Adverse events in patients with advanced urothelial carcinoma treated with erdafitinib: a retrospective pharmacovigilance study.

Purpose: On 12 April 2019, erdafitinib gained the first FDA approval as the second-line treatment for adult patients with locally advanced or metastatic urothelial cancer following progression during or after at least one previous line of platinum-based chemotherapy. However, the long-term safety profile of erdafitinib in a large patient population remains unexplored. The current study aimed to assess the adverse events (AEs) associated with erdafitinib through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Method: The reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms based on disproportionality were employed to quantify the signals of erdafitinib-associated AEs. Results: A total of 6,322,279 reports of AEs were retrieved from the FAERS database spanning 2019 to 2022, out of which, 700 reports of erdafitinib as the "primary suspected" were identified. These erdafitinib-induced AEs were observed across 24 targeted system organ classes (SOCs). After conforming to the four algorithms at the same time, a total of 441 signals of erdafitinib-induced AEs were detected across 23 SOCs. Notably, signals associated with metabolism and nutrition disorders, eye disorders, and skin and subcutaneous tissue disorders were among the most prevalent. The median onset time for AEs was found to be 54 days [interquartile range (IQR) 17-112 days], with a majority of AEs occurring within the initial 6 months after initiating erdafitinib (37.23% within the first month, 15.53% within the second month, and 16.79% within the third month). Conclusion: The findings of this study align with existing clinical observations, offering a comprehensive long-term post-marketing safety evaluation of erdafitinib. The results provide valuable evidence to enhance the understanding of erdafitinib's safety profile, aiding further research and guiding clinical practice.

Efficacy of compound aluminum sulfate injection as a monotherapeutic regimen in non-muscle invasive bladder cancer patients: a retrospective single-arm cohort study.

Background: Compound aluminum sulfate injection (CASI) originated from a Chinese traditional medicine, "Kuzhiye", and has been used in treating non-muscle invasive bladder cancer (NMIBC). Previous studies suggested that CASI was a potential monotherapeutic drug for NMIBC. However, the efficacy and safety of CASI in the treatment of NMIBC, as well as the long-term recurrence after treatment, need to be further evaluated. Methods: A multicenter retrospective single-arm cohort study was conducted. From 2006 to 2009, 101 patients (74 men and 27 women, aged 58.9±11.9 years) with T1 or benign NMIBC were enrolled. Each patient was directly injected with CASI through catheter needle into the root of NMIBC. Vital signs, electrocardiography, blood count, blood biochemistry, and urine analysis were re-examined on day 2 and day 14 after CASI injection, together with a cystoscopic examination 4 weeks after CASI treatment was performed for all patients to assess the clinical activity and safety of CASI. To study long-term efficacy, patients in center 2 were followed up for recurrence with a median follow-up time of 13.8 years. Results: For the 101 patients enrolled in this study, demographic characteristics in the 3 centers showed no significant differences. After CASI, 2 patients showed administration site-dependent, but not dose-dependent, increase in their aluminum concentration in 24 hours without obvious abnormality in blood biochemistry. The overall effective rate was 97.03%, including complete tumor necrosis in 94 patients. Treatment-related adverse events occurred in 20 patients (19.80%), including 9 drug-related and 11 cystoscopy-related adverse events (AEs). All AEs were endurable and disappeared within 2 weeks without any treatment. The maximum tolerated single dose of CASI was 21 mL. Among the 43 patients at center 2, 3 patients were excluded because they changed to other treatment regimen. As of April 2022, of the 40 patients enrolled, 22 had no recurrence and 7 relapsed. The follow-up time was 2-16.2 years. The other 11 patients were lost to follow up. Conclusions: CASI may be an effective and safe option for the treatment of NMIBC and is expected to be a potential monotherapy regimen for NMIBC.

Fe(III)-Doped Polyaminopyrrole Nanoparticle for Imaging-Guided Photothermal Therapy of Bladder Cancer.

