Assessment of delivered dose in prostate cancer patients treated with ultra-hypofractionated radiotherapy on 1.5-Tesla MR-Linac.

Objective: To quantitatively characterize the dosimetric effects of long on-couch time in prostate cancer patients treated with adaptive ultra-hypofractionated radiotherapy (UHF-RT) on 1.5-Tesla magnetic resonance (MR)-linac. Materials and methods: Seventeen patients consecutively treated with UHF-RT on a 1.5-T MR-linac were recruited. A 36.25 Gy dose in five fractions was delivered every other day with a boost of 40 Gy to the whole prostate. We collected data for the following stages: pre-MR, position verification-MR (PV-MR) in the Adapt-To-Shape (ATS) workflow, and 3D-MR during the beam-on phase (Bn-MR) and at the end of RT (post-MR). The target and organ-at-risk contours in the PV-MR, Bn-MR, and post-MR stages were projected from the pre-MR data by deformable image registration and manually adapted by the physician, followed by dose recalculation for the ATS plan. Results: Overall, 290 MR scans were collected (85 pre-MR, 85 PV-MR, 49 Bn-MR and 71 post-MR scans). With a median on-couch time of 49 minutes, the mean planning target volume (PTV)-V95% of all scans was 97.83 ± 0.13%. The corresponding mean clinical target volume (CTV)-V100% was 99.93 ± 0.30%, 99.32 ± 1.20%, 98.59 ± 1.84%, and 98.69 ± 1.85%. With excellent prostate-V100% dose coverage, the main reason for lower CTV-V100% was slight underdosing of seminal vesicles (SVs). The median V29 Gy change in the rectal wall was -1% (-20%-17%). The V29 Gy of the rectal wall increased by >15% was observed in one scan. A slight increase in the high dose of bladder wall was noted due to gradual bladder growth during the workflow. Conclusions: This 3D-MR-based dosimetry analysis demonstrated clinically acceptable estimated dose coverage of target volumes during the beam-on period with adaptive ATS workflow on 1.5-T MR-linac, albeit with a relatively long on-couch time. The 3-mm CTV-PTV margin was adequate for prostate irradiation but occasionally insufficient for SVs. More attention should be paid to restricting high-dose RT to the rectal wall when optimizing the ATS plan.

The potential biological effects of quercetin based on pharmacokinetics and multi-targeted mechanism in vivo.

Quercetin is a plant-derived polyphenol flavonoid that has been proven to be effective for many diseases. However, the mechanism and in vivo metabolism of quercetin remains to be clarified. It achieves a wide range of biological effects through various metabolites, gut microbiota and its metabolites, systemic mediators produced by inflammation and oxidation, as well as by multiple mechanisms. The all-round disease treatment of quercetin is achieved through the organic combination of multiple channels. Therefore, this article clarifies the metabolic process of quercetin in the body, and explores the new pattern of action of quercetin in the treatment of diseases.

Feasibility of prostatectomy without prostate biopsy in the era of new imaging technology and minimally invasive techniques.

BACKGROUND: Routinely, after receiving prostate specific antigen (PSA) testing and digital rectum examination, patients with suspected prostate cancer are required to undergo prostate biopsy. However, the ability of ultrasound-guided prostate biopsy to detect prostate cancer is limited. Nowadays, a variety of diagnostic methods and more sensitive diagnostic methods, such as multi-parameter prostate magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) can be applied clinically. Furthermore, laparoscopic/robot-assisted prostatectomy is also a safe and effective procedure for the treatment of benign prostatic hyperplasia. So maybe it is time to reconsider the necessary to perform prostate biopsy before radical prostatectomy. AIM: To explore the feasibility of radical prostatectomy without prostate biopsy in the era of new imaging technology and minimally invasive techniques. METHODS: From June 2014 to November 2018, 11 cases of laparoscopic radical prostatectomy without prostate biopsy were performed at the three tertiary medical centers involved in this study. All patients received prostate magnetic resonance imaging and prostate cancer was suspected, including six patients with positive 68Ga-PSMA PET/CT results. Laparoscopic radical prostatectomy and pelvic lymph node dissection were performed for all patients. RESULTS: All surgeries were accomplished successfully. The mean age was 69 ± 7.7 year, the mean body mass index was 24.7 ± 1.6 kg/m2, the range of serum PSA was 4.3 to >1000 ng/mL, and the mean prostate volume was 40.9 ± 18.3 mL. The mean operative time was 96 ± 23.3 min, the mean estimated blood loss was 90 ± 90.9 mL, and the median duration of catheter placement was 14 d. The final pathology confirmed that all specimens were prostate cancer except one case of benign prostatic hyperplasia. No major complications occurred in 90 d postoperatively. CONCLUSION: The current practice of mandating a prostatic biopsy before prostatectomy should be reconsidered in the era of new imaging technology and minimally invasive techniques. Radical prostatectomy could be carried out without the evidence of malignancy. Large-sample randomized controlled trials are definitely required to confirm the feasibility of this new concept.

