Methylation of PCDH17 and NEFH as prognostic biomarker for nonmetastatic RCC: A cohort study.

DNA methylation makes up a main part of the molecular mechanism of cancer evolution and has shown promising results in the prognosis of renal cell cancer (RCC). In this study, we investigated the possible association of promoter methylation of PCDH17, NEFH, RASSF1A, and FHIT, genes with the prognosis of nonmetastatic RCC patients. Cancerous and normal adjacent tissues from surgical specimens of 41 patients with long follow-up were treated for DNA isolation and bisulfite conversion. The gene promoter methylation was determined with quantitative methylation-specific PCR (qMSP). Wilcoxon signed-rank test was used for paired methylation comparisons, while univariate linear regression and Mann-Whitney test were applied for associating methylation status with clinical and disease characteristics. Cox regression proportional hazards models and Kaplan-Meier plots were used for survival analyses in reference to methylation status. Paired comparisons showed tissue-specific hypermethylation for PCDH17 (P < .001), NEFH (P < .001), RASSF1A (P = .032), while a positive association of methylation in normal tissues with age was demonstrated for PCDH17 (P < .001), RASSF1A (P < .001), FHIT (P < .001). PCDH17 was more methylated in cases with clear cell RCC (P = .015) and high-grade tumor (P = .013), while NEFH methylation was higher in locally advanced cases (P = .032). PCDH17 hypermethylation in cancerous and normal tissues was linked to shorter disease-specific survival (DSS, P = .026, P = .004), disease-free survival (DFS, P = .004, P = .019) while NEFH hypermethylation in cancerous tissues was related to shorter DSS (P = .032). Increased methylation difference of NEFH was also associated with shorter DSS (P = .041) and DFS (P = .020), while the corresponding parameter for PCDH17 was associated with poor DFS (P = .014). Kaplan-Meier curves for hypermethylation in cancer tissues demonstrated different clinical courses for PCDH17 (P = .017), NEFH (P = .023) regarding DSS, and PCDH17 (P = .001) regarding DFS. Our study not only highlights the prognostic value of promoter methylation of PCDH17 and NEFH in cancer tissues but also is the first report of the prognostic value of methylation alterations in normal tissues. Our findings are the first report of the prognostic value of methylation alterations in normal tissues, which can contribute to improved assessment of recurrence risk.

Hypoxia-Inducible Factor 2a Expression Is Positively Correlated With Gleason Score in Prostate Cancer.

BACKGROUND: One of the main factors in response to hypoxia in the tumor microenvironment is the hypoxia-inducible factor (HIF) pathway. Although its role in other solid tumors, particularly renal cell carcinoma, has been sufficiently elucidated, it remains elusive in prostate cancer. The aim of the present study was to investigate the expression of main proteins involved in this pathway and determine the correlation of the results with clinicopathological outcomes of patients with prostate cancer. METHODS: The immunohistochemical expression of HIF-1a, HIF-2a and their regulators, prolyl hydroxylase domain (PHD)1, PHD2 and PHD3 and factor inhibiting HIF (FIH), was assessed on a tissue microarray. This was constructed from radical prostatectomy specimens, involving both tumor and corresponding adjacent non-tumoral prostate tissues from 50 patients with localized or locally advanced prostate cancer. RESULTS: In comparison with non-tumoral adjacent tissue, HIF-1a exhibited an equal or lower expression in 86% of the specimens (P = 0.017), while HIF-2a was overexpressed in 52% (P = 0.032) of the cases. HIF-1a protein expression was correlated with HIF-2a (P < 0.001), FIH (P = 0.004), PHD1 (P < 0.001), PHD2 (P < 0.001) and PHD3 (P = 0.035). HIF-2a expression was positively correlated with Gleason score (P = 0.017) and International Society of Urological Pathologists (ISUP) grade group (P = 0.022). CONCLUSIONS: The findings of the present study suggest a key role for HIF-2a in prostate cancer, as HIF-2a expression was found to be correlated with Gleason score and ISUP grade of the patients. However, further studies are required to validate these results and investigate the potential value of HIF-2a as a therapeutic target in prostate cancer.

Decreased prolyl hydroxylase 3 mRNA expression in oncocytomas compared with clear cell renal cell carcinoma.

