Intratumoral fibrosis and patterns of immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Intratumoral fibrosis was positively correlated with histological grade of renal clear cell carcinoma (ccRCC) and intratumoral inflammation. However, the association of intratumoral fibrosis with the immune infiltration of ccRCC was few evaluated. METHODS: We used the second harmonic generation (SHG)-based imaging technology and evaluated the intratumoral fibrosis in ccRCC, and then divided the patients into the high fibrosis group (HF) and the low fibrosis group (LF). Meanwhile, the Kaplan-Meier survival curve analysis was performed to analyze the relationship between intratumoral fibrosis and the disease-free survival rate. Antibody arrays were used for seeking difference in cytokines and immune infiltration between the HF group (N = 11) and LF group (N = 11). The selected immune infiltration marker was then verified by immunohistochemistry (IHC) staining in 45 ccRCC samples. RESULTS: Out of 640 cytokines and immune infiltration markers, we identified 115 proteins that were significantly different in quantity between ccRCC and adjacent normal tissues. In addition, the Venn diagram indicated that six proteins, including Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), were significantly associated with intratumoral fibrosis (p < 0.05). The GO/KEGG enrichment analysis indicated that the proteins associated with intratumoral fibrosis were involved in the immunity and tumor-infiltrating lymphocytes. The expression of the CTLA4 was negatively correlated with collagen level, confirmed by IHC staining of CTLA4 (p < 0.05). CONCLUSIONS: The study indicated that the intratumoral fibrosis level was negatively correlated with the expression of CTLA4 in the tumor immune microenvironment of the ccRCC, which posed the potential value of targeting the stroma of the tumor, a supplement to immunotherapy. However, the specific mechanism of this association is still unclear and needs further investigation.

Predicting ureteral status below the ureteral calculi in patients undergoing ureteroscopic lithotomy.

BACKGROUND: During ureteroscopy, severe ureter straightness or contortion may occur before the stone is passed. PURPOSE: To identify clinical factors associated with distal ureteral status below the ureteral calculi in patients before surgery. MATERIAL AND METHODS: From October 2016 to March 2017, 101 patients with ureteral calculi who underwent ureteroscopic lithotripsy were reviewed. Patients who lacked clinical data and underwent preoperative indwelling ureteral stent placement were excluded. Univariate and multivariate analyses were performed to determine the clinical factors associated with intraoperative findings. RESULTS: A total of 101 patients were enrolled in the study (mean age = 54 years; mean stone size = 7.9 ± 4.5 mm). Overall, 25 of the 101 patients (24.7%) were diagnosed with poor distal ureteral status defined as intraoperative ureterostenosis or contortion resulting in a ureteroscope being unable to pass during the initial attempt. Univariate analysis showed significant differences in renal parenchyma thickness, ureteral wall thickening on imaging, and stone location (all, P < 0.05) with and without poor distal ureteral status. On multivariable analysis, renal parenchyma thickness (adjusted odds ratio [aOR] 0.288; 95% confidence interval [CI] 0.099-0.838; P = 0.022) and ureteral wall thickening on imaging (aOR 6.114; 95% CI 2.015-18.548; P = 0.001) independently predicted poor distal ureteral status. However, only renal parenchyma thickness was associated with severe ureter straightness or tortuosity that resulted in conversion. CONCLUSION: In conclusion, renal parenchyma thickness and ureteral wall thickening on imaging were associated with poor distal ureteral status. Therefore, patients with these predictive factors should undergo more intensive preparation before surgery.

A laparoscopic radical inguinal lymphadenectomy approach partly preserving great saphenous vein branches can benefit for patients with penile carcinoma.

