Effect of Hypertension on Outcomes of High-Risk Patients After BCG-Treated Bladder Cancer

Immunotherapy with Bacillus Calmette Guerin (BCG) is the most efficacious treatment for high-risk bladder cancer (BC) (Ta/T1 or carcinoma in situ) to reduce the risk of recurrence. Our aim was to evaluate whether hypertension and diabetes influence the outcome of patients with noninvasive BC treated with BCG instillations. In order to collect homogeneous data, we considered as "hypertensive" only those patients who had previous diagnosed hypertension and a history of taking medical therapy with antihypertensive drugs (AHT), and as "diabetic" only those prescribed oral antidiabetics or insulin (ADT). We analyzed 343 high-risk BC patients undergoing BCG 1995 2010) with a median follow-up of 116 months (range 48-238). The distribution of various kinds of AHT and antidiabetic drugs was homogeneous, with no significant differences (p > 0.05). In both univariate and multivariate analyses, the only statistically significant parameter propostic for recurrence after BCG treatment was AHT. Recurrence-liee survival curves showed a significant correlation with AHT (p = 0.0168, hazards ratio [HR] 1.45, 95% confidence interval [CI] 1.0692-1.9619); there was no correlation ( p = 0.9040) with ADT (HR 0.9750, 95% CI 0.6457-1.4721). After stratification of AHT and A.DT according to drug(s) prescribed, there were no significant differences in the BC recurrence rate (p > 0.05). In this study with a very long-term follow-up, hypertension alone (evaluated by AHT) revealed the increased risk of BC recurrence after BCG treatment. Several hypotheses have been formulated to support these findings, but further prospective studies are needed to both evaluate the real influence of hypertension and identify a possible prognostic factor to be used in selecting poor-prognosis BC patients as early candidates for surgical treatment

The bladder neck preservation in robot assisted radical prostatectomy: Surgical and pathological outcome

Introduction: The post-prostatectomy incontinence is influenced by multiple elements, anatomic components and biological factors. The bladder neck preservation, more accurate during robot assisted radical prostatectomy, works on two anatomic components responsible for post-prostatectomy continence. The bladder neck preservation spares the internal sphincter, which is responsible for passive continence, and results in earlier return to continence and lower rates of post-prostatectomy incontinence. Moreover, this surgical technique spares the zone of urothelium coaptation and provides primary resistance to the urine to maintain postprostatectomy continence. The potential risk of bladder neck positive surgical margins (PSM) may prevent the usage of the bladder neck preservation. Aim: The purpose of this study is to evaluate the surgical and pathological outcome in prostate cancer patients underwent robot assisted radical prostatectomy with bladder neck preservation. Materials and methods: Prospectively, we have collected demographic, clinical, surgical and pathological data of prostate cancer patients underwent robot assisted radical prostatectomy with bladder neck preservation, from January 2014 to December 2016, in Urological Clinic of the University of Padua. Moreover, it was valued the presence of alterations or continuous solutions of specimen external capsule, attributable to the surgical technique of bladder neck preservation, by microscopic and macroscopic pathological analysis. Results: According to D'Amico risk classification, 40 patients (45.4%) had a low risk neoplasia, 35 patients (39.8%) had an intermediate risk neoplasia, 13 patients (14.8%) had an high risk neoplasia. The median prostatic volume, valued on specimen, was 30.84 cc (21.5-44.75 cc). The median prostatic weight, valued on specimen, was 51 gr (36-67 gr). The pathological stage of disease was pT2a in 11 cases (12.5%), pT2b in 37 cases (42.1%), pT3a in 28 cases (31.8%), pT3b in 12 cases (13.6%). The pathological stage of lymph node involvement was pNx in 17 cases (19.3%), pN0 in 66 cases (75%), pN1 in 5 cases (5.7%). The prostate cancers diagnosed had a Gleason score at specimen of 6 in 10 cases (10.4%), 7 (3+4) in 30 cases (34.1%), 7 (4+3) in 20 cases (22.7%), 8 in 19 cases (21.6%) and 9 in 9 cases (10.2%). The prostatic base was involved by neoplasia in 14 patients (15.9%); of these, 5 patients (35.7%) had bladder neck PSM. The patients with bladder neck PSM had: a pathological stage of disease as pT3a in 2 cases (40%) and pT3b in 3 cases (60%); a pathological stage of lymph node involvement as pN0 in 2 cases (40%) and pN1 in 3 cases (60%); a Gleason score at specimen of 8 in 3 cases (60%) and 9 in 2 cases (40%); multiple PSM. Nobody had alterations or continuous solutions of specimen external capsule, attributable to surgical technique of bladder neck preservation. Conclusions: The bladder neck preservation, during robot assisted radical prostatectomy, is a safe oncological procedure resulting in a good functional outcome, about post-prostatectomy continence, working on two anatomic components responsible for post-prostatectomy continence. The bladder neck PSM are linked to neoplasia with adverse pathological features, rather than the bladder neck preservation

