BCG-induced formation of neutrophil extracellular traps play an important role in bladder cancer treatment.

Bacillus Calmette-Guerin (BCG) is one of the most effective treatments for bladder cancer. Little attention has been paid to the possible role of neutrophils in BCG immunotherapy. In this study, we examined neutrophil extracellular traps (NETs) formation induced by BCG stimulation, and found that BCG-induced NETs exerted cytotoxicity, induced apoptosis and cell-cycle arrest, and inhibited migration in bladder tumor cells. BCG-activated tumor cells but not non-activated ones elicited NETs formation, in which IL-8 and TNF-α from activated tumor cells both took effect. Moreover, NETs activated peripheral blood mononuclear cells (PBMCs) exhibited a higher expression of CD4 and Th1 cytokines. Additionally, the role of NETs in vivo contributed to the recruitment of T cells and monocytes-macrophages and tissue damage, thus preventing tumor growth. NETs proteins mainly caused these effects on tumor and cellular immunity. In conclusion, we demonstrated a novel immunoregulatory role for NETs in the early stages of BCG immunotherapy.

Prognostic value of miR-221 in human malignancy: evidence from 3041 subjects.

BACKGROUND: MiR-221, acting as onco-miR or oncosuppressor-miR, plays an important role in tumor progression; however, the prognostic value of miR-221 in human carcinomas is controversial and inconclusive. The objective of our study was to conducted a systematic review and meta-analysis of miR-221 in various types of human cancers. METHODS: An online search of up-to-date electronic databases, including PubMed and Embase, was conducted to identify as many relevant papers as possible. 32 papers involving 3041 patients with different carcinomas were included in the analysis. Hazard ratios (HRs) of miR-221 were used to evaluate prognostic values. RESULTS: Thirty-two papers involving 15 cancers were included. MiR-221 was associated with a worse overall survival (OS) in patients, and a combined HR was 1.93 (95% CI of 1.43-2.60, 2080 patients, 22 studies, I-squared = 80.4%, P = 0.000); however, the combined HR for relapse-free survival (RFS) was 1.37 (95% CI of 0.75-2.48, 625 patients, 7 studies, I-squared = 78.8%, P = 0.000), and disease-free survival (DFS) was 1.24 (95% CI of 0.60-2.56, 539 patients, 5 studies, I-squared = 81.8%, P = 0.000). CONCLUSION: MiR-221 was shown to be associated with a poor OS in human carcinomas, and thus may serve as a useful predictor of clinical outcomes.

Clinicopathological and prognostic significance of survivin expression in renal cancer patients: a meta-analysis.

BACKGROUND: Survivin has been reported to play a role in the diagnosis and prognosis of renal cell carcinoma (RCC); however, published data on this subject are conflicting. AIM: To conduct a meta-analysis to evaluate the impact of survivin as a prognostic marker and its association with clinicopathological variables in patients with RCC. METHOD: Comprehensive searches of electronic databases (PubMed, ISI Web of Knowledge Embase, Google Scholar Web and the Cochrane Library) were updated to June 2016 to retrieve eligible studies. The association strength was measured with relative risks (RRs) and pooled HRs with 95% CIs, which were extracted and pooled to determine the association between survivin expression and patient survival and clinicopathological features. RESULTS: Ten studies with 1063 cases of RCC were included. Positive survivin expression in RCC was associated with the TNM stage (pooled RR 1.49; 95% CI 1.07 to 2.07) or Fuhrman grade (pooled RR 1.63; 95% CI 1.15 to 2.32) in patients. The correlation between survivin expression and gender was not significant (pooled RR 0.97; 95% CI 0.83 to 1.15). In addition, a considerable association was found between survivin expression and overall survival for patients with RCC (pooled HR 1.94; 95% CI 1.24 to 3.05 (multivariate model) and 5.41; 95% CI 4.08 to 7.17 (univariate model)). CONCLUSIONS: Our results indicate that survivin is of prognostic significance in patients with RCC.

Down-regulation of Sphk2 suppresses bladder cancer progression.

