The Role of Immunohistochemical Analysis as a Tool for the Diagnosis, Prognostic Evaluation and Treatment of Prostate Cancer: A Systematic Review of the Literature

Background: Prostate cancer (PCa) is a heterogeneous disease that lends itself toward numerous therapeutic options depending on its risk stratification. One of the greatest challenges in PCa urologic practice is to select patients who should be referred for biopsy and, for those patients who are diagnosed with cancer, to differentiate between patients with indolent disease from those with an unfavorable prognosis and, to determine ideal patient management and avoid unnecessary interventions. Accordingly, there is a growing body of literature reporting immunohistochemical studies with the objective of determining a prostate cancer prognosis. Among the most frequent biomarkers studied are Ki-67, p53, PTEN, MYC, and ERG. Based on these findings, we systematically reviewed articles that assessed the role of these main prognostic markers in prostate cancer.Methods: Consistent with PRISMA guidelines, we performed a systematic literature search throughout the Web of Science and PubMed Medline databases. We considered all types of studies evaluating the role of Ki-67, p53, PTEN, MYC, and ERG immunohistochemical analysis in prostate cancer until July 2017.Results: We identified 361 articles, 44 of which were summarized in this review. Diagnostically, no single immunohistochemical marker was able to define a tumor as benign or malignant. Prognostically, Ki-67, p53, and MYC were related to the tumor grade given by Gleason score and to the tumor stage (higher levels related to higher tumor grade). Furthermore, Ki-67 was also related to higher PSA levels, shorter disease-free intervals and shorter tumor-specific survival; the latter was also related to p53. The loss of PTEN protein expression showed a higher association with biochemical recurrence and with a worse prognosis, beyond that predicted by the Gleason score and tumor stage. ERG staining also showed a strong association with biochemical recurrence.Conclusion: There are several studies relating immunohistochemical markers with clinical-laboratorial outcomes in prostate cancer, the most frequent being Ki-67, p53, ERG, PTEN, and MYC. However, none of these markers have been validated by literary consensus to be routinely applied in medical practice

Catheter-associated urinary infections and consequences of using coated versus non-coated urethral catheters-outcomes of a systematic review and meta-analysis of randomized trials

Coated urethral catheters were introduced in clinical practice to reduce the risk of catheter-acquired urinary tract infection (CAUTI). We aimed to systematically review the incidence of CAUTI and adverse effects in randomized clinical trials of patients requiring indwelling bladder catheterization by comparing coated vs. non-coated catheters. This review was performed according to the 2020 PRISMA framework. The incidence of CAUTI and catheter-related adverse events was evaluated using the Cochran-Mantel-Haenszel method with a random-effects model and reported as the risk ratio (RR), 95% CI, and p-values. Significance was set at p 14 days) (RR 0.82 95% CI 0.68-0.99, p = 0.04). There was no difference between the two groups in the incidence of the need for catheter exchange or the incidence of lower urinary tract symptoms after catheter removal. The benefit of coated catheters in reducing CAUTI risk among patients requiring long-term catheterization should be balanced against the increased direct costs to health care systems when compared to non-coated catheters

Complications and outcomes of tubeless versus nephrostomy tube in percutaneous nephrolithotomy: A systematic review and meta-analysis of randomized clinical trials

