LGALS3 cfDNA methylation in seminal fluid as a novel prostate cancer biomarker outperforming PSA.

BACKGROUND: The unmet challenge in prostate cancer (PCa) management is to discriminate it from benign prostate hyperplasia (BPH) due to the lack of specific diagnostic biomarkers. Contemporary research on potential PCa biomarkers is directed toward methylated cell-free DNA (cfDNA) from liquid biopsies since epigenetic mechanisms are strongly involved in PCa development. METHODS: In the present research, cfDNA methylation of the LGALS3 gene in blood and seminal plasma of PCa and BPH patients was assessed using pyrosequencing, as well as LGALS3 DNA methylation in tissue biopsies. Liquid biopsy samples were taken from patients with clinical suspicion of PCa, who were subsequently divided into two groups, that is, 42 with PCa and 55 with BPH, according to the histopathological analysis. RESULTS: Statistically significant higher cfDNA methylation of LGALS3 in seminal plasma of BPH than in PCa patients was detected by pyrosequencing. ROC curve analysis showed that it could distinguish PCa and BPH patients with 56.4% sensitivity and 70.4% specificity, while PSA did not differ between the two patient groups. In contrast, there was no statistically significant difference in LGALS3 cfDNA methylation in blood plasma between the two patient groups. In prostate tumor tissue, there was a statistically significant DNA hypermethylation of LGALS3 compared to surrounding nontumor tissue and BPH tissue. CONCLUSIONS: The DNA hypermethylation of the LGALS3 gene represents an event specific to PCa development. In conclusion, LGALS3 cfDNA methylation in seminal fluid discriminates early PCa and BPH presenting itself as a powerful novel PCa biomarker highly outperforming PSA.

Cystic dysplasia of the rete testis accompanying ipsilateral renal agenesis in a young adult: a case report.

A 31-year-old man with left-sided testicular pain lasting a couple of months was referred to our urology department due to a suspected testicular tumor. Physical examination showed a hard, thickened, and small left testis on palpation with a diffuse, inhomogeneous ultrasonographic appearance. After a urologic examination, a left-sided inguinal orchiectomy was performed. The testis, epididymis, and spermatic cord were sent to pathology. Gross examination revealed a cystic cavity filled with brown fluid and the surrounding brownish parenchyma measuring up to 3.5 cm in diameter. Histologic examination showed a cystically dilated rete testis lined with cuboidal epithelium and a positive immunohistochemical reaction to cytokeratins. Microscopically, the cystic cavity was a pseudocyst filled with extravasated erythrocytes and abundant clusters of siderophages. The siderophages extended into the testicular parenchyma, surrounding the seminiferous tubules and spreading out around the ducts of the epididymis, which were also cystically dilated with siderophages inside their lumina. On the basis of clinical data, histological, and immunohistochemical analysis, the patient was diagnosed with cystic dysplasia of the rete testis. The literature shows an association between cystic dysplasia of the rete testis and ipsilateral genitourinary anomalies. Therefore, our patient underwent a multi-slice computed tomography scan, which revealed ipsilateral renal agenesis, a right seminal vesicle cyst reaching up to the iliac arteries, and a multicystic formation cranial to the prostate.

Methylation pattern of caveolin-1 in prostate cancer as potential cfDNA biomarker.

High prevalence and mortality of prostate cancer (PCa) are well known global health issues. Novel biomarkers for better identifying patients with PCa are the subject of extensive research. Prostate specific antigen (PSA) shows low specificity in screening and diagnostics, leading to unnecessary biopsies and health costs. Eighty patients with PCa and benign prostate hyperplasia (BPH) were included in the study. We analyzed CAV1 gene expression and methylation in tissue. CAV1 cfDNA methylation from blood and seminal plasma was accessed as a potential PCa biomarker. Although methylation in blood plasma did not differ between PCa and BPH patients, methylation in seminal plasma showed better PCa biomarker performances than tPSA (AUC 0.63 vs. AUC 0.52). Discrimination of BPH and Gleason grade group 1 PCa patients from patients with higher Gleason grade groups revealed very good performance as well (AUC 0.72). CAV1 methylation is useful biomarker with potential for further seminal plasma cfDNA research, but its diagnostic accuracy should be improved, as well as general knowledge about cfDNA in seminal plasma.