Bladder cancer is the second most common urological malignancy around the world and is by far the most frequent urological malignancy in China. The abnormal expression of sphingosine kinase 2 (SphK2) is associated with tumor progression and a poor patient survival rate, however, the effect of SphK2 on the bladder cancer cells remains unclear. The aim of the paper was to study the expression of SphK2 in bladder cancer and the role of SphK2 on the cell proliferation, metastasis, and apoptosis in bladder cancer in vitro. Our results showed that SphK2 is up-regulated in bladder cancer tissues compared with the corresponding adjacent non-neoplastic tissues, and the expression level of SphK2 was significantly higher in human bladder cancer cells in comparison with normal bladder epithelial cells. Silencing of SphK2 could inhibit the proliferation ability of T24 cells in vitro. In addition, SphK2 knockdown could induce a significant increase in the number of apoptotic cells. Furthermore, the transwell assay also showed significant cell migration inhibition in SphK2 siRNA transfectant compared with cell lines transfected with NC. Thus, this study suggested that SphK2 inhibition may provide a promising treatment for bladder cancer patients.

[Analysis of the diagnosis and treatment of desmoplastic small round cell tumor].

OBJECTIVE: To explore the clinical diagnostic features and treatment of desmoplastic small round cell tumor (DSRCT), and to improve the understanding and management of this tumor. METHODS: The clinicopathological data of nine patients treated in our hospital from October 2004 to June 2014 were retrospectively analyzed and a review of the literature was made. The clinical manifestations, pathological characteristics, diagnosis and differential diagnosis, treatment and prognosis of this tumor were summarized and analyzed. RESULTS: Nine patients with DSRCT, 5 males and 4 females, with an average age of 21 years (range 8-56 years) were included in this study. Ultrasound examination revealed irregular low-density mass shadow in the abdominal cavity. CT examination found that 6 cases had abdominal and retroperitoneal multiple solid tumor nodules, uneven density, and visible low density fluid area. Postoperative pathological examination revealed that the tumor cells were small, mostly elliptic, gathered to form clear structure of nests with clear irregular boundaries. The central portion of large tumor nests often showed necrosis. Scattered fibroblasts and large amount of hyalinization of collagen fibers were seen in the interstitial tissue around the nests. Six patients received laparotomy surgery, however, all failed to resect the tumor completely. Three patients received postoperative chemotherapy, i. e. two cases had carboplatin and paclitaxel chemotherapy, and one case of chemotherapy regimen not specified. Two patients had radiation and chemotherapy (no concrete plan was available). Another case was lost to follow-up. Two of the three patients without surgery received chemotherapy with CAP (cyclophosphamide+adriamycin+carboplatin) and total rectal lesions, pelvic and inguinal lymph nodes, ilium metastases radiation therapy. Another one patient received EP regimen (DDP+VP16) which was then changed into a TP chemotherapy alone. Eight of the nine cases died shortly after surgery, and only one patient treated with chemotherapy alone was still alive after 11 months of follow-up. CONCLUSIONS: Desmoplastic small round cell tumor is a very rare, special type of soft tissue tumor, with very poor prognosis. This tumor may be preliminarily diagnosed according to the imaging characteristics and detection of tumor markers, however, final diagnosis is made by pathology. Surgery is the priority of treatment, combined with complementary radiation and chemotherapy.

Meta-analysis of studies on the association between the NF-κB1-94ins/del ATTG promoter polymorphism and cancer.

Nuclear factor-kappa B (NF-κB), a cell survival signal, is involved in carcinogenesis. Polymorphism of NF-κB1 is associated with cancer by several studies. This study aims to perform a comprehensive meta-analysis of studies and determine the association between the NF-κB1-94ins/del ATTG promoter polymorphism and cancer. Twenty-five case-control studies (7,281 cases and 10,039 controls) were included. We used odds ratios (ORs) to assess the strength of the association, and 95 % confidence intervals (CIs) to identify precision of the estimate. Overall, NF-κB1-94ins/del ATTG promoter polymorphism was significantly associated with decreased susceptibility to cancer in overall population under homozygote (for DD vs. WW: OR = 0.74, 95 % CI = 0.58-0.96), recessive (for DD vs. WD+WW: OR = 0.82, 95 % CI = 0.69-0.99), dominant (for DD+WD vs. WW: OR = 0.84, 95 % CI = 0.71-1.00), and allele (for D vs. W: OR = 0.88, 95 % CI = 0.78-0.98) model. Subgroup analysis for ethnicity found that NF-κB1-94ins/del ATTG promoter polymorphism was significantly associated with decreased susceptibility to cancer in Asians (for DD vs. WW: OR = 0.54, 95 % CI = 0.40-0.74; for WD vs. WW: OR = 0.75, 95 % CI = 0.69-0.81; for DD vs. WD+WW: OR = 0.70, 95 % CI = 0.55-0.90; for DD+WD vs. WW; OR = 0.66, 95 % CI = 0.56-0.78; for D vs. W: OR = 0.75, 95 % CI = 0.65-0.86), but the association was not found in Caucasians. The findings suggest that NF-κB1-94ins/delATTG promoter polymorphism is significantly associated with decreased susceptibility to cancer in overall and Asian population.

