Genomic Alterations of Signaling and DNA Damage Repair Pathways in Non-Muscle Invasive Bladder Cancer.

The aim of the study was to demonstrate the most common genetic alterations and evaluate possible targets involving phosphatidylinositol-3-OH kinase (PIK3)/AKT/mammalian target of rapamycin (mTOR) signaling and DNA damage repair (DDR) pathways for personalized treatment in patients with non-muscle invasive bladder cancer (NMIBC). Alterations of these pathways were observed in 89.5% and 100% of patients, respectively. Among them, BARD1 was more frequently altered in low/intermediate-risk cases, but PARP4 was more frequently affected in intermediate/high-risk patients. The possible target feasibility of BARD1 and PARP4 alterations should be evaluated for personalized treatment using PARP-inhibitors in NMIBC. It is important to detect high tumor mutation burden (TMB) in patients in terms of immunotherapy.

Sextant Biopsy-Based Criteria for Clinically Insignificant Prostate Cancer Are Also Valid for the 12-Core Prostate Biopsy Scheme: A Multicenter Study of Urooncology Association, Turkey.

BACKGROUND: Epstein criteria based on sextant biopsy are assumed to be valid for 12-core biopsies. However, very scarce information is present in the current literature to support this view. OBJECTIVES: To investigate the validity of Epstein criteria for clinically insignificant prostate cancer (PCa) in a cohort of the currently utilized 12-core prostate biopsy (TRUS-Bx) scheme in patients with low-risk and intermediate-risk PCa. METHOD: Pathological findings were separately evaluated in the areas matching the sextant biopsy (6-core paramedian) scheme and in all 12-core schemes. Patients were divided into 2 groups according to the final pathology report of RP as true clinically significant PCa (sPCa) and insignificant PCa (insPCa) groups. Predictive factors (including Epstein criteria) and cutoff values for the presence of insPCa were separately evaluated for 6- and 12-core TRUS-Bx schemes. Then, different predictive models based on Epstein criteria with or without additional biopsy findings were created. RESULTS: A total of 442 patients were evaluated. PSA density, biopsy GS, percentage of tumor and number of positive cores, PNI, and HG-PIN were independent predictive factors for insPCa in both TRUS-Bx schemes. For the 12-core scheme, the best cutoff values of tumor percentage and number of positive cores were found to be ≤50% (OR: 3.662) and 1.5 cores (OR: 2.194), respectively. The best predictive model was found to be that which added 3 additional factors (PNI and HG-PIN absence and number of positive cores) to Epstein criteria (OR: 6.041). CONCLUSIONS: Using a cutoff value of "1" for the number of positive biopsy cores and absence of biopsy PNI and HG-PIN findings can be more useful for improving the prediction model of the Epstein criteria in the 12-core biopsy scheme.

A candidate antineoplastic herbal agent for bladder cancer: Ankaferd Blood Stopper.

BACKGROUND AND AIMS: Ankaferd Blood Stopper (ABS) was used for in vitro studies of osteosarcoma and colon carcinoma cancer cell lines to reveal the apoptotic and antineoplastic effects. The aim of this study is to evaluate the antineoplastic effect of ABS on bladder cancer cell cultures. METHODS: We prospectively collected minimum 0.5 cm parts of fresh frozen tumour samples from patients with bladder tumour from 2015 to 2017. Primary bladder cancer cultures were produced from the frozen tumour samples. Two different doses of ABS were used on cancer cell cultures. Viability tests of each cell cultures were performed. Flow cytometry was used for the determination of apoptosis and necroptosis. We also checked the effect of ABS on different stages, grade and variant histology of bladder cancer cells. The results of all cancer cell cultures were compared with their own controls. RESULTS: This study included 24 patients. Mean age of patients was 66.2 ± 11.7 years (34-83 years), where 19 of them (79.5%) were males and five (20.5%) were females. When we compared the data, we found decreased cancer cell viability ratio in each ABS group compared with their own controls. Necroptosis was observed in the great majority of ABS groups, and necroptosis and apoptosis were observed in some cell cultures. CONCLUSIONS: In this study, we demonstrated the cytotoxic effect of ABS on bladder cancer cells. The results of this study suggests planning of animal model of bladder cancer for ABS with intravesical application as an antineoplastic agent. In the future, ABS may be a candidate intravesical treatment agent for bladder cancer.

