[Ectopic seminal tract opening in enlarged prostatic utricle: A report of 22 cases].

OBJECTIVE: To explore the diagnosis, classification and treatment of ectopic seminal tract opening in enlarged prostatic utricle (EPU). METHODS: We retrospectively analyzed the clinical data on 22 cases of ectopic seminal tract opening in EPU confirmed by spermography, EPU open cannula angiography or intraoperative puncture of the vas deferens and treated by transurethral incision of EPU, cold-knife incision or electric incision of EPU, full drainage of the anteriorwal, and open or laparoscopic surgery from October 1985 to October 2017. RESULTS: Five of the patients were diagnosed with ectopic opening of the vas deferens and the other 17 with ectopic opening of the ejaculatory duct in EPU. During the 3－48 months of postoperative follow-up, symptoms disappeared in all the cases, semen quality was improved in those with infertility, and 2 of the infertile patients achieved pregnancy via ICSI. CONCLUSIONS: Ectopic seminal tract opening in EPU is rare clinically. Spermography is a reliable method for the diagnosis of the disease, and its treatment should be aimed at restoring the smooth flow of semen based on proper classification and typing of the disease.

A 30-year retrospective study of rare ectopic seminal tract opening cases.

Ectopic seminal tract opening is a rare congenital malformation. Until recently, there has been a lack of comprehensive reporting on the condition. The purpose of this retrospective study is to summarize the experience of diagnosis and treatment of this condition based on 28 clinical practice cases throughout the past 30 years. We conducted auxiliary examinations on such patients including routine tests, imaging examinations, and endoscopy. Among these 28 cases, there were ectopic opening of vas deferens into enlarged prostatic utricles (6 cases); ejaculatory ducts into enlarged prostatic utricles, Müllerian ducts cysts, and urethras (18 cases, 2 cases, and 1 case, respectively); and ectopic opening of the unilateral vas deferens and the contralateral ejaculatory duct into enlarged prostatic utricle (1 case). The size of the enlarged prostatic utricle, the type of ectopic seminal tract opening, and the opening's location effectively assisted in the selection of clinical treatment methods, including transurethral fenestration of the utricle, transurethral cold-knife incision, open operation, laparoscopic operation, and conservative treatment. Satisfactory effect was achieved during follow-up. In conclusion, a definite diagnosis and personalized treatment are especially important for patients with ectopic seminal tract opening.

FOXM1 contributes to docetaxel resistance in castration-resistant prostate cancer by inducing AMPK/mTOR-mediated autophagy.

Docetaxel-mediated chemotherapy is the first line therapy for metastatic castration-resistant prostate cancer (CRPC) patients, but its therapeutic benefit is limited by the development of resistance. Although Forkhead box protein M1 (FOXM1) has been implicated in prostate tumorigenesis and metastasis, its role in docetaxel resistance has not been studied. Here, we showed that FOXM1 expression was upregulated in the docetaxel resistant CRPC cell lines (PC3-DR and VCaP-DR) and knockdown of FOXM1 sensitized the cells to docetaxel both in vitro and in vivo. In addition, autophagy was found to be significantly enhanced in resistant cells. Moreover, FOXM1 overexpression cells showed increased autophagic flux and higher numbers of autophagosomes. Knockdown of ATG7, beclin-1 or cotreatment with chloroquine, partly restored sensitivity to docetaxel in the FOXM1-overexpressing cells. Mechanistically, FOXM1 targeted AMPK/mTOR to activate the autophagy pathway and altered docetaxel response in CRPC. These findings identify the role of FOXM1 as well as the mechanism underlying FOXM1 action in docetaxel sensitivity and may, therefore, aid in design of CRPC therapies.

Efficacy of gefitinib­celecoxib combination therapy in docetaxel­resistant prostate cancer.

