[Establishment and validation of a novel nomogram to predict overall survival after radical nephrectomy].

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.

[Long-term survival analysis of 1 367 patients treated with radical nephrectomy from a single center].

Objective: To report the long-term survival of renal cell carcinoma (RCC) patients treated with radical nephrectomy in Sun Yat-sen University Cancer Center. Methods: We retrospectively analyzed the clinical, pathological and follow-up records of 1 367 non-metastatic RCC patients treated with radical nephrectomy from 1999 to 2020 in this center. The primary endpoint of this study was overall survival rate. Survival curves were estimated using the Kaplan-Meier method, and group differences were compared through Log-rank test. Univariate and multivariate Cox analysis were fit to determine the clinical and pathological features associated with overall survival rate. Results: A total of 1 367 patients treated with radical nephrectomy with complete follow-up data were included in the study. The median follow-up time was 52.6 months, and 1 100 patients survived and 267 died, with the median time to overall survival not yet reached. The 5-year and 10-year overall survival rates were 82.8% and 74.9%, respectively. The 5-year and 10-year overall survival rates of Leibovich low-risk patients were 93.3% and 88.2%, respectively; of Leibovich intermediate-risk patients were 82.2% and 72.3%, respectively; and of Leibovich high-risk patients were 50.5% and 30.2%, respectively. There were significant differences in the long-term survival among the three groups (P<0.001). The 10-year overall survival rates for patients with pT1, pT2, pT3 and pT4 RCC were 83.2%, 73.6%, 55.0% and 31.4%, respectively. There were significant differences among pT1, pT2, pT3 and pT4 patients(P<0.001). The 5-year and 10-year overall survival rates of patients with lymph node metastasis were 48.5% and 35.6%, respectively, and those of patients without lymph node metastasis were 85.1% and 77.5%, respectively. There was significant difference in the long-term survival between patients with lymph node metastasis and without lymph node metastasis. The 10-year overall survival rate was 96.2% for nuclear Grade 1, 81.6% for nuclear Grade 2, 60.5% for nuclear Grade 3, and 43.4% for nuclear Grade 4 patients. The difference was statistically significant. There was no significant difference in the long-term survival between patients with localized renal cancer (pT1-2N0M0) who underwent open surgery and minimally invasive surgery (10-year overall survival rate 80.5% vs 85.6%, P=0.160). Multivariate Cox analysis showed that age≥55 years (HR=2.11, 95% CI: 1.50-2.96, P<0.001), T stage(T3+ T4 vs T1a: HR=2.37, 95% CI: 1.26-4.46, P=0.008), local lymph node metastasis (HR=3.04, 95%CI: 1.81-5.09, P<0.001), nuclear grade (G3-G4 vs G1: HR=4.21, 95%CI: 1.51-11.75, P=0.006), tumor necrosis (HR=1.66, 95% CI: 1.17-2.37, P=0.005), sarcomatoid differentiation (HR=2.39, 95% CI: 1.31-4.35, P=0.005) and BMI≥24kg/m(2) (HR=0.56, 95%CI: 0.39-0.80, P=0.001) were independent factors affecting long-term survival after radical nephrectomy. Conclusions: The long-term survival of radical nephrectomy in patients with renal cell carcinoma is satisfactory. Advanced age, higher pathological stage and grade, tumor necrosis and sarcomatoid differentiation were the main adverse factors affecting the prognosis of patients. Higher body mass index was a protective factor for the prognosis of patients.

[Efficacy and safety evaluation of immunotherapy combined with targeted therapy as second-line treatment in patients with metastatic non-clear cell renal cell carcinoma].