[Toll-like receptor 4 expression of human peripheral blood mononuclear cells treated by recombinant hIFN-α-2b-BCG and its role of immune activation].

OBJECTIVE: To examine the toll-like receptor 4 (TLR4) expression of human peripheral blood mononuclear cells (hPBMC) treated with recombinant bacillus Calmette-Guérin (rBCG) and its role of immune activation. METHODS: hPBMC was treated with recombinant human interferon (hIFN)-α-2b-BCG (rBCG) or wild BCG (wBCG) in vitro and the TLR4 expression detected by flow cytometry. The TLR4 functional blocking antibodies were applied for intervening the TLR4 signaling pathway of hPBMC. Then rBCG, wBCG, hIFN-α-2b and phosphate-buffered solution (PBS) were used to stimulate the hPBMC of blocking and non-blocking groups. The changes of human tumor necrosis factor-alpha (hTNF-α), human interleukin-12 (hIL-12) and hIFN-γ between the blocking and non-blocking groups by ELISA. RESULTS: The expression of TLR4 in hPBMC treated with rBCG or wBCG were stronger than that treat with PBS (all P < 0.05). In TLR4 non-blocking groups the expressions of hTNF-α and hIFN-γ were rBCG group > wBCG group > hIFN-α-2b group > PBS group, the expressions of hIL-12 was hIFN-α-2b group > PBS group > rBCG group > wBCG group (all P < 0.05). Application of TLR4 functional blocking antibodies to intervene hPBMC 48 h, comparing the changes in rBCG group, wBCG group, hIFN-α-2b group and PBS group, the expressions of hIFN-γ in TLR4 blocking groups (27.3 ± 1.2, 20.6 ± 0.9, 20.3 ± 0.8, 18.4 ± 0.7)were significantly inhibited than those in non-blocking groups (84.6 ± 1.3, 34.0 ± 1.0, 24.9 ± 0.9, 22.9 ± 0.7) (all P < 0.05). The expressions of hTNF-α in TLR4 blocking groups (1431 ± 28, 1032 ± 21, 104 ± 6, 109 ± 4) were significantly inhibited than those in non-blocking groups (1553 ± 28, 1065 ± 31, 343 ± 6, 299 ± 4) (all P < 0.05). The expressions of hIL-12 in TLR4 blocking groups (0.646 ± 0.005, 0.592 ± 0.015, 0.638 ± 0.008, 0.595 ± 0.019) were significantly inhibited than those in non-blocking groups (1.120 ± 0.012, 0.946 ± 0.015, 1.254 ± 0.011, 1.112 ± 0.024) (all P < 0.05). CONCLUSION: rBCG regulates the secretion of Th1 cytokines through the TLR4 signaling pathway.

[Effect of recombinant hIFN-alpha-2b-BCG on mouse bladder tumor MB49 cells in vitro].