BACKGROUND: Inguinal lymphadenectomy (iLAD) is effective for penile carcinoma treatment, but usually results in many complications. This study aims to clinically evaluate the feasibility and clinical significance of a laparoscopic radical iLAD approach partly preserving great saphenous vein branches for penile carcinoma patients. METHODS: A total of 48 patients with penile cancer who underwent laparoscopic radical iLAD with retention of the great saphenous vein in Henan Cancer Hospital from 2012 Jan to 2020 Dec were included in this study. Sixteen penile carcinoma patients who underwent laparoscopic radical iLAD preserving parts of superficial branches of the great saphenous vein were identified as the sparing group, and the matched 32 patients who incised those branches were identified as control group. This new procedure was performed by laparoscopy, preserving parts of superficial branches of the great saphenous vein, superficial lateral and medial femoral veins. Clinicopathological features and perioperative variables were recorded. Postoperative complications, including skin flap necrosis, lymphorrhagia, and lower extremity edema were analyzed retrospectively. RESULTS: We found that the operative time of the sparing group is significantly longer than the control group (p = 0.011). There was no statistical difference in intraoperative blood loss, the lymph node number per side, average time to remove the drainage tube and postoperative hospital stay between the two groups. Compared to the control group, the sparing group showed a significantly decreased incidence of lower extremity edema (p = 0.018). The preservation of parts of superficial branches of the great saphenous vein was mainly decreased the incidence of edema below ankle (p = 0.034). CONCLUSIONS: This study demonstrated that the iLAD with preserving parts of superficial branches of the great saphenous vein, with a decreased incidence of postoperative complications, is a safe and feasible approach for penile cancer.

[Immunotherapy Based on Tumor Microenvironment in Renal Cell Carcinoma].

Renal cell carcinoma (RCC) is a common lethal urological cancer,the distant metastasis of which is the leading cause of death.Although targeted agents have remarkably improved the overall prognosis of RCC patients,nearly all the patients eventually acquire therapeutic resistance.With the advent of immune checkpoint inhibitors,immunotherapy based on tumor microenvironment (TME) has shown a broad scope in clinical application.The deepening understanding of TME leads to the changes of therapeutic strategies for advanced RCC,and the combination of targeted therapy and immunotherapy is exhibiting a promising prospect.Herein,we reviewed the TME characteristics,candidate predictive biomarkers,and possible targets for future development of drugs against RCC.

The Clinical Effects of Utilizing Allogeneic Acellular Dermal Matrix in the Surgical Therapy of Anterior Urethral Stricture.

OBJECTIVE: The aim of this study was to estimate the clinical effects of allogeneic acellular dermal matrix (ADM) in the surgical therapy of anterior urethral stricture (AUS). METHODS: We retrospectively collected the clinical data of 49 patients with AUS who underwent urethral repair surgery with ADM in the Department of Urology of the Peking University People's Hospital, and in the First Affiliated Hospital of the People's Liberation Army, from September 2015 to January 2019. The changes in urine flow rate and conditions of urethral mucosal coverage were observed as well as complications and outcomes, and statistical analysis was performed. RESULTS: The average maximum urine flow rates at the 1st, 6th, and 12th month post-surgery were 16.3 ± 1.5, 15.0 ± 1.9, and 14.6 ± 2.1 mL/s, respectively. These values were significantly higher than the preoperative maximum urine flow rate, 1.3 ± 0.5 mL/s (p < 0.05). Cystoscopy was performed in 11 patients 12 months after surgery, with microscopic assessment revealing good urethral epithelial mucosal coverage. Only 2 patients developed infection 2-4 weeks after surgery, while 7 patients developed noninfective urethral restricture 6-10 months after surgery and 1 patient developed urinary fistula 5 months after surgery. All of these statuses improved after receiving appropriate treatment. CONCLUSIONS: Use of ADM represents a new option for the surgical management of AUS repair and reconstruction, with positive clinical effects. In addition, it has the advantages of convenient for operation procedures and access, with no need for additional sampling surgery.

Iron fluoride hollow porous microspheres: facile solution-phase synthesis and their application for Li-ion battery cathodes.

Iron fluoride cathodes have been attracting considerable interest due to their high electromotive force value of 2.7 V and their high theoretical capacity of 237 mA h g(-1) (1 e(-) transfer). In this study, uniform iron fluoride hollow porous microspheres have been synthesized for the first time by using a facile and scalable solution-phase route. These uniform porous and hollow microspheres show a high specific capacity of 210 mA h g(-1) at 0.1 C, and excellent rate capability (100 mA h g(-1) at 1 C) between 1.7 and 4.5 V versus Li/Li(+) . When in the range of 1.3 to 4.5 V, stable capacity was achieved at 350 mA h g(-1) at a current of 50 mA g(-1) .

Case report: Isolated eyelid metastasis of ccRCC 5 years after receiving radical nephrectomy.

