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A 55-year-old woman with dyspnea was diagnosed with a 9.5cm left renal clear cell carcinoma and extensive metastatic disease. Initial treatment with Sunitinib was effective but discontinued due to severe dermatitis. Nivolumab therapy led to complete metastasis resolution and consequently nephrectomy was performed at 12 months. Postoperatively, she developed Vogt-Koyanagi-Harada-like disease, necessitating Nivolumab suspension and vision improvement with corticosteroids. After 24 disease-free months, a new contralateral renal lesion and pulmonary metastases were identified, prompting cabozantinib treatment. This resulted in clinical improvement and a partial response at the first follow-up.

The diagnosis of antibody-mediated rejection has become more common and represents a major cause of kidney graft loss. The ideal treatment remains unknown, with little evidence supporting the use of a specific therapy. The definition of antibody-mediated rejection is based on serologic (presence and/or development of donor-specific antibodies) and histologic (evidence of acute tissue injury with C4d deposition or other signs of antibody interaction with the vascular endothelium) criteria. Antibody-mediated rejection without donor-specific antibodies is a subcategory with a defying diagnosis. This particularly entity is increasingly being reported as an important cause of allograft dysfunction in kidney transplantation. We describe the case of a kidney transplant recipient with a low immunological risk and delayed graft function due to an antibody-mediated rejection with negative donor-specific antibodies.

To the Editor, Upper urinary tract obstruction (UUTO) is a common scenario in clinical practice, and it is caused by a variety of diseases. Lithiasis, tumours and strictures are some of the principal aetiologies. Multiple factors may influence both the need for decompression of the obstructed collecting system and the urgency of procedure...

Penile fracture with urethral injury is uncommon. Diagnosis is usually based on clinical history and physical examination. Nonetheless, atypical presentation obliges complementary examinations to be performed.We report a case of a 45-years-old man with urethral bleeding after a blunt penile trauma that was ultimately diagnosed as having a cavernous body laceration on top of an urethral rupture.

Introduction: Infertility, the inability to conceive, constitutes a major problem in modern societies. It affects 10 to 15 percent of couples in the United States. Evaluation of infertile men is usually complex and often demands a testicular biopsy. Materials and methods: We reviewed all azoospermic men submitted to testicular biopsy, in our center, during infertility investigation between January 2015 and December 2021. Results: A total of 117 patients with a mean age of 36.5 was considered. Biopsy was positive, as defined by the presence of viable spermatozoids by microscopy, in 48.7% of patients (n = 57). Patients were divided in two separate groups based on positive (PB) or negative biopsy (NB) and compared. PB-group had normal serum total testosterone levels and higher than NB-group (3.7 ng/mL vs. 2.85 ng/mL, p = 0.021), and normal serum FSH levels and lower than NB-group (6.0 mIU/mL vs. 16.0 mIU/mL, p < 0.001). The groups were similar concerning serum LH levels (3.9 mIU/mL vs. 6.3 mIU/mL, p = 0.343. Conclusions: Predicting outcomes of testicular biopsy is a difficult task. Our study found that men with normal testicular volume, normal levels of testosterone and FSH and those with type 1 diabetes mellitus had a higher probability of positive testicular biopsy.

Introduction: Stage I seminoma has a very good prognosis, yet approximately 15% have subclinical metastatic disease and will relapse after orchidectomy alone. Several management approaches have been investigated. We aimed to evaluate the clinical outcomes of real-world patients with stage I seminoma, analysing prognostic factors influencing treatment choice and oncological outcomes. Methods: Retrospective, single institution study, with 55 patients diagnosed with clinical stage I seminoma between 2007 and 2020. Selected patients were analysed regarding three management approaches - surveillance, adjuvant radiotherapy and adjuvant carboplatin AUC7. Overall survival and progression-free survival outcomes were analysed. Predictors of treatment choice were determined, and predictors of recurrence were analysed in patients on active surveillance. Results: The median follow-up time was 91 months (13-165). Overall survival at 10 years was 98.2%. Stage I seminoma patients had a 1-, 3- and 10-year progression free survival of 98%, 94% and 89%, respectively. Three-year progression free survival was 92.0% for those on active surveillance (IC95%, 91.5-92.5%), 95.2% for carboplatin (IC95%, 94.8-95.6%) and 100% for those on adjuvant radiotherapy (p > 0.05). All relapses on active surveillance protocols occurred during the first 24 months. Overall, 43% of patients who underwent adjuvant treatment reported adverse effects of therapy, with higher incidence on radiotherapy group (63%). Conclusions: Stage I seminoma have excellent prognosis, high cure rates, and low treatment-associated morbidity. Active surveillance is a safe modality when applied to selected patients. Adjuvant radiotherapy and adjuvant chemotherapy with carboplatin show similar results, with fewer adverse effects on chemotherapy arm.