Prognostic value of intraductal carcinoma for adjuvant radiotherapy candidates after radical prostatectomy.

OBJECTIVE: To investigate the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens and predictive value of IDC-P for biochemical recurrence and adjuvant therapy decision. METHOD: We retrospectively evaluated patients who were performed RP between 2000 and 2014. Among, 67 patients who had stage pT3a tumour with negative surgical margin (Group 1, n = 35) and who had stage pT2 tumour with positive surgical margin (Group 2, n = 32) were included in the study. RP specimens were re-evaluated for the presence of IDC-P component and other prognostic factors. In both the groups, prognostic factors were compared according to the presence of IDC-P and biochemical recurrence status. RESULTS: In Group 1, IDC-P was detected in five cases and biochemical recurrence was detected in three cases. Patients with IDC-P showed significantly higher biochemical recurrence than those without IDC-P (P = .002). In univariate analysis, IDC-P was found to be significantly associated with worse progression-free survival (P < .001). In Group 2, IDC-P was detected in four cases and biochemical recurrence was detected in 10 cases. Also, tumour volume was significantly higher in patients with IDC-P than those without IDC-P (P = .02). IDC-P was also significantly associated with worse progression-free survival in Group 2 (P = .033). CONCLUSIONS: In both the groups, IDC-P was a prognostic factor for progression-free survival and/or biochemical recurrence. Especially in these patients, the presence of IDC-P might be helpful for postoperative adjuvant therapy management decision.

[Evaluation of solid pulmonary nodules in patients with bladder cancer with computed tomography based texture analysis method: Is it possible to differentiate metastatic - non-metastatic nodules?] / Bilgisayarli tomografi tabanli doku analizi yöntemi ile mesane kanserli hastalarda solid pulmoner nodüllerin degerlendirilmesi: Metastatik - metastatik olmayan nodül ayrimini yapmak mümkün mü?

INTRODUCTION: Solid Pulmonary Nodule (SPN) is defined as parenchymal radiopacity smaller than 3 cm in diameter. Evaluating the metastatic nature of the SPNs detected in the thorax computed tomography (TCT) examination for staging purposes in cancer patients becomes a fundamental problem for the physician. Invasive procedures, additional imaging or follow-up imaging, are often used to differentiate metastatic and non-metastatic nodules. In this study, we aimed to distinguish SPNs detected in patients diagnosed with bladder cancer (BC) as metastatic and non-metastatic nodules by texture analysis. MATERIALS AND METHODS: TCT images of patients diagnosed with BC in our hospital from January 2007 until December 2017 were retrospectively evaluated. A total of 46 patients with SPN, including metastatic (n= 19) and non-metastatic (n= 27), were included in the study. Short axis diameter, long-axis diameter, nodule volume and volume histogram values of the nodules were obtained. Chisquare test was used to evaluate dependent variables, and the Mann-Whitney U test was used to evaluate independent variables. ROC curves of the obtained data were plotted. Statistically, the significant p-value was determined as less than 0.05. RESULT: A significant difference was found between SPN long axis, short axis and volume values. In the volumetric histogram analysis, the maximum density value and the mean density value were found to be statistically significant. When the average of the highest densities in the volume histogram data was evaluated, the area under the curve value was 0.702 (95% CI, 519-854). The metastatic nodule could be distinguished with a sensitivity of 88% and a specificity of 70% when the volume histogram has the maximum density threshold of 50 HU. CONCLUSIONS: In this study, we concluded that SPN detected on CT images can be distinguished as metastatic and non-metastatic nodules using texture analysis method without invasive procedures.

8-armed octopus: Evaluation of clinicopathologic prognostic factors of urothelial carcinoma of the upper urinary system

