Síndrome de Birt-Hogg-Dubé: afectación pulmonar en 2 casos / Birt-Hogg-Dubé Syndrome: Lung Involvement in 2 Cases

RESUMEN El síndrome de Birt-Hogg-Dubé es una rara enfermedad autosómica dominante cau sada por la mutación patogénica del gen de la foliculina, que se expresa principal mente en tres órganos que incluyen el pulmón, la piel y el riñón, y produce quis tes pulmonares, tumores renales y cutáneos. Desde el punto de vista respiratorio es poco sintomática, pero los quistes presentan alto riesgo de neumotórax, por lo que es imprescindible realizar una adecuada semiología radiológica de los quistes para un diagnóstico oportuno. Los tumores más importantes son los renales porque incluyen varios tipos de carcinomas renales; debido a esto requieren seguimiento estricto y, en muchos, casos cirugía. Presentamos dos casos de pacientes con este síndrome; uno confirmado por la mutación genética y el otro, por la confirmación histológica de fibrofoliculoma, ambos criterios mayores para el diagnóstico de esta enfermedad. Es fundamental el diagnóstico temprano de esta entidad de acuerdo con lo expuesto an teriormente, por lo que hacemos esta revisión con una amplia discusión sobre la afec tación pulmonar, la semiología radiológica de los quistes y los criterios diagnósticos.

ABSTRACT The Birt-Hogg-Dubé syndrome is a rare autosomal dominant disease caused by the pathogenic mutation of the folliculin gene, which is mainly expressed in three organs that include the lung, the skin and the kidney, and produces lung cysts, and renal and skin tumors. From the respiratory point of view, it doesn't have many symptoms, but cysts have high risk of pneumothorax, so it is indispensable to carry out the correct radiological semiology of the cysts for a timely diagnosis. The most important tumors are the renal, because they include several types of renal carcinomas; that is why they require strict follow-up and, in many cases, surgery. We present two cases of patients with this syndrome: one confirmed by the genetic mutation, and the other one by the histological confirmation of fibrofolliculoma, both major criteria for the diagnosis of this disease. The early diagnosis of this entity is of fundamental importance, according to what has been previously presented, so we conduct this review with a broad discus sion about lung involvement, the radiological semiology of the cysts, and diagnostic criteria.

A multicenter retrospective study of immunotherapy for metastatic renal cell carcinoma / 中华泌尿外科杂志

Objective:To evaluate the efficacy and side effects of PD-1 monoclonal antibody in the treatment of advanced metastatic renal cell carcinoma in China.Methods:The clinical data of 117 patients with advanced metastatic renal cell carcinoma (mRCC) treated with PD-1 monoclonal antibody from October 2016 to February 2022 were retrospectively analyzed. There were 87 males (74.4%) and 30 females (25.6%), with an average age of (57.9±10.9) years old, BMI of (23.6±3.4) kg/m 2and smoking history of 79 (67.5%). There were 44 cases (37.6%) with hypertension, 19 (16.2%) cases of diabetes. The ECOG score of 59.8% (70/117) patients was 0, 33.3% (39/117) was 1, 4.3% (5/117) was 2, and 2.5% (3/117) was 3. The pathological type of 104 cases were renal clear cell carcinoma (ccRCC), 8 cases of papillary renal cell carcinoma, 2 cases of chromophobe cell carcinoma, 2 cases of collecting duct carcinoma and 1 case of eosinophilic cell carcinoma. The general condition of the overall population and the overall survival (OS) of relevant subgroups were analyzed. Secondary goals included progression free survival (PFS), objective response rate (ORR), adverse reactions, overall survival (OS), and progression free survival (PFS). Results:65.8% (77 / 117) of the patients chose targeted combined with PD-1 monoclonal antibody in the first-line treatment. The main targeted drugs were acitinib (81.8%, 63 / 77), tirelizumab (37.6%, 29 / 77) and cindilimab (25.9%, 20 / 77). After first-line treatment, 19.6.1% (23 / 117) patients needed to be converted to second-line treatment, and 15 patients changed the type of PD-1 antibody during treatment. In addition, the targeted drug of combined therapy was replaced by acitinib in 8 patients. The main causes of drug withdrawal were disease progression (70.7%, 29 / 41) and death (29.2%, 12 / 41). The median OS of the overall population was 35.6 (19-60) months and PFS was 12.1 (1-60) months. The ORR of the overall population was 47.8% (56 / 117). 4.2% (5/117) patients had complete remission, another 17.0% (20/117) patients were in stable condition, and 43.5% (51 / 117) patients were in partial remission. In the first-line treatment, the median PFS time of targeted combined with PD-1 monoclonal antibody was 12.6 (1-30) months, the median PFS time of PD-1 single drug immunotherapy was 10.5 (1-60) months. In the second-line treatment, the PFS of patients treated with PD-1 monoclonal antibody was 10.1 (4-19) months, and that of patients treated with PD-1 monoclonal antibody combined with targeted therapy was 11.7 (1-25) months. The most common adverse reactions were elevated blood pressure (18.5%, 23 / 124), followed by hypothyroidism (15.3%%, 19/124), rash (14.5%, 18 / 124), elevated transaminase (10.5%, 13 / 124) and bone marrow suppression (9.7%, 12/124). 9.4% (11 / 117) patients needed to reduce the related adverse reactions by interrupting the treatment control of PD-1 monoclonal antibody.Conclusions:The safety and efficacy of PD-1 monoclonal antibody in domestic patients are better, and the side effects are less. The efficacy and safety of PD-1 monoclonal antibody combined with targeted therapy in the real world population are consistent with many key clinical trials abroad. PD-1 monoclonal antibody combined with targeted drugs can be popularized in the domestic MRCC population.