Objective: To assess the association of C reactive protein/Albumin ratio (CAR) with progression free survival (PFS) and overall survival (OS) in castration resistant metastatic prostate cancer (mCRPC) patients. Materials and methods: A transversal study was conducted, including all patients diagnosed with mCRPC within a Central Hospital Urological Oncology consultation between December 2019 and December 2021 (n = 178) and that were submitted to systemic therapy. CRP and albumin results were collected at the beginning of the systemic treatment for mCRPC in 103 patients and, in 75 patients already under treatment at the start of the study, on that occasion (December 2019). All patients were then followed. CAR was correlated with PFS and OS. OS and PFS were measured from the day the CRP and Alb were collected until the event of interest or the final date of follow-up. The sample was divided in two groups according to an optimal cutoff point found in a ROC curve. Results: The sample showed a median age of 75.76 ± 9.17 years old. Using a cut-off point of 0.22, patients with a CAR ≤ 0.22 (63.2%) showed, compared to CAR > 0.22, longer PFS (15.92 vs. 9.46 months, r = -0.13, p < 0.05) and OS (p = < 0.05, 25,72 vs. 15.79 months, r = -0,24, p < 0.05). Better OS in patients with CAR ≤ 0.22 vs > 0.22 was detected on both the group evaluated at the beginning of systemic treatment (26.96 vs 17.63 months, p < 0.05) and the group of patients already under treatment (23.90 vs 11.54 months, p < 0.05). Dividing the sample according to the first line treatment chosen, we found OS of 26.25 vs 5.9 months (p < 0.05), 27.71 vs 22.57 months (p < 0.05) and 27.36 vs 23.75 months (p = 0.12), for docetaxel, abiraterone and enzalutamide, respectively. Conclusions: According to this study, higher values of CAR are associated with lower PFS and OS in mCRPC patients. We found a cut-off value of 0.22 providing the best discrimination for prognosis. CAR is a good prognosis biomarker, irrespective of the moment of evaluation and chosen treatment option.

The effect of anti-algics on tumor progression and the overall survival of patients is controversial and remains unclear. Herein, we disclose the in vitro effects of the local anesthetics lidocaine, ropivacaine, and levobupivacaine on breast (MCF7), prostate (PC3, LNCaP), and bladder (TCCSUP, HT1376) cancer cell lines, both as monotherapy and in combination with standard-of-care therapeutics. Assays for cell proliferation, viability, death profile, and migration were performed. Additionally, we explored the clinical outcomes of opioid use through a cross-sectional study involving 200 metastatic prostate cancer patients. The main clinical data collected included the type of opioid therapy administered, dosage, treatment duration, disease progression, and overall survival. Results obtained demonstrate that treatment with local anesthetics has a promising selective anti-tumor effect on these types of cancer, with higher effects when associated with docetaxel. This points out the use of local anesthetics as an added value in the treatment of prostate carcinoma patients. Alternatively, chronic opioid use was correlated with reduced overall survival (p < 0.05) and progression-free survival (p < 0.05) at each treatment line in the observational study. While these results provide valuable insights, larger prospective studies are imperative to comprehensively evaluate the clinical impact of opioid analgesics in prostate cancer patients.