Quercetin protects against chronic prostatitis in rat model through NF-κB and MAPK signaling pathways.

BACKGROUND: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common disease of urology, of which the pathogenesis and therapy remain to be further elucidated. Quercetin has been reported to improve the symptoms of CP/CPPS patients. We aimed to verify the therapeutic effect of quercetin on CP/CPPS and identify the mechanism responsible for it. METHODS: A novel CP/CPPS model induced with Complete Freund Adjuvant in Sprague Dawley rats was established and the prostates and blood specimens were harvested for further measurement after oral administration of quercetin for 4 weeks. RESULTS: Increased prostate index and infiltration of lymphocytes, up-regulated expression of IL-1ß, IL-2, IL-6, IL-17A, MCP1, and TNFα, decreased T-SOD, CAT, GSH-PX, and increased MDA, enhanced phosphorylation of NF-κB, P38, ERK1/2, and SAPK/JNK were detected in CP/CPPS rat model. Quercetin was identified to ameliorate the histo-pathologic changes, decrease the expression of pro-inflammatory cytokines IL-1ß, IL-2, IL-6, IL-17A, MCP1, and TNFα, improve anti-oxidant capacity, and suppress the phosphorylation of NF-κB and MAPKs. CONCLUSIONS: Quercetin has specific protective effect on CP/CPPS, which is mediated by anti-inflammation, anti-oxidation, and at least partly through NF-κB and MAPK signaling pathways.

A Retrospective Study Comparing Surgical and Early Oncological Outcomes between Intracorporeal and Extracorporeal Ileal Conduit after Laparoscopic Radical Cystectomy from a Single Center.

BACKGROUND: Robot-assisted/laparoscopic intracorporeal ileal conduit (ICIC) has been reported in many experienced centers. Whether laparoscopic ICIC is superior to extracorporeal ileal conduit (ECIC) and whether laparoscopic ICIC should be promoted is still controversial. The aim of the study was to compare surgical and early oncological outcomes between patients undergoing laparoscopic radical cystectomy (LRC) with ICIC and ECIC. METHODS: From January 2011 to June 2016, a total of 45 patients with bladder cancer underwent LRC with ileal conduit at our department, of whom 20 patients underwent LRC with ECIC and 25 patients underwent LRC with ICIC. Data of each patient's characteristics, surgical outcomes, and short-term oncological outcomes were collected and analyzed. RESULTS: LRC with ileal conduit was performed successfully on all 45 patients. There were no significant differences in patients' characteristics, mean total operative time, and mean estimated blood loss between the ICIC and ECIC groups. Median time of flatus and oral intake was shorter in the ICIC group compared with the ECIC group (3 vs. 5 days, P = 0.035; 4 vs. 5 days, P = 0.002). The complications rates did not show significant difference between the two groups within the first 90 days postoperatively (P = 0.538). Cancer staging showed 45% of patients in the ECIC group and 36% in the ICIC group had a pathologic stage of T3 or T4, and 50% of patients in the ECIC group and 44% in the ICIC group had a pathologic stage of N1 or N1+. Kaplan-Meier analysis showed no significant difference in overall survival at 24 months (60% vs. 62%, P = 0.857) between the ECIC and ICIC groups. CONCLUSIONS: ICIC after LRC may be successful with the benefits of faster recovery time. No significant difference was found in complications and oncological outcomes between ICIC and ECIC. However, larger series with longer follow-up are needed to validate this procedure.