The correlation of intratumoral fibrosis with the prognosis of clear cell renal cell carcinoma / 中华泌尿外科杂志

Objective:To investigate the correlation of intratumoral fibrosis with the prognosis of clear cell renal cell carcinoma (ccRCC).Methods:The correlation of the transcriptional expression of the primary collagen with the prognosis in ccRCC was evaluated using the Cancer Genome Atlas (TCGA) database, including 530 ccRCC patients with complete information. Of them, 344 cases were male, 186 cases were female. The age of 264 cases was ≤ 60 years, and the age of 266 cases was > 60 years. The pathology grade of 241 patients was G 1-2 grade, and the pathology of 281 cases were G 3-4 grade, 8 cases were undetermined grade. There were 322 cases with AJCC stage Ⅰ-Ⅱ and 205 cases with AJCC stage Ⅲ-Ⅳ, and 3 cases with undetermined stage. There were 420 cases in M 0 and 78 cases in M 1, and 32 cases without distant metastases information. Furthermore, the paraffin sections of 158 non-cystic ccRCC patients confirmed by pathology from November 2005 to November 2017 were further used to evaluate the level of collagen of ccRCC and the status of the pseudocapsule by the Masson staining, Sirius red staining and multicolor immunofluorescence staining of collagen Ⅰ and collagen Ⅲ. Of them, 112 cases were male, 46 cases were female. There were 100 cases with age ≤ 60 years, and 58 cases with age > 60 years. The pathology grade of 111 cases were G 1-2, and the pathology grade of 47 cases were G 3-4. There were 144 cases with AJCC stage Ⅰ-Ⅱ, 14 cases with AJCC stage Ⅲ-Ⅳ. Kaplan-Meier survival curve were used to analyze the relationship between tumor collagen parameters and the overall survival prognosis of patients with ccRCC. Results:The transcriptome results of the TCGA database indicated that the expression level of COL1A1 in ccRCC tissues was significantly higher than that in adjacent normal tissues ( P<0.001). The high expression of collagen suggested a worse overall survival prognosis ( HR=1.165, P=0.002). In addition, the high ratio of COL1A1/COL3A1 indicated a worse overall survival prognosis ( HR=1.901, P<0.001) compared with the low ratio. We further confirmed that the abundance of collagen in tumor was significantly increased compared with the normal adjacent tissues by the Masson staining [41.0 (14.0-75.0) vs.15.0 (3.0-57.0), P<0.001] and the Sirius red staining [42.5 (10.0-90.0) vs.10.0 (2.5-60.0), P<0.001] on 30 ccRCC tissues and adjacent normal tissues. Based on the Masson staining, we found that high collagen abundance in tumor tissue was associated with more G 3-4 grade of tumor compared with low collagen abundance (38.5% vs.21.3%, OR=2.316, 95% CI 1.146-4.681, P=0.023). Kaplan-Meier survival curve showed that higher collagen abundance was associated with a worse overall survival prognosis in ccRCC ( HR=2.630, P=0.007). However, incomplete fibrous pseudocapsule was associated with a worse overall survival prognosis ( HR=11.140, P<0.001). Conclusions:In ccRCC, intratumoral collagen fiber level was overexpressed. High intratumoral collagen level and incomplete fibrous pseudocapsule may indicate a poor overall survival prognosis.

Advance in renal cell carcinoma in 2022 ASCO-GU / 中华泌尿外科杂志

ASCO-GU is one of the landmark meetings of urogenital cancer. Within 2022 meeting, the extended follow up result of adjuvant pembrolizumab after nephrectomy in renal cell carcinoma as well as the efficacy and safety of neoadjuvant Axitinib and avelumab for local advanced renal cell carcinoma have been released. There were also explorations in local therapy for oligometastasis, novel combination system therapy and regiments alterations. The further research protocol of immunostimulatory IL-2 cytokine prodrug and PARP inhibitor for metastatic RCC were also disclosed.

The research progress in the treatment of advanced sarcomatoid renal cell carcinoma / 中华泌尿外科杂志

Sarcomatoid renal cell carcinoma is a highly malignant tumor with sarcomatoid dedifferentiation, which has rapid progression, high mortality rate and poor prognosis. Studies have shown that cytoreductive surgery, chemotherapy or targeted therapy are not effective to patients with advanced sarcomatoid renal cell carcinoma. With the further study of pathogenesis and molecular biological characteristics of sarcomatoid renal cell carcinoma, it is found that the expression levels of PD-1 and PD-L1 in it are higher than those of other subtypes, so the combination of immune checkpoint inhibitors and immunotherapy combined with targeted therapy have become the first-line therapy. This article mainly reviews the latest treatments for advanced sarcomatoid renal cell carcinoma, including surgery, chemotherapy, targeted drugs, immunotherapy and so on.