Background/aim: This study was designed to determine the characteristic features of upper urinary system urothelial carcinomas (UUSUCs) and to evaluate the clinicopathological parameters associated with prognosis. Materials and methods: A total of 74 cases of UUSUC were included, from three different centers. Demographic data and histopathological features such as tumor localization, concomitant tumor in the urinary system, distant metastasis with overall survival and disease-free survival obtained from the hospital records were evaluated retrospectively. Histopathologic prognostic features such as grade, perineural invasion, lymphovascular invasion, tumor necrosis, and surgical margin status were also evaluated. Results: Seventy cases (94.6%) underwent open nephroureterectomy whereas 4 cases (5.4%) had laparoscopic nefroureterectomy. Thirty-eight (51.4%) cases were located in the pelvis, 7 (9.5%) in the ureter, 29 (39.2%) both in the pelvis and ureter. Fifty-six (75.7%) cases were alive; however, 18 (24.3%) patients were found to be dead. pTa, pT1, pT2, pT3, and pT4 tumors were reported in 16 (21.6%), 13 (17.6%), 4 (5.4%), 28 (37.8%), and 13 (17.6%) patients, respectively. Histopathologically, 17 cases (23%) were low-grade, 57 cases (77%) were high-grade. Statistically significant correlation was observed between overall survival and lymph node metastasis, distant metastasis, tumor necrosis, and differentiation by univariate analysis. Only distant metastasis was statistically associated with overall survival by multivariate analysis. We found no significant relationship between disease-free survival and all parameters. Conclusion: Differentiation and necrosis of tumor, lymph node involvement, and presence of distant metastasis is associated with the overall survival of urothelial carcinoma of the upper urinary system.

Chemical shift magnetic resonance imaging could predict subclinical cortisol production from an incidentally discovered adrenal mass.

CONTEXT: To investigate whether any association between chemical shift magnetic resonance (MRI) findings, cortisol secretion and pathological findings exists that could predict subclinical hypercortisolism (SCH) in patients with adrenal incidentalomas (AI). DESIGN: Retrospective, cross-sectional study in a tertiary centre. PATIENTS: Sixty-eight subjects with AIs and 13 patients with Cushing's syndrome (CS). Patients with AIs were categorized according to cortisol levels post 1 mg dexamethasone (post-DST). MEASUREMENTS: Visual inspection of the lipid content of the adrenal tumour and calculation of adrenal-to-spleen ratio (ASR), the signal intensity index (SII), volume and the assessment of the association between pathological, radiological and hormonal findings in surgically treated patients. RESULTS: Percentage of clear cells was correlated with ASR (r = -.525, P = .01), SII (r = .465, P = .025), post-DST cortisol (r = -.711, P < .001) and ACTH (r = .475, P = .046). By ANOVA and post hoc analysis, patients with CS and five subjects with a post-DST cortisol greater than 137 nmol/L differed significantly in ASR and SII from those with a post-DST cortisol less than 50 nmol/L. An ASR level higher than 0.245 (OR 19.7, 95% CI 1.5-257.5; P = .023) and a SII level lower than 78.37 (OR 15.6, 95% CI 1.2-20; P = .034) remained as the independent predictors for SCH while age, presence of arterial hypertension or tumour volume did not make significant contribution to the models. CONCLUSIONS: Cortisol hypersecretion by adrenal adenomas is associated with distinctive MRI characteristics. The quantitative assessment of intracellular lipid in an AI could help distinguish patients with a clear phenotype of SCH.

Suture granuloma after orchiectomy: sonography, doppler and elastography features.

Suture granuloma is a mass forming benign lesion that develops at the site of surgery as a foreign body reaction to non-absorbable suture material. We present a case of suture granuloma that developed at the inguinal region after orchiectomy, and define the sonography, color Doppler sonography and real-time ultrasound elastography findings in correlation with the histopathological findings.

Testicular calculus: A rare case.

BACKGROUND: Testicular calculus is an extremely rare case with unknown etiology and pathogenesis. To our knowledge, here we report the third case of testicular calculus. A 31-year-old man was admitted to our clinic with painful solid mass in left testis. After diagnostic work-up for a possible testicular tumour, he underwent inguinal orchiectomy and histopathologic examination showed a testicular calculus. Case hypothesis: Solid testicular lesions in young adults generally correspond to testicular cancer. Differential diagnosis should be done carefully. Future implications: In young adults with painful and solid testicular mass with hyperechogenic appearance on scrotal ultrasonography, testicular calculus must be kept in mind in differential diagnosis. Further reports on this topic may let us do more clear recommendations about the etiology and treatment of this rare disease.

Spectrum of nontumoral renal pathologies in tumor nephrectomies: nontumoral renal parenchyma changes.

