Mitochondria-Targeted Nanoadjuvants Induced Multi-Functional Immune-Microenvironment Remodeling to Sensitize Tumor Radio-Immunotherapy.

It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and immune depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand-1 (PD-L1) overexpression and transforming growth factor-ß (TGF-ß) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily. In this study, it is revealed that inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) can serve as a highly effective multi-immune pathway regulation strategy through PD-L1, collagen, and TGF-ß co-depression. Then, IR-LND is prepared by combining the mitochondria-targeted molecule IR-68 with LND, which then is loaded with liposomes (Lip) to create IR-LND@Lip nanoadjuvants. By doing this, IR-LND@Lip more effectively sensitizes RT by generating more DNA damage and transforming cold tumors into hot ones through immune activation by PD-L1, collagen, and TGF-ß co-inhibition. In conclusion, the combined treatment of RT and IR-LND@Lip ultimately almost completely suppressed the growth of bladder tumors and breast tumors.

The m6A methylation landscape, molecular characterization and clinical relevance in prostate adenocarcinoma.

Background: Despite the recent progress of therapeutic strategies in treating prostate cancer (PCa), the majority of patients still eventually relapse, experiencing dismal outcomes. Therefore, it is of utmost importance to identify novel viable targets to increase the effectiveness of treatment. The present study aimed to investigate the potential relationship between N6-methyladenosine (m6A) RNA modification and PCa development and determine its clinical relevance. Methods: Through systematic analysis of the TCGA database and other datasets, we analyzed the gene expression correlation and mutation profiles of m6A-related genes between PCa and normal tissues. Patient samples were divided into high- and low-risk groups based on the results of Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis. Subsequently, differences in biological processes and genomic characteristics of the two risk groups were determined, followed by functional enrichment analysis and gene set enrichment (GSEA) analysis. Next, we constructed the protein-protein interaction (PPI) network of differentially expressed genes between patients in high- and low-risk groups, along with the mRNA-miRNA-lncRNA network. The correlation analysis of tumor-infiltrating immune cells was further conducted to reveal the differences in immune characteristics between the two groups. Results: A variety of m6A-related genes were identified to be differentially expressed in PCa tissues as compared with normal tissues. In addition, the PPI network contained 278 interaction relationships and 34 m6A-related genes, and the mRNA-miRNA-lncRNA network contained 17 relationships, including 91 miRNAs. Finally, the immune characteristics analysis showed that compared with the low-risk group, the levels of M1 and M2 macrophages in the high-risk group significantly increased, while the levels of mast cells resting and T cells CD4 memory resting significantly decreased. Conclusions: This study provides novel findings that can further the understanding of the role of m6A methylation during the progression of PCa, which may facilitate the invention of targeted therapeutic drugs.

Recent advances in aptamer-based therapeutic strategies for targeting cancer stem cells.

Cancer stem cells (CSCs) are believed to be the main cause of chemotherapy resistance and tumor relapse. Various therapeutic strategies to eliminate CSCs have been developed recently. Aptamers, also called "chemical antibodies", can specifically bind with their molecular targets through special tertiary structures. The advantages of aptamers, such as lower immunogenicity and smaller size, make them superior to conventional antibodies. Therefore, aptamers have been used widely as targeting ligands for CSC-targeted therapeutic strategies in different tumor types. To date, various therapeutic cargoes have been conjugated to aptamers to kill CSCs, such as chemotherapy drugs, small interfering RNAs, and microRNAs. Aptamer-based targeted therapies for CSCs have made great progress in recent years, especially the development of multifunctional aptamer-based therapeutic strategies. Besides, cell-systematic evolution of ligands by exponential enrichment has been applied to screen new aptamers that might have a higher binding ability for CSCs. In this review, we focus on recent advances and introduce some new modalities of aptamer-drug conjugates against CSCs. Some considerations of the advantages and limitations of different aptamer-based targeted therapies for CSCs are also discussed.

Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate.

BACKGROUND: Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC. METHODS: Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays. RESULTS: PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models. CONCLUSION: These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.

Single-site multiport vs. conventional multiport robot-assisted radical prostatectomy: A propensity score matching comparative study.