OBJECTIVE: To investigate the antitumor effect of recombinant IFN-alpha-2b-BCG on mouse bladder cancer MB49 cells in vitro, and to explore its antitumor mechanisms. METHODS: MB49 cells were co-cultured with recombinant BCG or wild BCG, and than were examined by light and transmission electron microscopy. The cell growth was assessed by MTT assay, and apoptosis rate and MHC-I of the MB49 cells was detected by flow cytometry using AO and Hoechst33258 fluorescence immunostaining. RESULTS: The hIFN-alpha-2b-BCG-treated tumor cells showed slow growth, detachment of some cells, and various degree of degeneration. Light microscopy revealed organelle disorganization, chromatin aggregation, nuclear pyknosis, and cytolysis in some cells. Cellular membrane bulged and some bubbles were seen under fluorescence microscope using AO staining. Hoechst33258 assay also depicted frequent apoptosis in the tumor cells. The MTT assay showed that rBCG more actively than the wild BCG inhibited the proliferation of MB49 cells. The apoptosis rate of the recombinant BCG group was 19.7% and 46.6% at the time point of 24 h and 48 h, respectively, significantly higher than 10.8% and 20.9%, respectively, in the wild BCG group. The results of flow cytometry indicated that both types of BCG enhanced the expression of MHC-I in the MB49 cells, but more effective in the recombinant BCG group. CONCLUSION: The recombinant hIFN-alpha-2b-BCG has more strong immuno-modulatory properties, anti-tumor effect on MB49 cells and induces apparent cytotoxicity in the bladder cancer cells in vitro.

Gene Expression in Human Polymorphonuclear Neutrophils (PMNs) Stimulated by Bacillus Calmette-Guérin (BCG).

Neutrophils are the most abundant leukocytes in the blood. Moreover, neutrophils form the first line of host immune defense against bacterial and fungal invasion, and also play an important part in inflammatory and immune system responses. Intravesical bacillus Calmette-Guérin (BCG) has been shown to reduce and delay tumor progression to muscle-invasive disease after transurethral resection of bladder tumors (TRUBTs). Following intravesical BCG, neutrophils gather around tissues infected by BCG in the early stage of inflammatory and immune responses. In our previous study, we reported that BCG induced the formation of neutrophil extracellular traps (NETs), which play an important role in tumor treatment. Therefore, in the present study, we analyzed the gene expression profile of neutrophils stimulated by BCG through high-throughput arrays, which helped us determine the potential roles of neutrophils in BCG immunotherapy. The results showed that the expression of neutrophil genes led to changes in the early stage of BCG stimulation. The changed genes were involved in many functions of neutrophils such as mobility, proliferation, and secretion of cytokines, chemokines, and adhesion molecules. These changes in neutrophil biological functions may play an essential role in BCG induction of inflammatory and immune responses, and in anti-tumor processes.

Retraction: Graphene oxide/DNA-decorated electrode for the fabrication of microRNA biosensor.

[This retracts the article DOI: 10.1039/C5RA12373A.].

Serine/threonine kinase 32C is overexpressed in bladder cancer and contributes to tumor progression.

Tumor markers of bladder cancer (BC) have been investigated for many years, but the clinical treatment based on these biomarkers is still unsatisfactory. STK32C, a member of the serine/threonine protein kinase of AGC superfamily, was first found to be highly expressed in brain tissues; however, the role of STK32C in malignant disease has not been determined. Data from TCGA database showed that the STK32C gene is overexpressed in BC and a number of other human tumors. In the current study, immunohistochemistry revealed that high expression of STK32C protein in tumor tissues was significantly associated with poor clinico pathologic features and a short relapse-free survival (RFS) in patients with BC. Slicing of STK32C inhibited tumor cell proliferation, migration and invasion in vitro. In vivo animal experiments demonstrated that knocking-down of STK32C restricted the growth of tumor cells in mice. Finally, microarray analysis revealed that silencing of STK32C inhibited the activity of the HMGB1 pathway and regulated the expression of key genes in this pathway. In conclusion, our study showed novel promoting roles for STK32C in human tumors, which may provide a new therapeutic target for the patients with BC.

A retrospective analysis of the correlation between AXL expression and clinical outcomes of patients with urothelial bladder carcinoma.