Resistance to docetaxel is a major clinical problem in castration­resistant prostate cancer (CRPC). We have previously reported that the combined inhibition of epidermal growth factor receptor (EGFR) and cyclooxygenase­2 (COX­2) led to an increased antitumor activity of docetaxel in CRPC. In the present study, we explored the efficacy of the combination of EGFR inhibition (by gefitinib) and COX­2 inhibition (by celecoxib) as a potential treatment for docetaxel­resistant CRPC. We established two docetaxel­resistant prostate cancer cell lines, PC3/DR and DU145/DR, by culturing PC3 and DU145 cells in docetaxel in a dose­escalating manner. The EGFR and COX­2 protein expression levels were determined. The effects of gefitinib and celecoxib on cell proliferation, apoptosis and invasion in vitro and in vivo were evaluated. In vitro changes in Bcl­2, FOXM1 and ABCB1 expression were analyzed. The expression of Ki­67 and cleaved­caspase­3 was also examined in DU145/DR tumor tissue. The enhanced expression of EGFR and COX­2 was observed in docetaxel­resistant CRPC relative to the parental cell lines. MTT, clone formation and fluorescence­activated cell sorting (FACS) analyses demonstrated that gefitinib and celecoxib in combination decreased cell viability and enhanced the rate of apoptosis when compared with either drug used alone. Additionally, the combination treatment was superior in inhibiting cell invasion and induced significant decreases in Bcl­2, FOXM1 and ABCB1 expression levels. Furthermore, the gefitinib­celecoxib combination inhibited DU145/DR tumor growth to a greater extent than either treatment used individually. The expression of Ki­67 was reduced, whereas cleaved­caspase­3 protein expression was increased in the tumors from the combination therapy group. In conclusion, the combined inhibition of EGFR and COX­2 by gefitinib and celecoxib may overcome docetaxel resistance in human CRPC. These findings provided a molecular basis for the clinical application of a novel combination therapy for docetaxel­resistant CRPC.

[Diagnosis and treatment of ejaculatory duct cyst: A report of 2 cases and review of the literature].

OBJECTIVE: To investigate the diagnosis and treatment of ejaculatory duct cyst. METHODS: This study included 2 male patients present at the hospital for hemospermia and abnormal sensation in the perineal region in July and August 2014. Both underwent transrectal ultrasonography, routine semen examination, CT, MRI, cystoscopy, and vesiculography before transurethral fenestration of the cysts and pathological examination of the cyst wall specimens. Analyses were made on the clinical presentations, imaging features, pathological characteristics, differential diagnosis and treatment of ejaculatory duct cyst and relevant literature was reviewed. RESULTS: The cyst wall was mainly composed of smooth muscle, the inner wall lined with pseudostratified ciliated columnar epithelia, and with positive expressions of CD10 and Muc6 proteins on immunohistochemical staining, which indicated renal iatrogenic ejaculatory duct cyst. The patients were followed up for 18 and 20 months, respectively. All symptoms disappeared and no recurrence occurred after surgery. Routine semen examination for the two patients showed the semen volumes to be 3.5 and 3.1 ml, sperm concentrations 35 and 32 ×106/ml, grade a sperm 32.0 and 26.0%, grade b sperm 18.0 and 31.0%, and semen liquidation time 30 and 34 minutes, respectively. CONCLUSIONS: Pelvic cystic masses can be detected by transrectal ultrasonography, CT and MRI, but definite diagnosis relies on vesiculography, pathological examination and immunohistochemical staining. Transurethral fenestration is safe and effective for the treatment of ejaculation duct cyst.

Targeting AXL overcomes resistance to docetaxel therapy in advanced prostate cancer.

Resistance to docetaxel is a major clinical problem in advanced prostate cancer. The overexpression of AXL receptor tyrosine kinase (AXL) has been correlated with chemotherapeutic drug resistance. However, the role of AXL expression in docetaxel resistance in prostate cancer is yet unclear. In this study, we demonstrate that AXL is overexpressed and activated independent of Gas6 in docetaxel-resistant prostate cancer cells (PC3-DR and DU145-DR). Moreover, we show that forced overexpression of AXL in PC3 and DU145 cells is sufficient to induce resistance to docetaxel in these cell lines. Notably, genetic or pharmacologic inhibition of AXL in the resistant models suppressed cell proliferation, migration, invasion, and tumor growth, and these effects were significantly augmented when AXL inhibition was combined with docetaxel treatment. Mechanistically, we found that AXL inhibition led to reversion of the epithelial-mesenchymal transition (EMT) phenotype and decreased the expression of ATP-binding cassette B1 (ABCB1). Overall, our results identify AXL as an important mediator of docetaxel resistance in prostate cancer. We propose that AXL-targeted therapy, in combination with docetaxel, has the potential to improve the response to docetaxel therapy and reduce resistance induced by prolonged docetaxel therapy in prostate cancer.

[Expression of AXL enhances docetaxel-resistance of prostate cancer cells].