Introduction: The presence of blood in the urine should be promptly investigated to rule out urological malignancies, bladder cancer being the most frequent. Given its frequency among general population and the lack of unlimited health resources in an era of cost-effectiveness, it is important to prioritize patients with higher risk of malignancy. Objectives: To identify predictive factors of bladder cancer among patients presenting with hematuria. Patients and Methods: We retrospectively reviewed 296 cases referred to our department for hematuria. We evaluated different demographic, clinical and ultrasound features to uncover possible associations with diagnosis of bladder cancer in those patients, to estimate the individual risk of being diagnosed with bladder cancer during the investigation of hematuria. Results: A total of 296 patients were studied for hematuria between January 1, 2017 and December 31, 2019, 23.6% of those having ultimately bladder cancer confirmed after transurethral resection. Older age, male gender (OR 2.727, p = 0.069), a history of smoking (OR 3.84, p < 0.05), recurrent hematuria (OR 3.396, p < 0.05) and positive ultrasound exam for bladder cancer (OR 30.423, p < 0.05) were identified as predictors of bladder cancer in patients with hematuria. Conclusions: This study suggests that it is possible to reliably estimate the risk of bladder cancer in patients with hematuria, using clinical and imaging data to help defining who should be investigated first and in whom the investigation could be postponed.

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Background: The impact of positive surgical margins (PSMs) after partial nephrectomy (PN) is controversial. Objective: To evaluate the risk factors for a PSM and its impact on overall survival. Design, setting, and participants: This is a retrospective study of 388 patients were submitted to PN between November 2005 and December 2016 in a single centre. Two groups were created: PSM and negative surgical margin (NSM) after PN. A p value of

Introduction: Urolithiasis is common worldwide, with ureteric stones being a particular burden. Ureteroscopy (URS) is one of the most useful procedures in treating ureteric stones not passed spontaneously; this procedure has a complication risk of 4%. Negative URS, with described rates up to 15%, represents an avoidable patient risk and use of medical resources. Objectives: To describe rates and identify predictive factors for negative URS and to define strategies which would minimize patient and financial burden from these unnecessary procedures. Materials and methods: A retrospective cohort study analyzed patients who underwent URS in our Center to treat ureteric stones over a period of 2 years. Patient age, gender, and comorbidities, as well as laboratory and imaging findings, were analyzed. Results: 262 patients underwent URS for ureteric stones. The female population was 50.8% with a mean age of 56.89 years. A total of 78 (29.8%) URS procedures were negative. Univariate analysis showed a higher prevalence of negative URS in female patients, as well as in primary, smaller, and radiolucent stones. At multivariate analysis, a logistic regression model correctly classified 76% of patients, with smaller stone size and radiolucency being significant predictors of negative URS. Discussion and conclusions: Our Center showed a high rate of negative URS, higher than commonly described in the literature. Female patients tend to have an even higher rate, possibly due to unnoticed passage of stones. Patients with small, radiolucent stones showed the highest rates of negative URS.

Patients with a failed kidney allograft have steadily increase in recent years and returning to dialysis after graft loss is one of the most difficult transitions for chronic kidney disease patients and their assistant physicians. The management of these patients is complex and encompasses the treatment of chronic kidney disease complications, dialysis restart and access planning, immunosuppression withdrawal, graft nephrectomy, and evaluation for a potential retransplant. In recent years, several groups have focused on the management of the patient with a failing renal graft and expert recommendations are arising. A review of Pubmed, ScienceDirect and the Cochrane Library was performed focusing on the specific care of these patients, from the management of low clearance complications to concerns with a subsequent kidney transplant. Conclusion: There is a growing interest in the failing renal graft and new approaches to improve these patients’ outcomes are being defined including specific multidisciplinary programs, individualized immunosuppression withdrawal schemes, and strategies to prevent HLA sensitization and increase retransplant rates.

An increasing number of patients waitlisted for kidney transplantation have a previously failed graft. Retransplantation provides a significant improvement in morbidity, mortality, and quality of life when compared to dialysis. However, HLA sensitization is a major barrier to kidney retransplantation and the majority of the highly sensitized patients are waiting for a subsequent kidney transplant. A multidisciplinary team that includes immunogeneticists, transplant nephrologists and surgeons, and adequate allocation policies is fundamental to increase access to a kidney retransplant. A review of Pubmed, ScienceDirect, and the Cochrane Library was performed on the challenges of kidney retransplantation after graft loss, focusing on the HLA barrier and new strategies to overcome sensitization. Conclusion: Technical advances in immunogenetics, new desensitization protocols, and complex allocation programs have emerged in recent years to provide a new hope to kidney recipients with a previously failed graft.