Non-neoplastic changes are not rarely seen in renal parenchyma of nephrectomy specimens removed for primary renal neoplasms. These changes often involve both kidneys, thus causing impairment of renal function, reducing patient's quality of life and sometimes threatening it. Renal tissue accompanying the tumor provides an opportunity in order to evaluate these changes. However, the clinician should make available clinical and laboratory findings involving renal functions of the patient to the pathologist. It is also important that the pathologist must have appropriate knowledge and experience in nephropathology. In this study, we aimed to correlate these changes with the clinical data and make inquiries regarding our experience with nonneoplastic kidney pathology. Consecutive 403 nephrectomy specimens with primary renal neoplasms submitted to our department between 2003 and 2009 were re-examined. Twenty-three nephrectomy materials from 21 patients had non-neoplastic changes, 2 of which were bilateral. Patient follow-up data were obtained from electronic medical records. Of all cases, eight had diabetic nephropathy; 2, amyloidosis; 5, segmental proliferative and/or sclerotic glomerulonephritis; and 6, cystic renal changes. These findings were seen in 5% of nephrectomy specimens diagnosed as clear cell renal cell carcinoma (RCC), chromophobe cell RCC and oncocytoma, whereas this rate was two times higher in nephrectomy specimens with papillary RCC. Most patients with renal failure who were diagnosed with clear cell carcinoma died within the first two years. Despite limited number of cases in our series, prognosis of cases with clear cell RCC were poorer. Consequently, we think that non-neoplastic changes should be reported along with the details regarding the tumor in order to achieve best treatment planning.

Penile lesion with inguinal adenopathy after intravesical Bacillus Calmette-Guerin instillation therapy.

Intravesical Bacillus Calmette-Guérin (BCG) is widely used as an adjuvant therapy in the treatment of non-muscle-invasive bladder cancer. BCG is generally well tolerated, though localized and systemic infectious complications may occur. Infection of the glans and inguinal adenopathy are rare local complications of intravesical BCG therapy. Traumatic urethral catheterization is one of the main causes. We report the case of a 75-year-old male who developed granulomatous balanitis and enlarged inguinal lymph nodes after five cycles of intravesical BCG treatment for transitional cell carcinoma of the bladder. Histology revealed giant cell granuloma. Oral antituberculous treatment was initiated with subsequent full recovery of penile lesions and adenopathy. Physicians who administer BCG must be familiar with the possible complications and their adequate management and should inform patients about the side-effects accordingly.

Anna Karenina principle in personalized treatment of bladder cancer according to oncogram: which drug for which patient?

Aim: To evaluate the ex vivo efficacy of chemotherapy, immunotherapy and targeted agents with the oncogram method in patients with bladder cancer and determine the most appropriate personalized treatment agent using immune markers. Materials & methods: Bladder cancer tissues were obtained from each patient. After cultivation, cell cultures were divided into 12 groups for each patient and 11 drugs were administered. Cell viability and immunohistochemistry expression were examined. Results: A good response rate was determined to be a 23% viability drop. The nivolumab good response rate was slightly better in PD-L1-positive patients and the ipilimumab good response rate was slightly better in tumoral CTLA-4-positive cases. Interestingly, the cetuximab response was worse in EGFR-positive cases. Conclusion: Although good responses of drug groups after their ex vivo application by using oncogram were found to be higher than control group, this outcome differed on a per patient basis.

Bladder cancer primary cell cultures were shown to be effective for drug sensitivity and also able to be used ex vivo in the process of determining personalized treatment. The ex vivo efficacy of 11 different agents was evaluated with oncogram in bladder cancer cell cultures obtained from patients. Together with clinicopathological features, evaluation of drug responses detected by oncogram can provide important information for pretreatment drug selection when deciding on individualized treatment.