Objective: This study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitor combined tyrosine kinase inhibitor (TKI) therapy versus TKI monotherapy as the second-line regimen for patients with metastatic non-clear cell renal carcinoma (nccRCC) who failed first-line TKI therapy. Methods: The clinicopathological data of 67 patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020 were retrospectively analyzed, including 22 patients who received TKI monotherapy and 45 patients who received TKI plus PD-1 inhibitor as the second-line therapy. The efficacy was assessed according to Response Evaluation Criteria in Solid Tumors version 1.0/1.1 (RECIST 1.0/1.1), the Kaplan-Meier method was used to plot the survival curves, and the Log rank test was used to analyze the differences in the survival between the two groups. Treatment-related adverse events (AEs) after treatment were observed in both groups. Results: The overall objective response rate (ORR) and disease control rate (DCR) were 37.3% (25/67) and 56.7% (38/67), respectively. The overall second-line progression-free survival (PFS) was 7.7 months and Overall Survival (OS) was 25.2 months. The ORR and DCR of patients in the combination therapy group were 48.9% (22/45) and 71.1% (32/45), respectively, which were significantly improved compared with the TKI monotherapy group [13.6% (3/22) and 27.3% (6/22), respectively] (P=0.007 and P=0.001, respectively). The median PFS of 9.2 months for second-line treatment was longer in patients in the combination therapy group than in the TKI monotherapy group (5.2 months, P=0.001), but the median OS was not statistically different between the two groups (28.2 months vs 20.8 months, P=0.068). Common treatment-related AEs included hypertension, diarrhea, fatigue, stomatitis, hand-foot syndrome, and hypothyroidism. The incidence of hypothyroidism was higher in the combination therapy group [40.0% (18/45)] than in the TKI monotherapy group [22.7% (5/22), P=0.044]; the incidence of other treatment-related AEs between the two groups were not statistically significant (all P>0.05). Conclusion: Immune-targeted combination therapy was more effective than TKI monotherapy alone and was well tolerated in the treatment of metastatic nccRCC patients who failed first-line TKIs.

Decoding the Possible Molecular Mechanisms in Pediatric Wilms Tumor and Rhabdoid Tumor of the Kidney through Machine Learning Approaches.

Objective: Wilms tumor (WT) and Rhabdoid tumor (RT) are pediatric renal tumors and their differentiation is based on histopathological and molecular analysis. The present study aimed to introduce the panels of mRNAs and microRNAs involved in the pathogenesis of these cancers using deep learning algorithms. Methods: Filter, graph, and association rule mining algorithms were applied to the mRNAs/microRNAs data. Results: Candidate miRNAs and mRNAs with high accuracy (AUC: 97%/93% and 94%/97%, respectively) could differentiate the WT and RT classes in training and test data. Let-7a-2 and C19orf24 were identified in the WT, while miR-199b and RP1-3E10.2 were detected in the RT by analysis of Association Rule Mining. Conclusion: The application of the machine learning methods could identify mRNA/miRNA patterns to discriminate WT from RT. The identified miRNAs/mRNAs panels could offer novel insights into the underlying molecular mechanisms that are responsible for the initiation and development of these cancers. They may provide further insight into the pathogenesis, prognosis, diagnosis, and molecular-targeted therapy in pediatric renal tumors.

Absolute quantitative proteomics using the total protein approach to identify novel clinical immunohistochemical markers in renal neoplasms.

BACKGROUND: Renal neoplasms encompass a variety of malignant and benign tumors, including many with shared characteristics. The diagnosis of these renal neoplasms remains challenging with currently available tools. In this work, we demonstrate the total protein approach (TPA) based on high-resolution mass spectrometry (MS) as a tool to improve the accuracy of renal neoplasm diagnosis. METHODS: Frozen tissue biopsies of human renal tissues [clear cell renal cell carcinoma (n = 7), papillary renal cell carcinoma (n = 5), chromophobe renal cell carcinoma (n = 5), and renal oncocytoma (n = 5)] were collected for proteome analysis. Normal adjacent renal tissue (NAT, n = 5) was used as a control. Proteins were extracted and digested using trypsin, and the digested proteomes were analyzed by label-free high-resolution MS (nanoLC-ESI-HR-MS/MS). Quantitative analysis was performed by comparison between protein abundances of tumors and NAT specimens, and the label-free and standard-free TPA was used to obtain absolute protein concentrations. RESULTS: A total of 205 differentially expressed proteins with the potential to distinguish the renal neoplasms were found. Of these proteins, a TPA-based panel of 24, including known and new biomarkers, was selected as the best candidates to differentiate the neoplasms. As proof of concept, the diagnostic potential of PLIN2, TUBB3, LAMP1, and HK1 was validated using semi-quantitative immunohistochemistry with a total of 128 samples assessed on tissue micro-arrays. CONCLUSIONS: We demonstrate the utility of combining high-resolution MS and the TPA as potential new diagnostic tool in the pathology of renal neoplasms. A similar TPA approach may be implemented in any cancer study with solid biopsies.