Objective: Robot-assisted radical prostatectomy (RARP) is a dynamically evolving technique with its new evolution of single-site RARP. Here we sought to describe our extraperitoneal technique, named the single-site multiport RARP (ssmpRARP) using the da Vinci Si® platform and compare it with the transperitoneal conventional multiport RARP (cmpRARP). Materials and Methods: Data were retrospectively collected for patients who underwent RARP for localized prostate cancer from June 2020 to January 2022 in a single center. Propensity score matching was performed based on age, prostate size, body mass index, neoadjuvant hormonal therapy usage, prostate-specific antigen levels, and clinical T stage. The differences between the matched two groups were investigated. Results: Of the patients, 20 underwent ssmpRARP and 42 underwent cmpRARP during the period. After matching, 18 patients from each group were selected. Median follow-up was 7.8 months (2-12 months) for the ssmpRARP group, and 15.0 months (3-26 months) for cmpRARP. The demographic features between the two groups were comparable. The median total operative time, estimated blood loss, pathologic data, early follow-up outcomes, and hospitalization stays and costs were similar between the two groups. The ssmpRARP group tended to return to their bowel activities earlier (44.78 ± 10.83 h vs. 54.89 ± 12.97 h, p = 0.016). There were no significant differences in complication rates. Conclusions: We demonstrated the feasibility and safety of performing extraperitoneal ssmpRARP using the da Vinci Si® robotic platform. Our technique showed comparable short-term outcomes with the transperitoneal cmpRARP. Prospective trials and long-term follow-up are necessary to confirm these results.

"Light green up": Indocyanine Green Fluorescence Imaging-guided Robotic Bilateral Inguinal Lymphadenectomy by the Hypogastric Subcutaneous Approach for Penile Cancer.

Background: Inguinal lymphadenectomy is of great significance in the management of penile cancer, which aims to mitigate the progression of lymph node metastasis. It is important to improve the efficiency of lymph node dissection and reduce surgical complications. Objective: To detail a novel technique for robotic bilateral inguinal lymphadenectomy through the hypogastric subcutaneous approach by indocyanine green (ICG) fluorescence imaging, which promotes the identification and dissection of inguinal lymph nodes with considerable safety. Design setting and participants: Ten eligible penile cancer patients who underwent ICG fluorescence imaging-guided robotic bilateral inguinal lymphadenectomy were prospectively enrolled (ICG group). Sixteen patients who underwent the surgery without ICG were retrospectively set as the control (non-ICG) group. Follow-up records for at least 12 mo were required. Surgical procedure: Inguinal lymphadenectomy was performed by the hypogastric subcutaneous approach. The ICG solution was subcutaneously injected into the prepuce at the beginning of surgery, and ICG fluorescence imaging-guided robotic-assisted bilateral inguinal lymphadenectomy was conducted. Measurements: Clinical outcomes were collected. The primary study outcome measurement was the number of dissected inguinal lymph nodes. Results and limitations: The numbers of inguinal overall, superficial, and deep lymph nodes retrieved were all higher in the ICG than in the non-ICG group (p < 0.05). No patients had severe perioperative complications. No difference was found in the overall complication rate and 12-mo survival between two groups (p > 0.05). Conclusions: ICG fluorescence imaging-guided robotic inguinal lymphadenectomy via the hypogastric subcutaneous approach is feasible and safe for patients with penile cancer, which is beneficial for dissecting more inguinal lymph nodes with few surgical complications. Patient summary: We developed a promising indocyanine green fluorescence imaging-guided technique to perform robotic bilateral inguinal lymphadenectomy on patients with penile cancer, which conduces to remove more inguinal lymph nodes with limited complications.

Negative Effects of Stromal Neutrophils on T Cells Reduce Survival in Resectable Urothelial Carcinoma of the Bladder.

Urothelial carcinoma of the bladder (UCB) is a major type of bladder cancer with a distinct tumor microenvironment (TME). Although neutrophils are the main component of myeloid cells in the TME, the clinical significance and function of the neutrophils remain unclear in UCB. Here, we observed CD66b+ neutrophils were predominantly enriched in the stroma of UCB tissues and their levels emerged as an independent prognostic factor for overall survival (P = 0.006, n = 237), and were positively associated with age (P = 0.033), tumor stage (P < 0.0001), nodal metastasis (P = 0.045), and histological grade (P < 0.0001). Furthermore, we found that CD66b+ neutrophils were frequently co-localized with CD4+ T cells (R=0.35, P = 0.0067), CD8+ T cells (R=0.52, P<0.0001) and Cleaved Caspase-3+ apoptosis cells (R=0.44, P = 0.0007) in the stroma of UCB tissue. In addition, better effects of T cells on patients' survival were markedly reduced by neutrophils and T cells co-infiltration. Moreover, we confirmed bladder tumor cell supernatant treated neutrophils suppressed T cell proliferation and activation, and promoted T cell apoptosis through GM-CSF induced PD-L1 in vitro. The expression of PD-L1 by neutrophils was also detected in fresh UCB tissues by using flow cytometric analysis. These data suggested that stromal CD66b+ neutrophils may potentially represent a reliable marker of poor prognosis for UCB patients, and neutrophils might play an immunosuppressive role on T cell immunity partially via the expression of PD-L1.