Clinicopathologic features and prognosis of Xp11.2/TFE3 gene fusion associated renal cell carcinoma in adults / 中华泌尿外科杂志

Objective:To investigate the clinicopathological features and prognosis of adult Xp11.2/TFE3 gene fusion-associated renal cell carcinoma (TFE3 RCC).Methods:The clinical data of 55 patients with TFE3 RCC admitted to the First Affiliated Hospital of Zhejiang University Medical College from January 2013 to February 2021 were retrospectively analyzed, including 26 males and 29 females. The patients’ mean age was (40.6 ± 14.7) years. The median tumor size was 4.0 (1.9-20.0) cm. Tumors were located in the left kidney in 30 cases (54.5%) and the right kidney in 25 cases (45.5%). Preoperative imaging assessment was well-circumscribed in 41 patients (74.5%) and ill-defined in 14 patients (25.5%). There were 2 cases of regional lymph node metastasis and 2 cases of distant metastasis, including 1 case of lung metastasis and 1 case of bone metastasis. Preoperative staging included stage I in 38 patients (69.1%), stageⅡ in 5 patients (9.1%), stage Ⅲ in 9 patients (16.4%), and stageⅣin 3 patients (5.5%). Nephron-sparing surgery was performed in 31 patients (56.4%) and radical nephrectomy in 24 patients (43.6%). Progression-free survival curves were plotted by the Kaplan-Meier method and analyzed by the log-rank test. Cox proportional hazards regression model was applied for multivariate analysis of factors influencing progression-free survival.Results:Postoperative pathological stage included pT 1 in 41 patients (74.5%), pT 2 in 5 patients (9.1%), pT 3 in 8 patients (14.5%), and pT 4 in 1 patient (1.8%). Four patients (7.3%) had N 1 stage and 2 (3.6%) had M 1 stage. After immunohistochemical analysis, TFE3 showed diffuse strong positive reaction in 55 patients, cathepsin K positive in 36 patients (65.5%), CD10 positive in 48 patients (87.3%), CK7 positive in 7 patients (12.7%), CA-IX positive in 2 patients (3.6%), and PAX8 positive in 35 patients (63.6%). Two cases were tested by fluorescent in situ hybridization (FISH), and the results were positive. The proportion of nuclei with mitotic signals was 40% and 30%, respectively. The median follow-up time was 27 (3-96) months. The results of survival analysis showed that the 3-year and 5-year progression-free survival rates were 80.0% and 64.0%, respectively. The results of univariate analysis showed that tumor size ( P = 0.009), pT stage ( P<0.001), regional lymph node invasion ( P = 0.003), and surgical approach ( P = 0.006) were associated with the prognosis of TFE3 RCC patients. Multivariate analysis of the Cox model was performed on significant univariate factors, and its results showed that pT stage ( HR=4.824, 95% CI 1.129-20.604, P=0.034) and regional lymph node invasion ( HR=5.522, 95% CI 1.066-28.611, P = 0.042) were independent prognostic factors for progression-free survival in TFE3 RCC patients. The results of stratified analysis showed that for patients with pT 1 disease, the effect of surgical approach on the prognosis of patients was not statistically significant ( P=0.091). The 3-year progression-free survival rates for nephron-sparing surgery and radical nephrectomy were 94.7% and 81.5%, respectively. Conclusions:Given that TFE3 RCC imaging studies often lack characteristic features, diagnosis mainly relies on immunohistochemical analysis and FISH tests. Most of the patients with TFE3 RCC have a better prognosis after surgical treatment. However, pT stage and regional lymph node invasion were prognostic factors in patients with TFE3 RCC.

The correlation analysis of preoperative platelet parameters with the clinicopathological features of renal cell carcinoma / 中华泌尿外科杂志

Objective:To investigate the correlation between preoperative platelet parameters and clinicopathological features of renal cell carcinoma.Methods:The data of 452 patients with renal cell carcinoma treated in the Peking University Third Hospital from January 2015 to December 2016 were retrospectively analyzed, including 308 males and 144 females, and the mean age was 56.5(15-86) years. There were 178 cases, 72 cases, and 42 cases combined with hypertension, diabetes, and coronary heart disease, respectively. Preoperative platelet parameters were the mean PLT of 218.56(72-568)×10 9/L, MPV of 9.65(6.2-20.5)fl, PDW of 14.44(7.9-23.1) fl, and PCT of 20.72%(8%-49%). The data of 253 patients with simple renal cysts were selected as the controls, including 140 males and 113 females, and the mean age was 58(9-84) years. There were 178 cases, 72 cases, and 42 cases combined with hypertension, diabetes, and coronary heart disease, respectively. Preoperative platelet parameters were the mean PLT of 207.08(84-362)×10 9/L, MPV of 9.50(6.9-13.9)fl, PDW of 14.59(8.9-21.6)fl, and PCT of 19.49%(9%-36%). Propensity score matching method was used to balance the baseline differences between the two groups, and the differences of platelet parameters between the two groups were compared. The correlation between different clinicopathological characteristics of renal cell carcinoma and platelet parameters was analyzed. Multivariate logistic regression model was used to explore the risk factors of renal cell carcinoma with lymph node or distant metastasis. Results:After matching the baseline data, PLT( t=1.993, P=0.047) and PCT( t=2.396, P= 0.017) in renal cell carcinoma group were significantly higher than those in controls. Among 452 cases in renal cell carcinoma, there were 395 cases (87.4%) with clear cell renal cell carcinoma and 57 cases (12.6%) with non-clear cell renal cell carcinoma. For pathological stage, there were 325 cases (71.9%) of T 1-T 2 stage and 127 cases (28.1%) of T 3-T 4 stage. In addition, there were 444 cases (98.2%) of N 0 stage, 8 cases (1.8%) of N 1 stage, 428 cases (93.6%) of M 0 stage, and 24 cases (6.4%) of M 1 stage. There were 320 cases of nuclear grade Ⅰ-Ⅱ, 99 cases of nuclear grade Ⅲ-Ⅳ, and 33 cases without nuclear grade. Preoperative high PLT was significantly correlated with T 3-T 4( t=3.409, P=0.001), M 1( t=2.772, P=0.011) and nuclear grade Ⅲ-Ⅳ( t=2.859, P=0.005). Low MPV was significantly correlated with M 1( t=2.981, P=0.003). Low PDW was correlated with T 3-T 4( t=2.567, P=0.011). High PCT was significantly correlated with T 3-T 4( t=2.722, P=0.007) and nuclear grade Ⅲ-Ⅳ( t=3.011, P=0.003). Multivariate logistic regression analysis showed that PLT( OR=1.007, 95% CI 1.002-1.012, P=0.009), clear cell renal cell carcinoma( OR=4.467, 95% CI 1.574-12.679, P=0.005)and nuclear grade Ⅲ-Ⅳ( OR= 5.554, 95% CI 2.399-12.856, P<0.001)were independent risk factors for lymph node or distant metastasis of RCC. Conclusions:PLT and PCT are higher in patients with renal cell carcinoma compared to simple renal cysts. High PLT, PCT, and low MPV, PDW are correlated with the poor clinicopathological characteristics of renal cell carcinoma. Preoperative PLT can be used as an independent risk factor for lymph node or distant metastasis of renal cell carcinoma.