Diagnostic accuracy and cytomorphological spectrum of Wilms tumour in fine needle aspiration biopsy cytology samples supplemented with cell blocks.

OBJECTIVE: Paediatric malignant renal neoplasms are subjected to neoadjuvant chemotherapy as per Societe Internationale d'Oncologie Pediatrique; International Society of Pediatric Oncology (SIOP) protocol. An accurate tissue diagnosis is required prior to institution of chemotherapy, and hence the aim of this study was to evaluate the diagnostic accuracy of fine needle aspiration biopsy cytology (FNABC) along with cell block histology. MATERIALS AND METHODS: A retrospective audit of all paediatric renal neoplasms diagnosed by FNABC between 2015 and 2019 was performed. Histopathology correlation was done wherever available. WT cases were subjected to detailed cytomorphological evaluation. RESULTS: A total of 121 cases of paediatric renal neoplasms including 109 WT, four clear cell sarcoma, one malignant rhabdoid tumour and three mesoblastic nephroma were evaluated. The age range was 4 weeks to 8 years. FNABC samples were adequate for diagnosis in 120 of 121 cases (99.18%) and a definitive cytological diagnosis was achieved in 117 cases (96.7%). The specificity and sensitivity for a cytopathological diagnosis of WT were 98.7% and 97.4%, respectively. On detailed cytomorphological analysis of 68 histopathology-proven WT, 40 (58.8%) cases were triphasic, 23 (35.3%) were biphasic and four were composed of blastema only. The corresponding cell blocks provided additional information over the conventional smears in 23 (33.8%) cases, with epithelial or mesenchymal elements recognised and evidence of rhabdomyoblastic differentiation. CONCLUSION: FNABC along with cell block histology is highly accurate for diagnosis of WT and other malignant paediatric renal neoplasms and is recommended as the technique of choice in centres with cytopathology expertise for establishing a cellular diagnosis prior to commencement of neoadjuvant chemotherapy.

Modest efficacy of nivolumab plus ipilimumab in patients with papillary renal cell carcinoma.

PURPOSE: Combined immunotherapy of nivolumab plus ipilimumab for intermediate- and poor-risk metastatic clear cell renal cell carcinoma showed prolonged progression-free survival and high objective response rate in a randomized phase III clinical trial. However, the efficacy of this treatment for papillary renal cell carcinoma remains unclear. In the present study, we analysed the efficacy of nivolumab plus ipilimumab therapy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. MATERIALS AND METHODS: This is a retrospective study of 30 patients with metastatic renal cell carcinoma who received nivolumab and ipilimumab as first-line therapy between December 2015 and May 2020. The objective response rate, progression-free survival and toxicity were compared between the two groups (clear cell renal cell carcinoma and papillary renal cell carcinoma). RESULTS: Out of 30 patients, 7 and 23 were diagnosed with papillary renal cell carcinoma and clear cell renal cell carcinoma, respectively. With a median follow-up of 7.2 months, the median progression-free survival was significantly shorter in papillary renal cell carcinoma than in clear cell renal cell carcinoma (2.4 vs. 28.1 months, P = 0.014). Of the seven patients with papillary renal cell carcinoma, one had partial response, one had stable disease and five had progressive disease, resulting in an objective response rate of 14.2%, which was lower compared to that of clear cell renal cell carcinoma (14.2 vs. 52.1%, P = 0.06). Discontinuation due to toxicity was not observed with papillary renal cell carcinoma, meanwhile 60.8% of patient with clear cell renal cell carcinoma discontinued treatment due to toxicity. CONCLUSION: Nivolumab plus ipilimumab had modest efficacy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Nivolumab plus ipilimumab remains an option for a limited number of patients with intermediate- or poor-risk papillary renal cell carcinoma.

The diagnostic utility of diffusion weighted MRI imaging and ADC ratio to distinguish benign from malignant renal masses: sorting the kittens from the tigers.