Mitostatin Is Down-Regulated in Human Prostate Cancer and Suppresses the Invasive Phenotype of Prostate Cancer Cells

MITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in nude mice. Conversely, targeting endogenous Mitostatin by siRNA and anti-sense strategies in PC3 and DU145 prostate cancer cells enhanced the malignant phenotype in both cell lines. In agreement of these anti-oncogenic roles, we discovered that Mitostatin was absent in ∼35% (n = 124) of prostate tumor samples and its overall reduction was associated with advanced cancer stages. Collectively, our findings indicate that MITOSTATIN may acts as a tumor suppressor gene in prostate cancer and provide a novel cellular and molecular mechanism to be further exploited and deciphered in our understanding of prostate cancer progression

Collecting duct carcinoma of the kidney: an immunohistochemical study of 11 cases

BACKGROUND: Collecting duct carcinoma (CDC) is a rare but very aggressive variant of kidney carcinoma that arises from the epithelium of Bellini's ducts, in the distal portion of the nephron. In order to gain an insight into the biology of this tumor we evaluated the expression of five genes involved in the development of renal cancer (FEZ1/LZTS1, FHIT, TP53, P27(kip1), and BCL2). METHODS: We studied eleven patients who underwent radical nephrectomy for primary CDC. All patients had an adequate clinical follow-up and none of them received any systemic therapy before surgery. The expression of the five markers for tumor initiation and/or progression were assessed by immunohistochemistry and correlated to the clinicopathological parameters, and survival by univariate analysis. RESULTS: Results showed that Fez1 protein expression was undetectable or substantially reduced in 7 of the 11 (64%) cases. Fhit protein was absent in three cases (27%). The overexpression of p53 protein was predominantly nuclear and detected in 4 of 11 cases (36%). Immunostaining for p27 was absent in 5 of 11 cases (45.5%). Five of the six remaining cases (90%) showed exclusively cytoplasmic protein expression, where, in the last case, p27 protein was detected in both nucleus and cytoplasm. Bcl2 expression with 100% of the tumor cells positive was observed in 4 of 11 (36%) cases. Statistical analysis showed a statistical trend (P = 0.06) between loss and reduction of Fez1 and presence of lymph node metastases. CONCLUSIONS: These findings suggest that Fez1 may represent not only a molecular diagnostic marker but also a prognostic marker in CDC

Diffuse leptomeningeal glioneuronal tumours: clinico-pathological follow-up.

Glioneuronal tumours are a group of primary brain neoplasms of relatively recent acquisition in the World Health Organization (WHO) Classification of the Central Nervous System tumours. In diagnostic practice it is still possible to encounter glioneuronal tumours that cannot be placed into any of the well-defined WHO categories despite a growing list of entities. We have recently published four paediatric cases of diffuse leptomeningeal tumours that cannot be easily classified in the currently used CNS WHO classification, but which have histological and immunohistochemical criteria to be considered as glioneuronal tumours. The clinical, neuroradiological and pathological long-term follow-up of an unusual diffuse leptomeningeal glioneuronal tumour is presented herein

Good tolerability of maintenance temozolomide in glioblastoma patients after severe hematological toxicity during concomitant radiotherapy and temozolomide treatment: report of two cases