Adrenocortical carcinomas (ACC) are aggressive tumors with a poor prognosis. Histological scores are advised for the diagnosis, however, there are borderline cases that may be misjudged as adrenocortical adenomas (ACA). The three main scores used are: Weiss Modified System (WMS), Reticulin Algorithm (RA), and Helsinki Score (HS). We intend to compare the accuracy of the three scores in ACC diagnosis and to identify predictive factors of overall survival (OS). Retrospective study (2004–2016) at Centro Hospitalar e Universitário de Coimbra of the adrenal tumors, classified as ACC or ACA, with a history of posterior tumor relapse/metastases, without lesions in the contralateral adrenal gland: 13F and 6M, with a median age of 51 ± 12.41 years. Nodules’ median size was 9.20 ± 6.2 cm. Patients had a median OS of 52 ± 18.6 months, with 57.9% and 46.3%, at 3 and 5 years. Seven patients had local recurrence and nine had metastases. Thirteen cases were in stage II. The WMS and the HS allowed a diagnosis of ACC in 15 cases and the RA defined ACC in 17 cases. All cases had, at least, focal disruption of the reticulin framework. More than 5 mitosis/50 HPF was associated with worse OS: 49.67 ± 21.43 versus 108.86 ± 14.02 months ( p = 0.026). In patients with stage II, tumor size ⩾10 cm was associated with worse OS: 19.25 ± 7.15 versus 96.11 ± 16.7 months ( p = 0.007), confirmed by multivariate analysis ( p = 0.031). The correct diagnosis of ACC is a pathologist responsibility. The RA seems the most accurate. Any loss of the reticulin framework should raise awareness for malignancy. In patients on stage II, a size ⩾10 cm is a predictor of worse prognosis.

Introduction: To reduce cold ischemia time (CIT), many kidney transplants are performed in the early morning. Conducting complex surgeries in the early morning may influence the surgeon's technical capacity and rate of surgical complications (SC). Aim: Evaluate the influence of surgery start hour (SSH) regarding duration of surgery (DS), immediate diuresis (ID), SC and acute rejection (AR); evaluate the influence of CIT regarding SC, ID, and AR. Methods: 2855 cadaveric transplants performed between June 1980 and March 2018 were retrospectively evaluated. Regarding SSH, two groups were created: Group M (00: 00h-05.59h, n = 253) and Group D (06: 00h - 23: 59h, n = 2602). Analyzing the impact of SSH on DS, ID, SC and AR. Evaluate the relationship between CIT (< 18h, 18-30h and > 30h) on ID, SC and AR utilizing univariate and multivariate statistical analysis with SPSS. Results and Conclusion: Groups M and D were comparable in all evaluated demographic variables (p > 0.05), except cold ischemia time (Group M with higher CIT, p < 0.001). Regarding univariate analysis, Surgery start hour did not influence DS (p = 0.344), and SC (p = 0.264), but related with higher ID (p = 0.028) and AR (p = 0.018). CIT related with immediate diuresis (p = 0.020) and acute rejection (p < 0.001) but did not relate with complications (p = 0.734). Regarding multivariate analysis, SSH only influenced immediate diuresis (p = 0.026) and did not influenced acute rejection (p = 0.055). CIT influenced immediate diuresis (p = 0.019) and acute rejection (p < 0.001). Surgery start hour influences Immediate diuresis. With this study, we conclude that the priority must be a short cold ischemia time.