BACKGROUND: MRI is playing an increasing role in risk stratification and non-invasive diagnosis of the undifferentiated small renal mass. This study was designed to assess the reliability of MRI in diagnostic evaluation of renal masses, specifically characterising lesions with diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values. METHODS: This is a retrospective analysis of patients undergoing MRI as part of their clinical workup for a renal mass suspicious for renal cell carcinoma (RCC) on CT or ultrasound followed by biopsy and/or surgical excision. All cases were conducted on 3 Tesla MRI, with conventional breath-held sequences, DWI and dynamic contrast enhanced phases. Tumour regions of interest were evaluated on ADC maps and compared with T2 weighted and post-contrast images. RESULTS: Of the 66 renal tumours included, 33 (50.0%) were Clear Cell RCC, 11 (16.7%) were Oncocytoma, nine (13.6%) were Angiomyolipoma (AML), nine (13.6%) were Papillary RCC and four (6.1%) were Chromophobe RCC. Oncocytoma had the largest ADC values, significantly larger than AMLs and all RCC subtypes (p < 0.001). The average ADC value was also significantly larger in Clear Cell RCCs compared to AMLs, and other RCC subtypes (p < 0.001). CONCLUSIONS: MRI with DWI/ADC imaging may aid the differentiation of oncocytomas from RCCs and stratify RCC subtypes, Further studies are required to validate these findings. TRIAL REGISTRATION: Not applicable/retrospective study.

[Eosinophilic solid and cystic renal cell carcinoma: a clinicopathological analysis of four cases].

Objective: To study the clinicopathological characteristics and prognosis of eosinophilic solid and cystic renal cell carcinoma (ESC RCC). Methods: The clinical pathologic data of 4 cases of ESC RCC diagnosed and treated from 2017 to 2019 at the Second Hospital of Longyan City, the Second Affiliated Hospital of Fujian Medical University, and the Zhangzhou Municipal Hospital were collected. The expression of different antibodies was detected by immunohistochemistry, and the diagnosis and differentiate diagnosis were investigated. Results: The 4 ESC RCC cases included 2 males and 2 females, the average age of these patients was 40 years, ranged from 31 to 51 years. The tumors were composed of solid area mixed with giant vesicles and microcapsules of varying sizes. The cyst cavity was lined by neoplastic cells with voluminous eosinophilic cytoplasm and hobnail arrangement. The solid area appeared as diffuse flaky, dense acinar or nested arrangement, the local area was island-shaped and tubular, mixed with a small amount of histiocytes and lymphocytes. Neoplastic cells contained voluminous eosinophilic cytoplasm with obvious fine or coarse particles, eosinophilic globules in part of the cytoplasm, and intracytoplasmic vacuoles in some areas. Immunohistochemical results showed that tumor cells were CK20 expressed (3/3, 2 cases were sparsely positive and 1 case was patched strongly positive), Vimentin (4/4) and CD10 (4/4) sparsely positive, while Actin, HMB45, Melan-A, CD117 and CK7 were negative in all cases. Ki-67 proliferation index was about 1%. Two cases were followed up and the progression free survival were 18 and 24 months, respectively. Conclusions: ESC RCC has unique histomorphological manifestations, CK20(+ ) and CK7(-) are helpful for its diagnosis, and it has common molecular karyotype changes, supporting it as a unique tumor entity. The overall prognosis of the patient is good.

Laparoscopic partial nephrectomy without clamping the renal pedicle.

