhanced CT can provide good prediction of type Ⅱ pRCC and atypical ccRCC preoperatively,improve the diagnostic accuracy and provide guidance for future clinical treatment.

The correlation between preoperative MR imaging features of clear cell renal cell carcinoma and the incidence of metastasis / 实用放射学杂志

Objective To investigate the correlation between preoperative MR imaging features and the incidence of tumor metastasis in clear cell renal cell carcinoma.Methods The clinical and preoperative MR imaging data of 64 patients with clear cell renal cell carcinoma were analyzed retrospectively.According to the occurrence of metastasis,the patients were divided into non-metastasis group(n=42)and metastasis group(n=22).The clinical and imaging features of the two groups were analyzed with univariate analysis and multivariate logistic regression.Results The results of the univariate analysis showed that among the clinical and preoperative MR imaging data,there was no significant difference between the two groups in gender,tumor location and intra-tumoral cystic changes(P>0.05),but the patient's ages,clinical symptoms,tumor sizes,necrosis,capsule breakthrough,low signal nodules in T2WI,venous thrombosis,TNM stages,and Fuhrman grades were significantly different between two groups(P<0.05).Multivariate logistic regression analysis showed that low signal nodules in T2WI was an independent predictor of metastasis of clear cell renal cell carcinoma(P=0.028).Combined with diffusion weighted imaging(DWI)sequence,the average apparent diffusion coefficient(ADC)in related areas was measured.The ADC value of low signal nodules area was(0.541±0.101)×10-3 mm2/s in the metastasis group,and the ADC value of non-low signal nodules area was(0.972±0.113)×10-3 mm2/s(P<0.001).Conclusion The metastasis of clear cell renal cell carcinoma is often accompanied by low signal nodules in T2WI in tumors.Combined with the lower ADC value,they can be used as the characteristic imaging features to effectively evaluate the risk of metastasis of clear cell renal cell carcinoma.

Relationship between serum miR-21 and miR-27b levels and prognosis of patients with renal clear cell carcinoma / 实用医学杂志

Objective To explore the relationship between serum miRNA-21 and miR-27b levels and prognosis of patients with renal clear cell carcinoma.Methods A total of 118 patients with renal clear cell carcinoma admitted to the Qinghai University Hospital from February 2019 to April 2021 were selected as the study subjects,and another 118 healthy patients in the same period as the control group.Real time fluorescence quantitative polymerase chain reaction(PCR)was used to detect the expression of miR-21 and miR-27b in the serum of all subjects.The relative expression levels of serum miR-21 and miR-27b between the patients with renal clear cell carcinoma and healthy control patients were compared.The expression and correlation of serum miR-21 and miR-27b in the patients with renal clear cell carcinoma of different pathological stages and Fuhrman grading were analyzed.The relationship between the expression of serum miR-21 and miR-27b and the survival and prognosis of the patients was explored as well.Results The expression levels of serum miR-21 and miR-27b in the patients with renal clear cell carcinoma were higher than those in the healthy control group(P＜0.05).The serum miR-21 expression level in stage Ⅲ patients was higher than in stageⅠ(P＜0.05),while the serum miR-21 expression level in the stage Ⅳ patients was higher than that in stagesⅠ,Ⅱ,and Ⅲ(P＜0.05).The expression level of miR-27b in the serum of patients gradually increased across the four stages,with a significant difference(P＜0.05).The pathological staging was positively correlated with the expression of miR-21 and miR-27b(P＜0.001).The expression levels of miR-21 and miR-27b in serum of patients gradually increased across grades Ⅰ,Ⅱ and Ⅲ by Fuhrman grading,with significant difference(P＜0.05).Fuhrman grading was positively correlated with the serum miR-21 and miR-27b expression(P＜0.001).There was a statistically significant difference in the survival curve between the miR-21 high expression group and the low expression group(P＜0.05).There was a statistically significant difference in the survival curve between the high expression group and the low expression group of miR-27b(P＜0.05).Conclusion The expression levels of serum miR-21 and miR-27b in patients with renal clear cell carcinoma is indicative of the progression and prognosis of the patient's condition.