Introduction: The most common sites of clear cell renal cell carcinoma(ccRCC) metastasis are the lung, bones, liver and brain; eyelid metastasis is a rare occurrence. Case presentation: We report a case of ccRCC metastasis to the left eyelid after radical nephrectomy, and remission after sunitinib treatment. Conclusions: Although the probability of eyelid metastasis rate is very low, tumor metastasis to the eyelid skin is possible after radical nephrectomy. Therefore, any rash like changes on the skin during the review procedure cannot be ignored by the physician.

Clinical study of renal artery cold perfusion combined with laparoscopic nephron retention in the treatment of complex renal angiomyolipoma.

Objective: The aim of this study is to summarize the surgical experience of renal artery cold perfusion combined with laparoscopic nephron preserving surgery for the treatment of complex renal angiomyolipoma and to evaluate the safety and feasibility of this surgical protocol. Materials and methods: Clinical data of nine patients who received renal artery cold perfusion combined with laparoscopic nephron preserving surgery for complex renal angiomyolipoma in our hospital from February 2017 to August 2020 were retrospectively analyzed. The study parameters included imaging findings, total renal function before and after surgery, glomerular filtration rate (GFR) of affected kidney before and after surgery, and related complications. Results: Eight of the nine patients successfully completed the operation, one patient was intolerant to renal artery balloon implantation, and the success rate of the operation was 88.89%. The mean maximum tumor diameter was 6.8 cm, and RENAL score was 7 points. Postoperative total renal function and GFR of the affected kidney had no significant changes compared with that before surgery, and imaging examination showed no tumor residue or recurrence. Conclusion: This surgical procedure is safe and feasible for complex renal angiomyolipoma and can be used as a surgical option for renal hamartoma. The long-term effect needs to be confirmed by further studies.

PD-1 inhibitor toripalimab with gemcitabine as a neoadjuvant therapy for muscle-invasive bladder urothelial carcinoma: A case report.

RATIONALE: Routine neoadjuvant therapy for muscle-invasive bladder urothelial carcinoma prior to radical surgery is curative. With the increase in cancer immunotherapy, neoadjuvant immunotherapy has been used as an important complement to neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma. Toripalimab is a recombinant, humanized IgG4 monoclonal antibody directed against programmed cell death protein 1 and received the first global approval for the treatment of unresectable or metastatic melanoma in China on December 17, 2018. PATIENT CONCERNS AND DIAGNOSIS: A 57-year-old man was admitted to our hospital because of hematuria for 1 week. The patient was diagnosed pathologically with muscle-invasive bladder urothelial carcinoma. INTERVENTIONS AND OUTCOMES: The patient received neoadjuvant toripalimab combined with gemcitabine therapy. The patient showed partial response. Subsequently, radical cystectomy was performed. LESSONS: Toripalimab combined with gemcitabine exhibited accurate antitumor activity and may be a promising novel neoadjuvant therapy for muscle-invasive urothelial carcinoma.

Case report: Gemcitabine intravesical hyperthermic infusion combined with tislelizumab in muscle invasive bladder urothelium carcinoma.

Background: Muscle invasive bladder urothelium carcinoma is a common urinary tract tumor. With the deepening of research, more and more treatment methods are applied in clinical practice, extending the life of patients. Among them, the clinical application of chemotherapeutic intravesical hyperthermia and tumor immunotherapy provides new ideas for our treatment. Case report: An 81-year-old female patient was diagnosed with stage T2N0M0 bladder cancer in our hospital. Because the patient and her family were keen to preserve her bladder, they declined surgery and opted for combined chemotherapy. After informed consent from the patient and her family, she received cisplatin combined with gemcitabine intravesical hyperthermic infusion. But the side effects of cisplatin made her intolerable to chemotherapy. With their informed consent we changed her to intravenous tislelizumab in combination with gemcitabine intravesical hyperthermic infusion to continue her treatment. During the subsequent follow-up visits, we found a surprising effect of the treatment. Conclusion: Gemcitabine intravesical hyperthermia therapy combined with intravenous tislelizumab in the treatment of muscle invasive bladder urothelium carcinoma may provide a new possible therapeutic strategy of some patients who are inoperable or refuse surgery.

The Significance of Fibrosis Quantification as a Marker in Assessing Pseudo-Capsule Status and Clear Cell Renal Cell Carcinoma Prognosis.