INTRODUCTION: Renal cell carcinoma (RCC) accounts for about 2-3% of all malignancies in adults and 90-95% of renal neoplasms. Curative treatment is eminently surgical, the first reports describing the laparoscopic partial nephrectomy (LPN) date from the beginning of the 1990s since then LPN has been consolidated as a safe and reproducible procedure. In order to improve the results of the LPN in relation to the postoperative renal function, while retaining the benefits of minimally invasive surgery, some surgeons began to implement the technique of laparoscopic partial nephrectomy without renal pedicle clamping (LPNWRPC) in selected cases. OBJECTIVE: To compare the perioperative, oncological and functional results of patients submitted to LPN with renal pedicle clamping (LPNRPC) and LPNWRPC in the hospitals linked to our institution. MATERIAL AND METHOD: All patients' charts were submitted to LPN from January 2000 to January 2016. Data were collected and analyzed retrospectively, patients were divided into two groups: LPNRPC (RPC group) and LPNWRPC (WRPC group). RESULTS: Data from 177 patients submitted to LPN for renal neoplasms were collected, 88 patients (49.7%) in the RPC group and 89 (50.3%) in the WRPC group. Surgical margins were positive in 2.56% of patients in the RPC group and 3.70% in the WRPC group. There was no significant difference despite the technique applied. Clavien 3 or 4 postoperative complications occurred in five cases (5.68%) in the RPC group and three cases in the WRPC group (3.7%), with no significant difference between the groups. Patients in the RPC group developed higher levels of creatinine in the postoperative period (creatinine 1.01 ± 0.16 preoperative vs. 1.12 ± 0.18 postoperatively, p = 0.031) and worsened filtration rate (EGFR) (preoperative 79.18 ± 16.28 × 74.43 ± 21.06 post-operative, p = 0.017). DISCUSSION: Our casuistry agrees with the results of previous studies with regard to major bleeding in patients submitted to LPNWRPC when compared to those submitted to LPNWRPC. However, although bleeding and surgical time were higher in the WRPC group, there was no impact on patients' postoperative evolution regarding both the need for transfusion of blood products and serious complications. In the high-complexity tumors, the mean warm ischemia time (WIT) in the RPC group was higher, this was probably responsible for a better response in the WRPC group evolving patients with lower creatinine levels and better postoperative glomerular filtration rates. CONCLUSION: LPNWRPC has been shown to be equally effective, safe, feasible, with low blood transfusion rates and postoperative complications comparable to LPNRPC, and has similar oncological results. Main impact factor in long-term renal dysfunction is WIT, which can be completely eliminated with the use of LPNWRPC.

From Wilms to kidney tumors: which ones require a biopsy?

Ninety percent of childhood renal tumors are Wilms tumors (nephroblastoma). While the Children's Oncology Group (COG) recommends primary surgery, the International Society of Paediatric Oncology (SIOP) recommends neoadjuvant chemotherapy, which can be initiated without histological confirmation if the presentation is typical for Wilms tumor. This review article describes the clinical, biological and radiologic criteria used by the SIOP community to consider diagnostic biopsy, i.e. when the renal origin is doubtful, when a pseudotumor is suspected or when a non-Wilms histology may be anticipated.

Differentiating between malignant and benign renal tumors: do IVIM and diffusion kurtosis imaging perform better than DWI?

OBJECTIVE: To quantitatively compare the diagnostic values of conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) in differentiating between malignant and benign renal tumors. METHODS: Multiple b value DWIs and DKIs were performed in 180 patients with renal tumors, which were divided into clear cell renal cell carcinoma (ccRCC), non-ccRCC, and benign renal tumor group. The apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean kurtosis (MK), and mean diffusivity (MD) maps were calculated. The diagnostic efficacy of various diffusion parameters for predicting malignant renal tumors was compared. RESULTS: The ADC, D, and MD values of ccRCCs were higher, while D*, f, and MK values were lower than those of benign renal tumors (all p < 0.025). The D* and f values of non-ccRCCs were lower than those of benign renal tumors (p = 0.002 and p < 0.001, respectively). The difference of ADC, D, MD, and MK values between non-ccRCCs and benign renal tumors was not statistically significant (p > 0.05). The ADC, D, MD, and f values of ccRCCs were higher, while MK values were lower than those of non-ccRCCs (all p < 0.001). The AUC values of ADC, D, D*, f, MK, and MD were 0.849, 0.891, 0.708, 0.656, 0.862, and 0.838 for differentiating ccRCCs from benign renal tumors, respectively. The AUC values of D* and f were 0.772 and 0.866 for discrimination between non-ccRCCs and benign renal tumors, respectively. CONCLUSION: IVIM parameters are the best, while DWI and DKI parameters have similar performance in differentiating malignant and benign renal tumors. KEY POINTS: • The D value is the best parameter for differentiating ccRCC from benign renal tumors. • The f value is the best parameter for differentiating non-ccRCC from benign renal tumors. • Conventional DWI and DKI have similar performance in differentiating malignant and benign renal tumors.

Active Surveillance of Small (< 4 cm) Bosniak Category 2F, 3, and 4 Renal Lesions: What Happens on Imaging Follow-Up?