We aimed to perform a systematic review of randomized trials to summarize the evidence on the safety and stone-free rate after Tubeless percutaneous nephrolithotomy (PCNL) (ureteral stent/catheter, no nephrostomy) compared to Standard PCNL (nephrostomy, with/without ureteral stent/catheter) to evaluate if the tubeless approach is better. The inverse variance of the mean difference with a random effect, 95% Confidence Interval (CI), and p values was used for continuous variables. Categorical variables were assessed using Cochran-Mantel-Haenszel method with the random effect model, and reported as Risk Ratio (RR), 95% CI, and p values. Statistical significance was set at p < 0.05 and a 95% CI. 26 studies were included. Mean operative time was significantly shorter in the Tubeless group (MD-5.18 min, 95% CI - 6.56, - 3.80, p < 0.00001). Mean postoperative length of stay was also significantly shorter in the Tubeless group (MD-1.10 day, 95% CI - 1.48, - 0.71, p < 0.00001). Incidence of blood transfusion, angioembolization for bleeding control, pain score at the first postoperative day, the number of patients requiring postoperative pain medication, fever, urinary infections, sepsis, perirenal fluid collection, pleural breach, hospital readmission, and SFR did not differ between the two groups. Incidence of postoperative urinary fistula was significantly lower in the Tubeless group (RR 0.18, 95% CI 0.07, 0.47, p = 0.0005). This systematic review shows that tubeless PCNL can be safely performed and the standout benefits are shorter operative time and hospital stay, and a lower rate of postoperative urinary fistula.Universita Politecnica delle Marche within the CRUI-CARE Agreemen

Bladder involvement in systemic lupus erythematosus

Objective: To study bladder involvement in systemic lupus erythematosus patients through clinical and laboratorial evaluation, ultrasonography, radiological and endoscopic examination. Methods: Thirty-nine patients, either outpatients or inpatients at the Department of Rheumatology of Hospital das Clínicas da Faculdade de Medicina from Universidade de São Paulo were evaluated as to clinical and laboratorial data. All patients were submitted to ultrasonographic evaluation of the upper urinary tract, radiological and endoscopic examinations of the middle and lower urinary tracts. Rresults: Mean age of patients varied between 13 and 62 years (median = 29 years). Thirty-six were females and three were males. The disease varied from 6 months to 22 years (median three years and one month). Clinical and laboratory activity of the disease was present in 30 patients. Twenty-two patients had the diagnosis of lupus established for three years or more. Twenty-five patients were asymptomatic and all had received corticosteroids for treatment at least once. Twenty-three received antimalarial drugs; ten received cytostatics, and seven patients received non-steroid anti-inflammatory drugs. Upper urinary tract ultrasonography was normal in all cases but one with staghorn calculus associated with neurogenic bladder secondary to neurological involvement by the disease. Vesicoureteral reflux was observed in two cases. Other two patients had significant post-voiding residual urine, both with neurogenic bladder secondary to nervous system involvement by lupus. The average bladder maximum capacity in an awaken patient was 342 mL, and was decreased in 18.9% of cases. This subgroup of patients presented a greater frequency of urinary symptoms and greater use of cytostatic drugs (Z > Z5%). A pathognomonic cystoscopic pattern of bladder involvement in systemic lupus erythematosus could not be established. Cystoscopic aspects similar to those seen in the initial or minor forms of interstitial cystitis were present in 43.2% of patients. This finding was more frequent when cytostatic drugs were used for treating the disease. Cconclusions: There was bladder involvement in systemic lupus erythematosus, even in asymptomatic patients, demonstrated by the occurrence of cystoscopic abnormalities or by reduced bladder maximum capacity associated with the presence of suprapubic pain, urinary irritation symptoms and the use of cytostatic drugs