INTRODUCTION: Hypoxia inducible factors (HIF) and prolyl hydroxylase domain (PHD) enzymes play a central role in tumor progression in clear cell renal cell carcinoma (ccRCC). However, there are currently no data regarding the behavior of this pathway (HIF/PHD) in a large number of benign renal tumors, the oncocytomas. The aim of the present study was to compare the expression levels of these factors between ccRCC and oncocytoma tumors. MATERIAL AND METHODS: A total of 56 fresh frozen specimens from patients with ccRCC and 14 oncocytoma specimens were analyzed via reverse transcription-quantitative polymerase chain reaction in order to assess the expression levels of HIF-1α, HIF-2α, PHD1, PHD2, and PHD3. The analysis involved both fresh frozen tumor samples as well as adjacent normal kidney tissues. RESULTS: In ccRCC, HIF-1α and HIF-2α levels were upregulated in 65.5% and 71.4% of cases, respectively. PHD3 was downregulated only in 15.4% of the ccRCC cases, in contrast with oncocytoma cases, which exhibited low expression levels in the majority. The upregulation of PHD3 messenger RNA (mRNA) levels in ccRCC when compared with oncocytoma was statistically significant (P<0.001). No other comparisons (HIF-1α, HIF-2α, PHD1, and PHD2) were significantly different. HIF-2α and PHD3 mRNA expression levels were negatively correlated with Fuhrman Grade (P=0.029 and P=0.026, respectively) in ccRCC. CONCLUSION: To the best of our knowledge, this is the first time that the HIF/PHD pathway was compared between ccRCC and a common benign tumor, identifying the upregulation of PHD3 as the possible underlying factor guiding the difference in the behavior of ccRCC.

mRNA overexpression of prolyl hydroxylase PHD3 is inversely related to nuclear grade in renal cell carcinoma.

The aim of the present study was to evaluate the relative mRNA expression levels of genes involved in the hypoxia inducible factor (HIF) signalling pathway in renal cell carcinoma (RCC) and to analyse their associations with clinicopathological parameters and survival outcomes. Reverse transcription-quantitative PCR was used to quantify the mRNA expression levels of HIF-1α, HIF-2α, prolyl hydroxylase (PHD)1, PHD2 and PHD3 in formalin-fixed paraffin-embedded (FFPE) tumour tissue samples from 41 patients with RCC, including 33 cases of clear cell RCC (ccRCC). FFPE samples of corresponding adjacent normal kidney tissues were used as a comparison. mRNA expression levels were analysed in regard to clinical parameters, histological type, stage, nuclear grade, cancer specific survival and overall survival. Compared with adjacent normal kidney tissue, HIF-1α levels were lower in 16/33 ccRCC samples (48.48%), while HIF-2α, PHD1 and PHD2 levels did not exhibit a specific expression pattern. By contrast, the PHD3 mRNA level was higher in 29/33 (87.87%) of the tumour samples. HIF-1α was positively associated with HIF-2α, PHD1 and PHD2. HIF-2α levels were associated with PHD1, PHD2 and PHD3, while PHD3 was strongly associated with PHD2. PHD3 mRNA levels were inversely associated with nuclear grade (P=0.015). However, in univariate analysis, PHD3 was not associated with cancer-specific or overall survival rates. The present findings suggest an important involvement of PHD3 in ccRCC, since PHD3 mRNA expression was inversely associated with nuclear grade. However, PHD3 mRNA levels did not have an independent prognostic value. Further studies are required to investigate whether PHD3 could be used as either a therapeutic target or prognostic marker.

Expression of HIF-2a in clear-cell renal cell carcinoma independently predicts overall survival.

The purpose of this study is to evaluate the expression and the prognostic role of main factors, involved in the hypoxia pathway, in patients with clear-cell renal cell carcinoma (ccRCC). Immunohistochemical expression of Hypoxia inducible factors (HIF) HIF-1a, HIF-2a, prolyl hydroxylases PHD1, PHD2, PHD3, and factor inhibiting HIF (FIH) was assessed on a tissue microarray, containing tumour and corresponding normal kidney tissue from 66 patients underwent surgery for ccRCC. Expression levels were evaluated in relation to T stage, Fuhrman grade, cancer-specific, and overall survival (OS). Cytoplasmatic expression of HIF-2a was positively correlated with expression of HIF-1a (p = 0.011). HIF-1a expression was also positively correlated with PHD3 and FIH (p = 0.020 and p = 0.039). Expression of HIF-1a was associated with lower Fuhrman grade (p = 0.008), while HIF-2a overexpression with unfavourable grade (p = 0.026). PHD3 was significant downregulated (84.8%). Age, LDH, presence of necrosis, Fuhrman grade, T stage, and HIF-2a cytoplasmatic expression were significant associated with OS of patients in univariable analysis. In multivariable analysis, HIF-2a expression (p = 0.006) and T stage (p = 0.001) remained as the only independent predictors for overall survival. These results indicate that HIF-2a overexpression not only is inversely correlated with Fuhrman grade in ccRCC, but also represents a strong independent prognostic factor for a poor overall survival.