OBJECTIVE. The purpose of this study was to determine the percentage of small (< 4 cm) Bosniak category 2F, 3, and 4 lesions that regress during active surveillance. MATERIALS AND METHODS. In this retrospective study, a hospital database was searched from January 1, 2005, through September 9, 2017, for small (< 4 cm) Bosniak category 2F, 3, and 4 lesions studied with initial and follow-up unenhanced and contrast-enhanced CT or MRI. Prospective Bosniak categories were recorded. Two blinded radiologists retrospectively reassigned Bosniak categories to the initial and last follow-up studies. Interreader variability was analyzed. Rates of stability, regression, and progression were calculated and stratified by size. Logistic regression was used to assess the effects of lesion size, lesion growth, and duration of follow-up on the change in Bosniak categories. RESULTS. The search identified 123 patients (85 men, 38 women) with 138 renal lesions (according to the blinded readings, 83 Bosniak category 2F, 37 category 3, and 18 category 4) and followed for 1-12.3 years (median, 2.7 years). Fifty-one percent (70/138) of the lesions were smaller than 2 cm. Eighty-eight percent (73/83) of category 2F lesions were downgraded or remained stable. Forty-five percent (25/55) of category 3 or 4 lesions were downgraded to 2F or lower. Kappa values were 0.94 between the two readers and 0.72-0.76 between the readers and the prospective Bosniak categories. There was no association between initial size, change in size, or duration of follow-up and change in Bosniak category. CONCLUSION. Approximately one-half of small (< 4 cm) Bosniak category 3 and 4 cystic renal lesions were downgraded, and the majority (88%) of small Bosniak category 2F lesions regressed or remained stable during active surveillance. Therefore, small size should be a consideration for conservative management.

A huge benign fibrous histiocytoma arising from the renal capsule: report of a case.

BACKGROUND: Neoplasms originating in the renal capsule are very rare. Benign fibrous histiocytoma(BFH) most commonly occurs in the dermis and subcutis, few cases of this tumor appear in the renal capsule. In particular, BFH larger than 20 cm are scarce. Here we report a rare huge one measuring 23 × 13 × 7 cm. CASE PRESENTATION: We report a 64-year-old man who presented with a few-months history of dull pain in the right groin. The tumor had its point of origin in the renal capsule which is a rare condition. Histologically, the tumor was composed of intersecting fascicles of fibroblastic cells forming a "storiform" pattern. Immunohistochemical studies were also performed, ultimately leading to the diagnosis of BFH. The patient was treated with radical nephrectomy. No recurrence was detected 4 months after surgery. CONCLUSIONS: BFH arising from the renal capsule was very rare. In particular, the case of more than twenty centimeters is extremely rare. The clinical presentation of renal BFH might be only a mass. However, differential diagnosis from renal cell carcinoma proved to be impossible before surgical intervention. It is difficult to diagnose only by means of histopathology, but the immunohistochemical method can provide a clear and definite diagnosis.

Short-term complications for percutaneous ultrasound-guided biopsy of renal masses in adult outpatients.

Background Ultrasound-guided percutaneous kidney tumor biopsy (UGPKB) plays an important role in the diagnosis of renal tumor but there are no consensuses with respect to the length and the extend of the post-biopsy observation period. Purpose To assess the short-term complication rate after UGPKB and to evaluate whether the onset of complications allows for the procedure to be performed in an outpatient setting with same-day discharge. Material and Methods Between March 2012 and March 2014, a total of 287 UGPKB were performed in an outpatient setting at a Danish university referral center. All patient records were retrospectively reviewed and post-biopsy complications as well as biochemical parameters were registered. Results The overall complication rate was 3.8% (11 patients). Major complications occurred in 1.0% of all cases (three patients); one patient with ongoing bleeding that required intervention and two patients with septicemia. Minor complications occurred in 2.8% of cases (eight patients); six patients with self-limiting gross hematuria, one patient with small asymptomatic subcapsular hematoma, and one patient with vasovagal syncope. The timing of both minor and major complication onset ranged from the time of biopsy and up to four days after discharge. Conclusion UGPKB of indeterminate renal masses in adult patients in an outpatient setting appears to be a safe procedure with a very low rate of major complications. Same-day discharge after renal mass biopsy seems feasible.

Differentiating Renal Neoplasms From Simple Cysts on Contrast-Enhanced CT on the Basis of Attenuation and Homogeneity.