Clinically, the surgical treatment of bladder cancer often faces the problem of tumor recurrence, and the surgical treatment combined with postoperative chemotherapy to inhibit tumor recurrence also faces high toxicity and side effects. Therefore, the need for innovative bladder cancer treatments is urgent. For the past few years, with the development of nano science and technology, imaging-guided therapy using nanomaterials with both imaging and therapy functions has shown great advantages and can not only identify the locations of the tumors but also exhibit biodistributions of nanomaterials in the tumors, significantly improving the accuracy and efficacy of treatment. In this work, we synthesized Fe(III)-doped polyaminopyrrole nanoparticles (FePPy-NH2 NPs). With low cytotoxicity and a blood circulation half-life of 7.59 h, high levels of FePPy-NH2 NPs accumulated in bladder tumors, with an accumulation rate of up to 5.07%ID/g. The coordination of Fe(III) and the amino group in the structure can be used for magnetic resonance imaging (MRI), whereas absorption in the near-infrared region can be applied to photoacoustic imaging (PAI) and photothermal therapy (PTT). MRI and PAI accurately identified the location of the tumor, and based on the imaging data, laser irradiation was employed accurately. With a high photothermal conversion efficiency of 44.3%, the bladder tumor was completely resected without recurrence. Hematological analysis and histopathological analysis jointly confirmed the high level of safety of the experiment.

Functional Nanomedicines for Targeted Therapy of Bladder Cancer.

Bladder cancer is one of most common malignant urinary tract tumor types with high incidence worldwide. In general, transurethral resection of non-muscle-invasive bladder cancer followed by intravesical instillation of chemotherapy is the standard treatment approach to minimize recurrence and delay progression of bladder cancer. However, conventional intravesical chemotherapy lacks selectivity for tumor tissues and the concentration of drug is reduced with the excretion of urine, leading to frequent administration and heavy local irritation symptoms. While nanomedicines can overcome all the above shortcomings and adhere to the surface of bladder tumors for a long time, and continuously and efficiently release drugs to bladder cancers. The rapid advances in targeted therapy have led to significant improvements in drug efficacy and precision of targeted drug delivery to eradicate tumor cells, with reduced side-effects. This review summarizes the different available nano-systems of targeted drug delivery to bladder cancer tissues. The challenges and prospects of targeted therapy for bladder cancer are additionally discussed.

Synergistically Enhanced Mucoadhesive and Penetrable Polypeptide Nanogel for Efficient Drug Delivery to Orthotopic Bladder Cancer.

Intravesical chemotherapy has been recommended after the gold standard of transurethral resection of the bladder tumor to prevent bladder cancer (BC) from local recurrence in the clinic. However, due to rapid urine excretion and barrier protection of the bladder wall, the clinical performances of chemotherapeutic drugs are severely compromised. In the present work, a smart positively charged disulfide-crosslinked nanogel of oligoarginine-poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine) (R9-PEG-P(LP-co-LC)) was prepared to prolong the retention period and enhance the penetration capability of chemotherapeutic agent toward the bladder wall. PEG significantly improved the aqueous dispersibility of the 10-hydroxycamptothecin (HCPT)-loaded R9-PEG-P(LP-co-LC) (i.e., R9NG/HCPT) and enhanced the mucoadhesive capability by the nonspecific interaction between PEG chain and the bladder mucosa accompanied with the electrostatic interaction between the cationic R9 and negatively charged bladder mucosa. Besides, R9, as a cell-penetrating peptide, efficiently penetrated through the cell membrane and delivered carried cargo. The disulfide bond endowed the selective release behavior of HCPT triggered by the intracellular reductive microenvironment. As an advanced chemotherapeutic nanoformulation, the smart R9NG/HCPT demonstrated superior cytotoxicity against human BC 5637 cells in vitro and remarkably enhanced tumor suppression activity toward orthotopic BC models of mouse and rat in vivo, indicating its great potential in the clinical intravesical BC chemotherapy.

Preparation and Characterization of Chitosan Nanoparticles for Chemotherapy of Melanoma Through Enhancing Tumor Penetration.