Preoperative Nomogram prediction model for lymph node metastasis in patients with renal cell carcinoma / 中华泌尿外科杂志

Objective:To identify preoperative clinical predictors of positive lymph nodes in patients with renal cell carcinoma (RCC)and provide a preoperative predictive model.Methods:The data of 173 RCC patients who underwent either retroperitoneal lymph node dissection or biopsy at a single institution from January 2016 to December 2020 were retrospectively analyzed. There were 109 males and 64 females, with an average age of (53.29±13.58) years, median tumor diameter of 70 (23-150) mm, 68 patients with local symptoms, 24 patients with systemic symptoms, and 56 patients with ECOG score ≥1. There were 96 patients with tumor pseudocapsule, 23 patients with renal vein or inferior vena cava tumor thrombus, 114 patients in stage T 1-2, 59 patients in stage T 3-4, 22 patients with distant metastasis and 88 patients with lymph node metastasis by preoperative imaging examination. Univariate analysis was performed by Mann-Whitney U test or Chi-square test, and multivariate logistic regression analysis was used to determine preoperative predictors of pathologic lymph node positivity. The significant variables were then included in a novel Nomogram to predict the probability of lymph node invasion.C-index and Bootstrap self-sampling methods were used to evaluate the discrimination and consistency of the model. Results:Of the 173 patients, 49(28.32%)and 124(71.68%)had pN 1 and pN 0 disease, respectively. Among 88 patients with suspected lymph node involvement (cN 1) assessed by preoperative imaging, only 47.73%(42/88) were confirmed to be pathologically positive. However, 8.24% (7/85) of the 85 patients with negative lymph nodes (cN 0) assessed by preoperative imaging were pathologically positive. Age, ECOG score, symptoms at presentation, tumor pseudocapsule, metastasis at diagnosis, clinical tumor stage, clinical nodal status, clinical nodal size, D-dimer, lactate dehydrogenase, microscopic hematuria were significant in the univariate analysis ( P<0.05). On multivariable analyses, the most informative independent predictors were age, clinical tumor stage, clinical nodal status, clinical nodal size and microscopic hematuria ( P<0.05). A Nomogram with good performance was developed to predict the probability of lymph node metastasis. The C-index of the model was 0.954, the calibration curve of forecasting curve with the ideal curve fit was good, indicating that the model has a good consistency. Conclusions:Younger age, microscopic hematuria, suspected lymph node involvement in imaging, larger lymph node diameter and higher T stage were independent risk factors for renal cell carcinoma with lymph node metastasis. The Nomogram based on the above factors has good identification and calibration ability, which can help predict the probability of lymph node metastasis of renal cell carcinoma before surgery.

Monitoring of sunitinib blood concentration and analysis of its safety and efficacy in Chinese patients with metastatic renal cell carcinoma / 中华泌尿外科杂志