Identification of an IDO1-based immune classifier for survival prediction of upper tract urothelial carcinoma.

The limited response rate of immunotherapy in upper tract urothelial carcinoma (UTUC) might be attributed to additional immunosuppressive mechanisms in vivo. As a promising immune checkpoint target, the expression and prognostic role of indoleamine 2,3-dioxygenase 1 (IDO1) in UTUC remains unknown. In this study, the expression and prognostic value of IDO1 was analyzed in 251 patients from 3 independent cohorts. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to construct an IDO1-based immune classifier and external validation was performed to further validate the classifier. RNA sequencing and immunofluorescence were used to explore the immune contexture of different risk groups stratified by classifier. We found that high IDO1 expression on tumor cells (TC) indicated a poorer overall survival and disease-free survival in all cohorts. Patients with high expression of IDO1 TC possessed increased infiltration of CD4+ , CD8+ and Foxp3+ T cells. An immune classifier based on intratumoral CD8+ lymphocytes, IDO1 TC, and stromal PD-L1 expression status was developed, with its area under the curves (AUCs) values for overall survival at 5 y being 0.79 (95% confidence interval [CI] 0.65-0.93) in the discovery cohort, 0.75 (95% CI 0.58-0.92) and 0.78 (95% CI 0.65-0.92) in the internal and external validation cohorts, respectively. The high-risk group stratified by the immune classifier was associated with immunosuppressive contexture, accompanied by enhanced CD8+ T cells exhaustion patterns. Our IDO1-based immune classifier can provide a superior accuracy for survival prediction and lead to individual stratification of UTUC immune subtypes.

Targeting the Proteasome in Advanced Renal Cell Carcinoma: Complexity and Limitations of Patient-Individualized Preclinical Drug Discovery.

BACKGROUND: Systemic treatment options for metastatic renal cell carcinoma (RCC) have significantly expanded in recent years. However, patients refractory to tyrosine kinase and immune checkpoint inhibitors still have limited treatment options and patient-individualized approaches are largely missing. PATIENTS AND METHODS: In vitro drug screening of tumor-derived short-term cultures obtained from seven patients with clear cell RCC was performed. For one patient, a patient-derived xenograft (PDX) mouse model was established for in vivo validation experiments. Drug effects were further investigated in established RCC cell lines. RESULTS: The proteasome inhibitor carfilzomib was among the top hits identified in three of four patients in which an in vitro drug screening could be performed successfully. Carfilzomib also showed significant acute and long-term cytotoxicity in established RCC cell lines. The in vivo antitumoral activity of carfilzomib was confirmed in a same-patient PDX model. The cytotoxicity of carfilzomib was found to correlate with the level of accumulation of ubiquitinated proteins. CONCLUSIONS: In this proof-of-concept study, we show that patient-individualized in vitro drug screening and preclinical validation is feasible. However, the fact that carfilzomib failed to deliver a clinical benefit in RCC patients in a recent phase II trial unrelated to the present study underscores the complexities and limitations of this strategy.

Development and validation of a PD-L1/PD-1/CD8 axis-based classifier to predict cancer survival of upper tract urothelial carcinoma after radical nephroureterectomy.