Introduction: Hospitals are dealing with patients who may have clinical discharge but cannot return to their home due to non-medical issues. Material and Methods: Cross-sectional analysis of all the cases referred to the Integrated Care Network during the year 2016. Evaluation of waiting times, typology, reason for referral and clinical parameters. IBM SPSS 24.0 software was used for all statistical analyses. Results: In the evaluated period, 2294 patients were discharged from our department. Of these, 55 were referred to Integrated Care Network. The mean length of hospitalization of the patients referred to the network was 20.6 ± 11.4 days, and the mean overall length of hospital stay in the period analyzed was 4.8 ± 0.9 days. The mean time between hospitalization and referral for continuing care was 10.7 ± 7.2 days. The time between referral and discharge of the hospital was 10.0 ± 8.7 days. Thirty-nine (70.9%) patients were hospitalized for oncological diseases. The most common referral was to Palliative Care units (n = 16; 29.1%). Patients referred to Palliative Care units showed the largest waiting times between the referral for the network and the hospital discharge, 12.2 ± 10.51 days. We observed 289 hospitalization days with patients who had no need of specialized urological care. Discussion: In order to reduce time between referral to the network and hospital discharge, there is a need for enhanced cooperation and coordination among doctors, nurses and social workers. Conclusion: Early identification by physicians and nurses of patients who will require care after discharge will provide a better response from social workers and increased hospital performance.

Objectives: Clinical approach of prostate cancer (PCa) biochemical recurrence (BCR) is an ever-changing topic. Prostate-specific membrane antigen positron emission tomography ([68Ga]Ga-PSMA-11 PET-CTPSMA PET-CT) has shown good potential in this field. The aim is to evaluate PSMA PET-CT detection rate in PCa BCR and assess its impact on clinical outcome. Material and methods: Out of 319 patients with PCa who underwent PSMA PET-CT between October 2015 and June 2019, 70 had developed BCR after treatment with curative intent. Two groups were created: one with BCR after surgery (RP group) (N: 48; 68.6%) and other with BCR after radiotherapy (RT group) (N: 22; 31.4%). Clinical, analytical, pathological and PSMA PET-CT results were evaluated. Results: Initial age was different between groups (p = 0.008). RP patients were mainly at intermediate risk (85.1% vs 42.9%, p = 0.001) while RT patients were at low risk of recurrence (8.5% vs 47.6%, p = 0.001). In RP and RT groups, PSMA PETCT detected, respectively, pelvic relapse in 31.3% and 63.6%, and extrapelvic relapse in 18.8% and 31.8%. Salvage treatment was performed in 61.9% (n = 26) of RP patients and in 15% (n = 3) of RT patients, p < 0.001. Of RP patients submitted to salvage treatment, 59.1% achieved complete remission. Concerning these patients, local radiotherapy led to complete remission in 68.4% (n = 13). Of RT patients submitted to salvage treatment, two had complete remission and one had partial remission.Concerning detection rate, PSMA PET-CT was positive for pelvic relapse when pre-PET PSA ≥ 0.8 ng/mL (RP) or ≥ 2.3 ng/mL (RT) and for extrapelvic relapse when PSA ≥ 0.4 ng/mL (RP) or ≥ 3.5 ng/mL (RT), p > 0.05. Conclusions: Biochemical persistence rate after salvage therapy was similar (30-40%). The cut-off PSA values for pelvic relapse detected on PSMA PET-CT were ≥ 0.8 ng/mL (RP) and ≥ 2.3 ng/mL (RT).

Colorectal cancer (CRC) is a major health burden and may arise as a complication of solid organ transplantation. Our study aimed to assess the incidence of the CRC in kidney and liver transplanted patients at a tertiary and reference center and to describe their clinical and pathological features.Twelve patients, 10 men and two women, with a mean age of 60 years, composed our cohort, ten of them submitted to CRC resection. Transplanted organ was liver in five patients and kidney in seven. Regarding overall survival, patients submitted to renal transplantation were all deceased 5 years after CRC diagnosis, while those subjected to hepatic transplantation had a survival of 60% at the fifth year.Pathology examination showed seven patients with advanced disease (stage III/IV) and high amount of necrosis. Tumor microenvironment was disturbed, with low inflammatory infiltrate, absence of natural killer cells and no PD-L1 expression. CRC exhibited microsatellite instability in 40%, with expression of cancer stem cell markers (CD133, CD44 and ALDH1), as well as P53 (50%) and KRAS mutations (41.7%).CRC cancer after kidney and hepatic transplantation is a rare, but aggressive and deadly event. Regular follow-up should be instituted in these patients.