[Plasmakinetic enucleation of the prostate versus holmium laser enucleation of the prostate for benign prostatic hyperplasia].

OBJECTIVE: To evaluate the clinical effects of plasmakinetic enucleation of the prostate (PKERP) and holmium laser enucleation of the prostate (HoLEP) in the treatment of BPH. METHODS: We retrospectively analyzed the clinical data on 78 BPH patients treated by PKERP (n = 38) or HoLEP (n = 40) from January 2016 to October 2017. We recorded the operation time, intraoperative hemoglobin level, catheter-indwelling time, bladder irrigation time, hospital stay, 6-month postoperative IPSS, quality of life (QOL), maximum urinary flow rate (Qmax), postvoid residual urine (PVR), PSA level, International Index of Erectile Function (IIEF) and postoperative complications, and compared the obtained parameters between the two groups and some of them with the baseline. RESULTS: In comparison with the baseline, both the PKERP and HoLEP groups showed statistically significant differences at 6 months after surgery in the QOL score (4.82 ± 0.56 and 4.70 ± 0.67 vs 2.44 ± 0.69 and 2.92 ± 0.49, P < 0.01), IPSS (19.52 ± 4.96 and 19.44 ± 4.08 vs 9.56 ± 2.5 and 9.81 ± 2.5, P < 0.01), Qmax (ï¼»4.54 ± 1.86ï¼½ and ï¼»4.42 ± 2.89ï¼½ ml/s vs ï¼»17.72 ± 3.46ï¼½ and ï¼»17.27 ± 4.42ï¼½ ml/s, P < 0.01), and PVR (ï¼»83.73±55.33ï¼½ and ï¼»109.65 ± 89.58ï¼½ ml vs ï¼»19.93 ± 11.07ï¼½ and ï¼»18.31 ± 15.03ï¼½ ml, P < 0.01). Statistically significant differences were also found between the PKERP and HoLEP groups in the reduced hemoglobin level (ï¼»21.04 ± 16.96ï¼½ vs ï¼»7.88 ± 6.65ï¼½ g/dl, P = 0.01), catheter-indwelling time (ï¼»7.67 ± 2.27ï¼½ vs ï¼»3.93 ± 2.18ï¼½ d, P = 0.01), bladder irrigation time (ï¼»1.67 ± 0.62ï¼½ vs ï¼»1.3 ± 0.54ï¼½ d, P = 0.05), hospital stay (ï¼»4.22 ± 1.55ï¼½ vs ï¼»3.26 ± 0.9ï¼½ d, P = 0.01), and 6-month postoperative QOL score (ï¼»2.44 ± 0.69ï¼½ vs ï¼»2.92 ± 0.49ï¼½, P = 0.05), but not in the other parameters. CONCLUSIONS: Both PKERP and HoLEP are safe and effective for the treatment of BPH, the former more feasible in primary hospitals, while the latter with the advantages of less bleeding, shorter catheterization and hospital stay, and higher 6-month postoperative QOL score.

Laparoscopic radical cystectomy with novel orthotopic neobladder with bilateral isoperistaltic afferent limbs: initial experience