Pituitary Metastasis of Clear Cell Renal Carcinoma Mimicking Pituitary Macroadenoma ­ Case Report / Metástase de carcinoma renal de células claras em sela túrcica simulando macroadenoma hipofisário ­ Relato de caso

Introduction Pituitary tumors account for 25% of all primary brain tumors and for 15% of overall intracranial expansive masses. Pituitary metastases, in contrast, are a rare condition, estimated as 1.8% of all resected sellar lesions. We present here a rare case of clear cell renal carcinoma metastasis to the pituitary gland. Case Report A 65-year-old patient with holocranial headache and diplopia, whose physical examination showed right eye abduction palsy and ipsilateral anisocoria. Magnetic resonance imaging (MRI) of the pituitary revealed a heterogeneous mass in T1 weighted imaging with mild peripheral contrast enhancement and considerable growth during follow-up. Prolactin levels were high and dropped to normal after use of cabergoline, but remained normal even after the medication was halted. Biopsy was compatible with clear cell renal carcinoma. After surgery, the patient underwent radiotherapy, which was effective in reducing the volume of the lesion. Discussion Only 25 cases of pituitary metastasis arising from the kidney were reported in the literature between the years of 1957 and 2018. Metastases can reach the pituitary through hematogenous spread, cerebrospinal fluid, and contiguous bony lesions. Clinical presentation varies from vague complaints such as fatigue or headache to more specific signs like polyuria and polydipsia, and 60% of cases have clinical manifestations. Conclusion Case reports of pituitary metastases are low worldwide, with only 25 case reports of kidney metastases in over a 60-year period. The rarity of the lesions and hormonal alterations due to pituitary stalk compression can mislead diagnosis, and some patients may even never be diagnosed regarding their lower life span. In this report, radiotherapy was effective postresection, and accounts for a treatment option. All these issues account for the relevance of these case reports.

Introdução Os tumores hipofisários representam 25% de todos os tumores cerebrais primários e 15% das massas expansivas intracranianas totais. As metástases hipofisárias, por outro lado, são uma condição rara, estimada em 1,8% de todas as lesões selares ressecadas. Apresentamos aqui um caso raro de metástase de carcinoma renal de células claras para a glândula pituitária. Relato de caso Paciente de 65 anos com cefaleia holocraniana e diplopia, cujo exame físico mostrou paralisia de abdução do olho direito e anisocoria ipsilateral. A ressonância magnética (RM) da hipófise revelou uma massa heterogênea na imagem ponderada em T1 com leve realce periférico de contraste e crescimento considerável durante o acompanhamento. Os níveis de prolactina estavam altos e caíram para o normal após o uso de cabergolina, mas permaneceram normais mesmo após a interrupção da medicação. A biópsia foi compatível com carcinoma renal de células claras. Após a cirurgia, o paciente foi submetido à radioterapia, que foi eficaz na redução do volume da lesão. Discussão Apenas 25 casos de metástase hipofisária originada do rim foram relatados na literatura entre os anos de 1957 e 2018. As metástases podem atingir a hipófise por meio de disseminação hematogênica, líquido cefalorraquidiano e lesões ósseas contíguas. A apresentação clínica varia de queixas vagas, como fadiga ou dor de cabeça, a sinais mais específicos, como poliúria e polidipsia, e 60% dos casos têm manifestações clínicas. Conclusão Os relatos de casos de metástases hipofisárias são baixos em todo o mundo, com apenas 25 relatos de casos de metástases renais em um período de mais de 60 anos. A raridade das lesões e alterações hormonais devido à compressão do pedúnculo hipofisário podem enganar o diagnóstico, e alguns pacientes podem nunca ser diagnosticados em relação à sua menor expectativa de vida. Neste relato, a radioterapia foi eficaz após a ressecção e representa uma opção de tratamento. Todas essas questões são responsáveis pela relevância desses relatos de caso.

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.

Can CXCL13 be a prognostic marker in clear cell renal cell carcinoma?