Introduction: Prostatic multiparametric magnetic resonance (mpMRI) allows for guided prostate biopsy (PB). Objective: To evaluate localization agreement between mpMRI lesions and histology obtained by cognitive PB and radical prostatectomy (RP) surgical specimen (SS). Methods: Out of 115 consecutive cognitive biopsied patients, 37 with positive PB were studied. Sample was characterized regarding age, prostatic volume, PI-RADS, location of lesion on mpMRI, lesion dimension, total number of fragments obtain by PB, number of fragments directed to the lesion, number of fragments with prostatic adenocarcinoma (PCa) and ISUP classification. The relationship between mpMRI and SS piece was analysed in 15 patients who underwent RP. Results: Regarding agreement between mpMRI and PB, agreement of location was observed in 26 (70.3%); 7 (18.9%) presented PCa positive fragments in the suspected zone plus others in the same lobe; 3 (8.1%) in the suspected zone plus the contralateral lobe and 1 (2.7%) had no PCa in the suspected zone but had bilateral PCa. The total number of fragments with PCa was lower in cases with agreement between mpMRI and PB (p < 0.05). Regarding agreement between mpMRI and SS, 5 cases (33.3%) presented the same location as described by mpMRI, 5 (33.3%) showed ipsilateral lesions in other zones of the prostate; 4 (26.7%) presented extensive bilateral lesions on all prostate zones and 1 (6.7%) showed previously unknown contralateral lesions. None of the factors studied related mpMRI and RP (p > 0.05). Conclusions: Localization agreement of mpMRI vs PB and mpMRI vs SS was present in 26/37 (70.3%) and 5/15 (33.3%), respectively. That suggests the existence of other lesions (multifocality) not identified on mpMRI.

Objective: Our aim was to evaluate the effects of glucose levels and diabetes mellitus in prostate cancer (PCa) biology. Materials and methods: Two PCa cell lines (LNCap and PC3) were cultured in RPMI medium with different glucose concentrations [5mM (LG) and 25mM (HG)]. Expressions of androgen receptor, Her2/neu and glucose transporters (GLUT1, 3, 5 and 12) were evaluated by flow cytometry. Proliferation rate was assessed by colorimetric assay MTT and cellular characterization was performed by haematoxylin and eosin staining. Additionally, we performed a cross sectional analysis of 704 patients undergoing radical prostatectomy who were divided into two groups (diabetic and non-diabetic). An analysis of clinical and histological data seeking to identify the differences on tumor aggressiveness between the two groups was performed. Results: In LNCaP cell line, when the glucose concentration in the medium increased, there was an increased in AR expression. Regarding expression of Her2/neu receptor, medium’s glucose concentration significantly changed the expression of this receptor in both PC3 and LNCaP cell lines. Growth rate was higher on the HG medium for both cell lines. The clinical study of patients undergoing radical prostatectomy revealed no relationship between the presence of diabetes and the development of more aggressive tumours. Diabetic patients had significantly higher prostatic volumes, however, no significant difference was found between the relapse risk classification or the ISUP classification between the two groups. Conclusions: Our results showed that medium glucose concentration could influence prostate cancer cells growing but not the aggressiveness.

Objective: The last edition of the AJCC staging system eliminated the pT2 subclassification of prostate cancer (PCa). Our objective was to evaluate the association of pT2 subclassification with the oncological results of patients with PCa who underwent radical prostatectomy (RP). Material and methods: We evaluated 367 patients who underwent RP between 2009 and 2016, with pT2 disease in the final pathological evaluation. We assessed differences in rates of biochemical recurrence (BCR), metastasis and mortality between T2 substages (pT2a/b vs pT2c). Results: Fifty-three (14.4%) patients presented pT2a/b disease and 314 (85.6%) pT2c disease. The mean follow-up time was 4.9 ± 2.6 years. Grade group scores (p = 0.1) and prostate specific antigen (PSA) (p = 0.2) did not differed between pT2 substages. The rate of BCR in pT2a/b and pT2c patients was 11.3% and 18.2%, respectively (p = 0.2). Five (9.4%) patients with pT2a/b and 45 (14.3%) with pT2c substage underwent salvage radiotherapy (p = 0.3). The rate of positive surgical margins did not differ between groups (p = 0.2). Seven (2.2%) patients with pT2c had lymph nodes or distant metastases. The overall survival was 92.5% and 93.6% in pT2a/b and pT2c, respectively (p = 0.2). Conclusion: Our results are in accordance with the changes introduced in the 8th edition of the AJCC staging system in which the pT2 subclassification was eliminated.