Glioblastoma is the most common and aggressive primitive brain tumor in adults. Temozolomide (TMZ) administered daily with radiation therapy, followed by adjuvant TMZ has become the standard treatment. Although TMZ treatment has been considered to have a low toxicity profile, studies have noted the development of a severe myelosuppression, especially during the concomitant treatment; this toxicity may in some cases be prolonged and consequently treatment must be definitively discontinued. We analyzed two cases treated at our oncological center who developed severe and prolonged hematological toxicity during concomitant chemoradiotherapy treatment with TMZ. Hypothesizing that radiation therapy and daily TMZ could be the major causes of severe hematological toxicity during the concomitant phase, we decided to treat both patients with maintenance TMZ at the time of recovery of hematological values. Patients showed good tolerability without important myelosuppression. In conclusion, we suggest that glioblastoma patients with severe myelotoxicity during daily TMZ and radiation therapy be treated with maintenance TMZ at the time of blood value recovery

SMARCB1/INI1 Involvement in pediatric chordoma. A mutational and immunohistochemical analysis

Chordomas arise in the skull base and spine and usually occur in adults and are rare in the pediatric population. Cases of chordoma in pediatric age are often poorly differentiated, showing cytologic atypia, increased cellularity, and mitosis, and their aggressive behavior is associated with a high incidence of metastatic spread and a short patient survival. Recent studies have described loss of SMARCB1/INI1 protein in poorly differentiated chordomas associated not with point mutations but with SMARCB1/INI1 gene deletions instead. In this study, we considered immunohistochemistry and SMARCB1/INI1 mutational status to examine SMARCB1 status in a series of pediatric chordomas (7 classic and 1 poorly differentiated). We performed immunohistochemical tests for INI1, brachyury, S100, and cytokeratins and conducted a genetic analysis on the SMARCB1 coding sequence (NM_003073) using the Sanger method and multiplex ligation-dependent probe amplification to detect abnormal copy numbers of the gene locus. All 8 cases were positive for brachyury, whereas there was no nuclear SMARCB1/INI1 expression in 4 of the 8 cases, including the poorly differentiated chordoma. Genetic analysis identified a missense mutation in 2 cases and a nonsense mutation associated with loss of SMARCB1/INI1 protein and features of poorly differentiated tumor in 1. These mutations were novel variants occurring in heterozygosity, and they were judged to be pathogenic by 3 different bioinformatic tools. In 7 of 8 cases we performed multiplex ligation-dependent probe amplification, and 3 cases showed deletions at the SMARCB1 locus. Our results confirm the pathogenic involvement of SMARCB1/INI1 in childhood chordoma. We also describe 3 novel pathogenic mutations

Loss of FHIT expression in transitional cell carcinoma of the urinary bladder

Cytogenetic and loss of heterozygosity (LOH) studies demonstrated chromosome 3p deletions in transitional cell carcinoma (TCC), We recently cloned the tumor suppressor gene FNIT (fragile histidine triad) at 3p14.2, one of the most frequently deleted chromosomal regions in TCC of the bladder, and showed that it is the target of environmental carcinogens. Abnormalities at the FHIT locus have been found in tumors of the lung, breast, cervix, head and neck, stomach, pancreas, and clear cell carcinoma of the kidney. We examined six TCC derived cell lines (SW780, T24, Hs228T, CRL7930, CRL7833, and HTB9) and 30 primary TCC of the bladder for the integrity of the FHIT transcript, using reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate a potential role of the FHIT gene in TCC of the bladder. In addition, we tested expression of the Fhit protein in the six TCC-derived cell lines by Western blot analysis and in 85 specimens of primary TCCs by immunohistochemistry, Three of the six cell lines (50%) did not show the wild-type FHIT transcript, and Fhit protein was not detected in four of the six cell lines (67%) tested. Fhit expression also was correlated with pathological and clinical status. A significant correlation was observed between reduced Fhit expression and advanced stage of the tumors. Overall, 26 of 30 (87%) primary TCCs showed abnormal transcripts. Fhit protein was absent or greatly reduced in 61% of the TCCs analyzed by immunohistochemistry. These results suggested that loss of Fhit expression may be as important in the development of bladder cancer as it is for other neoplasms caused by environmental carcinogens