Holmium laser enucleation of the prostate as a secondary surgery following prostatic urethral lift.

Introduction: Prostatic urethral lift is a treatment option for benign prostatic hyperplasia, yet information on surgeries following this procedure is scarce. Case presentation: A 71-year-old man with persistent urinary retention following prostatic urethral lift underwent a secondary holmium laser enucleation of the prostate. The morcellation procedure, complicated by the presence of implants from the previous surgery, broke the morcellator blade. The fragmented blade was successfully retrieved without any organ damage. Postoperatively, the patient encountered no complications and showed improvement in his urinary symptoms. Conclusion: This case highlights the potential risk of device breakage when a secondary surgery, specifically the morcellation process, is performed following prostatic urethral lift. Care must be taken to prevent interaction between the implants and the morcellator. Our case demonstrates the efficacy of holmium laser enucleation of the prostate as a salvage surgical intervention for patients in whom prostatic urethral lift has failed.

Leiomyoma of the Prostate Treated via Holmium Laser Enucleation: A Case Report and Literature Review.

Leiomyoma is a rare tumor that arises from mesenchymal cells, with few reported cases of treatment using holmium laser enucleation of the prostate. A 74-year-old man with dysuria had a mass near the bladder neck in magnetic resonance imaging; this entity was suspected to be a leiomyoma. The patient underwent holmium laser enucleation of the prostate and one lobe was removed. However, the mass was firm and morcellation was difficult to break into small pieces. Therefore, it was fragmented via trans-urethral resection and removed with a curette. The postoperative course was favorable, with a positive clinical outcome. This case highlights the efficacy of holmium laser enucleation of the prostate in the management of prostatic leiomyoma and emphasizes its importance as a viable treatment option.

Simplified approach to the medial internal iliac region using a uretero-hypogastric nerve fascia development procedure for extended pelvic lymph node dissection during robot-assisted radical prostatectomy for high-risk prostate cancer.

INTRODUCTION: Although several clinical guidelines for prostate cancer (PC) recommend extended pelvic lymph node dissection (ePLND) during radical prostatectomy for high-risk cases, there are several issues to consider, including certain technical aspects. A simplified approach to the medial internal iliac region and paravesical arteries has not been established. The uretero-hypogastric nerve fascia (UHF) envelopes the ureter, hypogastric nerve, and pelvic autonomic nerves. To preserve the UHF, it is possible to approach the medial side of the internal iliac vessels without injuring any important tissue. We analyzed technical feasibility and lymph node (LN) yields. PATIENTS AND METHODS: After obtaining institutional review board approval, 265 high-risk PC patients with ePLND were identified. A da Vinci S or Xi robotic surgical system (Intuitive Surgical, Sunnyvale, CA, USA) was used. We divided the patients into conventional (non-UHF) method and modified (UHF) groups. The numbers of LNs removed, procedure-related complications, and surgical outcomes were analyzed. RESULTS: The median number of LNs removed was 19.0 in the non-UHF group and 22.0 in the UHF group (p = 0.004). Significantly more LNs were removed from the internal iliac region in the UHF group (p = 0.042). There was no difference in overall operative, console, or LN dissection time, or the severe complication rate (Clavien-Dindo grade ≥ III), between the non-UHF and UHF groups. CONCLUSIONS: Our simplified approach using the UHF development technique is technically feasible, has no major complications, and allows for the removal of significantly more LNs compared with the conventional method.

Influence of background characteristics in responders of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence.