The poor solubility and permeability of most chemotherapeutic drugs lead to unsatisfactory bioavailability combined with insufficient drug concentration. In this study, positively charged nanoparticles based on chitosan were developed and synthesized to enhance tumor penetration capability of 10-Hydroxycamptothecin (HCPT) in order to improve the chemotherapeutic effect of melanoma. The HCPT encapsulated nanoparticles were noted as NPs/HCPT. NPs/HCPT was characterized by dynamic light scattering and zeta potential measurements. In addition, cell uptake, in vitro cytotoxicity, apoptosis and in vivo antitumor activity of NPs/HCPT were further investigated. The average diameter of NPs/HCPT was approximately 114.6 ± 4.1 nm. The viability of murine melanoma cell lines (B16F10 and B16F1) was significantly decreased due to interaction with NPs/HCPT. Moreover, NPs/HCPT significantly inhibited the progression of tumors. These investigations implied that cationic NPs/HCPT could be potentially applied as a promising drug delivery nanosystem.

3-dimensional ultrasound-guided percutaneous nephrolithotomy: total free versus partial fluoroscopy.

PURPOSE: To provide a comprehensive analysis about safety and efficacy of fluoroscopy-free total ultrasound-guided percutaneous nephrolithotomy (TUPN) versus ultrasound with fluoroscopy-guided percutaneous nephrolithotomy (UFPN). PATIENTS AND METHODS: 3-dimensional ultrasound-guided PCNL was retrospectively analyzed in 377 patients from 2015 to 2017. TUPN was performed in 185 patients and UFPN was finished in 192 patients. In TUPN group, the entire procedures of puncture and dilation were real-time monitored by three-dimensional ultrasound alone. Conversely, in UFPN group, the puncture was performed under the guidance of real-time ultrasound, while the dilation was monitored by fluoroscopy. Preoperative demographic data, intraoperative parameters and postoperative complications were compared. RESULTS: Groups were comparable in baseline characteristics. Fifty percent of patients were Guy's score III-IV and over half of the patients were mild or none of hydronephrosis. All renal punctures were successfully performed. The primary successful rates of dilation were more than 95% in both groups (95.1% in TUPN and 95.8% in UFPN, p = 0.74). Two or more accesses were established in 33 patients (17.8%) in TUPN group and 25 patients (13%) in UFPN group (p = 0.20). Post-operative instant stone-free rates were 88.6% and 90.1%, TUPN versus UFPN, respectively, p = 0.65. Most of the complications were minor and there were no differences in Clavien-Dindo complications in both groups. Mean operating time and hospitalization were comparable. CONCLUSIONS: Our findings show that fluoroscopy-free total ultrasound-guided PCNL represents an alternatively safe and efficient approach for the treatment of renal stones. Further study will be required to evaluate fluoroscopy-free TUPN in various clinical settings.

Targeted multifunctional nanomaterials with MRI, chemotherapy and photothermal therapy for the diagnosis and treatment of bladder cancer.

Bladder cancer is a common urinary tract tumor in clinic, and its morbidity and mortality are always high. Surgical treatment is operator dependent, residual tumor cells often lead to tumor recurrence, and chemotherapy after surgery causes high side effects. So, it is urgent to develop new methods for the theranostics of bladder cancer. Among them, functional nanomaterials have shown good application in tumor theranostics, but they are rarely used in bladder cancer. In our work, we demonstrate the fabrication of folate-modified vincristine-loaded polydopamine-coated Fe3O4 superparticles (Fe3O4@PDA-VCR-FA SPs), and applied them in the theranostics of bladder cancer. The PDA shell not only improves the colloidal stability and biocompatibility, but also enhances the photothermal effect and prolongs the blood circulation half-life. The half-life of Fe3O4@PDA-VCR-FA SPs in blood is calculated as 2.83 h, and the tumor retention rate is 5.96 %ID g-1, these data are significantly higher than those before folic acid modification. The superparamagnetism of Fe3O4 and loading of vincristine endow Fe3O4@PDA-VCR-FA SPs with magnetic resonance imaging and chemotherapy capabilities. Further by employing NIR laser-triggered photothermal therapy, bladder tumors were ablated completely, and no recurrence was observed. Blood and histological tests of the major organs confirm that Fe3O4@PDA-VCR-FA SPs show good biosafety.