Renal Replacement Lipomatosis: From Conception to Birth.

Renal replacement lipomatosis is a rare disease characterized by renal parenchymal atrophy and proliferation of inflammatory and fatty cells within the renal sinus, hilum, and perirenal region. The exact pathogenesis is unknown, however more than 75% of cases are associated with renal stones. Here, we provide images from a case with 10 years of follow-up, outlining the radiographic progression of the disease through time. Although only histopathology can confirm the diagnosis, high clinical suspicion in combination with the radiographic findings can differentiate the disease from other fat-containing entities.

Assessing the Learning Curve of Holmium Laser Enucleation of Prostate (HoLEP). A Systematic Review.

We systematically assessed the learning curve of Holmium laser enucleation of the prostate using the available literature to identify, as our primary outcome, the average number of cases required to reach competency. A computerized search of PubMed and Scopus for articles published from inception through to January 2018 was performed including 24 studies with a total of 5173 patients. Even though different outcome measures require varying case-loads to reach a plateau, Holmium laser enucleation of prostate has an acceptable learning curve with a proposed figure approximating 25-50 cases, with a structured mentorship programme aiding for faster progress.

Pseudomyxoma Peritonei Arising From Urachal Mucinous Adenocarcinoma.

Pseudomyxoma peritonei is a rare clinical condition that can arise from various primary tumors with different biological behaviors. An intraperitoneal spread of mucus is the characteristic of the disease. Here, we provide images from a rare entity, a pseudomyxoma peritonei arising from urachal mucinous adenocarcinoma. If clinical suspicion is high, the preoperative imaging could be almost pathognomonic of the disease.

A Focused Review on the Effects of Preoperative 5α-Reductase Inhibitors Treatment in Patients Undergoing Holmium Laser Enucleation of the Prostate: What Do We Know So Far?

INTRODUCTION: The effects of medical therapy with finasteride or dutasteride during transurethral enucleation of prostate and tissue morcellation are not well defined. In theory, the risk of prostatic fibrosis versus the potential benefit of reduced intraoperative bleeding has been addressed as potential competing factors. The aim of this review was to provide evidence whether 5α-reductase inhibitors (5-ARIs) put the surgeon at a disadvantage or impact on patient outcomes. MATERIALS AND METHODS: We performed a literature search of PubMed, Scopus, and Web of Science databases. All articles in English language related to the topic were reviewed to provide data on the influence of preoperative 5-ARIs in holmium laser enucleation of prostate (HoLEP). RESULTS: Parameters of surgical efficiency such as enucleation time and efficiency, morcellation time, operating time, prostate tissue volume resected, energy, and saline usage were evaluated in the included studies. The review failed to show any definite impact of preoperative 5-ARI use on the mentioned parameters. One study, assessing the surgical difficulty using retrospective video recording analysis, showed that use of dutasteride increases the difficulty of enucleation step, which did not translate in statistical difference of surgical efficiency in an experienced level of surgeons. CONCLUSIONS: Overall, 5-ARIs do not seem to affect HoLEP. However, the quality of evidence is still quite poor in comparison with other surgical techniques. Further well-designed studies are required before making any definite recommendations on the use of 5-ARIs in patients undergoing HoLEP.

Should we expand the indications for varicocele treatment?

Current guidelines suggest that treatment of varicocele should be considered in patients with clinically palpable disease and abnormal semen parameters. However, the clinicians are often challenged with the decision whether to treat varicocele in patients with testicular pain or low testosterone levels. Moreover, varicocele is highly associated with DNA fragmentation due to the oxidative stress and it has been demonstrated that surgical repair of varicocele ameliorates oxidative stress markers and consequently the sperm DNA integrity. These new markers could have an adjunctive role to standard semen parameters especially when normal semen analysis is found in adult men with conventional methods. This review presents a contemporary overview of the rationale for varicocele treatment, as well as of the relationship between varicocele and other novel parameters such as DNA fragmentation index and reactive oxygen species. We will also discuss data from several recent series demonstrating that surgical treatment and especially microsurgical approach could resolve testicular pain, increase testosterone levels and fertility rate both in patients with non-obstructive azoospermia as well as in normozoospermia men. The correlation with progressive testicular failure will be also examined. We hope that this overview will provide clinicians with an evidence-based approach to managing these unanswered and conflicting topics.