OBJECTIVES: To determine if the male responders with post-prostatectomy incontinence in the ADRESU study, which is a clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells, are influenced by any background characteristics. METHODS: Briefly, autologous adipose-derived regenerative cells isolated from abdominal adipose tissue and a mixture of adipose-derived regenerative cells with fat tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Sixteen out of 43 patients (37.2%) responded to treatment (responders) and exhibited improvement in the urine leakage volume, defined as >50% reduction from baseline determined by the 24-hour pad test at 52 weeks of treatment (or last visit within 52 weeks). Background data such as age, body weight, method of prostatectomy, baseline frequency of leaks, number of leaks, number of pad changes, International Consultation on Incontinence Questionnaire-Short Form, King's Health Questionnaire, urodynamic urethral function including functional profile length and maximum urethral closure pressure, and abdominal leak point pressure were collected and compared between responders and nonresponders. RESULTS: None of the background factors influenced improvement in the responders as compared with the nonresponders. However, a significant between-group difference in the rates of decrease in urine leakage volume was noted in patients of younger age (<70 years), compared with those of older age (≥70 years) from 2 to 26 weeks of treatment. CONCLUSION: A greater decrease in urine leakage volume was noted in the younger patient group than in the older patient group.

[A Case of Multiple Renal Carcinomas with Three Different Subtypes].

We report a case of dialysis kidney with multiple renal carcinomas in three locations. A 74-year-old man who had a 20-year history of dialysis, was admitted to our hospital complaining of sudden right lateral area pain. Computed tomography (CT) scan revealed hemorrhage from the right dialyzed renal subcapsule. He underwent immediate transcatheter arterial embolization (TAE), but after 6 days the CT scan showed new active bleeding. A second TAE was performed, but, the CT scan several days later showed hemorrhage from the same site. So we decided to perform a right radical nephrectomy. Pathological results revealed three different renal carcinomas at sites different from the bleeding site. The presence of triple carcinomas in the same organ of the kidney is quite rare. Because of the high incidence of renal carcinoma associated with polycystic kidney disease in long-term hemodialysis patients and the possibility of multiple carcinomas as in this case, radical nephrectomy is recommended even in the case of spontaneous rupture.

A large adrenocortical adenoma surrounded with a renal arteriovenous malformation.

INTRODUCTION: Large adrenal adenomas are clinically rare. We report a case of a large adrenal adenoma with a renal arteriovenous malformation, mimicking a malignant adrenal tumor in preoperative imaging. CASE PRESENTATION: A 66-year-old woman presented to a local hospital with abdominal pain. A right adrenal tumor was detected, 66 mm in diameter and surrounded by thick and tortuous vessels. Based on the imaging findings, pheochromocytoma was suspected. However, clinical symptoms and endocrine abnormalities were absent, and radionuclide accumulation in scintigraphy was negative. Laparoscopic right adrenalectomy was performed. Intraoperatively, a notable growth of vessels forming a nidus surrounding the tumor was observed. Pathologically, this was diagnosed as an adrenocortical adenoma in conjunction with a renal arteriovenous malformation. CONCLUSION: We report a case of a large adrenal tumor surrounded with an arteriovenous malformation. To the best of our knowledge, this is the first reported case of this combination.

Transvaginal polytetrafluoroethylene mesh surgery for pelvic organ prolapse: 1-year clinical outcomes.

OBJECTIVES: To evaluate the safety and efficacy of transvaginal mesh surgery using a polytetrafluoroethylene mesh to treat pelvic organ prolapse. METHODS: This prospective observational study included women undergoing transvaginal mesh surgery for pelvic organ prolapse that used new polytetrafluoroethylene mesh cut into a shape similar to that of Elevate. We evaluated the subjective and objective outcomes at 3 and 12 months, as well as postoperative complication rates. RESULTS: This study included 55 patients. The pelvic organ prolapse quantification scores improved significantly at 3 and 12 months after surgery compared with scores before surgery. In four patients (7.3%), a pelvic examination showed stage 2 objective recurrence without subjective symptoms. Clavien-Dindo grades 2 and 3 perioperative complications were observed in 9.1% and 1.8% of the patients, respectively. Vaginal mesh exposure occurred in one patient (1.8%) at the time of the 3-month follow-up evaluation. The mesh was exposed at the proximal midline of the anterior vaginal wall. CONCLUSIONS: These findings show the safe and effective use of the polytetrafluoroethylene mesh for transvaginal mesh surgery.