Abstract Background Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. Main body The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in cancers that depend on hTERT activation. Knowing that telomeres are crucial for cellular self-renewal, the mechanisms responsible for telomere maintenance have a crucial role in cancer diseases and might be important oncological biomarkers. Thus, rather than quantifying TERT expression and its correlation with telomerase activation, the discovery and the assessment of the mechanisms responsible for TERT upregulation offers important information that may be used for diagnosis, prognosis, and treatment monitoring in oncology. Furthermore, a better understanding of these mechanisms may promote their translation into effective targeted cancer therapies. Conclusion Herein, we reviewed the underlying mechanisms of hTERT regulation, their role in oncogenesis, and the potential clinical applications in telomerase-dependent cancers.

Antitumor therapies based on Cold Atmospheric Plasma (CAP) are an emerging medical field. In this work, we evaluated CAP effects on bladder cancer. Two bladder cancer cell lines were used, HT-1376 (stage III) and TCCSUP (stage IV). Cell proliferation assays were performed evaluating metabolic activity (MTT assay) and protein content (SRB assay). Cell viability, cell cycle, and mitochondrial membrane potential (Δψm) were assessed using flow cytometry. Reactive oxygen and nitrogen species (RONS) and reduced glutathione (GSH) were evaluated by fluorescence. The assays were carried out with different CAP exposure times. For both cell lines, we obtained a significant reduction in metabolic activity and protein content. There was a decrease in cell viability, as well as a cell cycle arrest in S phase. The Δψm was significantly reduced. There was an increase in superoxide and nitric oxide and a decrease in peroxide contents, while GSH content did not change. These results were dependent on the exposure time, with small differences for both cell lines, but overall, they were more pronounced in the TCCSUP cell line. CAP showed to have a promising antitumor effect on bladder cancer, with higher sensitivity for the high-grade cell line.

Introdução: No carcinoma da próstata, é frequente, após terapêutica com intuito curativo, ocorrer recidiva bioquímica. O objectivo deste trabalho foi avaliar o impacto da PET/CT com fluorocolina-F18 no restadiamento e orientação destes doentes e analisar a influência, da estratificação de risco, dos valores do PSA e da terapêutica de supressão hormonal, na sensibilidade da técnica. Material e Métodos: Análise retrospectiva de 107 doentes com carcinoma da próstata em recidiva bioquímica que realizaram PET/CT com fluorocolina-F18 no nosso hospital, entre dezembro de 2009 e maio de 2014. Resultados: A sensibilidade global foi de 63,2% sendo 80,0% quando PSA > 2 ng/mL. Foi possível identificar doença à distância em 28% dos doentes. A sensibilidade aumentou de 40,0% em doentes de risco baixo e intermédio para 55,2% em doentes de alto risco. Sem terapêutica de supressão hormonal, a sensibilidade foi de 61,8% enquanto no grupo sob essa terapêutica, foi de 67,7%. Discussão: A PET/CT com fluorocolina-F18 forneceu informações relevantes, mesmo em doentes com baixos valores do PSA, contudo, com incremento significativo da sensibilidade nos doentes com PSA >2 ng/mL. A sensibilidade foi superior nos doentes de alto risco comparativamente com os de risco baixo e intermédio, contudo, sem uma diferença estatisticamente significativa. A terapêutica de supressão hormonal parece não influenciar a captação de Fluorocolina-F18 nos doentes resistentes à castração. Conclusões: Neste estudo, a PET/CT com fluorocolina-F18 apresentou bons resultados no restadiamento de doentes com carcinoma da próstata em recidiva bioquímica, distinguindo entre doença loco-regional e sistémica, informação com importantes consequências na definição da estratégia terapêutica.