Tumor Microenvironment-Responsive Nanoshuttles with Sodium Citrate Modification for Hierarchical Targeting and Improved Tumor Theranostics.

Enhancement of permeability and the retention effect is one of the main pathways for the accumulation of nanomaterials in tumor sites, but poor cellular internalization and rapid clearance of nanomaterials always hamper the efficacy of imaging diagnosis and treatment. With the consideration of both high tumor accumulation and cellular internalization, positively charged nanomaterials can adhere to the tumor cell membrane by an electrostatic force, which is conducive to cellular internalization, but they are easily recognized and cleared during blood circulation. However, negatively charged nanomaterials show an enhanced stealth-like effect and possess a long blood circulation time, which is conducive to tumor accumulation. Therefore, in this work, on the basis of the shielding effect of citrate ions to positive charge and the protonation under an acidic tumor microenvironment, pH-sensitive sodium citrate-modified polyaniline nanoshuttles (NSs) with negative charge during blood circulation but positive charge in tumor sites are designed. With this hierarchical targeting strategy, the blood circulation half-life increases from 4.35 to 7.33 h, and the retention rate of NSs in tumors increases from 5.29 to 8.57% ID/g. Because the retention rate of NSs is increased, the magnetic resonance imaging resolution and signal intensity are significantly improved. A synergistic treatment of tumors is further achieved by means of photothermal therapy with laser irradiation and chemotherapy via heat-stimulated drug release.

Tropomyosin-1 Functions as a Tumor Suppressor with Respect to Cell Proliferation, Angiogenesis and Metastasis in Renal Cell Carcinoma.

Background: Tropomyosin-1 (TPM1) has long been known to be an actin-binding cytoskeletal protein. Multiple recent studies have revealed that TPM1 is down-regulated in various malignant tumors, including renal cell carcinoma (RCC). Methods: To further verify its role in RCC, transfection of a reconstructed plasmid was used to bi-directionally regulate TPM1 levels. A colony formation assay, tube formation assay and invasion assay were adopted to assess cell proliferation, angiogenesis and metastasis, respectively, in the 786-O and ACHN cell lines. The xenograft tumor sizes were measured, and the microvessel density (MVD) was quantified. Western blot and immunohistochemistry (IHC) were used to detect key proteins involved in these processes. Results: The colony formation assay and xenograft tumor models illustrated that TPM1 up-regulation inhibited RCC cell proliferation. The tube formation assay and detection of vascular endothelial growth factor (VEGF) and cluster of differentiation 34 (CD34) in xenografts revealed that TPM1 up-regulation inhibited angiogenesis in RCC. The invasion assay and detection of the E-cadherin and matrix metalloproteinases 9 (MMP-9) levels in xenografts demonstrated that TPM1 up-regulation inhibited tumor metastasis in RCC. Opposing effects were absent in TPM1 down-regulation models. Conclusions: TPM1 functions as a tumor suppressor with respect to cell proliferation, angiogenesis and metastasis in RCC, suggesting that it is a potential therapeutic target for advanced RCC.

Ureteral inflammatory myofibroblastic tumor: A case report and literature review.