Atypical Presentation and Course of ACTH-independent Cushing's Syndrome in Two Families.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare genetic disease mainly associated with Carney complex (CNC), which is caused by germline mutations of the regulatory subunit type 1A (RIα) of the cAMP-dependent protein kinase (PRKAR1A) gene. We report three cases suffering from CNC with unique features in diagnosis and follow-up. All cases had obesity and a cushingoid appearance and exhibited laboratory characteristics of hypercortisolism. However biochemical and radiological examinations initially suggested Cushing's disease in one case . All of the cases were treated surgically; two of them underwent bilateral adrenalectomy at once, one of them had unilateral adrenalectomy at first but required contralateral adrenalectomy after nine months. Contrary to what is usually known regarding PPNAD, the adrenal glands of two cases (case 2 and 3) had a macronodular morphology. Genetic analyses revealed pathogenic variants in PRKAR1A (case 1: c.440+5 G>A, not reported in the literature; cases 2 and 3: c.349G>T, p.V117F). One case developed Hodgkin lymphoma five year after adrenalectomy, this association was not previously reported with CNC. The findings of these families provide important information for a better understanding of the genetic pathogenesis, diagnosis, and clinical management of CNC. Hodgkin lymphoma may be a component of CNC.

Unclassified renal cell carcinoma: a report of 56 cases.

UNLABELLED: What's known on the subject? and What does the study add? Unclassified RCC represents 0.7-5.7% of renal tumours. Limited reported data from two series suggests that unclassified RCC is an aggressive form of RCC, mainly because most cases are at an advanced stage at presentation, but overall and cancer-specific survival were not significantly different between unclassified and clear-cell RCC in an additional series of 38 patients. Our study of 56 cases of unclassified RCC describes the pathological features that can be applied to predict prognosis on a daily basis. In particular nuclear grade, TNM classification, tumour coagulative necrosis, tumour size, microvascular invasion and 2004 WHO histotype are independent predictors of disease-free and cancer-specific survival. OBJECTIVE: To evaluate the clinicopathological features and outcomes of 56 patients with unclassified renal cell carcinoma (RCC) meeting 2004 World Health Organization diagnostic criteria. PATIENTS AND METHODS: Urological pathology files of the participating institutions were reviewed and cases of unclassified RCC that met the inclusion criteria were retrieved. Nuclear grade, pT status, tumour size, regional lymph node involvement, distant metastases, coagulative tumour necrosis, mucin and sarcomatoid differentiation were evaluated in radical nephrectomy or nephron-sparing specimens. Significant factors in univariate analysis were then assessed by a multivariate analysis of independent prognostic factors using Cox proportional hazard regression analysis. RESULTS: Fifty-six cases met the histological criteria for unclassified RCC. Thirty-four (61%) cases were categorized as unrecognizable cell type (mean overall survival 47 months; median 36 months), 20 (36%) as composites of recognized types (mean overall survival 36 months; median 26 months), and two (4%) (mean survival 16 months; median 16 months) as pure sarcomatoid morphology without recognizable epithelial elements. Cox multivariate analysis showed nuclear grade (P = 0.020), stage (P < 0.001), tumour coagulative necrosis (P = 0.018), tumour size (P < 0.001), microvascular invasion (P < 0.001) and tumour histotype (P = 0.028) to be independent predictors of disease-free survival, with tumour size being the most significant (hazard ratio [HR] 9.068, 95% confidence interval [CI] 3.231-25.453). Nuclear grade (P = 0.026), stage (P < 0.001), tumour coagulative necrosis (P < 0.001), tumour size (P = 0.044), microvascular invasion (P < 0.001), tumour recurrence after surgery (P < 0.001) and tumour histotype (P = 0.056) were independent predictors of cancer-specific survival, with tumour recurrence after surgery being the most significant (HR 14.713, 95% CI 5.329-40.622). CONCLUSION: The prognosis of patients with unclassified RCC seems to be related to clinicopathological features known to be relevant in common forms of RCC.

Unusual case of severe late-onset cytomegalovirus-induced hemorrhagic cystitis and ureteritis in a renal transplant patient.