Background: CXCL13, B-lymphocyte chemoattractant, has been associated with many diseases and cancers. One of the malignancies that CXCL13 has been investigated is clear cell renal cell carcinomas which are the most common subtype of renal cancers. Aims and Objectives: The aim of this study is to evaluate the immunohistochemical staining patterns of CXCL13 in clear cell renal cell carcinomas and to determine its relationship with pathological tumor stage, risk factors, and prognostic parameters. Materials and Methods: In this study, 99 patients who underwent partial/radical nephrectomy diagnosed with clear cell renal cell carcinoma were included. Four micron sections were taken from paraffin embedded blocks containing sufficient tumor and kidney tissue. Samples were immunohistochemically stained with CXCL13 antibody. During microscopic examination, CXCL13 positive stained cells in ten high magnification fields were counted and evaluated using a semiquantitative H score: 3 × strongly stained + 2 × moderately stained + 1 × weakly stained. The cut-off value was set as 40 for values between 0 and 300. The low and high stained groups were compared with prognostic parameters and risk factors. Statistics: The difference of continuous variables between the two groups was examined with the t test and the distribution of categorical variables with the Chi-square test. A value of P < 0.05 was considered to be statistically significant. Results: The number of lymphocytes stained with CXCL13 in the tumor was higher than in the normal kidney parenchyma (p = 0.07). Intratumoral lymphocytes were highly stained with CXCL13 in 57.5% of pT3 cases and 31.7% of pT1 cases. The amount of intratumoral lymphocytes stained with CXCL13 increased in advanced pathological stages (p = 0.05). Nonsmoking cases were mostly in the low staining group (p = 0.06). Conclusion: The relationship we found between advanced pathological stage and intratumoral CXCL13 staining in our study suggests that CXCL13 has a prognostic value in this cancer.

Clinical characteristics and survival analysis of patients with clear cell papillary renal cell carcinoma based on SEER database / 现代泌尿外科杂志

【Objective】 To evaluate the clinical characteristics and survival of patients with rare clear cell papillary renal cell carcinoma (ccpRCC). 【Methods】 Clinical data of ccpRCC cases treated during 2016 and 2019 were analyzed, clinical characteristics were described, and survival was analyzed using the Kaplan-Meier method. 【Results】 In the SEER database, 191 ccpRCC cases with complete clinical data and positive histology were retrieved, including 112 males (58.7%) and 79 females (41.3%), 136 Grade 1-2 (71.2%) cases and 19 Grade 3-4 (10.0%) cases, 174 stage T1 (91.1%) cases and 17 stage T2-3 (8.9%) cases. Distant metastasis (lung metastasis combined with lymph node involvement and major vein involvement) occurred in one case, and vein tumor thrombosis occurred in two patients. Surgery especially radical nephrectomy and partial nephrectomy was performed in 181 patients (94.8%). One patient died due to recurrence, and 4 due to other causes. The 12-month and 24-month survival were 98.5% and 97.4%, respectively. 【Conclusion】 Patients with ccpRCC have low clinical stage and histological grade, minimal tumor progression and distant metastasis, good prognosis and extremely low disease-specific mortality. Radical nephrectomy and partial nephrectomy have significant therapeutic effects.

Clinicopathological features and prognosis of clear cell papillary renal cell carcinoma / 现代泌尿外科杂志