Comparison Between Ambulatory and Conventional Urodynamics of the Modified Orthotopic Hautmann Neobladder / 대한배뇨장애요실금학회지

PURPOSE: The aim of the present study was to determine the diagnostic accuracy of conventional and ambulatory urodynamic studies (UDS) in estimating neobladder function. METHODS: We evaluated 32 patients who underwent radical cystectomy and orthotopic Hautmann W neobladder with Abol-Enein-Ghoneim uretero-intestinal anastomosis for bladder cancer. The patients were initially examined by using both conventional and ambulatory UDS. RESULTS: Conventional UDS detected a very high mean intravesical pressure at maximum capacity (53.7+/-17.5 cm H2O). By contrast, the mean intravesical pressure detected by using ambulatory UDS (which reflects the dominant pattern of pressure variation during filling) was significantly lower (34.4+/-5.2 cm H2O, P<0.001). The comparison between intravesical pressure at half of maximum capacity in conventional UDS and the mean value in ambulatory UDS did not show significant difference (P=0.152). The mean voided volume in conventional UDS was greater than both the mean voided volume (P<0.001) and the mean maximum voided volume in ambulatory UDS (P=0.001). However, this difference did not affect the postvoid residual urine volume measured in both studies (P=0.207). Moreover, incontinence episodes recorded in ambulatory UDS were more frequent but not statistically significantly different from those recorded in conventional UDS (P=0.332). CONCLUSIONS: The estimation of neobladder function by means of ambulatory UDS seems to provide interesting research data for the mode of lower urinary tract function in patients with orthotopic substitution after radical cystectomy. The great high value in ambulatory UDS, in cases in which conventional UDS had failed, is due to the exposure of daily and nocturnal incontinence episodes, confirming our patients' complaints.

Dermal scarification versus intramuscular diclofenac sodium injection for the treatment of renal colic: a prospective randomized clinical trial.

The aim of the study is to determine whether dermal scarification is equally effective for treating acute renal colic compared to diclofenac sodium intramuscular therapy. A prospective, randomized controlled study was conducted with methodologic rigor based on CONSORT criteria. A total of 291 patients, aged ≥ 18 years, suffering from acute renal colic were included in this trial and randomly assigned in two groups. Patients in the first group (A) received endodermal injection (dermal scarification) of 1 ml normal saline at the area of intensity of pain. The second group (B) received 75 mg diclofenac sodium by intramuscular injection. The success of each method defined the primary end point. Pain intensity before and after treatment was assessed using a visual analog scale. The time onset and the duration of analgesia were also recorded. There was no significant difference between the two groups regarding hematuria (p = 0.158), stone identification at KUB (p = 0.751) and mean pain intensity (p = 0.609) before treatment initiation. The method was successful in 75.5 % of patients in group A and 74.3 % of patients in group B (p = 0.812). Mean pain reduction was comparable, 5.65 ± 3.05 in group A and 5.34 ± 2.99 in group B (p = 0.379), with dermal scarification eliciting its effect considerably faster, whereas the duration of analgesia was longer in the diclofenac group (p < 0.05). In conclusion, dermal scarification could constitute an alternative method for treating renal colic as it is equally effective compared to the standard treatment of diclofenac sodium.

High patient satisfaction after inflatable penile prostheses implantation correlates with female partner satisfaction.