Cytomegalovirus (CMV) infection is common in solid organ transplant recipients and accounts for the majority of graft compromise. Major risk factors include primary exposure to CMV infection at the time of transplantation and the use of antilymphocyte agents such as OKT3 (the monoclonal antibody muromonab-CD3) and antithymocyte globulin. It most often develops during the first 6 months after transplantation. Although current prophylactic strategies and antiviral agents have led to decreased occurrence of CMV disease in early posttransplant period, the incidence of late-onset CMV disease ranges from 2% to 7% even in the patients receiving prophylaxis with oral ganciclovir. The most common presentation of CMV disease in transplant patients is CMV pneumonitis followed by gastrointestinal disease. Hemorrhagic cystitis is a common complication following hematopoietic stem cell transplantation. The condition is usually due to cyclophosphamide-based myeloablative regimens and infectious agents. Even in these settings, CMV-induced cases occur only sporadically. Ureteritis and hemorrhagic cystitis due to CMV infection after kidney transplantation is reported very rarely on a case basis in the literature so far. We report here a case of late-onset CMV-induced hemorrhagic cystitis and ureteritis presenting with painful macroscopic hematuria and ureteral obstruction after 4 years of renal transplantation. The diagnosis is pathologically confirmed by the demonstration of immunohistochemical staining specific for CMV in a resected ureteral section. We draw attention to this very particular presentation of CMV hemorrhagic cystitis with ureteral obstruction in order to emphasize atypical presentation of tissue-invasive CMV disease far beyond the timetable for posttransplant CMV infection.

Role of intraoperative US in the decision for radical or partial nephrectomy.

PURPOSE: To investigate the effect of intraoperative ultrasonographic (US) findings on the decision for the type of nephrectomy to be performed in patients who had renal tumors that were preoperatively evaluated by using magnetic resonance (MR) imaging, with pathologic results as the reference standard. MATERIALS AND METHODS: The institutional review board approved the study protocol, and informed consent was obtained. Between June 2008 and September 2009, 44 patients (25 men, 19 women; mean age, 56.6 years; range, 28-76 years) with 46 renal tumors were prospectively assessed by using intraoperative US examinations to demonstrate tumor relationship with the nontumoral intact parenchyma. Findings at preoperative MR examinations were retrospectively evaluated by two radiologists to determine the type of surgery that would be recommended. The reference standard was results of pathologist's review of gross specimens and postoperative reports. The observers assigned their decisions as follows: score group 1, radical nephrectomy should be (should have been) performed; score group 2, partial nephrectomy can be (could have been) attempted; and score group 3, partial nephrectomy should be (should have been) performed. RESULTS: Radical nephrectomy was performed in 36 lesions. In all cases, the intraoperative US observer and the pathologist were concordant in the decision that radical nephrectomy versus partial nephrectomy could or should have been performed. MR observers 1 and 2 overcalled the need for radical nephrectomy in seven and four cases, respectively. Compared with pathologic results, the overall correlation of intraoperative US was 0.991, and the correlation for MR observer 1 was 0.786 and that for MR observer 2 was 0.731. CONCLUSION: Intraoperative US can be suggested as a valuable examination method in patients with tumors at a central location with suspicious renal sinus extension demonstrated by using MR imaging. The close cooperation of urologist and radiologist in renal tumor work-up could reduce performance of unnecessary radical nephrectomy.

The association between the histopathological features and microsatellite instability in young patients with urothelial carcinoma of the bladder.

OBJECTIVE: Bladder cancer under the age of 40 is extremely rare. Bladder cancer development involves complex and multi-stage processes, one of which is the DNA damage repair mechanism. In this retrospective study, we aimed to evaluate the histopathological features of bladder urothelial carcinoma seen in patients under 40 years of age and tumor microsatellite instability status using immunohistochemistry. METHODS: A total of 50 patients under the age of 40 with urothelial bladder carcinoma from two different centers in the same country were included. Expression of the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 was analyzed by immunohistochemistry. RESULTS: Age at the time of diagnosis ranged from 17 to 40 years old. Most tumors were non-invasive papillary urothelial carcinoma. Two cases had nuclear loss of MSH-6 and PMS-2. We observed that tumor grade, tumor stage, presence of tumor differentiation, and infiltrative growth pattern of the tumor have significant impact on prognosis, but microsatellite instability does not have an effective role in bladder carcinogenesis in young patients. CONCLUSIONS: Our results indicate that the presence of microsatellite instability is not related to the low tumor grade and stage in urothelial neoplasms in young patients, suggesting that urothelial carcinoma of the bladder in young patients may represent a genetically stable form of neoplasia.

Can we perform frozen section instead of repeat transurethral resection in bladder cancer?