Objective:To investigate the safety and efficacy of individualized sunitinib schedule for patients with metastatic renal cell carcinoma (mRCC) according to the monitoring results of plasma drug concentration.Methods:The clinical data of patients with mRCC who received sunitinib treatment in our center from January 2014 to December 2020 were retrospectively analyzed, including 20 patients who underwent monitoring of plasma drug concentration (monitoring group), and 45 patients, matched by propensity score matching, received sunitinib but did not undergo monitoring of plasma drug concentration during the same period (unmonitored group). In the monitoring group, there were 12 males and 8 females. The mean age was 52.9 years, and ECOG score ≤1 in 16 cases (80%). Three patients were in the IMDC favorable-risk group, 15 patients were in the intermediate-risk group, and 2 patients were in the high-risk group. There were 18 cases of clear cell carcinoma and 2 cases of non-clear cell carcinoma, 5 cases of ISUP grade 1-2 and 11 cases of grade 3-4. In the unmonitored group, there were 31 males and 14 females. The mean age was 57.7 years, and 30 patients had ECOG score ≤1, 15 cases ≥2. There were 10 cases in IMDC favorable-risk group, 23 cases in intermediate-risk group, and 12 cases in high-risk group. Thirty-seven cases were clear cell carcinoma and 8 cases were non-clear cell carcinoma, 8 cases were in ISUP grade 1-2 and 28 cases in grade 3-4. There were no statistically significant differences between the two groups in the above parameters ( P>0.05). The monitoring group used the regimen of taking sunitinib for 4 weeks and stopping for 2 weeks (4/2 week) in the first cycle. The blood concentration of sunitinib was monitored before the first cycle and on days 4, 7, 10, 14, 21 and 28, and personalized medication plan was formulated according to the curve of the blood concentration. The 4/2 week scheme was adopted in the undetected monitoring group.The two groups were compared in the incidence of adverse events (AEs), progression-free survival (PFS), overall survival (OS), tumor treatment response and other clinical outcomes. Results:In the monitoring group, 90% (18/20) of patients receiving sunitinib had a steady-state plasma concentration of more than 150ng/ml, of which 10 patients (50%) had a plasma concentration of 150-200 ng/ml and 8 patients (40%) had a plasma concentration of more than 200 ng/ml. Meanwhile, all patients with plasma concentration higher than 150 ng/ml developed severe AEs (grade 3 and above) after treatment. The other two patients' plasma concentration were 100-150 ng/ml, and did not have severe AEs.All patients in the monitoring group received individualized medication schedule adjustment according to the plasma drug concentration and the occurrence point of severe AEs, ensuring that the peak plasma drug concentration was maintained at about 100-150 ng/ml. Among them, 6 patients were changed to take 2 weeks and stop for 1 week (2/1 week schedule), 4 patients were changed to take 10 days and stop for 5 days (10/5 d schedule), 7 patients were changed to take 7 days and stop for 3 days (7/3 d schedule), and 3 patients were changed to take 5 days and stop for 2 days (5/2 d schedule). The incidence of severe AEs significantly decreased from 90% (18/20) to 35% (7/20), and the difference was statistically significant ( P=0.003), while the incidence of grade 3 and higher AEs was 55.6% (25/45) in the standard group, which was statistically significant compared with the incidence of severe AEs before adjustment in the monitoring group ( P=0.006). Further analysis of the efficacy difference between the two groups showed that the overall objective response rate in the monitoring group (40%, 8/20) was higher than that in the standard group (20%, 9/45), although the difference was not statistically significant ( P=0.09). Median PFS and OS were significantly longer in the monitored group than in the standard group (PFS: 23 vs. 10 months, P=0.002; OS: not reached vs.25 months, P=0.005). Conclusions:The bioavailability of sunitinib is high in mRCC patients, which may lead to higher plasma drug concentration, adjustment of medication regimen based on blood concentration monitoring significantly improved patient safety and clinical outcomes. However, further validation by larger-scale, multi-center and prospective studies is needed.

Treatment and prognosis of multiple primary malignant neoplasms complicated with renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate the treatment and prognosis of multiple primary malignant neoplasms (MPMN) complicated with renal cell carcinoma (RCC), and to make risk stratification.@*METHODS@#A retrospective study of 27 cases of MPMN with RCC in two centers, including the different tumors of MPMN, specific treatment methods, and the interval between primary cancers. At the same time, the survival conditions, including recurrence, metastasis and survival, were followed up for statistical analysis. The interval between the two kinds of primary cancer within 6 months was simultaneous MPMNs, and more than 6 months was metachronous MPMNs. For simple risk stratification of cases, as long as one of the MPMNs had a stage Ⅲ or higher malignancy, which was defined as high risk.@*RESULTS@#Among the 27 patients, 20 were male and 7 were female, with age at the time of diagnosis was 42-82 years, with an average age of (61.3±11.7) years. The age at the diagnosis of renal cancer was 43-87 years, with an average age of (66.0±11.3) years. There were 21 cases with duplex primary malignant neoplasms, 4 cases with triple primary malignant neoplasms, and 2 cases with quadruple primary malignant neoplasms. The interval between first cancer and second cancer was 0-360 months, with a median of 18 months. There were 17 cases of metachronous multiple primary malignant neoplasms and 10 cases of simultaneous multiple primary malignant neoplasms. The most common system of MPMN with comorbid RCC involved urologic system, digestive system and respiratory system. The most common locations of MPMN with comorbid RCC were bladder cancer, lung cancer and colon cancer. Follow-up time calcu- lated from the last cancer was 2-156 months, with a median of 32 months. And 14 cases survived and 13 cases died, with 11 cases being tumor related. Tumor stage was the risk factor of prognosis. Any kind of tumor stage in stage Ⅲ or above had a relatively poor prognosis.@*CONCLUSION@#MPMN complicated with RCC is relatively rare. Standard treatment should be used for each cancer type during the treatment process. The prognosis mainly depends on the highest stage of each tumor. Simple risk stratification shows that the prognosis of the high-risk group is worse. This simple stratification method may be helpful to predict the prognosis.