INTRODUCTION: Patient and female partner satisfaction after implantation of an inflatable penile prosthesis (IPP) assessed by objective means, and the correlation between the partners, is important for determining postoperative sexual life. AIM: The primary goal was to evaluate patients' erectile function and patients' and their partners' satisfaction after IPP implantation. A secondary aim was to investigate potential determinative factors of satisfaction according to device characteristics, demographics, and cause of erectile dysfunction (ED). METHODS: Ninety patients, who underwent IPP implantation as an alternative to refractory or undesirable medical treatment for ED, were evaluated. Patients who could not or refused to participate, or were out of a relationship, were excluded. The 69 remaining patients were evaluated for their pre- and postoperative erectile function and posttreatment satisfaction for themselves and their partners. MAIN OUTCOME MEASURES: Preoperative and postoperative scores on the International Index of Erectile Function Questionnaire-five items (IIEF-5) were compared. The Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) was given to males and their female partners. Patient demographics, etiology of ED, and implant characteristics were correlated also with patients' EDITS scores. RESULTS: Mean IIEF-5 scores demonstrated a significant improvement after IPP implantation: from 8.88±3.75 to 20.97±4.37 (P<0.001). The mean patients' EDITS score was 75.48±20.54, whereas mean female partners' score was 70.00±22.92, highlighting high posttreatment satisfaction for both. Regression analysis suggested a direct linear correlation of satisfaction between the sexual partners as a degree of satisfaction. There were no statistically significant differences according to level of education or implant characteristics. Concerning the etiology of ED, no conclusions could be made. CONCLUSIONS: Overcoming previous limitations in determining post-IPP implantation satisfaction, our study reiterates high rates of patient and partner satisfaction. Of particular note, patient satisfaction appears independent of prosthesis type and cylinder length.

Papillary cystadenoma of epididymis: Is there a need for further investigation in unilateral cases?

INTRODUCTION: The presence of a mass in the epididymis is not a common entity. The papillary cystadenoma of epididymis is a benign tumor which may occur sporadically or as a characteristic of von Hippel-Lindau disease. PRESENTATION OF CASE: We present a case of a 27-year-old man with a right scrotal mass who was treated with surgical excision. Histopathological examination revealed a clear cell epididymal papillary cystadenoma. A computed tomography scan that was performed later showed no other abnormality or any signs of von Hippel-Lindau disease. DISCUSSION: In this report, a case of a young man suffering from this rare tumor is discussed, focusing on the need of further evaluation in order to determinate if it occurs as a feature of VHL disease or as a sporadic form. CONCLUSION: In unilateral cases of papillary cystadenoma of epididymis such as our patient's, literature advocates that no further examinations and expensive genetic testing is required.

Pneumoscrotum as complication of blunt thoracic trauma: a case report.

Introduction. Pneumoscrotum is a rare clinical entity. It presents with swollen scrotal sac and sometimes with palpable crepitus. It has many etiologies. One of them is due to blunt trauma of the thoracic cage, causing pneumothorax and/or pneumomediastinum. Case Presentation. We report the case of an 82-year-old male who was transferred to the Emergency Department with signs of respiratory distress after a blunt chest trauma. A CT scan was obtained, and bilateral pneumothoraces with four broken ribs were disclosed. Subcutaneous emphysema expanding from the eyelids to the scrotum was observed, and a chest tube was inserted on the right side with immediate improvement of the vital signs of the patient. Discussion. Pneumoscrotum has three major etiologies: (a) local introduction of air or infection from gas-producing bacteria, (b) pneumoperitoneum, and (c) air accumulation from lungs, mediastinum, or retroperitoneum. These sources account for most of the cases described in the literature. Treatment should be individualized, and surgical consultation should be obtained in all cases. Conclusion. Although pneumoscrotum itself is a benign entity, the process by which air accumulates in the scrotum must be clarified, and treatment must target the primary cause.

Unilateral urinothorax can occur contralateral to the affected kidney.

Urinothorax is a rare cause of transudative pleural effusion with biochemical characteristics of urine, usually secondary to obstructive uropathy. Urine usually moves into the pleural space from the retroperitoneal or peritoneal space via diaphragmatic lymphatics or an anatomical diaphragm defect. A total of approximately 70 cases have been previously described in the literature, and in the vast majority of cases urinothorax is unilateral and ipsilateral to the side of obstructive uropathy, trauma or malignancy. This report describes a rare case of unilateral urinothorax occurring contralateral to the side of obstruction.

Urethral hairballs as a long-term complication of hypospadias repair: two case reports.

Many times hair-bearing urethral grafts have been used inadvertently in the treatment of hypospadias. This can be accompanied with numerous troublesome long-term complications such as formation of stones, diverticula, and hairballs. We report two cases of men with a history of hypospadias repair being affected by such complications. We also discuss about their management and the effect of thioglycolic acid instillation to stop hair growth in the urethra mucosa in the second case.