OBJECTIVE: To confirm frozen section (FS) method for muscularis propria (MP) sampling and to compare the FS method with the ReTUR section (RS) procedure to reduce needing for second resection that can cause waste of time for definitive treatment of muscle-invasive bladder cancer. METHODS: A total of 27 patients who admitted to our clinic and was performed transurethral resection of bladder tumor (TUR-BT) due to bladder tumor and had an indication of ReTUR were evaluated prospectively in the study. During the first TUR-BT procedure (as permanent section), FS examination was also performed to the patients. ReTUR was performed 2-6 weeks after the first TUR-BT procedure. RESULTS: Presences of MP were observed in 51.8% and 77.7% of FS and permanent section examinations. In the comparing of the presence of residual tumor in the methods, although 12 of 27 patients were found to have a residual tumor in FS, it was found to be in only 6 of 12 patients in RS. There was no statistical significance between FS and RS methods for MP sampling and detecting of residual tumor. CONCLUSIONS: FS was found to be a comparable method with the RS method (ReTUR procedure) for the sampling of MP and detecting of residual tumor, despite the limitations in the pathological examination FS. Especially in patients with detected residual tumor after the pathological consultation of FS during the procedure, re-resection can be a choice at the end of the first TUR-BT instead of ReTUR.

HN1 interacts with γ-tubulin to regulate centrosomes in advanced prostate cancer cells.

Prostate cancer is one of the most common cancer for men worldwide with advanced forms showing supernumerary or clustered centrosomes. Hematological and neurological expressed 1 (HN1) also known as Jupiter Microtubule Associated Homolog 1 (JPT1) belongs to a small poorly understood family of genes that are evolutionarily conserved across vertebrate species. The co-expression network of HN1 from the TCGA PRAD dataset indicates the putative role of HN1 in centrosome-related processes in the context of prostate cancer. HN1 expression is low in normal RWPE-1 cells as compared to cancerous androgen-responsive LNCaP and androgen insensitive PC-3 cells. HN1 overexpression resulted in differential response for cell proliferation and cell cycle changes in RWPE-1, LNCaP, and PC-3 cells. Since HN1 overexpression increased the proliferation rate in PC-3 cells, these cells were used for functional characterization of HN1 in advanced prostate carcinogenesis. Furthermore, alterations in HN expression led to an increase in abnormal to normal nuclei ratio and increased chromosomal aberrations in PC-3 cells. We observed the co-localization of HN1 with γ-tubulin foci in prostate cancer cells, further validated by immunoprecipitation. HN1 was observed as physically associated with γ-tubulin and its depletion led to increased γ-tubulin foci and disruption in microtubule spindle assembly. Higher HN1 expression was correlated with prostate cancer as compared to normal tissues. The restoration of HN1 expression after silencing suggested that it has a role in centrosome clustering, implicating a potential role of HN1 in cell division as well as in prostate carcinogenesis warranting further studies.

Assessment of ex-vivo efficacy (oncogram) of immunotherapeutic and chemotherapeutic agents in bladder cancer: A pilot study of personalized treatment.

PURPOSE: To investigate the ex-vivo efficacy of immunotherapeutics and chemotherapeutics in bladder cancer primary cell cultures, to assess the applicability of the method according to the results and to evaluate suitability of the oncogram method for personalized treatment of bladder cancer. METHODS: After receiving ethics committee approval, tumor tissue was obtained from patients with transurethral resection performed due to bladder tumor from 2015 to 2017. Primary culture was produced from the obtained fresh tissue. Each culture was divided into 6 groups. The control group had only medium applied, while the other groups had Bacillus Calmette Guerin (BCG), Interferon-α (IFN-α), Gemcitabine, BCG+IFN-α and BCG+Gemcitabine, respectively. Viability tests in the 24th hour were performed on each culture. The results of all cases were compared with their own controls. Also, results of each case were compared between the cases with similar pathologic results. RESULTS: The study assessed 24 bladder cancer cases. Mean patient age was 66.2±11.7 years (34-83), with 19 male (79.5%) and 5 female patients (20.5%). When data were compared between the groups, viability percentages were 31.2%, 30.9%, 27.7%, 32.1% and 29.4% in the BCG, IFN-α, Gemcitabine, BCG+IFN-α and BCG+Gemcitabine groups compared with their own controls (73.1%), respectively (p<0.001). In addition, we found that viability results were not similar in all cases. CONCLUSIONS: Cell cultures produced from bladder cancer tissue might help to determine sensitivity to treatment. This ex-vivo method (oncogram) is a simple and applicable method that can be used for personalized treatment before intravesical or systemic therapy.