Fibrosis plays an important role in tumor growth and progression, and thus, we aimed to determine whether renal fibrosis is correlated with the clinical and pathological characteristics and prognosis of clear cell renal cell carcinoma (ccRCC). Fibrosis, including intra-tumoral fibrosis (ITF), pseudo-capsule (PC) fibrosis and adjacent normal renal interstitial fibrosis, was evaluated in 73 pairs of ccRCC specimens using second harmonic generation combined with two-photon excitation fluorescence (SHG/TPEF). The clinical and pathological characteristics of the patients who were eligible for the present study were recorded. The associations between fibrosis and clinicopathological parameters were analyzed using a Mann-Whitney U test or logistic regression analysis. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and a Cox regression model. High-resolution images of fibrosis were captured from unstained slides using the SHG/TPEF approach. Both ITF and PC fibrosis were associated with tumor progression in ccRCC. Multivariate logistic regression analysis revealed a significant inverse association between the PC collagen proportional area (CPA) and PC invasion (p < 0.05), suggesting that PC CPA is an independent risk factor or marker for PC invasion. A significant decrease in progression-free survival (PFS), determined by Kaplan-Meier curves, was observed for patients with higher PC CPA status compared with those with lower PC CPA status (p < 0.05). Similar results were observed in patients with PC invasion. In multivariate Cox regression analysis, PC invasion and intra-tumoral necrosis were identified as independent prognostic factors for PFS. Our data suggest that ITF and PC fibrosis are associated with ccRCC progression. In addition, PC fibrosis may act as a marker of PC invasion and an effective quantitative measurement for assessing prognosis.

Expression of CREPT is associated with poor prognosis of patients with renal cell carcinoma.

Cell-cycle-associated and expression-elevated protein in tumor (CREPT) functions as a cell cycle modulator that enhances the transcription of cyclin D1 by interacting with RNA polymerase II. CREPT has been identified to be overexpressed in various human cancer types; however, the expression and significance of CREPT in renal cell carcinoma (RCC) has remained largely elusive. In the present study, increased expression of CREPT was identified in 46.7% RCC tissues compared with adjacent normal tissue (31.1%; P=0.032) using immunohistochemistry. Furthermore, overexpression of CREPT was significantly associated with the Tumor-Node-Metastasis stage (χ2=11.967, P=0.001) and Fuhrman grade (χ2=15.453, P<0.001). In addition, increased expression of CREPT was associated with poor overall survival (P=0.021) and disease-free survival (P=0.015) of patients according to Kaplan-Meier analysis. Cellular function assays demonstrated that knockdown of CREPT in the 786-O and 769P RCC cell lines suppressed their proliferative, colony formation, migratory and invasive capacity and led to cell cycle arrest in the G1 phase. In addition, the western blotting analysis demonstrated that CREPT may control the cell cycle through downregulation of cyclin D1 and c-myc. Collectively, the overexpression of CREPT was indicated to be a negative prognostic factor for RCC, and CREPT may serve as a novel therapeutic target for the treatment of RCC.

Acellular dermal matrix in premature ejaculation: A preliminary study.

BACKGROUND: To investigate the efficacy of acellular dermal matrix in penis augmentation (ADMPA) for premature ejaculation (PE). METHODS: A total of 39 patients treated with ADM in penis augmentation from June 2014 to December 2017 were evaluated. Detailed evaluations on PE were conducted before operation and at the 6-month and 2-year follow-up visits after operation. Self-estimated intravaginal ejaculatory latency time (IELT) and 5-item version of the International Index of Erectile Function (IIEF-5) were used to measure the ejaculation and the erectile function for all subjects. RESULTS: Compared to the baseline data, the IELT and IIEF-5 scores were increased, and PE was relieved at 6 months and 2 years after operation. No major complications occurred in the series. Minor complications were resolved with conservative treatment within 3 weeks. The psychosexual impact of the operation was beneficial in the majority of cases. CONCLUSION: Our survey systematically evaluated the effects of ADMPA for PE. ADMPA might be an optional surgical method in patients with PE, especially for those who seek penile augmentation. However, given the small amount of cases involved in this study, further studies on the effect of ADMPA for PE were still needed.

Overexpression of SOX18 promotes prostate cancer progression via the regulation of TCF1, c-Myc, cyclin D1 and MMP-7.