RATIONALE: Inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue neoplasm which has been described in a variety of locations. In the urogenital system, IMT predominantly occurs in the bladder and the kidney. IMT arising from the ureter is exceedingly rare and has been sporadically reported before. PATIENT CONCERNS: We reported an extremely exceptional case of IMT arising from the ureteral submucosa in a 54-year-old man. The patient was hospitalized with the main complaint of intermittent and moderate left abdominal pain for 2 months. DIAGNOSES AND INTERVENTIONS: Computed tomography scan revealed a nearly circular mass in the left upper ureter. Ureteroscopy showed that the ureteral lumen mucosa was smooth. However, the upper ureter was compressed and narrow. Renal dynamic imaging was performed and the measured glomerular filtration rate was 46.98 mL/min (right renal) and 9.77 mL/min (left renal), respectively. A retroperitoneoscopic radical nephroureterectomy was performed. The histopathologic examination revealed that the soft-tissue neoplasm was mainly composed of myofibroblastic spindle cells proliferation with mixed inflammatory infiltrate, containing lymphocytes, neutrophils, and eosinophils. On immunohistochemical staining, the tumor was positive for smooth muscle actin and Ki-67 (<1%+), indicating a confirmed diagnosis of ureteral IMT. OUTCOMES: The patient recovered well with no occurrence of complications. At 3-year follow-up, there was no radiologic evidence of tumor recurrence or metastasis and the man was well. LESSONS: Ureteral IMT is extremely rare and often asymptomatic, resulting in delayed diagnosis. Radiologic evidences may be suggestive of the diagnosis of IMT. However, it is necessary to make an accurate diagnosis in terms of histopathologic assessment. Complete lesion excision is the best therapeutic approach with rare recurrences and excellent survival.

Mucoadhesive Cationic Polypeptide Nanogel with Enhanced Penetration for Efficient Intravesical Chemotherapy of Bladder Cancer.

Initially, chemotherapy is effective for treatment of bladder cancer after transurethral resection of the bladder. However, certain patients progressively become unresponsive after multiple treatment cycles, which results from the rapid and almost complete excretion of clinically used formulations of antineoplastic agents with urinary voiding. Improving the mucoadhesiveness and penetrability of chemotherapeutic drugs are key factors in treatment of advanced bladder cancer. Here, a smart disulfide-crosslinked polypeptide nanogel of poly(l-lysine)-poly(l-phenylalanine-co-l-cystine) (PLL-P(LP-co-LC)) is developed to deliver 10-hydroxycamptothecin (HCPT) for treatment of orthotopic bladder cancer. The positively charged PLL-P(LP-co-LC) can significantly prolong the retention period and enhance the tissue permeability of HCPT within the bladder wall of rat. Moreover, the reduction-responsive polypeptide nanogel (i.e., NG/HCPT) possesses the capability to accurately and rapidly deliver HCPT in bladder cancer cells. NG/HCPT can significantly inhibit proliferation of human bladder cancer 5637 cells in vitro and enhance antitumor activity toward an orthotopic rat bladder cancer model in vivo. This work demonstrates that the smart polypeptide nanogel may function as a promising drug-delivery system for local chemotherapy of bladder cancer with unprecedented clinical benefits.

Photothermal-Activatable Fe3O4 Superparticle Nanodrug Carriers with PD-L1 Immune Checkpoint Blockade for Anti-metastatic Cancer Immunotherapy.

Checkpoint blockade immunotherapy has shown great potential in clinical cancer therapy, but the body's systemic immune must be fully activated and generates a positive tumor-specific immune cell response. In this work, we demonstrate the design of the immune-adjuvant nanodrug carriers on the basis of poly(ethylene glycol)- block-poly(lactic- co-glycolic acid) copolymer-encapsulated Fe3O4 superparticles (SPs), in which imiquimod (R837), a kind of Toll-like receptor 7 agonist, is loaded. The nanodrug carriers are defined as Fe3O4-R837 SPs. The multitasking Fe3O4-R837 SPs can destroy the 4T1 breast tumor by photothermal therapy (PTT) under near-infrared laser irradiation to generate the tumor-associated antigens because of the high efficiency of tumor magnetic attraction ability and photothermal effect. The PTT also triggers the release of R837 as the adjuvant to trigger a strong antitumor immune response. By further combining with the checkpoint blockade adjusted by programmed death ligand 1 (PD-L1) antibody, the Fe3O4-R837 SP-involved PTT cannot only eliminate the primary tumors but also prevent tumor metastasis to lungs/liver. Meanwhile, this synergistic therapy also shows abscopal effects by completely inhibiting the growth of untreated distant tumors through effectively triggering the tumors infiltrated by CD45+ leukocytes. Such findings suggest that Fe3O4-R837 SP-involved PTT can significantly potentiate the systemic therapeutic efficiency of PD-L1 checkpoint blockade therapy by activating both innate and adaptive immune systems in the body.