Optimizing first trocar access for robot-assisted radical prostatectomy: Optical trocar access through the upper abdominal quadrant using the Kii Fios First Entry trocar.

OBJECTIVES: A pre-equipped metal trocar is required to use as a camera trocar due to a specification change in the da Vinci X/Xi system (Intuitive Surgical). We observed slight slippage of a trocar placed by the open method. With optical trocar access (OTA), the initial trocar is viewed directly with a laparoscope during placement. Reports regarding OTA for robotic surgery are limited, particularly for robot-assisted radical prostatectomy (RARP). We modified the OTA procedure such that it was appropriate for RARP. PATIENTS AND METHODS: A total of 158 patients were enrolled in this study. The first trocar placement time (FTPT) was compared between the open and OTA groups. In the OTA group, the trocar was mainly placed through the upper abdominal quadrant. We also analyzed the differences between the conventional and modified OTA procedures using the Kii Fios First Entry trocar (Applied Medical). We examined the factors affecting the FTPT using linear regression models. A P value <.05 was considered significant. RESULTS: The FTPT was significantly shorter in the OTA group than the open group (P < .0001). The modified method was associated with a shorter FTPT (P = .0001). None of the patient characteristics affected the FTPT in either group. No major complications were observed. CONCLUSIONS: OTA was applied successfully during RARP. Use of the Kii Fios First Entry trocar with upper abdominal quadrant placement was suitable for RARP.

Regenerative treatment for male stress urinary incontinence by periurethral injection of adipose-derived regenerative cells: Outcome of the ADRESU study.

OBJECTIVES: To report the outcome of the ADRESU study, a multicenter, single-arm, investigator-initiated clinical trial to confirm the efficacy and safety of regenerative treatment for male patients with stress urinary incontinence. METHODS: The participants were male patients with mild-to-moderate stress urinary incontinence persisting for >1 year after prostatectomy. Autologous adipose-derived regenerative cells were isolated using the Celution system from adipose tissue obtained by liposuction. Adipose-derived regenerative cells and mixture of adipose-derived regenerative cells with adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. The primary end-point was the proportion of patients with improvement of the urine leakage volume at 52 weeks (or last visit within 52 weeks). Improvement of leakage volume was defined as a decrease from baseline >50% by the 24-h pad test. A total of 10 secondary end-points were set. RESULTS: A total of 45 patients satisfying the eligibility criteria were enrolled. The primary end-point was met; the proportion of patients with improvement in leakage volume at 52 weeks was 37.2% (95% confidence interval 23.0-53.3%). No serious adverse events with causal relationships to the adipose-derived regenerative cells were encountered. There was a progressive improvement in secondary end-points. In the King's Health Questionnaire, improvement of quality of life scores showed greater improvement in responders, as compared with non-responders. CONCLUSIONS: Findings from the ADRESU study suggest the efficacy and safety of regenerative treatment for male patients with mild-to-moderate stress urinary incontinence.

[A Case of a Congenital Right External Iliac Vein Defect Found after Robot-Assisted Radical Prostatectomy].

Congenital external iliac vein defects are extremely rare. A 56-year-old man underwent robotic prostatectomy (RARP) without pelvic lymph node dissection (PLND) for localized low-risk prostate cancer. Intraoperative findings revealed a markedly dilated vein on the dorsal side of the pubic bone,which was difficult to preserve and was therefore clipped. Sudden swelling and pain appeared in the right leg on day 2 after successful RARP. A contrast-enhanced computed tomography (CT) scan showed a deep vein thrombus (DVT) and lack of a right external iliac vein. Immediate heparinization improved the symptoms, and no other postoperative complications occurred. In the retrospective review,a large dilated vein lying transversely on the prostate surface was observed with a robotic scope,but no manipulation of the pelvic vessels was performed because PLND was not performed. Therefore,the dilated vein was not recognized as a shunt from the right femoral vein to the left external iliac vein. A preoperative staging CT scan,which faintly revealed the right external iliac vein,could be useful to identify this extremely rare deformity in advance of surgery. Although preoperative imaging examinations are often difficult to diagnose preoperatively,as in this case,we consider it important to use appropriate approaches and treatment when dealing with symptoms that arise during pelvic surgery in patients with many anatomical variations.