ABSTRACT Purpose To introduce a new method of constructing an orthotopic ileal neobladder with bilateral isoperistaltic afferent limbs, and to describe its clinical outcomes. Materials and Methods From January 2012 to December 2013, 16 patients underwent a new method of orthotopic ileal neobladder after laparoscopic radical cystectomy for bladder cancer. To construct the neobladder, an ileal segment 60cm long was isolated approximately 25cm proximally to the ileocecum. The proximal 20cm of the ileal segment was divided into two parts for bilateral isoperistaltic afferent limbs. The proximal 10cm of the ileal segment was moved to the distal end of the ileal segment for the right isoperistaltic afferent limb, and the remaining proximal 10cm ileal segment was reserved for the left isoperistaltic afferent limb. The remaining length of the 40cm ileal segment was detubularized along its antimesenteric border to form a reservoir. The neobladder was sutured to achieve a spherical configuration. Results All procedures were carried out successfully. The mean operative time was 330 min, mean blood loss was 328mL, and mean hospital stay was 12.5 days. The mean neobladder capacity 6 and 12 months after surgery was 300mL and 401mL, respectively. With a mean follow-up of 22.8 months, all patients achieved daytime continence and 15 achieved nighttime continence. The mean peak urinary flow rate was 11.9mL/s and 12.8mL/s at 6 and 12 months postoperatively, respectively. Conclusions This novel procedure is feasible, safe, simple to perform, and provides encouraging functional outcomes. However, comparative studies with long-term follow-up are required to prove its superiority.

Laparoscopic radical cystectomy with novel orthotopic neobladder with bilateral isoperistaltic afferent limbs: initial experience.

PURPOSE: To introduce a new method of constructing an orthotopic ileal neobladder with bilateral isoperistaltic afferent limbs, and to describe its clinical outcomes. MATERIALS AND METHODS: From January 2012 to December 2013, 16 patients underwent a new method of orthotopic ileal neobladder after laparoscopic radical cystectomy for bladder cancer. To construct the neobladder, an ileal segment 60cm long was isolated approximately 25cm proximally to the ileocecum. The proximal 20cm of the ileal segment was divided into two parts for bilateral isoperistaltic afferent limbs. The proximal 10cm of the ileal segment was moved to the distal end of the ileal segment for the right isoperistaltic afferent limb, and the remaining proximal 10cm ileal segment was reserved for the left isoperistaltic afferent limb. The remaining length of the 40cm ileal segment was detubularized along its antimesenteric border to form a reservoir. The neobladder was sutured to achieve a spherical configuration. RESULTS: All procedures were carried out successfully. The mean operative time was 330 min, mean blood loss was 328mL, and mean hospital stay was 12.5 days. The mean neobladder capacity 6 and 12 months after surgery was 300mL and 401mL, respectively. With a mean follow-up of 22.8 months, all patients achieved daytime continence and 15 achieved nighttime continence. The mean peak urinary flow rate was 11.9mL/s and 12.8mL/s at 6 and 12 months postoperatively, respectively. CONCLUSIONS: This novel procedure is feasible, safe, simple to perform, and provides encouraging functional outcomes. However, comparative studies with long-term follow-up are required to prove its superiority.

The intriguing role of fibroblasts and c-Jun in the chemopreventive and therapeutic effect of finasteride on xenograft models of prostate cancer.

In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer (PCa) while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP (PC3) cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERK1/2 were evaluated. In LNCaP (PC3) mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, fibroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERK1/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERK1/2 were noted in the presence of c-Jun-/- fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride's therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

[Laparoscopic partial nephrectomy with highly selective clamping of renal arterial branches].

OBJECTIVE: To explore the feasibility and efficiency of new clamping technique of renal arterial branches during laparoscopic partial nephrectomy. METHODS: Between March and June 2011, 10 patients (6 males, 4 females) with small renal tumor underwent laparoscopic partial nephrectomy with highly selective clamping of renal arterial branches. The mean age was (47 ± 13) years and the mean tumor size (2.8 ± 0.9) cm. Operative duration, estimated blood loss, time for highly selective clamping of renal arterial branches, postoperative hospital stay, indwelling duration of drainage tube and complications were recorded. RESULTS: The operations were successfully performed in all patients. The mean operative duration was (101 ± 23) min, the mean estimated blood loss 112 ml and the mean time for the clamping of renal arterial branches (28 ± 6) min. There was neither blood transfusion nor conversion into open surgery. The mean indwelling duration of drainage tube was (5.0 ± 1.3) days and the mean postoperative hospital stay(8.0 ± 0.8)days. The recovery of all patients was uneventful. CONCLUSION: Highly selective clamping of renal arterial branches is a new method of protecting renal function during laparoscopic partial nephrectomy. Further studies and a longer follow-up are warranted.