【Objective】 To investigate the clinicopathological features and prognosis of clear cell papillary renal cell carcinoma (CCPRCC). 【Methods】 The clinicopathological and follow-up data of 40 CCPRCC patients treated during Jun. 2011 and Oct.2021 were retrospectively analyzed. The prognosis was compared with that of 40 cases of clear cell renal cell carcinoma (ccRCC) and 19 cases of papillary renal cell carcinoma (PRCC) treated in the same period. Survival analysis was performed by Log-rank test and Kaplan-Meier survival curves were plotted. 【Results】 Among the 40 patients, 28 were male and 12 were female, aged 31-84 years; 38 cases had unilateral and 2 cases had bilateral tumors; 3 cases had multifocal lesions. All patients received surgery. The maximum diameter of the masses ranged from 3.0 to 95.0 mm, with an average of (27.6±18.1) mm. Pathological grade was Fuhrman 1-2 in all cases. Immunohistochemical tests were positive for CK7 and CA-IX. During the follow-up of 5-129 (average 56) months, 1 case died after bone metastasis, 2 had ipsilateral recurrence, and 1 developed primary esophageal cancer. CCPRCC patients had a significantly better prognosis than CCRCC (P<0.001) and PRCC (P=0.005) patients, while there was no significant difference in the prognosis between CCRCC and PRCC patients (P=0.93). 【Conclusions】 CCPRCC has low malignancy. The diagnosis relies on characteristic pathological and immunohistochemical features. Surgery is an effective treatment. CCPRCC has a better overall prognosis than CCRCC and PRCC.

Effects of immune infiltration-related gene CSAG1 on the progression of renal clear cell carcinoma / 现代泌尿外科杂志

【Objective】 To explore the correlation between CSAG1 expression and the prognosis and tumor-infiltrating lymphocytes in renal clear cell carcinoma (RCCC), and to predict the survival and tumor progression. 【Methods】 The gene expression profiles and clinical information of CSAG1 were downloaded from the Cancer Genome Atlas (TCGA). Based on the differential mRNA expression, GO annotation and KEGG pathway analysis were performed. The relationship between CSAG1 and tumor immune infiltration was assessed with Tumor Immunoassay Resource (Timer 2.0) database. The mRNA expression of CSAG1 in human RCCC specimens was validated with qRT-PCR. 【Results】 CSAG1 expression was significantly higher in RCCC tissues than in normal tissues (P<0.05). The qRT-PCR results revealed that the mRNA level of CSAG1 was consistent with that predicted by bioinformatic analysis. The KEGG analysis and GO annotation indicated high GSAG1 expression in RCCC was related to transmembrane transport, tricarboxylic acid cycle and lysosome. CSAG1 expression was positively related to the infiltration of pDC, aDC, CD8+ T cells, cytotoxic cells, TFH, TH1 cells, Tem, NK CD56dm cells, Treg and T cells, but negatively correlated with macrophage infiltration. 【Conclusion】 CSAG1 may be associated with poor prognosis of RCCC and become a potential immunotherapy target.

Comparison of diagnostic performance of Clear Cell Likelihood Score v1.0 and v2.0 for clear renal cell carcinoma / 南方医科大学学报

OBJECTIVE@#To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM).@*METHODS@#We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient.@*RESULTS@#In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05).@*CONCLUSION@#ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.

Exploratory study of WHO/ISUP classification of renal clear cell carcinoma pre-scholarly prediction based on ultrasonographic radiomics / 中华超声影像学杂志

Objective:To predict the clinical value of World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of clear cell renal cell carcinoma (ccRCC) pre-scholarly based on ultrasound imaging group.Methods:Clinical and ultrasound imaging data of patients with surgically pathologically confirmed ccRCC at Tianjin Medical University Cancer Institue and Hospital from January 2021 to October 2022 were retrospectively collected and divided into a low grade group (grade Ⅰ and Ⅱ, 105 cases) and a high grade group (grade Ⅲ and Ⅳ, 70 cases) using WHO/ISUP pathological grading criteria. The clear image of the largest diameter of the tumor was selected and imported into ITK-SNAP software for manual segmentation of the image and extraction of ultrasonographic radiomics features. The patients were randomly divided into a training group and a test group in the ratio of 7∶3, with 122 cases in the training group and 53 cases in the test group. Stable radiomics features were obtained by dimensionality reduction. The support vector machines (SVM) algorithm was applied to predict the pathological grading of ccRCC. Finally, a clinical-ultrasound imaging model, an ultrasonographic radiomics model and a comprehensive model combining the two were constructed. The predictive effects of the three models were analyzed by the area under the ROC curve (AUC). The performance of each model was evaluated by applying the calibration curve. The net benefit of patients was obtained by applying the decision curve.Results:A total of 873 radiomics features were extracted, and 10 features were finally obtained for model construction after dimensionality reduction. Final test results showed that the AUC, sensitivity, specificity and accuracy of the clinical-ultrasound imaging model were 0.68, 0.47, 0.78, 0.66. The AUC, sensitivity, specificity and accuracy of the ultrasonographic radiomics model were 0.74, 0.53, 0.88, 0.74. The AUC, sensitivity, specificity and accuracy of the comprehensive model were 0.84, 0.63, 0.86, 0.77. The AUC of the comprehensive model being larger than that of the clinical-ultrasound imaging model ( Z=-3.224, P=0.001) and ultrasonographic radiomics model ( Z=-2.594, P=0.009). The calibration curves showed that the comprehensive model was more stable than the other two models. The decision curve showed a higher net clinical benefit for the comprehensive model than for the other two models within a threshold of 0.1-1.0. Conclusions:The preoperative prediction of ccRCC pathological grading by the radiomics model based on ultrasound images is effective. The comprehensive model constructed by combining relevant clinical and ultrasound parameters has better performance, which can help predict ccRCC pathological grading preoperatively to a certain extent. It is crucial to help physicians choose the best management plan in the era of personalized medicine.