OBJECTIVE: The purpose of this study is to compare the attenuation and homogeneity of renal neoplasms with those of cysts on contrast-enhanced CT. MATERIALS AND METHODS: A total of 129 renal neoplasms and 24 simple cysts were evaluated. Two readers determined whether each mass was qualitatively heterogeneous or homogeneous. Mean, minimum, and maximum attenuation values were measured. Statistical analysis was performed. RESULTS: A total of 116 heterogeneous renal cell carcinomas (RCCs) (99 clear cell, four papillary, four oncocytic, seven chromophobe, and two unclassified RCCs), 13 homogeneous RCCs (10 papillary, two oncocytic, and one chromophobe RCC), and 24 cysts (all of which were homogeneous) were evaluated. All homogeneous RCCs had mean attenuation values of more than 42 HU, whereas renal cysts had mean attenuation values of up to 30 HU (p < 0.001). Two readers qualitatively and identically categorized all RCCs as homogeneous or heterogeneous (κ = 1.0; p < 0.001). CONCLUSION: Homogeneous simple renal cysts can have mean attenuation values of up to 30 HU, as determined by contrast-enhanced CT, whereas homogeneous RCCs have mean attenuation values as low as 42 HU, with no overlap occurring between the two groups. These data suggest that further evaluation of a homogeneous renal mass with a mean attenuation value of 30 HU or less on a contrast-enhanced CT scan likely is unwarranted.

Is Multiparametric MRI Useful for Differentiating Oncocytomas From Chromophobe Renal Cell Carcinomas?

OBJECTIVE: The purpose of this study was to retrospectively evaluate the diagnostic accuracy of multiparametric MRI to differentiate oncocytoma from chromophobe renal cell carcinoma (RCC). MATERIALS AND METHODS: In this retrospective study, 26 histologically confirmed oncocytomas and 16 chromophobe RCCs that underwent full MRI examination were identified in 42 patients (25 men and 17 women) over a 6-year period. Demographic data were recorded. Double-echo chemical-shift, dynamic contrast-enhanced T1- and T2-weighted images, and apparent diffusion coefficient (ADC) maps were reviewed independently by two radiologists blinded to pathologic results. Signal-intensity index (SII), tumor-to-spleen signal-intensity ratio, ADC ratio, three wash-in indexes, and two washout indexes were calculated and compared using univariate and ROC analyses. Sensitivity and specificity analyses were performed to calculate diagnostic accuracy. RESULTS: All carcinomas and nine oncocytomas were resected; the remaining 17 oncocytomas were biopsied. Patient age (for oncocytomas: mean, 68.2 years; range, 43-84 years; for RCCs: mean, 60.8 years; range, 20-79 years) and tumor size (for oncocytomas: mean, 35.5 mm; range, 12-98 mm; for RCCs: mean, 37.2 mm; range, 9-101 mm) did not differ significantly across groups (p = 0.132 and 0.265, respectively). Good interobserver agreement was observed for all measurements but four. Oncocytomas presented significantly higher ADC (p = 0.002) and faster enhancement (p = 0.007-0.012) but lower SII (p = 0.03) than carcinomas. This combination provided sensitivity of 92.3% (24/26), specificity of 93.8% (15/16), and accuracy of 92.9% (39/42) for the detection of oncocytomas. CONCLUSION: Multiparametric MRI helps to accurately differentiate oncocytomas from chromophobe RCCs with high sensitivity and specificity.

[Expression of LIM and SH3 protein 1 in renal clear cell carcinoma and its effects on invasion and migration of renal clear cell carcinoma 786-O cells].