The expression status of programmed cell death-ligand 1/programmed cell death 1 (PD-L1/PD-1) and the infiltration of CD8+ T cells in tumor tissues are considered to be related to immunotherapy efficacy and patient prognosis. The purpose of this study is to clarify the prognostic value of the PD-L1/PD-1/CD8 axis, and to develop and validate a comprehensive scoring system based on multiple immune variables to predict cancer survival of upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). The immunohistochemical method was used to detect the expression of PD-L1, PD-1, and CD8 in cancer tissues of UTUC patients after RNU. Then, an immunoscore was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression model in the training cohort (n = 120), and it was verified in the validation cohort (n = 54). We found that infiltration of PD-L1+ immune cells (ICs), stromal PD-1+ tumor-infiltrating lymphocytes (TILs), and intratumoral CD8+ TILs was associated with poor overall survival (OS). The immunoscore based on the three immune variables further divided the patients into low- and high-risk groups, and there was a significant difference in the survival rate. A nomogram was constructed by combining tumor-node-metastasis (TNM) stage and immunoscore, and the area under the curve of the receiver-operating characteristic (ROC) (0.78) for predicting 5-year mortality was better than that of the TNM stage (0.70) and immunoscore (0.76). Our results show that the PD-L1/PD-1/CD8 axis-based classifier have potential clinical application to predict cancer survival of UTUC patients after RNU.

Serum CCL27 predicts the response to Bacillus Calmette-Guerin immunotherapy in non-muscle-invasive bladder cancer.

The prediction of the response to Bacillus Calmette-Guerin (BCG) can help identify non-muscle-invasive bladder cancer (NMIBC) patients that may be better served with alternative therapy. Several cytokine profiles present promising results, but they are difficult to use in clinical practice. In this prospective, longitudinal study, we tried to identify reliable serum cytokines/chemokines to predict the response to BCG using samples collected before and during BCG induction therapy. We used the Bio-plex multiplex assays to identify potential BCG failure-related serum cytokines/chemokines in the discovery set (n = 13). After screening, we identified CCL27 as the top candidate biomarker for predicting the response to BCG (P = .003). In the validation set, we found that the AUC of the baseline CCL27 was 0.730 (95% CI 0.515-0.945, P = .040) along with 67% sensitivity, 78% specificity. The changes from baseline to last timepoint can also distinguish BCG responders from non-responders (AUC: 0.726, 95% CI 0.474-0.979, P = .044). Moreover, the combination score of serum CCL27 (CSCCL27), based on the baseline and changes of CCL27, could further improve the predictive accuracy with an AUC of 0.897 (95% CI 0.790-1.000, P < .001). The correlations between CCL27 and local/systemic immunologic parameters were further analyzed. The level of serum CCL27 was strongly correlated with regulatory T cells (Tregs) in the tumor microenvironment (P = .002), indicating that CCL27 may promote the recruitment of Tregs into the tumor microenvironment. Our results show that serum CCL27 may represent a practical and reliable marker for the prediction of the response to BCG in NMIBC.

PD-1 topographically defines distinct T cell subpopulations in urothelial cell carcinoma of the bladder and predicts patient survival.

INTRODUCTION: The pre-existing tumor-infiltrating T cell landscape in urothelial cell carcinoma of the bladder (UCB) may obtain prognostic significance and guide treatment decisions, particularly regarding immunotherapy. However, the current studies typically lead to inconsistent conclusions due to the extreme heterogeneity of T cells in cancer. Herein, we investigated the heterogeneity, distribution and clinical significance of tumor-infiltrating T cells based on PD-1 expression, their spatial organization, and the balance between subsets in a series of UCB patients. METHODS: Flow cytometry for PD-1, CD4, and CD8 was performed in 6 UBC patients and 5 healthy donors. A series of 155 UBC patients with tissue slides were stained for triple color immunofluorescence. Stromal and intratumoral regions of the cancer tissue were respectively evaluated. Features derived from triple staining were analyzed for their correlations with clinical characteristics and patient prognosis. RESULTS: Flow cytometric analysis showed PD-1+ T cells were more frequently accumulated at the tumor site than in blood (p < 0.001). The proportion of PD-1+ T cells within CD4+ and/or CD8+ T cells is higher in the intratumoral region, as compared with the stroma by immunofluorescence evaluation (all p < 0.001, n = 155). Moreover, a high proportion of PD-1+ T cells within T cells in the intratumoral region, but not in the stroma, was predictive of a poorer overall survival (p = 0.0075) and recurrence-free survival (p = 0.0062), and was positively associated with aggressive clinical features (all p < 0.05). However, a low CD4/CD8 ratio among the PD-1+ T cells in the tumor stroma, but not in the intratumoral region, was significantly associated with shorter overall survival (p = 0.0164) and recurrence-free survival (p = 0.0016), which emerged as an independent predictor in multivariate analysis for UCB patients. CONCLUSIONS: Taken together, our results emphasize that PD-1 expression in T cell subsets, based on their topographic micro-localizations, provides valuable prognostic information for UCB patients.