Surgical insights for the management of variant histology in renal cell carcinoma

ABSTRACT Purpose: To review the current literature regarding variant (non-clear) histology of renal cell carcinoma (RCC) and the clinical management of these renal tumors. Material and Methods: A PubMed database search was performed in May 2020 focusing on variant RCC, its diagnosis and associated syndromes, tumor characteristics, and options for management. Results: A broad range of pathological, clinical and diagnostic characteristics amongst non-ccRCC variants were found to have an impact on the overall management of these tumors. The imaging modalities, frequency of surveillance, and timing for intervention were found to be dependent on the type of genetic alterations, type of histology, and tumor growth rates. The timing and type of surgery as well as the systemic therapy are tailored to the specific tumor type and patient. Conclusion: The findings of this review suggest that clinical management should be considered and adjusted for patients with non-ccRCC histological variants based on tumor subtype and genetic alterations.

Dietary and circulating vitamin D and risk of renal cell carcinoma: a meta-analysis of observational studies

ABSTRACT Objective: This meta-analysis is the first to evaluate the associations of circulating and dietary intake of vitamin D with risk of risk of renal cell carcinoma (RCC). Our findings showed that higher circulating vitamin D level and dietary vitamin D intake were associated with a reduced risk of RCC. The possible explanation might be attributed to the anti-inflammatory effect, inhibiting cell proliferation, inducing cell differentiation and apoptosis. Materials and Methods: We searched the MEDLINE, EMBASE, and Scopus databases from their inception points through December 2018 for observational studies. The pooled relative risks (RRs) with corresponding 95% CIs were calculated using random-effects or fixed-effects models. The Newcastle-Ottawa scale was employed to assess the quality of the included studies. Results: A total of 9 publications were included in this meta-analysis. An overall analysis of the highest versus lowest intake levels revealed that circulating vitamin D level was protectively associated with risk of RCC 0.76 (95% CI: 0.64-0.89, P=0.001), with no evidence of heterogeneity (I2=38.8%, P=0.162). In addition, dietary vitamin D intake was associated with a reduced risk of RCC (RR: 0.86; 95% CI: 75-0.99, P=0.030). Statistical heterogeneity was not identified (I2=28.8%, P=0.199). Subgroup analyses results showed the gender differences, and the associations were significant in results with women participants (RR: 0.70; 95% CI: 0.55-0.88) and case-control studies (RR: 0.80, 95% CI: 0.67-0.95). Conclusion: Higher circulating vitamin D level and higher dietary vitamin D intake both might be associated with a reduced risk of RCC. Further high-quality randomized controlled trials are required in the future to confirm our results.

Enfermedad renal crónica y aparición de metástasis posterior a nefrectomía radical y parcial por carcinoma renal de células claras / Chronic kidney disease and clear renal cell carcinoma metastasis following radical or partial nephrectomy

RESUMEN Introducción: El uso de la nefrectomía parcial para el tratamiento del carcinoma de células renales en estadios tempranos se ha convertido en una de las intervenciones preferidas para estos pacientes en la Argentina. Sin embargo, sus resultados en el país a largo plazo aún se desconocen. En este estudio analizamos la progresión a enfermedad renal crónica y aparición de metástasis posterior a nefrectomía parcial y radical, en pacientes con carcinoma de células renales. Material y métodos: Se realizó un estudio de cohorte retrospectivo. Se incluyeron a todos los pacientes con carcinoma renal de células claras en estadio T1 que, entre 2006 y 2012, se sometieron a nefrectomía parcial en nuestro hospital. Se realizó un seguimiento hasta enero del 2018. Resultados: Se incluyeron 32 pacientes (19 con nefrectomía radical y 13 con nefrectomía parcial). Comparado con el grupo de nefrectomía parcial, los individuos sometidos a nefrectomía radical presentaron mayor progresión a enfermedad renal crónica (nefrectomía radical 63,2% vs nefrectomía parcial 15,4%; p=0,007). No existieron diferencias en el tiempo de seguimiento de ambos grupos (nefrectomía radical 69,3 ± 23,8 vs nefrectomía parcial 72,5 ± 26,9 meses; p=0,73). Los sujetos sometidos a nefrectomía radical tuvieron 11 veces mayor riesgo de progresión a enfermedad renal crónica que los de nefrectomía parcial (HR ajustado 11,12, IC95 1,24-99,9; p=0,031) ajustado por los demás factores de riesgo tradicionales. Ningún paciente con estadio T1a presentó metástasis durante todo el seguimiento, independientemente del tipo de cirugía. Conclusión: En nuestro estudio, la nefrectomía parcial preserva mejor la función renal a largo plazo que la nefrectomía radical y tiene un excelente perfil de seguridad oncológico en pacientes con carcinoma de células renales en estadio T1a. La nefrectomía radical fue un factor de riesgo independiente de progresión a enfermedad renal crónica.

ABSTRACT Introduction: Partial nephrectomy to treat early-stage renal cell carcinoma has become one of the surgeries of choice for patients in Argentina. However, long-term results in the country are unknown. In this study, we analyzed the progression to chronic kidney disease and the appearance of metastasis after partial or radical nephrectomy in renal cell carcinoma patients. Methods: A retrospective, cohort study was conducted. We included all patients suffering from T1 stage clear cell renal carcinoma who, between 2006 and 2012, underwent partial nephrectomy in our hospital. Follow-up continued until January 2018. Results: Thirty-two patients were included (19 had undergone radical nephrectomy and 13, partial nephrectomy). Subjects who had radical nephrectomy showed a more rapid progression to chronic kidney disease as compared to the subjects in the partial nephrectomy group (radical nephrectomy 63.2% vs. partial nephrectomy 15.4%; p=0.007). There were no differences in the follow-up period in both groups (radical nephrectomy 69.3% ± 23.8 months vs. partial nephrectomy 72.5 ± 26.9 months; p=0.73). Risk of progression to end-stage chronic kidney disease was 11 times higher for subjects who had undergone radical nephrectomy as compared to subjects who had had partial nephrectomy (adjusted HR 11.12; 95% CI: 1.24-99.9; p=0.031), adjusted by the rest of traditional risk factors. None of the T1a patients had metastasis during follow-up, regardless of the type of surgery. Conclusion: According to the findings of our study, partial nephrectomy preserves long-term renal function better than radical nephrectomy and has an excellent oncologic safety profile in T1a stage renal cell carcinoma patients. Radical nephrectomy was an independent risk factor of progression to chronic kidney disease.