Analysis of clinical characteristics of ovarian clear cell carcinoma in perimenopausal women based on ultrasound imaging / 中华老年医学杂志

Objective:To examine the ultrasound images, clinical features, intraoperative conditions, and pathological features of ovarian clear cell carcinoma(OCCC)during perimenopause, in order to improve the early diagnosis of OCCC via ultrasound examination.Methods:A retrospective analysis of 29 patients, aged 42-72(56.8±7.4)years, who were surgically treated and pathologically diagnosed with OCCC at our hospital between 1 September 2015 and 31 December 2022, including 10 in the non-menopausal phase, 3(10.3%)in early menopausal transition, 7(24.1%)in late menopausal transition, and 19(65.5%)in the post-menopausal phase.The number of pregnancies(1.86±1.04)and the number of births(0.97±0.56)were also recorded.Results:In 29 cases, the masses contained solid components, and the ultrasound manifestations were as follows: (1)single-compartment cystic masses(solid components accounted for <50% of the total volume)were found in 11 cases, with clear borders, regular morphology, ground-glass echoes inside the cystic cavity, multiple solid protrusions inside the cystic cavity, and blood flow signals inside the solid components on color Doppler flow imaging(CDFI); (2)multi-compartment cystic masses(solid components accounted for <50% of the total volume)occurred in 8 cases, with largely clear borders, ground-glass echoes inside the cystic cavity, multiple solid protrusions inside the cavity, thick walls where the protrusions were attached, varying thickness of walls separating the cystic cavities, and blood flow signals inside the solid components, walls where there were solid attachments and thicker parts of the separating walls on CDFI; (3)there were 7 cases with predominantly solid cystic masses(the solid components accounted for >50% of the total volume), unclear borders, poor translucency, irregular morphology of the solid components, uneven internal echoes, and blood flow signals in the solid component on CDFI; (4)solid masses(the solid components accounted for >95%of the total volume)were seen in 3 cases with unclear borders, irregular morphology, uneven internal echoes, and a small number of cystic cavities(cystic portion <5%), with poor translucency in the cystic cavities and blood flow signals in the solid components on CDFI.Intraoperative exploration of ascites was performed in 17 cases, and adhesion between the mass and surrounding organs was found in 27 cases.Postoperative pathological results revealed 26 cases with high grade tumors and 3 cases with intermediate grade tumors.There were 3 cases with bilateral OCCC, 13 with left side OCCC and 13 with right side OCCC.According to the FIGO pathological staging system, 12 cases were in stage Ⅰ, 10 in stage Ⅱ, 5 in stage Ⅲ and 2 in stage Ⅳ.Comparison of different pathological stages(early stages Ⅰ and Ⅱ versus late stages Ⅲ and Ⅳ)showed statistically significant differences in the ratio of pathological stages between patients with different ultrasonographic manifestations( χ2=11.163, P<0.05), and the results of two-by-two comparisons showed that OCCC patients with ultrasonographic manifestations of solid masses(solid component accounting for >95%of the total volume)were more often in the late stage at the time of onset, while OCCC patients with a high number of cystic components within the lesions were more likely to be in the early stage at the time of onset.OCCC patients with more cystic components in the lesions tended to have an earlier onset and a better prognosis. Conclusions:When ultrasound imaging shows primarily a single chamber cystic solid mass in a patient in the perimenopausal phase with an endometriosis history, together with signs of specialized examination and pelvic adhesion during transvaginal sonography, a diagnosis of OCCC should be suspected.It is of great significance to pay attention to transvaginal sonography examination, ultrasound image features and clinical symptoms in perimenopausal women for the early diagnosis of OCCC.