Sex determining region Y (SRY)-box 18 (SOX18) gene encodes transcription factors that have been recently confirmed to be overexpressed in various human types of cancer and maintain the malignant behavior of cancer cells. However, the role and its potential function in prostate cancer (PCa) has not been demonstrated and the mechanisms of SOX18 involved in tumor progression remain largely unclear. In the present study, the expression of SOX18 was analyzed in 98 PCa and 81 adjacent non-tumor tissues using immunohistochemistry. The data showed that SOX18 was overexpressed in 72 of 98 (73.5%) PCa tissues compared with that in 28 of 81 (34.6%) non-tumor tissues. In addition, the expression of SOX18 was related with the clinical features of patients with PCa. To explore the potential role of SOX18 in PCa cells, Cell Counting Kit-8 (CCK-8), migration, invasion and xenograft assays were performed. Our data showed that knockdown of SOX18 decreased the proliferation, migration and invasion of PCa cells in vitro, in addition to the tumor growth in vivo. Markedly, SOX18 knockdown caused the decreased expression of TCF1, c-Myc, cyclin D1 and MMP-7. In conclusion, SOX18 was overexpressed in PCa and may regulate the malignant capacity of cells via the upregulation of TCF1, c-Myc, cyclin D1 and MMP-7.

Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma.

BACKGROUND: The involvement of lipid metabolism in tumourigenesis and the progression of clear cell renal cell carcinoma (ccRCC) have been reported. However, the role of phospholipid profile alterations in ccRCC has not yet been systematically explored. In the present study, we compared the phospholipid compositions between ccRCC and paired normal renal tissues. METHODS: The phospholipid compositions of paired ccRCC and normal renal tissues were evaluated using liquid chromatography tandem mass spectrometry (LC/MS/MS). To evaluate the mRNA and protein levels of lysophosphatidylcholine acyltransferase (LPCAT), which converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), qRT-PCR, western blotting and immunohistochemistry were performed. The correlations of LPCAT1 expression with clinicopathological features and prognosis were assessed. In addition, siRNAs were used to knockdown LPCAT1 expression in ccRCC cell lines, and its effect on cell proliferation, cell cycle, migration and invasion were investigated. RESULTS: The phospholipid compositions of ccRCC and normal renal tissues were significantly different. Multiple LPC species were decreased and corresponding PC species were increased in cancer tissues. The mRNA and protein levels of LPCAT1 were up-regulated in ccRCC tissues compared with normal renal tissues, and LPCAT1 expression was significantly correlated with unfavourable pathological features (higher tumour grade, higher TNM stage and larger tumour size) and overall survival. In cell line experiments, LPCAT1 knockdown depleted PCs, inhibited cell proliferation, migration and invasion and induced cell cycle arrest at the G0/G1 phase. CONCLUSION: Selective changes in PC and LPC composition were observed in ccRCC tissues. The overexpression of LPCAT1 promotes the development and progression of ccRCC, likely through the conversion of LPC to PC.

Involvement of cancer-derived IgG in the proliferation, migration and invasion of bladder cancer cells.

It is widely accepted that immunoglobulin (Ig), the classical immune molecule, is extensively expressed in many cell types other than B-cells (non-B-IgG), including some malignant cells. The expression of Ig in malignant cells has been associated with a poor prognosis. In the present study, immunohistochemical analysis detected strong positive staining of IgG in three bladder cancer cell lines, the cancer cells in 77 bladder cancer patient samples and the cells in 3 cystitis glandularis tissue samples, while negative staining was observed in 4 specimens of normal transitional epithelial tissues. Importantly, functional transcripts of IgG with unique VHDJH rearrangement patterns were also found in bladder cancer cells. The knockdown of IgG in bladder cancer cell lines using small interfering RNA significantly inhibited the proliferation, migration and invasion of the cells. Notably, high IgG expression, as determined by immunostaining, was significantly correlated with a high histological grade and recurrence. The results of the present study suggested that IgG expression is involved in the malignant biological behavior and poor prognosis of bladder cancer. Therefore, IgG may serve as a novel target for bladder cancer therapy.

IgG is involved in the migration and invasion of clear cell renal cell carcinoma.

OBJECTIVE: To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis. MATERIALS AND METHODS: By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines. RESULTS: By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC. CONCLUSION: IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.