OBJECTIVE: To explore the effect of the AXL expression on the chemosensitivity of prostate cancer PC-3 and DU145 cells to docetaxel and possible mechanisms. METHODS: Using Western blot, we examined the expressions of the AXL protein, p-AXL and Gas6 in the docetaxel-resistant PC-3 (PC-3-DR) and DU145 (DU145-DR) cells stimulated with gradually increased concentrations of docetaxel. We transfected the PC-3 and DU145 cells with negative NC ShRNA and AXL-ShRNA, respectively, which were confirmed to be effective, detected the proliferation, apoptosis and cycle distribution of the cells by CCK8, MTT and flow cytometry after treated with the AXL-inhibitor MP470 and/or docetaxel, and determined the expression of the ABCB1 protein in the PC-3-DR and DU145-DR cells after intervention with the AXL-inhibitor R428 and/or docetaxel. RESULTS: The expression of the AXL protein in the PC-3 and DU145 cells was significantly increased after docetaxel treatment (P <0.05). The expressions AXL and p-AXL were remarkably higher (P <0.05) while that of Gas6 markedly lower (P <0.05) in the PC-3 and DU145 than in the PC-3-DR and DU145-DR cells. The inhibitory effect of docetaxel on the proliferation and its enhancing effect on the apoptosis of the PC-3 and DU145 cells were significantly decreased at 48 hours after AXL transfection (P <0.05). MP470 obviously suppressed the growth and promoted the apoptosis of the PC-3-DR and DU145-DR cells, with a higher percentage of the cells in the G2/M phase when combined with docetaxel than used alone (P <0.05). R428 markedly reduced the expression of ABCB1 in the PC-3-DR and DU145-DR cells, even more significantly in combination with docetaxel than used alone (P <0.05). CONCLUSIONS: The elevated expression of AXL enhances the docetaxel-resistance of PC-3 and DU145 prostate cancer cells and AXL intervention improves their chemosensitivity to docetaxel, which may be associated with the increased cell apoptosis in the G2/M phase and decreased expression of ABCB1.

Ectopic opening of cystic dilatation of the ejaculatory duct into enlarged prostatic utricle.

A 28-year-old man was referred to our department for the management of recurrent hemospermia during the past 5 years. Genital examination and hormonal levels were normal. Semen analysis showed no change in volume and pH; however, hemospermia and asthenozoospermia were observed. Ultrasonography and computed tomography scan revealed the presence of a cystic lesion with calcification in the terminal part of seminal vesicles adjoining the prostate gland. The following vasography and endoscopic retrograde urethrography demonstrated 2 communicating cystic dilatations arising from the verumontanum. The diagnosis of cystic dilatation of the ejaculatory duct opening into an enlarged prostatic utricle was reached. Transurethral unroofing of the cyst was separately performed with a successful outcome. The characteristic of the 2 cystic dilatations was confirmed by pathologic examination. To the best of our knowledge, this is the first case of ectopic cystic dilatation of the ejaculatory duct opening into an enlarged prostatic utricle.

[Prostatic middle lobe hyperplasia correlates with bladder outflow obstruction: analysis of 131 cases].

OBJECTIVE: To analyze the correlation between the size of prostatic middle lobe hyperplasia and the degree of bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH). METHODS: This study included 131 BPH patients who presented with dysuria between May 2008 and June 2010. The prostate volume and intravesical prostatic protrusion (IPP) were measured by transabdominal ultrasound, Qmax and detrusor pressure at Qmax (P(det@ Qmax)) detected by urodynamic examination, the obstruction degree and detrusor contractility judged using the LinPURR Figure, and the AG value calculated (AG = P(det@ Qmax) -2Qmax). The degrees of BOO were compared between different groups of IPP by variance analysis, and the prostate volume, IPP and AG values underwent Bivariate correlation analysis. RESULTS: IPP was highly positively correlated with BOO when it was > 10 mm (r = 0.821, P < 0.01), while PV and BOO had a lower correlation (r = 0.475, P < 0.01). There was also a high positive correlation between IPP and P(det@ Qmax) (r = 0.865, P < 0.01). CONCLUSION: A close correlation exists between prostatic middle lobe hyperplasia and BOO, and evaluating IPP by ultrasound is a reliable method to determine the degree of BOO.

[Clinical value of aneusomy of chromosomes in exfoliated urothelial cells to predict the recurrence of superficial bladder cancer after complete transurethral resection].