BACKGROUND: Immunohistochemistry (IHC) analysis of primary tumors revealed that AXL expression is associated with survival in patients with different cancers. The objective of our study is to investigate the relationship between the expression of AXL and clinical outcomes of patients with bladder carcinoma (BC). METHODS: A total of 407 samples from The Cancer Genome Atlas (TCGA) database and 203 patients with clinical and pathological diagnosis of BC in our hospital were used to assess the association of AXL and clinical outcomes of BC patients. IHC was performed to evaluate the expression of AXL in tumor tissue collected after surgical treatment. RESULTS: Data from TCGA showed that AXL mRNA expression was significantly associated with poor clinical-pathological characters and short overall survival (OS) of BC patients. In our study, AXL was significantly related to worse pathological T-stage (pT), lymph node metastasis (pN), and tumor grade. In univariate analysis, abundant AXL was significantly associated with the worse OS. In multivariate analysis, AXL, as well as pT, pN, and Ki67, was an independent prognostic factor in predicting the survival of patients. CONCLUSIONS: AXL was an unfavorable prognostic factor, which was associated with poor clinical outcomes of BC patients.

Giant malignant pheochromocytoma in an elderly patient: A case report.

RATIONALE: Malignant pheochromocytoma is a rare disease and surgical resection is the only curative treatment. PATIENT CONCERNS: An 81-year-old man of Chinese ethnicity was found to have a giant retroperitoneal tumor. DIAGNOSES: B-scan ultrasonography and CT scan presented a mass above the left kidney, measuring 13.5 × 10 .6 × 9.8 cm. Subsequent analysis of 24-h urinary catecholamines and vanillylmandelic acid, as well as of blood catecholamines and blood cortisol, showed no elevated levels. INTERVENTIONS: The patient was treated with surgery. OUTCOMES: The result from immunohistochemical staining confirmed the presence of malignant pheochromocytoma. After three months follow-up, the blood pressure and serum potassium were all within normal limits, no post-operative complications, no tumor recurrence and metastasis were found. LESSONS: This is the oldest patient known to have histologic documentation of this disease. Giant malignant pheochromocytomas are rare entities requiring clinical suspicion coupled with strategic diagnostic evaluation to confirm the diagnosis, personalized therapeutic treatment is required, particularly among elderly population.

Gene therapy of renal cancer using recombinant adeno-associated virus encoding human endostatin.

Renal cell carcinoma (RCC) is characterized by robust angiogenesis during tumor development. Various therapies are not able completely eradicated tumor relapse. The present study targeted angiogenesis and developed a recombinant adeno-associated virus (rAAV) vector containing human endostatin gene for human kidney cancer gene therapy. Prophylactic and therapeutic RCC models were established in nude mice by subcutaneous inoculation of RCC cells and intra-muscular or intra-tumor injection of rAAV-Endostatin. The growth of xenograft tumors was evaluated by tumor volume and weight. The microvessel density (MVD) was used to measure the anti-angiogenesis effect of rAAV-Endostatin. The toxic effect of rAAV-Endostatin was also examined. In the therapeutic model, tumor-bearing mice with rAAV-Endostatin intra-tumor injection demonstrated slow tumor growth (32.63±9.75) compared with control groups with intratumoral rAAV-enhanced yellow florescent protein (EYFP) injections (21.50±11.42) and the RPMI-1640 group (21.75±10.48 days, for tumors to reach ~300 mm3). MVD of the xenografts treated with rAAV-Endostatin was 8.30±3.14/0.739 mm2 whereas that of control groups was 13.87±4.09/0.739 mm2 (rAVV-EYFP) and 13.76±3.50/0.739 mm2 (RPMI-1640). No significant side effects associated with rAAV-endostatin use were identified in the vital organs. rAAV-Endostatin demonstrated significant anti-angiogenesis and antitumor activities. It may serve as an effective agent for renal cancer gene therapy.

The prognostic values of tumor-infiltrating neutrophils, lymphocytes and neutrophil/lymphocyte rates in bladder urothelial cancer.