To investigate the anti-carcinogenic effects of Atorvastatin (Atorva) on a rat bladder carcinogenesis model with N-butyl-N-(4-hydroxibutil)nitrosamine (BBN), four male Wistar rat groups were studied: (1) Control: vehicle; (2) Atorva: 3 mg/kg bw/day; (3) Carcinogen: BBN (0.05%); (4) Preventive Atorva: 3 mg/kg bw/day Atorva + BBN. A two phase protocol was used, in which the drug and the carcinogen were given between week 1 and 8 and tumor development or chemoprevention were expressed between week 9 and 20, when the bladders were collected for macroscopic, histological and immunohistochemical (p53, ki67, CD31) evaluation. Serum was assessed for markers of inflammation, proliferation and redox status. The incidence of bladder carcinoma was: control 0/8 (0%); Atorva 0/8 (0%); BBN 13/20 (65%) and Atorva + BBN 1/8 (12.5%). The number and volume of tumors were significantly lower in the Atorva + BBN group, with a marked reduction in hyperplasia, dysplasia and carcinoma in situ lesions. An anti-proliferative, anti-inflammatory and antioxidant profile was also observed in the preventive Atorva group. p53 and ki67 immunostaining were significantly increased in the BBN-treated rats, which was prevented in the Atorva + BBN group. No differences were found for CD31 expression. In conclusion, Atorvastatin had a clear inhibitory effect on bladder cancer development, probably due to its antioxidant, anti-proliferative and anti-inflammatory properties.

Renal cell carcinoma with smooth muscle stroma (RCCSMS) is a rare and controversial renal cancer type with indolent behavior. This separation of this entity from other types of renal cell carcinoma is supported by recent published studies but not yet recognized by the World Health Organization. We present a case of a 72 years old female, with incidental finding on abdominal ultrasound of a renal nodule with 1.5cm. The patient underwent partial nephrectomy and the pathological evaluation showed an epithelial tumor composed of nests and trabeculae of polygonal cells with clear cytoplasm and low grade nuclear features, surrounded by an abundant stroma composed by fascicles of spindle cells without significant pleomorphism or mitoses. Immunohistochemically, the epithelial cells showed strong and diffuse positivity for CK7, CD10, vimentin and EMA; staining for RCC was focal. The stromal cells were positive for vimentin, smooth muscle actin, HHF35, desmin and caldesmon; ER and PR were negative. The staining for HMB45 and Melan-A was negative in both components. So the final diagnosis of RCCSMS was made. It’s important to be aware of this entity in order to differentiate RCCSMS from renal cancers with less favorable prognosis and higher degree of malignancy, like clear cell renal cell carcinoma, especially with sarcomatoid change.

To evaluate the effect of a cyclooxygenase 2 inhibitor, celecoxib (CEL), on bladder cancer inhibition in a rat model, when used as preventive versus as curative treatment. The study comprised 52 male Wistar rats, divided in 5 groups, during a 20-week protocol: control: vehicle, carcinogen: 0.05% of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), CEL: 10 mg/kg/day of the selective COX-2 inhibitor Celebrex, preventive CEL (CEL+BBN-P), and curative CEL (BBN+CEL-C) groups. Although tumor growth was markedly inhibited by the preventive application of CEL, it was even aggravated by the curative treatment. The incidence of gross bladder carcinoma was: control 0/8(0%), BBN 13/20(65%), CEL 0/8(0%), CEL+BBN-P 1/8(12.5%), and BBN+CEL-C 6/8(75%). The number and volume of carcinomas were significantly lower in the CEL+BBN-P versus BBN, accompanied by an ample reduction in hyperplasia, dysplasia, and papillary tumors as well as COX-2 immunostaining. In spite of the reduction of tumor volumes in the curative BBN+CEL-C group, tumor malignancy was augmented. An anti-inflammatory and antioxidant profile was encountered only in the group under preventive treatment. In conclusion, preventive, but not curative, celecoxib treatment promoted a striking inhibitory effect on bladder cancer development, reinforcing the potential role of chemopreventive strategies based on cyclooxygenase 2 inhibition.