Tropomyosin-1 promotes cancer cell apoptosis via the p53-mediated mitochondrial pathway in renal cell carcinoma.

Tropomyosin-1 (TPM1), a widely expressed actin-binding protein, is downregulated in many tumors and associated with cancer progression. A previous study from our group suggested that TPM1 could be involved in renal cell carcinoma (RCC) apoptosis, but the mechanisms and details remained unknown. The present study aimed to further examine the proapoptotic effects of TPM1 and investigate the underlying mechanisms in RCC cell lines. Results from cell viability, DAPI staining and apoptosis assays demonstrated that TPM1 upregulation inhibited cell proliferation and promoted cell apoptosis in both 786-O and ACHN RCC cell lines. However, TPM1 knockdown in the two RCC cell lines did not result in the opposite effects on cell proliferation or cell apoptosis. Comet assay and western blotting results demonstrated that TPM1 overexpression induced DNA damage and decreased the expression levels of the antiapoptotic factor BCL2 apoptosis regulator, while increasing the expression levels of the proapoptotic factors BCL2 associated X, Caspase-3 and p53 in 786-O and ACHN cells. The present findings suggest that TPM1 overexpression in RCC cell lines can induce tumor cell apoptosis via the p53-mediated mitochondrial pathway. Further studies are needed to fully elucidate the potential of TPM1 as a candidate for RCC targeted therapy in the future.

Urological complications after radical hysterectomy with postoperative radiotherapy and radiotherapy alone for cervical cancer.

Radiotherapy is a reliable method to cure cervical cancer patients, but it could cause serious urological complications after the treatment due to the anatomical location of the cervix. The main purpose of this retrospective analysis is to study the incidence, latency, and therapeutic efficacy of urological complications caused by radical hysterectomy with postoperative radiotherapy or radiotherapy alone in patients with cervical cancer.A retrospective analysis was conducted on patients with cervical cancer who received radical hysterectomy with postoperative radiotherapy or radiotherapy alone at the First Hospital of Jilin University between January 2010 and May 2016. The urological complications were confirmed by clinical manifestation, ultrasound, computed tomography (CT), nuclear scintigraphy, and assessment of renal function. All the patients with urological complications received conventional treatment, including conservative, electrosurgery, ureteral stents, nephrectomy, and neoplasty. The onset time of radiation injury symptoms was confirmed according to the medical history and follow-up. The surveillance for the therapeutic effects for these complications was accomplished by cystoscopy, imaging, and laboratory assessment.The overall rate of urological complications after treatment was 3.26%, comprising 2.12% ureteral obstruction, 0.98% radiocystitis, and 0.16% vesicovaginal fistula. The incidence of ureteral obstruction in patients treated with radical hysterectomy with postoperative radiotherapy and radiotherapy alone was not statistically significant (2.18% vs 1.59%, P > .05). The median onset time of radiocystitis and ureteral obstruction was 10 months (0-75 months) and 12 months (2-66.3 months), respectively. The onset time of vesicovaginal fistula was 3.5 months. After the appropriate treatment, the majority of the complications were under control.The incidence of urological complications is acceptable. There was no statistical difference in the risk between patients treated with radical hysterectomy with postoperative radiotherapy and radiotherapy alone. The latency period between radiotherapy and the manifestation of urological complications may be relatively long. So it is crucial to underline long-term follow-up after radiotherapy. The majority of urological complications were alleviated after symptomatic treatment and the patients with cervical cancer achieved long-term remissions or cures.

Application of Prepuncture on the Double-tract Percutaneous Nephrolithotomy Under Ultrasound Guidance for Renal Staghorn Calculi: First Experience.