Tumor-infiltrating neutrophils (TINs) and lymphocytes (TILs) are found to play essential roles in many tumors and associate with the prognosis of patients. But, the prognostic values of TINs, TILs and NLR (neutrophils-lymphocytes ratio) in bladder cancer (BC) are still undefined. The object of our study was to systematically interrogate the associations of these immune cells with clinical outcomes of BC patients. In our study, a total of 102 patients pathologically diagnosed with BC were included. CD66b+ and CD8+ antibodies were used to mark neutrophils and CD8+ lymphocytes by immunohistochemistry. The results found that TINs and NLR were significantly associated with pathological T-stages of tumors (P < 0.01), but TILs were not. And TINs were also related to pathological tumor grades (P = 0.012). Regarding the prognostic values, TINs was related to the high risk of recurrence in non-muscle invasive BC (NMIBC) patients. Elevated TINs and NLR were associated with poor overall survivals of BC patients, whereas higher TILs were related to longer survivals (P < 0.01). Multivariate analysis showed that both of TINs (HR 2.427, 1.024-5.752, P = 0.044) and NLR (HR 3.529, 1.147-10.864, P = 0.028) were independent unfavorable prognosis markers. In conclusion, Tumor infiltrating immune cells, including TINs, TILs and NLR were important markers in predicting the prognosis of bladder cancer patients. TINs and NLR were more likely to be negative predictors, but TILs were favorable in patients with BC.

Prognostic value of microRNA-155 in human carcinomas: An updated meta-analysis.

BACKGROUND: miR-155 functions as an oncomiR or as an oncosuppressor-miR in human cancer. Although miR-155 has been researched in many cancers, its prognostic value is uncertain. METHODS: We performed a literature search in up-to-date electronic databases including PubMed and Embase to obtain as many relevant articles as possible. Combined hazard ratios (HR) of miR-155 for outcome were analyzed. RESULTS: A total of 24 papers researching different cancers were included in this meta-analysis. Combined HRs showed that miR-155 was significantly associated with a poorer OS with HR = 1.99 (1.34-2.96) (I-squared = 83.1%, P = 0.000). Combined HR of PFS/RFS/DFS was 1.95 (1.14-3.33) (I-squared = 75.9%, P = 0.000) and CSS/DSS was 2.50 (0.73-8.58) (I-squared = 87.7%, P = 0.000). CONCLUSION: Increased miR-155 expression was associated with poorer survival in human carcinoma and as such may be valuable in predicting outcome.

Preoperative peripheral plasma fibrinogen level is an independent prognostic marker in penile cancer.

BACKGROUND AND AIM: High levels of peripheral plasma fibrinogen have recently been revealed that related to poor clinical prognosis in various types of malignant tumors. The purpose of this research was to identify the prognostic significance of the preoperative peripheral serum fibrinogen level in patients with penile cell carcinoma. METHODS: This retrospective research included 72 penile cancer patients with date about their serum fibrinogen value before surgery who undergone either partial or radical penectomy at The 2nd Hospital of Tianjin Medical University between January 2002 to January 2012. They had a mean follow-up of 30.8 months. To determine the factors that were significant in predicting a patient's prognosis, univariate and multivariate analyses were performed according to the Cox proportional hazards regression model. RESULTS: The 5-year cancer specific survival (CSS) rate was 62.4% of patients with preoperative fibrinogen levels below 340 mg/dl and 41.9% for those with higher levels (p = 0.001). Multivariate analysis revealed that the pathological T stage (p < 0.001), tumor grade (p = 0.036), postoperative chemotherapy (p = 0.041), nodal metastasis(p < 0.001), pathological type (p < 0.001) and fibrinogen (p = 0.023) were independent prognostic factors for survival. Patients with low fibrinogen level (<340mg/dl) had significantly longer CSS and the different survival rate were defined using the log-rank test. CONCLUSIONS: The high preoperative peripheral serum fibrinogen level was related to poor survival in penile cancer patients. Fibrinogen may serve as a powerful predictor of CSS in penile cancer patients.

Giant bladder stone in a male patient: A case report.

BACKGROUND: In recent years, bladder stones are increasing in China. However, a giant bladder stone is rarely found nowadays. METHODS: A case of a 54-year-old man who presented with a >9-year history of urinary frequency and urgency and macrohematuria for the past 3 days, was examined by ultrasound scan, kidney-ureter-bladder x-ray, and computed tomography. Then, the patient received a cystolithotomy. RESULTS: His suprapubic area was hard when palpated. An ultrasound scan showed hydronephrosis of both kidneys and expanded ureters. A kidney-ureter-bladder x-ray showed a large stone within the bladder, and computed tomography revealed that the stone occupied most of the bladder. A large bladder stone composed of magnesium ammonium phosphate, weighing 1048 g, and measuring 13.3*8.0*9.7cm in size was removed. CONCLUSION: This rare case is, to the best of our knowledge, the largest bladder stone case reported to date in China. For patients with only Lower urinary tract symptoms, bladder stone should be taken into consideration when other signs occur, such as recurrent urinary tract infection and hematuria.