Coffee diterpenes kahweol acetate and cafestol synergistically inhibit the proliferation and migration of prostate cancer cells.

BACKGROUND: Coffee inhibits the progression of prostate cancer; however, the direct mechanism through which coffee acts on prostate cancer cells remains unclear. This study aimed to identify the key compounds of coffee that possess anti-cancer effects and to investigate their mechanisms of action. METHODS: The anti-proliferation and anti-migration effects of six potentially active types of coffee compounds, including kahweol acetate, cafestol, caffeine, caffeic acid, chlorogenic acid, and trigonelline hydrochloride, were evaluated using LNCaP, LNCaP-SF, PC-3, and DU145 human prostate cancer cells. The synergistic effects of these compounds were also investigated. Apoptosis-related and epithelial-mesenchymal transition-related proteins, androgen receptor in whole cell and in nucleus, and chemokines were assessed. A xenograft study of SCID mice was performed to examine the in vivo effect of coffee compounds. RESULTS: Among the evaluated compounds, only kahweol acetate and cafestol inhibited the proliferation and migration of prostate cancer cells in a dose-dependent manner. The combination treatment involving kahweol acetate and cafestol synergistically inhibited proliferation and migration (combination index <1) with the induction of apoptosis, the inhibition of epithelial-mesenchymal transition, and decrease in androgen receptor, resulting in the reduction of nuclear androgen receptor in androgen receptor-positive cells. Moreover, kahweol acetate and cafestol downregulated CCR2 and CCR5 without an increase in their ligands, CCL2 and CCL5. The xenograft study showed that oral administration of kahweol acetate and cafestol significantly inhibited tumor growth. CONCLUSION: Kahweol acetate and cafestol synergistically inhibit the progression of prostate cancer. These coffee compounds may be novel therapeutic candidates for prostate cancer.

Predictors of persistent stress urinary incontinence after transvaginal mesh repair.

BACKGROUND: We evaluated the effect of transvaginal mesh (TVM) surgery for voiding function and continence using noninvasive examination and questionnaire. The present study aimed to ascertain which categories of patients need concomitant mid-urethral sling (MUS) after TVM surgery. METHODS: We included women who underwent TVM procedure between November 2009 and October 2013. Data from noninstrumented uroflowmetry and questionnaires about urinary symptoms were analyzed. RESULTS: The present study investigated the cases of 961 women who underwent TVM surgery. The persistence of stress urinary incontinence (SUI) was 57.6%. Almost all the parameters measured using uroflowmetry and questionnaires significantly improved in all types of urinary incontinence 12 months after surgery. A history of hysterectomy, preoperative high flow (corrected maximum flow rate > 1.5), and preoperative urge urinary incontinence were independent risk factors for the persistence of SUI. CONCLUSIONS: TVM for pelvic organ prolapse improved subjective and objective voiding function. Mixed urinary incontinence (MUI) patients with high urinary flow may be suitable for concomitant MUS with TVM because of the high level of SUI persistence.

C-C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment.

Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling.

Both High and Low Serum Total Testosterone Levels Indicate Poor Prognosis in Patients with Prostate Cancer.