Survival nomogram for patients with bone metastatic renal cell carcinoma: A population-based study

ABSTRACT Purpose: Increased attention has been focused on the survival of renal cell carcinoma (RCC) patients with bone metastasis. This study proposed to establish and evaluate a nomogram for predicting the overall survival (OS) and cancer-specific survival (CSS) of RCC patients with bone metastasis. Materials and Methods: RCC patients with bone metastasis between 2010 and 2015 were captured from the surveillance, epidemiology and end results (SEER) database. Univariate and multivariate cox regressions were performed to assess the effects of clinical variables on OS and CSS. The nomogram based on the Cox hazards regression model was developed. Concordance index (C-index) and calibration curve were performed to evaluate the accuracy of nomogram models, receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were conducted to assess the predict performance. Results: A total of 2.471 eligible patients were enrolled in this study. The patients were assigned to primary (n=1.672) and validation (n=799) cohorts randomly. The 1-, 2-, and 3-year OS and CSS nomogram models were constructed based on age at diagnosis, sex, marital status, pathological grade, T-stage, N-stage, brain/liver/lung metastasis, surgery, radiotherapy and chemotherapy. The c for OS and CSS prediction was 0.730 (95% confidence interval [CI]: 0.719-0.741) and 0.714 (95%CI:0.702-0.726). The calibration curves showed significant agreement between nomogram models and actual observations. ROC and DCA indicated nomograms had better predict performance. Conclusions: The nomograms for predicting prognosis provided an accurate prediction of OS and CSS in RCC patients with bone metastasis, and contributed clinicians to optimize individualized treatment plans.

Partial nephrectomy provides equivalent oncologic outcomes and better renal function preservation than radical nephrectomy for pathological T3a renal cell carcinoma: A meta-analysis

ABSTRACT Purpose: Radical nephrectomy (RN) is the standard surgical type for pathological stage T3a (pT3a) renal cell carcinoma (RCC). Recently, some studies have suggested equivalence between partial nephrectomy (PN) and RN for oncologic control and have shown the benefits of PN for better renal function. We conducted this meta-analysis to assess oncologic outcomes, perioperative outcomes and renal function between two groups among patients with pT3a RCC. Materials and methods: PubMed, Scopus, Web of Science, Science Direct, Ovid MEDLINE, The Cochrane Library, Embase and Google Scholar were searched for eligible articles. The endpoints of the final analysis included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), surgical complications, operative time, estimated blood loss (EBL), serum creatinine and estimated glomerular filtration rate (eGFR). Results: Twelve studies of moderate to high quality, including 14.152 patients, were examined. PN showed superiority for renal functional preservation, providing higher eGFR (WMD=12.48mL/min; 95%CI: 10.28 to 14.67; P <0.00001) and lower serum creatinine (WMD=-0.31mg/dL; 95%CI: −0.40 to −0.21; P <0.00001). There were no significant differences between PN and RN regarding operative time, EBL, surgical complications, OS, RFS and CSS. Despite inherent selection bias, most pooled estimates were consistent in sensitivity analysis and subgroup analysis. More positive margins were found in the PN group (RR=2.42; 95%CI: 1.25-4.68; P=0.009). Conclusions: PN may be more suitable for treating pT3a RCC than RN because it provides a similar survival time (OS or RFS) and superior renal function. Nevertheless, this result is still disputed, and more high-quality studies are required.

Research progress of CT texture analysis in the diagnosis of renal tumors / 中华全科医师杂志

The classification and differentiation of renal tumors are related to the choice of therapeutic modalities and prognosis of patients. CT texture analysis is an objective and quantitative assessment of tumor heterogeneity based on the distribution and relationship characteristics of pixel or voxel gray levels in images, which can make up for the subjective limitations of traditional image visual analysis methods for diagnosis. In this article, CT texture analysis and its application in the diagnosis of renal tumors are reviewed and the limitations are also discussed.

Research progress on MiT family translocation related renal cell carcinoma / 中华泌尿外科杂志

Microphthalmia-associated transcription (MiT) family translocation related renal cell carcinoma (RCC) is an important type of renal cell carcinoma, which was included in the new classification of renal tumors by the World Health Organization (WHO) as an independent subtype in 2016. This type of renal cell carcinoma mainly includes Xp11.2 translocation /TFE3 gene fusions associated with renal cell carcinoma and T (6; 11)(p21; q12)/TFEB gene fusion-associated renal cell carcinoma, which has similar clinical features, histology, immunohistochemistry, and molecular genetics, but is significantly different from other renal cell carcinomas. In this review, the clinicopathology and genetics of MiT family translocation associated renal cell carcinoma were reviewed in order to provide guidance and help to the clinical and pathologic work.