OBJECTIVE: To evaluate the effect of prepuncture on the double-tract percutaneous nephrolithotomy (PCNL) under ultrasound guidance for renal staghorn calculi. METHOD: Double-tract or even multi-tract is necessary for the treatment of staghorn calculi. However, intraoperative injury, exudation, bleeding, and influence of original tract might lead to difficulty in second puncture, thus prolonging operating time, and even lead to puncture failure. We retrospectively reviewed the records of 178 patients with renal staghorn calculi who received double-tract PCNL in our department. Sixty-three patients received non-prepuncture double-tract PCNL (group A) and 115 patients underwent prepuncture double-tract PCNL (group B). In group A, the second tract was established after failing to further fragment by the first tract. In group B, based on the preoperative computed tomography, intravenous pyelography, and intraoperative ultrasound images, 2 optimal punctual positions were set. The first guidewire was manipulated in the pelvicalyceal system after successful puncture. However, we routinely performed the other puncture and a preplaced second wire was put into the collecting system as a potential second tract. RESULTS: The mean operating time was longer in group A than that in group B (P = .033). There was no statistical difference between group A and group B in postoperative instant stone-free rate and final stone-free rate. In the non-prepuncture double-tract PCNL group, blood transfusion rate was 7.9% (5/63) and it was only 1.7% (2/115) in the prepuncture double-tract PCNL group (P = .042). CONCLUSION: In the treatment of renal staghorn calculi, prepuncture double-tract PCNL can shorten operating time and reduce the occurrence of blood transfusion events. This new method might be worth generalizing.

Rare adrenal gland incidentaloma: an unusual Ewing's sarcoma family of tumor presentation and literature review.

BACKGROUND: Members of the Ewing's sarcoma family of tumor (ESFT) are malignant neoplasms and rarely observed in the adrenal gland. CASE PRESENTATION: We report an extremely exceptional case of ESFT rising from the adrenal gland in a 57-year-old Chinese man. The patient was hospitalized with abdominal swelling for 2 months. Computed tomography (CT) scan revealed a nearly-circular mass measuring about 8.1 × 10.6 cm in the right adrenal region. The patient underwent right adrenal resection. Histopathologic examination found the tumor was composed of small round blue cells forming typical Homer-Wright rosettes in focal area. The immunohistochemical analysis confirmed the case to be ESFT, which was positive for membranous CD99 and nuclear FLI-1. The patient was scheduled for four courses of large doses of chemotherapy and died for cancer metastasis one year later after surgery. CONCLUSIONS: Histopathological evidence of Homer-Wright rosettes and immunohistochemical markers positivity, such as CD99 and FLI-1, are valuable factors for ESFT diagnosis, although cytogenetic analysis is considered as the gold standard. Complete surgery is the treatment of choice for ESFT and adjuvant radiotherapy and combination chemotherapy can significantly improve the survival rate of postoperative patients.

Positively charged polypeptide nanogel enhances mucoadhesion and penetrability of 10-hydroxycamptothecin in orthotopic bladder carcinoma.

Bladder cancer (BC) has become a serious public health problem due to its continuously rising incidence, high recurrence rate, and poor quality of life. Intravesical instillation of chemotherapy, one of common and important treatment strategy for BC, is restricted partially due to the short residence time and the low penetration ability of current antineoplastic agent formulations in clinic. Herein, a positively charged disulfide-core-crosslinked polypeptide nanogel of poly(l-lysine)-poly(l-phenylalanine-co-l-cystine) (PLL-P(LP-co-LC)) was synthesized. 10-Hydroxycamptothecin (HCPT) was loaded into the core via a facile diffusion to obtain loading nanogel (i.e., NG/HCPT). The reduction-responsive cationic polypeptide nanogel not only showed a high drug-loading efficiency, a prolonged residence time, and an improved tissue penetration capability, but also demonstrated an ability to accurately and rapidly release HCPT in bladder cancer cells. NG/HCPT exhibited superior cytotoxicity against human T24 bladder cancer cells compared to that of free HCPT in vitro. Moreover, the positively charged loading nanogel exhibited significantly enhanced antitumor efficacy and reduced side effects toward orthotopic bladder cancer model in vivo. Overall, the smart polypeptide nanogel with enhanced residence and permeability provides a promising drug delivery platform for local chemotherapy of BC.