Clinicopathological features and prognosis of non-clear cell renal cell carcinoma of pT 3a stage / 中华泌尿外科杂志

Objective:To investigate the clinicopathological characteristics and prognosis of pT 3a stage non-clear cell renal cell carcinoma (nccRCC). Methods:The clinical data of 438 patients with pT 3a stage renal cell carcinoma treated by surgery at Peking University Third Hospital from March 2013 to March 2023 were retrospectively analyzed. Among them, there were 58 cases in the nccRCC group and 380 cases in the clear cell RCC (ccRCC) group. There were statistically significant differences in age, American Society of Anesthesiologists (ASA) classification, and comorbidities between the two groups (all P<0.05). Therefore, propensity score matching was used to adjust the baseline data of the two groups. After matching, there were 58 cases in the nccRCC group and 232 cases in the ccRCC group. There were no statistically significant differences in gender (male/female: 34/24 cases and 165/67 cases), age (53.3±16.8 years and 56.6±11.6 years), ASA classification (1/2/3/4: 19/34/5/0 cases and 60/163/8/1 cases), comorbidities (present/absent: 16/42 cases and 76/156 cases), tumor maximum diameter [6.7 (5.3, 8.4) cm and 5.8 (4.6, 7.8) cm], and nephron sparing surgery(yes/no: 4/54 cases and 15/217 cases) (all P > 0.05). The overall survival (OS) and progression-free survival (PFS) of two groups were compared, the Kaplan-Meier method was employed to plot survival curves. Cox proportional hazards regression model was used to analyze the relationship between different pT 3a characteristics in the nccRCC group and progression-free survival. Results:In the matched cohort, the median follow-up time for the nccRCC group and ccRCC group were 28.0 (16.3, 45.3) months and 31.0 (18.0, 57.0) months, respectively. The pathological types in the nccRCC group included chromophobe renal cell carcinoma (20 cases, 34.5%), papillary renal cell carcinoma (20 cases, 34.5%), Xp11.2 translocation renal cell carcinoma (8 cases, 13.8%), mucinous tubular and spindle cell carcinoma (3 cases, 5.2%), and other or unclassified renal cell carcinoma (7 cases, 12.1%). There was no statistical significance between the nccRCC and ccRCC groups in terms of invasion of the renal vein without involvement of the vein wall (yes/no: 5/53 cases and 41/191 cases), vascular invasion (yes/no: 18/40 cases and 52/180 cases), invasion of the perirenal fat (yes/no: 15/43 cases and 39/193 cases), invasion of the renal pelvis and sinus (yes/no: 51/7 cases and 200/32 cases), or sarcomatoid differentiation (yes/no: 2/56 cases and 4/228 cases)(all P > 0.05). However, there was a statistically significant difference in lymph node involvement (yes/no: 3/229 cases and 9/49 cases, P < 0.01). The 5-year PFS and OS of nccRCC group were 67% (95% CI 52%-86%) and 70% (95% CI 55%-89%) respectively. While the 5-year PFS and OS of ccRCC group were 78% (95% CI 70%-86%) and 87% (95% CI 81%-93%) respectively. There was no statistically significant difference in PFS between the two groups ( P>0.05), but there was a statistically significant difference in OS ( P<0.01). Furthermore, within specific pathological types, the 5-year PFS and OS rates of chromophobe renal cell carcinoma were 88% (95% CI 67%-100%) and 86% (95% CI 63%-100%) respectively, followed by papillary renal cell carcinoma with 5-year PFS of 55% (95% CI 33%-91%) and 5-year OS of 65% (95% CI 44%-97%), and Xp11.2 translocation renal cell carcinoma with 5-year PFS of 38% (95% CI 9%-100%) and 5-year OS of 43% (95% CI 10%-100%). The difference in PFS and OS between ccRCC, chromophobe renal cell carcinoma, papillary renal cell carcinoma, and Xp11.2 translocation renal cell carcinoma was statistically significant ( P<0.01). In addition, the multivariate Cox regression analysis revealed that the independent risk factor for PFS in nccRCC patients is the invasion of the renal vein without venous wall involvement ( HR = 8.0, 95% CI 1.8-36.2, P<0.01). Conculsions:Compared to ccRCC, pT 3a nccRCC is more prone to lymph node metastasis. Among them, papillary renal cell carcinoma and Xp11.2 translocation renal cell carcinoma have a poorer prognosis, resulting in an overall lower survival period for pT 3a nccRCC patients. Among different pT 3a characteristics, invasion of the renal vein without invading the vein wall is an independent risk factor for PFS in nccRCC patients.