A case report of renal cell carcinoma with two different histology on ipsilateral kidney / 中华泌尿外科杂志

Co-occurrence of renal cell carcinoma with two different histology is very rare. Here we present a 61-year-old gentleman with right renal mass in clinics. The diagnosis was right renal cell carcinoma by two different enhanced mass showing on CT scan. Right laparoscopic nephrectomy was performed. Pathology showed that one mass was papillary renal cell carcinoma, the other was clear cell renal cell carcinoma. No recurrence or metastasis was found during 36 months of follow up.

Prognosis value of immune-related gene CEBPB in clear cell renal cell carcinoma / 中华泌尿外科杂志

Objective:To explore the correlation between CCAAT enhancer binding protein beta (CEBPB) expression and clinical characteristics in ccRCC, and to investigate the effect of CEBPB on proliferation and invasion of ccRCC cells.Methods:Between March 2020 to December 2020, the transcriptome and clinical data of 537 ccRCC cases were downloaded from TCGA database, and the correlation of CEBPB expression with clinical characteristics of ccRCC were analyzed. Univariate and multivariate Cox regression analysis were used to determine the effect of CEBPB expression on the prognosis of ccRCC patients. The correlation between CEBPB expression and immunocyte infiltration in ccRCC was investigated via TIMER database. The expression levels of CEBPB mRNA and protein in human renal tubular epithelial cell line HK2 and ccRCC cell lines (Caki-1, ACHN, 786O, 769P and A498) were determined by real-time PCR and western blot, respectively. After transfected with NC siRNA or CEBPB siRNA for 48 h, the proliferation and invasion of ACHN cells and 786O cells were determined by using MTT assay and invasion assay, respectively.Results:TCGA databases analysis revealed that, compared with normal kidney tissue, the expression of CEBPB mRNA in ccRCC was up-regulated by 2.55-fold ( P<0.05). CEBPB expression was positively correlated with age, tumor grade, tumor stage, lymph node metastasis and distant metastasis ( P<0.05). The tumor grade ( HR=1.703, P=0.040), tumor stage( HR=1.773, P=0.026), distant metastasis ( HR=3.080, P<0.001) and the high expression of CEBPB ( HR=1.874, P=0.003) were independent poor prognostic factors for ccRCC patients. The analysis results by using TIMER database showed that CEBPB expression was positively correlated with infiltrating levels of B cells (Rho=0.168), M2 macrophages (Rho=0.373), Tregs (Rho=0.348), neutrophils (Rho=0.194), and natural killer T cell (Rho=0.421) in ccRCC. The expression level of CEBPB mRNA in Caki-1, ACHN, 786O, 769P and A498 cells was (9.43±1.25)-fold, (5.44±0.82)-fold, (4.50±0.52)-fold, (4.88±0.73)-fold and (7.50 ± 1.04)-fold of HK2 cells, respectively. The expression level of CEBPB protein was (6.22±0.45)-fold, (5.84±0.85)-fold, (6.51±0.55)-fold, (6.23±0.62)-fold and (3.84±0.45)-fold of HK2 cells, respectively ( P<0.05). MTT assay showed that the proliferation rates of ACHN cells and 786O cells at 24, 48, 72, 96 h were (98.4±1.7)% and (99.0±1.4)%, (97.8±2.1)% and (98.5±1.5)%, (101.3±1.2)% and (97.6±1.7)%, (97.5±2.0)% and (99.1±1.3)% in NC siRNA group, and (68.8±5.8)% and (79.5±6.2)%, (57.9 ± 6.1)% and (70.8±5.1)%, (50.9±4.6)% and (66.8±4.9)%, (43.2±5.0)% and (60.5±5.3)% in CEBPB siRNA group. Compared with NC siRNA group, the proliferation activity of ACHN cells and 786O cells was significantly inhibited in the CEBPB siRNA group ( P<0.05). Cell invasion assay showed that the invasion activity of ACHN cells and 786O cells were (95.0±5.2)% and (97.3±4.4)% in NC siRNA group, (35.2±5.4)% and (26.7±3.3)% in CEBPB siRNA group, respectively ( P<0.05). Compared with NC siRNA group, the invasion activity of ACHN cells and 786O cells were significantly inhibited in the CEBPB siRNA group ( P<0.05). Conclusions:CEBPB was highly expressed in ccRCC, which was closely related to the prognosis and immunocyte infiltration of ccRCC patients. Silencing the expression of CEBPB significantly inhibited the proliferation and invasion of ccRCC cells

The metastasis of renal cell carcinoma to the contralateral ureter: a case report / 中华泌尿外科杂志

The metastasis of renal cell carcinoma to the ureter is a rare phenomenon, and synchronal detection of metastasis to the contralateral ureter is a rarer phenomenon. A 62-year-old male patient with painless hematuria was examined and detected a renal cell carcinoma on the right kidney and bleeding from the left ureter. Ureteroscopy revealed a tumor in the left upper ureter, and biopsy suggested clear cell carcinoma. Laparoscopic radical nephrectomy was performed to resect the right renal cell carcinoma, and the pathology revealed a clear cell carcinoma, with Fuhrman nuclear grade 2 class. The ureteral tumor was resected 3 months later and the pathology revealed renal clear cell carcinoma. Sunitinib was used for 37 months, and there was no tumor recurrence or metastasis so far.