Genetics of Prostate Carcinoma.

The aim of this review is to provide a brief overview of some current approaches regarding diagnostics, pathologic features, treatment, and genetics of prostate carcinoma (PCa). Prostate carcinoma is the most common visceral tumor and the second most common cancer-related cause of death in males. Clinical outcomes for patients with localized prostate cancer are excellent, but despite advances in prostate cancer treatments, castrate-resistant prostate cancer and metastatic prostate cancer patients have a poor prognosis. Advanced large-scale genomic studies revealed a large number of genetic alterations in prostate cancer. The meaning of these alterations needs to be validated in the specific prostate cancer molecular subtype context. Along these lines, there is a critical need for establishing genetically engineered mouse models, which would include speckle type BTB/POZ protein and isocitrate Dehydrogenase (NADP (+)) 1 mutant, as well as androgen receptor neuroendocrine subtypes of prostate cancer. Another urgent need is developing highly metastatic prostate cancer models, as only up to 17% of available models display bone metastases and exhibit a less typical neuroendocrine prostate cancer or sarcomatoid carcinoma. Moreover, androgen deprivation and relapse should be mimicked in the genetically engineered mouse models, as androgen independence may yield a better model for metastatic castrate-resistant prostate cancer. The development of such refined animal models should be guided by comparative genomics of primary versus corresponding metastatic tumors. Such an approach will have the potential to illuminate the key genetic events associated with specific molecular prostate cancer subsets and indicate directions for effective therapy. CONCLUSION: Despite excellent results in the treatment of localized prostatic carcinoma, castrate-resistant prostate cancer and metastatic prostate cancer have a poor prognosis. Advanced large-scale genomic studies revealed a large number of genetic alterations in PCa. Experimental models of prostate carcinoma in genetically modified mice could provide new data about the genetic changes in such cancers and help in developing better animal models for treatment resistant prostate carcinomas.

Elastic Stable Intramedullary Nailing for Treatment of Pediatric Femoral Fractures; A 15-Year Single Centre Experience.

OBJECTIVE: To analyze outcomes of treatment and complications in children treated with elastic stable intramedullary nailing (ESIN) due to femoral fracture. METHODS: From May 2002 until May 2018 case records of 103 patients (76 male and 27 female), with median age of 9 (range, 3-17) and follow-up of 92 months, who underwent ESIN because of displaced femoral fracture were retrospectively reviewed. The patient's information including age, sex, side involved, trauma mechanism, type of fracture, associated injuries, neurovascular status, complications, operation time, duration of hospital stay, time to implant removal were analyzed. The surgical procedure implied a reposition of bone fragments and osteosynthesis with titanium elastic nails introduced through an incision over the lateral and medial border of the distal femoral metaphysis. RESULTS: All patients achieved complete radiographic healing at a mean of 8.5 (range, 5-15) weeks. Nine (8.49%) postoperative complications were recorded: three entry site skin irritation, two cases of valgus angulation and one case of nail protrusion, re-fracture, Varus angulation and delayed union. All complications, except case of re-fracture and one valgus angulation, were treated conservatively, with no long term consequences for the patients. Two patients were re-operated. After removal of nails all patients recovered complete function of the extremity, without long term consequences. CONCLUSION: The ESIN for treatment of femoral fractures shows very good functional and cosmetic results. It allows an early functional and cast-free follow-up with a quick pain reduction. Because of the excellent objective and subjective results, the operative stabilization of femoral fractures with ESIN should be recommended to all pediatrics patients.