LNX1 inhibits the proliferation,invasion and migration of renal clear cell carcinoma cells by regulating TIAM1/ERK signaling pathway / 肿瘤

Objective:To investigate the effect of ligand of numb-protein X1(LNX1)on the proliferation,invasion and migration of renal clear cell carcinoma cells and its underlying molecular mechanism. Methods:Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the mRNA expression level of LNX1 in renal clear cell carcinoma tissues and its relationship with the prognosis of patients with renal clear cell carcinoma.LNX1 gene specific shRNA(shLNX1)was delivered into renal clear cell carcinoma cell lines 786-O and ACHN by lentiviral infection,and flag-LNX1 plasmid was delivered into 786-O and ACHN cells by transient transfection.CCK-8 assay and colony formation assay were used to assess the effects of LNX1 silencing or overexpression on the proliferation of 786-O and ACHN cells.Transwell assay was used to evaluate the effects of LNX1 silencing or overexpression on the invasion and migration of 786-O and ACHN cells.Bioinformatics analysis was used to screen the downstream target genes of LNX1.Western blotting was used to examine the effects of LNX1 silencing or overexpression on the expression level of T-lymphoma invasion and metastasis-inducing protein 1(TIAM1)as well as the expression levels of total and phosphorylated ERK(phospho-ERK,p-ERK)in the ERK signaling pathway downstream of TIAM1 in 786-O and ACHN cells.786-O and ACHN cells overexpressing LNX1 were treated with proteasome inhibitor MG132,and the protein expression level of TIAM1 was analyzed by Western blotting.Finally,myc-TIAM1 recombinant plasmid was transfected into LNX1-overexpressing cells.Then,the expression levels of proteins in the ERK signaling pathway and the abilities of proliferation,invasion and migration of 786-O and ACHN cells were examined by Western blotting,colony formation assay and Transwell assay,respectively. Results:The mRNA expression level of LNX1 in renal clear cell carcinoma tissue was decreased(P＜0.05)and was positively correlated with the survival time of patients with renal clear cell carcinoma(P＜0.001).LNX1-silencing 786-O and ACHN cells and LNX1-overexpressing 786-O and ACHN cells were constructed successfully.After LNX1 silencing,the proliferation,invasion and migration of 786-O and ACHN cells were significantly enhanced(all P＜0.05).After LNX1 overexpression,the abilities of proliferation,invasion and migration of 786-O and ACHN cells were significantly decreased(all P＜0.05).Bioinformatics analysis identified TIAM1 as a potential target of LNX1.After silencing LNX1,the protein expression levels of TIAM1 and p-ERK were significantly increased(all P＜0.05),while the expression level of ERK remained unchanged.After LNX1 overexpression,the protein expression levels of TIAM1 and p-ERKwere significantly decreased(all P＜0.01),while the expression level of ERK was unchanged.Treatment with proteasome inhibitor MG132 increased the protein expression level of TIAM1 in LNX1-overexpressing 786-O and ACHN cells(P＜0.01 and P＜0.001).After LNX1-overexpressing cells were transfected with myc-TIAM1 plasmid,the protein expression level of p-ERK was increased,the abilities of cell proliferation,invasion and migration were enhanced(all P＜0.05),and the expression level of ERK protein remained unchanged. Conclusion:LNX1 inhibits the proliferation,invasion and migration of renal clear cell carcinoma cells by degrading TIAM1 which further regulates the phosphorylation of ERK.