Objective: To investigate the expression of LIM and SH3 protein 1 (LASP1) in renal cell carcinoma and its significance in the invasion and migration of renal clear cell carcinoma 786-O cell line. Methods: The expression level of LASP1 in 41 cases of renal cell carcinoma tissues and normal renal tissues was analyzed by immunohistochemistry. The relationship between the expression level of LASP1 and clinical characteristics was further analyzed. Expression of LASP1 in 10 cases of tumor tissues with or without lymph node metastasis was analyzed by Western blot. Furthermore, small interfering RNA (siRNA) targeting LASP1 was constructed and transfected into 786-O cells to downregulate LASP1 expression. The interference effect of LASP1 siRNA on LASP1 protein and the expression of related proteins in epithelial mesenchymal transition (EMT) pathway were detected by Western blot. The effects of LASP1 knockdown on cell proliferation, migration and invasion and gene expression were then assessed using CCK8 assay, transwell cell migration system and western blot analysis, respectively. Results: The positive rate of LASP1 expression in renal clear cell carcinoma tissues was 90.2% (37/41), which was significantly higher than that in the adjacent tissues (29.3%, P=0.002). The expression of LASP1 in renal cell carcinoma was positively correlated with lymph node metastasis and TNM stage of renal cell carcinoma (P<0.05). The results of Western blot showed that LASP1 (0.696±0.053) was highly expressed in renal cell carcinoma (1.459±0.628), especially in cases with lymph node metastasis (2.692±0.186, P<0.05). The LASP1 siRNA remarkably down-regulated the expression of LASP1 protein in 786-O cells. The abilities of proliferation, invasion and migration of 786-O cells were decreased significantly in the LASP1 siRNA groups.The relative expression of E-cadherin protein in the siRNA group (0.848±0.020) was significantly higher than those in the siRNA-NC group (0.671±0.018) and control group (0.691±0.037, P<0.05). The relative expression of N-cadherin protein in the siRNA group (0.449±0.047) was significantly lower than those in the siRNA-NC group (0.613±0.018) and control group (0.633±0.045, P<0.05). The relative expression of vimentin protein in the siRNA group (0.477±0.029) was significantly lower than those in the siRNA-NC group (0.598±0.069) and control group (0.633±0.045, P<0.05 for both). Conclusions: LASP1 is highly expressed in renal clear cell carcinoma, which is closely related to the development of the cancer. The effects of LASP1 on the invasion and migration of 786-O cells and lymph node metastasis may be related to the EMT.

[Expression and clinical significance of HMGA2 in renal carcinoma].

Objective: To detect the high mobility group A2 (HMGA2) expression in renal carcinoma, and to explore the relationship with clinicopathological features and its significance for prognosis. Methods: 50 renal carcinoma specimens, 50 corresponding adjacent normal kidney tissue samples, and 40 benign renal tumor specimens were used in this study. The expressions of HMGA2 mRNA and protein were detected by RT-PCR, Western blot and immunohistochemical assays, and its relationship with clinicopathological features and prognosis in the renal carcinoma patients was analyzed. Results: The RT-PCR results showed that the relative expression levels of HMGA2 mRNA in the renal carcinoma, benign renal tumor tissues, and adjacent normal renal tissues were 0.84±0.23, 0.19± 0.06 and 0.08±0.04, respectively, and the expression in renal carcinoma tissue was significantly higher than those of the other 2 groups (P<0.01). The Western blot results showed that the relative expression levels of HMGA2 protein in the renal carcinoma, benign renal tumor tissues, and adjacent normal renal tissues were 0.91±0.24, 0.12±0.04 and 0.03±0.01, respectively, and the expression in renal carcinoma tissue was significantly higher than those of the other 2 groups (P<0.01). Immunohistochemical results showed that the expression of HMGA2 protein exhibited brown and tan granular, which mainly distributed in the cell nuclei. Among the 50 cases of renal carcinoma, 34 cases exhibited positive expression, with a positive rate of 68.0%. Among the 40 cases of benign tumor tissues, 3 cases had positive expression, with a positive rate of 7.5%, while among the 50 cases of adjacent normal renal tissues, there was only 1 case exhibiting positive expression of HMGA2 protein, with a positive rate of 2.0%. The protein expression of HMGA2 was significantly higher in the renal carcinoma than in the benign tumors and normal renal tissues (P=0.004). There was no statistically significant difference in the association of HMGA2 protein expressions with age, sex, tumor size and histological type (P>0.05), while significant difference did exist in the association with different statuses of TNM staging and lymph node metastasis (P<0.05). The median time to progression (TTP) in 34 HMGA2 protein-positive patients was (22.36±1.48) months and that of 16 HMGA2 protein-negative patients was (34.55±1.87) months (P<0.05). Conclusions: HMGA2 plays an important role in the tumorigenesis and development of renal carcinoma, and may be used as an important predictor for estimating the prognosis of renal carcinoma. HMGA2 might become a new diagnostic and prognostic marker for renal carcinoma.