Microenvironment-Derived FGF-2 Stimulates Renal Cell Carcinoma Cell Proliferation through Modulation of p27Kip1: Implications for Spatial Niche Formation and Functional Intratumoral Heterogeneity.

BACKGROUND/OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is characterized by a high degree of functional intratumoral heterogeneity (ITH). This is highlighted by the finding that tumor cell proliferation and intracellular signaling occur preferentially in the tumor periphery. The driving forces for such a spatial organization are largely unknown. Herein, we investigate the role of the tumor microenvironment in the control of tumor cell proliferation and functional ITH. METHODS: Conditioned media (CM) derived from nonmalignant peritumoral kidney tissue were used to stimulate RCC cells in vitro. A neutralization assay was used to characterize the role of FGF-2 in the CM. The molecular mechanisms underlying the action of CM on RCC cells were investigated using immunoblotting, flow cytometry and immunofluorescence microscopy. Lastly, a series of ccRCCs were stained for Ki-67 and p27Kip1, and expression was analyzed in both tumor periphery and center. RESULTS: We show that CM derived from nonmalignant kidney cells adjacent to an RCC can downregulate the expression of the CDK inhibitor p27Kip1 through enhanced protein degradation in an FGF-2-dependent fashion. FGF-2 functions mainly through the PI3K/AKT pathway downstream of its receptors, and RCC cells with constitutively high AKT activity show not only an enhanced degradation of p27Kip1 through the Emi1-Skp2 axis, but also a subcellular mislocalization of p27Kip1 to the cytoplasmic compartment. Such a mislocalization was also detected in the tumor periphery in vivo suggesting that p27Kip1 plays an important role in shaping this spatial niche. CONCLUSIONS: Our results suggest that the tumor microenvironment is involved in shaping the tumor peripheral niche by stimulating the enhanced proliferation that is characteristic for this zone.

Microlocalization and clinical significance of stabilin-1+ macrophages in treatment-naïve patients with urothelial carcinoma of the bladder.

PURPOSE: Emerging evidence has shown that macrophages (Mφs) at different tumor sites have diverse clinical attributes. Stabilin-1 is a multi-functional scavenger marker for specialized tumor-associated Mφs. This study investigates the relationship between the density and microlocalization of stabilin-1+ Mφs within tumors and the clinical outcomes of patients with urothelial carcinoma of the bladder (UCB). METHODS: In this retrospective study, 283 UCB patients who received radical cystectomy or transurethral resection were examined. Immunohistochemistry and immunofluorescence analyses were used to colocalize the expression of stabilin-1 with other markers for Mφs (CD14, CD68, CD163, and CD206). Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival (OS) and recurrence-free survival (RFS). RESULTS: In UCB tissues, stabilin-1 was primarily expressed on Mφs, as evident from triple immunofluorescence staining for stabilin-1 and Mφ markers. Stabilin-1+ Mφs were often more prominent in stromal regions rather than intratumoral regions in UCB tissues (P < 0.0001). After dichotomization at the median cell density for stabilin-1+ Mφs, only intratumoral stabilin-1+ Mφ density was a predictor of poor OS (P < 0.001) and RFS (P = 0.026). Moreover, intratumoral stabilin-1+ Mφ density was positively associated with tumor stage (P < 0.01) and histological grade (P < 0.01), and emerged as an independent prognostic factor for OS (HR 2.371; P < 0.0001), but not for RFS (HR 1.491; P = 0.061). CONCLUSIONS: Our findings indicate that intratumoral stabilin-1+ Mφs could potentially be used as a pro-tumoral prognostic marker for UCB patients.

Prospective single center trial of next-generation sequencing analysis in metastatic renal cell cancer: the MORE-TRIAL.

AIM: Targeted therapies have substantially improved the survival of patients with metastatic clear cell renal cell cancer. No prognostic or predictive biomarkers are available. Comprehensive genetic profiling offers the opportunity to define prognostic and predictive signatures aiming at a more personalized approach to treatment. METHODS: In this prospectively conducted cohort study, tumor tissue and liquid biopsies are sampled at baseline and upon first and second progression under systemic treatment. Samples will be analyzed by whole-exome sequencing to generate prognostic and predictive patterns for systemic therapies. DISCUSSION: This study is aiming at exploring genetic profiles with prognostic and predictive value in metastatic renal cell cancer patients. Clonal evolution facilitating resistance to systemic treatment will be investigated by repeat biopsies.