Preoperative neutrophil-lymphocyte ratio and fibrinogen level in patients distinguish between muscle-invasive bladder cancer and non-muscle-invasive bladder cancer.

INTRODUCTION: The aim of this study was to explore if the preoperative neutrophil-lymphocyte ratio (NLR) and fibrinogen level can help in distinguishing between muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). METHODS: We identified 669 patients who underwent surgery at our institution, and evaluated their preoperative NLRs and fibrinogen levels. Patients were divided into two groups, NMIBC (group-I) and MIBC (group-II), according to the postoperative pathology. For the intergroup comparison, data obtained from the two groups were evaluated using independent samples t-test. The cutoff value of the NLR, fibrinogen level, and integrated NLR and fibrinogen level was determined with receiver operating characteristic (ROC) curve. RESULTS: The mean NLRs of group-I and group-II were found as 2.71±2.46 and 4.66±8.00, respectively (P<0.001). The fibrinogen levels of the two groups were ~3.13±0.70 g/L and 3.41±0.84 g/L, respectively (P=0.001). Whether the NLR, fibrinogen level, and integrated NLR and fibrinogen level can help in distinguishing between MIBC and NMIBC was evaluated with ROC curve. The cutoff value of NLR was estimated as 2.01 according to the Youden index. With this value, sensitivity was found as 67.1%, specificity was 52.7%, and area under receiver operating characteristic (ROC) curve (AUC) was 0.601 (P=0.031). The cutoff value of fibrinogen level was estimated as 3.17 g/L according to the Youden index. Accordingly, sensitivity was found as 58%, specificity was 58%, and AUC was 0.60 (P=0.001). The cutoff value of integrated NLR and fibrinogen level was found as 0.166; the sensitivity was found as 86%, specificity was 42%, and AUC was 0.801 (P=0.01). CONCLUSION: The data obtained in this study suggested that 67.1% of Ta-T1 tumors were likely to be invasive if the NLR was >2.01 and 58% were likely to be invasive if the fibrinogen level was >3.17 g/L. When we used both the NLR and fibrinogen level to distinguish between the MIBC and NMIBC, sensitivity was found to be 86%, and specificity was 42%.

Antimicrobial susceptibility of hospital acquired Stenotrophomonas maltophilia isolate biofilms.

AIMS: We sought to characterize the antibiotic susceptibility of strains of Stenotrophomonas maltophilia isolated from clinical samples, and the role of Stenotrophomonas maltophilia biofilm in antibiotic resistance. METHODS: Fifty-one clinical Stenotrophomonas maltophilia isolates were obtained from patients with nosocomial infection in the surgical wards and ICUs of six general hospitals in Tianjin, China. In vitro models of Stenotrophomonas maltophilia biofilms were established and confirmed by scanning electron microscopy and fluorescence microscopy with silver staining. The minimal inhibitory concentrations and biofilm inhibitory concentrations of commonly used antibiotics were determined. RESULTS: 47 of 51 strains were resistant to three or more antibiotics. 42 of 51 strains formed Stenotrophomonas maltophilia biofilms in vitro. Stenotrophomonas maltophilia biofilm formation greatly reduced sensitivity to most tested antibiotics, but not to levofloxacin. However, in the presence of erythromycin scanning electron microscopy revealed that levofloxacin inhibited Stenotrophomonas maltophilia biofilm formation. Factorial ANOVA revealed that erythromycin enhanced susceptibility to levofloxacin, cefoperazone/sulbactam, and piperacillin (p<0.05), and an ΔE model revealed that levofloxacin and erythromycin acted synergistically in biofilms, suggesting specific use of combined macrolide therapy may represent an effective treatment for Stenotrophomonas maltophilia infection. CONCLUSIONS: Antibiotics could act synergistically to combat the protection conferred to clinical isolates of Stenotrophomonas maltophilia by biofilms. Macrolide antibiotics may be effective where used in combination.