OBJECTIVE: To analyze the chromosomal karyotype aberrations of exfoliated urothelial cells in superficial bladder cancer patients and the correlation thereof to recurrence of carcinoma. METHODS: Voided urine samples were collected from 42 patients with pathologically confirmed recurrent bladder cancer and 24 bladder cancer patients without pathologically confirmed recurrence, all of which had undergone complete transurethral resection and had been followed up for more than 3 years. Fluorescence in situ hybridization (FISH) was used with Spectrum Green to label the chromosome 7 and Spectrum Red to label the chromosome 17 of the exfoliated urothelial cells. RESULTS: The aneuploidy rates of chromosomes 7 and 17 were 48.5% (32/66) and 50.0% (33/66) respectively, and the co-aneuploidy rate of chromosomes 7 and 17 was 25.8% (17/66). In the patients with G(2/3) superficial bladder cancer, the aneuploidy rate of chromosomes 17 of those with recurrence was 64.3%, significantly higher than that of patients without recurrence (22.2%, P < 0.05). However, there were not significant differences in the aneuploidy rates of chromosomes 7 and 17 in the pT(a) and pT(1) superficial bladder cancer patients with or without recurrence (all P > 0.05), however, the co-aneuploidy rate of chromosomes 7 and 17 of the patients with recurrence was 47.8%, significantly higher than that of the patients without recurrence (12.5%, P < 0.05). Fourteen of the 42 patients with recurrence showed progression, i.e., with increased grade or stage (>/= pT(2)). The aneuploidy rates of chromosomes 7 and 17 of these 14 patients were 78.6% and 92.9% respectively, both significantly higher than those of the 28 patients without progression (42.9% and 46.4% respectively, both P < 0.05). CONCLUSION: Abnormality in the chromosomes in exfoliated urothelial cells of superficial bladder cancer patients using FISH technique helps predict recurrence and progression of the cancer.

Preliminary study of feasibility of whole body diffusion weighted imaging in diagnosis of metastasis of tumor.

OBJECTIVE: To evaluate the feasibility of whole body diffusion weighted imaging (DWI) in the diagnosis of metastatic tumor. METHODS: Fifty-six patients (40 males and 16 females, age ranging from 29 to 84 years with a mean age of 57 years) with a variety of primary tumors were investigated by whole body DWI combined with computed tomography (CT) and/or conventional magnetic resonance imaging (MRI) scans. Twelve patients underwent positron emission tomography. The final diagnosis was made on the basis of CT or high resolution CT result for lung lesion and MRI or CT result for skull, abdomen and other parts. All tumors were classified into four groups by their diameter: below 1.0 cm, 1.0-1.9 cm, 2.0-2.9 cm, and above 3.0 cm. The sensitivity and specificity of whole body DWI in the detection of metastatic tumor were analyzed. RESULTS: The sensitivities of whole body DWI for screening metastasis of the four groups were 38%, 75%, 97%, and 100%, respectively. Whole body DWI showed the highest sensitivity and specificity for detecting metastasis of the skeletal system. It was difficult to find metastatic tumor whose diameter was below 1.0 cm, or lymph nodes located in the pelvis with diameter below 2.0 cm. CONCLUSIONS: Whole body DWI is a promising method in the diagnosis of metastastic tumors. With the perfection of scanning parameter, whole body DWI should be a new effective whole body technique for tumor detection.

[PI-3K and p38MAPK pathways upregulate the epidermal growth factor induced cyclooxygenase-2 expression in PC-3 cells].

OBJECTIVE: To investigate the effect of PI-3K and p38MAPK signal pathways on the cyclooxygenase-2 (COX-2) expression induced by the epidermal growth factor (EGF) in PC-3 cells. METHODS: PC-3 cell proliferation was detected by methylthiazolyl tetrazolium (MTT) assay after stimulated by EGF (0 microg/L), EGF (10 microg/L), EGF (10 microg/L) + LY294002 (20 micromol/L) and EGF (10 microg/L) + SC203580 (20 micromol/L), and so was the COX-2 expression in the PC-3 cells by RT-PCR and Western blot assay after stimulated the same way for 24 hours. ELISA was used to determine the changes of PGE2 in the culture medium. RESULTS: LY294002 and SC203580 signficantly inhibited PC-3 cell proliferation (P < 0.05), COX-2 expression and PGE2 production after EGF stimulation (P < 0.05). CONCLUSION: EGF can stimulate PC-3 cells into proliferation and induce COX-2 mRNA and the upregulation of its protein expression, while LY294002 and SC203580 can inhibit EGF from the above effects on PC-3 cells.