Generation of autochthonous mouse models of clear cell renal cell carcinoma: mouse models of renal cell carcinoma.

Renal cell carcinoma (RCC) is one of the 10 most common cancers worldwide, and to date, a strong systemic therapy has not been developed to treat RCC, even with the remarkable modern advances in molecular medicine mostly due to our incomplete understanding of its tumorigenesis. There is a dire unmet need to understand the etiology and progression of RCC, especially the most common subtype, clear cell RCC (ccRCC), and to develop new treatments for RCC. Genetically engineered mouse (GEM) models are able to mimic the initiation, progression, and metastasis of cancer, thus providing valuable insights into tumorigenesis and serving as perfect preclinical platforms for drug testing and biomarker discovery. Despite substantial advances in the molecular investigation of ccRCC and monumental efforts that have been performed to try to establish autochthonous animal models of ccRCC, this goal has not been achieved until recently. Here we present a review of the most exciting progress relevant to GEM models of ccRCC.

[Diagnostic and therapeutic characteristics of the preoperatively misclassified complicated renal cysts].

OBJECTIVE: To explore the clinical features and treatment options of patients undergoing surgical masses excision for preoperatively misclassified complicated renal cysts. METHODS: Retrospective analysis was performed on clinical records of patients who received partial or radical nephrectomy at Department of Urology of Peking Union Medical College Hospital with postoperatively pathological examination as benign renal cysts from January 2008 to December 2014. RESULTS: There were a total of 31 patients meeting the inclusion criteria for analysis. Among them 4 patients were classified as Bosniak II renal cysts by preoperative ultrasonography and/or computed tomography (CT), 7 patients as Bosniak IIF and III respectively, 3 patients as Bosniak IV, as well as 10 patients as renal solid masses. The average max diameter of the lesions was 3.34 ± 2.45 cm (ranging from 0.8 cm to 14.3 cm), with 83.87% lesions less than 4 cm. Eighteen patients (58.06%) received open partial nephrectomy, while 13 patients underwent laparoscopic partial or radical nephrectomy. CONCLUSIONS: A considerable number of patients received unnecessary partial or even radical nephrectomy for misclassified benign renal cysts. Small high-density renal cysts could not only mimic solid renal masses on ultrasonography and plain CT, but also present pseudoenhancement on enhanced CT, thus easily leading to a misdiagnosis as solid renal tumors.

Angiomyolipoma being surgically excised for presumed kidney carcinoma.

OBJECTIVE: To explore the important factors involved in angiomyolipoma (AML) being preoperatively misclassified and surgically removed for presumed kidney carcinoma. MATERIALS AND METHODS: From 2008 to 2014, AML was pathologically confirmed in 38 patients who underwent radical or partial nephrectomy for presumed malignant renal tumor. Control group 1 were patients with renal cell carcinoma (RCC) matched for age and tumor size; control group 2 were patients with typical AML matched for age and sex. Pertinent data of the studied group and its matched control groups were recorded and analyzed. RESULTS: The mean age of the patients in study group was 48.11 ± 12.92 years, and the mean tumor size was 3.12 ± 1.68 cm (range 0.9-9.4). More than 84 % of the misclassified AMLs measured ≤4 cm, and over 21 % patients underwent radical nephrectomy. The only statistically significant feature between the misdiagnosed AML group and the matched RCC group is mean age (48.11 ± 12.92 vs. 56.92 ± 10.28, P = 0.002). Compared with the matched typical AML group, the misdiagnosed AML group has smaller mean tumor size (3.12 ± 1.68 vs. 5.85 ± 3.33, P < 0.001), but more patients undergoing radical nephrectomy (21.05 vs. 0 %, P = 0.003). Two main imaging features, which are hypoechoic on ultrasonography and fat density on computed tomography (CT), were statistically different between the two groups. The misdiagnosis of AML was significantly associated with no fat density on CT (OR 5.528, P = 0.004) and hypoechoic on ultrasonography (OR 3.845, P = 0.017). CONCLUSIONS: A number of AMLs were misdiagnosed as RCCs, causing a large number of unnecessary surgeries. No fat density on CT and no hyperechoic on ultrasonography resulting from small tumor size were the two most important factors causing AML being excised for presumed kidney carcinoma. Ultrasonography and CT cannot differentiate atypical AML from kidney carcinoma effectively, so improved renal biopsy and noninvasive biomarkers are urgently warranted to prevent us from excising benign renal tumor aggressively.