Mechanism of nuclear protein 1 in the resistance to axitinib in clear cell renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To explore the potential mechanism of resistance to axitinib in clear cell renal cell carcinoma (ccRCC), with a view to expanding the understanding of axitinib resistance, facilitating the design of more specific treatment options, and improving the treatment effectiveness and survival prognosis of patients.@*METHODS@#By exploring the half maximum inhibitory concentration (IC50) of axitinib on ccRCC cell lines 786-O and Caki-1, cell lines resistant to axitinib were constructed by repeatedly stimulated with axitinib at this concentration for 30 cycles in vitro. Cell lines that were not treated by axitinib were sensitive cell lines. The phenotypic differences of cell proliferation and apoptosis levels between drug resistant and sensitive lines were tested. Genes that might be involved in the drug resistance process were screened from the differentially expressed genes that were co-upregulated in the two drug resistant lines by transcriptome sequencing. The expression level of the target gene in the drug resistant lines was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The expression differences of the target gene in ccRCC tumor tissues and adjacent tissues were analyzed in the Gene Expression Profiling Interactive Analysis (GEPIA) public database, and the impact of the target gene on the prognosis of ccRCC patients was analyzed in the Kaplan-Meier Plotter (K-M Plotter) database. After knocking down the target gene in the drug resistant lines using RNA interference by lentivirus vector, the phenotypic differences of the cell lines were tested again. WB was used to detect the levels of apoptosis-related proteins in the different treated cell lines to find molecular pathways that might lead to drug resistance.@*RESULTS@#Cell lines 786-O-R and Caki-1-R resistant to axitinib were successfully constructed in vitro, and their IC50 were significantly higher than those of the sensitive cell lines (10.99 μmol/L, P < 0.01; 11.96 μmol/L, P < 0.01, respectively). Cell counting kit-8 (CCK-8) assay, colony formation, and 5-ethynyl-2 '-deoxyuridine (EdU) assay showed that compared with the sensitive lines, the proliferative ability of the resistant lines decreased, but apoptosis staining showed a significant decrease in the level of cell apoptosis of the resistant lines (P < 0.01). Although resistant to axitinib, the resistant lines had no obvious new replicated cells in the environment of 20 μmol/L axitinib. Nuclear protein 1 (NUPR1) gene was screened by transcriptome sequencing, and its RNA (P < 0.0001) and protein expression levels significantly increased in the resistant lines. Database analysis showed that NUPR1 was significantly overexpressed in ccRCC tumor tissue (P < 0.05); the ccRCC patients with higher expression ofNUPR1had a worse survival prognosis (P < 0.001). Apoptosis staining results showed that knockdown ofNUPR1inhibited the anti-apoptotic ability of the resistant lines to axitinib (786-O, P < 0.01; Caki-1, P < 0.05). WB results showed that knocking downNUPR1decreased the protein level of B-cell lymphoma-2 (BCL2), increased the protein level of BCL2-associated X protein (BAX), decreased the protein level of pro-caspase3, and increased the level of cleaved-caspase3 in the resistant lines after being treated with axitinib.@*CONCLUSION@#ccRCC cell lines reduce apoptosis through theNUPR1 -BAX/ BCL2 -caspase3 pathway, which is involved in the process of resistance to axitinib.