Histological aspects of the bladder in systemic lupus erythematosus

Objectives: to study pathological data from bladders of systemic lupus erythematosus patients, correlate them to clinical events and the use of therapeutic drugs, and compare them to bladder histopathological findings in individuals not affected by systemic lupus erythematosus. Methods: thirty-nine out or inpatients of the Department of Rheumatology at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, diagnosed with systemic lupus erythematosus were clinically and cystoscopically evaluated. Bladder biopsy was also performed. As a normal parameter, bladders taken from 20 corpses collected at the Death Verification Department  of São Paulo city, without autolysis or evidence of urinary tract or autoimmune disease were also histologically studied. This group was considered as a Control Group. A correlation among clinical, cystoscopic and histopathological data was carried out. Rresults: the patients’ mean age was 29 years (range 13-62). Thirty-six were females and three were males. Twenty-five patients were asymptomatic during the study period. In the Control Group the age range was 20-65 years. Nineteen were females (95%) and one was male (5%). Cystoscopic examination of the group with systemic lupus erythematosus showed interstitial pattern in 16 cases (41.0%) and normal in 15 (38.5%). The bladder was normal in four patients (10.3%). Chronic unspecific cystitis was observed in 18 (46.2%) patients. In the remaining, several alterations were found, including bladder vasculitis in seven patients (17.9%). The mean number of mast cells in the bladder area was 2.223/mm2. In the Control Group, unspecific cystitis was found in three cases (15.0%). No other abnormalities were found. The mean number of mast cells in this group was 0.777/mm2 (±2.7). Chronic unspecific cystitis, bladder vasculitis and the mean number of mast cells were compared with each other and no statistical differences were found (p > 0.05). There were statistically significant differences between the two groups regarding chronic unspecific cystitis and bladder vasculitis (Z = 2.078 > Z5% = 1.645 and Z = 1.777 > Z5% = 1.645) and also mean number of mast cells (Z = 2.387 > Z5% = 1.673). There were statistically significant differences between the proportion of mast cell infiltrate and presence of suprapubic pain as well as use of antimalarial drugs. The other analysis did not show statistically significant differences. There was no statistical evidence of dependence among the events: cystoscopy with interstitial pattern and chronic unspecific cystitis (p > 0.237); cystoscopy with interstitial pattern and bladder vasculitis(p > 0.325); cystoscopy with interstitial pattern and mast cell infiltrate (p > 0.277). Cconclusions: the bladder in systemic lupus erythematosus may be involved even in the absence of clinical manifestations. The involvement of the bladder in systemic lupus erythematosus was characterized mainly by the finding of chronic unspecific cystitis, bladder vasculitis and mast cell infiltrate. The presence of chronic unspecific cystitis was significantly greater in patients with the disease than in the Control Group, and the same occurred with bladder vasculitis. The number of mast cells/mm2 was higher than normal in patients with systemic lupus erythematosus. This finding was associated to suprapubic pain upon bladder repletion and to use of antimalarial drugs

Non-occupational risk factors for bladder cancer

More than 60 thousand new cases of bladder cancer are diagnosedeach year in the United States, accounting for approximately 13thousand deaths annually. In recent decades, the overall incidenceof bladder cancer seems to be rising and this may be due to thelatent effects of tobacco abuse, other non-occupational risk factors,industrial carcinogens, as well as the overall aging of our population.Cultural and socioeconomic factors also contribute substantially tothe etiology of bladder cancer and may play an even more importantrole than the occupational environment. In this paper, it is reviewedthe main established or proposed non-occupational factors associatedwith bladder cancer development

Video game as a preoperative warm-up for laparoscopic surgery

Objective: The aim of the present study was to assess the influence of video game as warm-up before dry-lab laparoscopic activities. Methods: Eleven medical students participated in this prospective randomized crossover study. Students were divided into two groups. Students in Group 1 had to execute an interrupted suture with the dominant hand using a standardized technique (non-video game group). Students in Group 2 performed the same suture, but after playing a video game match (video game group). After this initial task, groups were crossed. The time spent to complete each task was recorded, and the participants and observers had to judge the performance for each laparoscopic exercise. These variables were used as a measure of performance. Rresults: Mean time for laparoscopic surgery in this subset of inexperienced laparoscopic students was similar between non-video game versus video game groups (254.6 ± 187.7 versus 255.8 ± 183.6; p = 0.875). Subjective impression of observers regarding students’ performance was also similar (p = 0.662), but subjective impression of the participant about his own performance was different between both groups, with 64.7 versus 20.0% of participants that considered their performance good for video game versus non-video game groups (p = 0.044). Cconclusions: In conclusion, video games used as warm-up for laparoscopic practice seem to make inexperienced surgeons more confident and comfortable with the procedures, even though objective measures, as operative time and observers’ impression of surgeons’ performance do not seem to be affected by video game warm-up