BACKGROUND/AIM: Androgen-androgen receptor (AR) signal is known as a powerful driver of prostate cancer progression. We previously reported the limitation of prostate-specific antigen (PSA) at diagnosis as a prognostic biomarker of prostate cancer. Although serum total testosterone (TT) level has been reported as a prognostic biomarker for prostate cancer, its usability is still controversial. We examined the potential and characteristics of TT as a biomarker. PATIENTS AND METHODS: Serum TT levels of patients who underwent prostate biopsy were measured, and prostate cancer-specific survival (PCaSS), overall survival (OS), and the correlation between staging and serum TT level were analyzed. RESULTS: Of 379 biopsied patients, 255 were diagnosed with prostate cancer. The patients were divided into five groups according to their serum TT levels; patients with serum TT levels of <2 or ≥8 ng/ml (ENDs) had worse PCaSS and OS compared with those with middle serum TT levels between 2 and 8 ng/ml (MIDs). Moreover, ENDs showed a tendency of having castration-resistant cancer with advanced stage (T4 or N1 or M1). The TNM stage in ENDs was significantly higher than in MIDs. CONCLUSION: Although low serum TT level has been reported to indicate worse outcome in patients with prostate cancer, this study showed that both low as well as high serum TT levels indicate poor prognosis.

Evaluation of Factors Affecting Metastasis for Renal Cell Carcinoma Based on Current Guidelines in Japan.

BACKGROUND/AIM: To analyze the suitability for metastasis evaluation of each pathologic item on the Fourth Edition of the General Rule for Clinical and Pathologic Studies on Renal Cell Carcinoma in Japan. PATIENTS AND METHODS: We retrospectively examined 457 cases of renal operation after 2011 using the current edition of the guidelines. RESULTS: The mean postoperative follow-up period was 25.3 months. Radical nephrectomy was performed in 264 cases, whereas partial nephrectomy was performed in 193 cases. Including the 33 cases discovered after operation, the overall number of metastatic cases was 68 (14.9%). Using the current edition of the guidelines, the items of histologic grade, morphology of tumor invasion, tumor pseudocapsule, and intrarenal metastasis were all correlated with distant metastasis. CONCLUSION: This is the first report showing that each item on the current Japanese guidelines for renal cell cancer was useful for predicting metastasis.

Androgen replacement therapy for cancer-related symptoms in male advanced cancer patients: study protocol for a randomised prospective trial (ARTFORM study).

Recent studies reveal that hypogonadism with low serum androgen levels is associated with advanced cancer and induction of most cancer-related symptoms. We designed an ARTFORM study to evaluate the efficacy of androgen replacement therapy in male advanced cancer patients. The ARTFORM study is an investigator-initiated, randomised controlled trial comparing intramuscle injection of testosterone enanthate with non-administration in male advanced cancer patients with non-curative locally advanced or metastatic lesions. Serum total and free testosterone levels are measured and patients with low testosterone level are randomised. The primary endpoint is the difference in validated health-related quality of life questionnaires at week 12. Trial registration of the ARTFORM study is assigned to University hospital Medical Information Network, Center identifier UMIN 000010939. J. Med. Invest. 64: 202-204, August, 2017.

Design of a single-arm clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence in Japan: the ADRESU study protocol.

BACKGROUND: Male stress urinary incontinence is a prevalent condition after radical prostatectomy. While the standard recommendation for the management of urine leakage is pelvic floor muscle training, its efficacy is still unsatisfactory. Therefore, we have focused on regenerative therapy, which consists of administering a periurethral injection of autologous regenerative cells from adipose tissue, separated using the Celution® system. Based on an interim data analysis of our exploratory study, we confirmed the efficacy and acceptable safety profile of this treatment. Accordingly, we began discussions with Japanese regulatory authorities regarding the development of this therapy in Japan. The Ministry of Health, Labour and Welfare suggested that we implement a clinical trial of a new medical device based on the Pharmaceutical Affaires Act in Japan. Next, we discussed the design of this investigator-initiated clinical trial (the ADRESU study) aimed at evaluating the efficacy and safety of this therapy, in a consultation meeting with the Pharmaceuticals and Medical Device Agency. METHODS: The ADRESU study is an open-label, multi-center, single-arm study involving a total of 45 male stress urinary incontinence patients with mild-to-moderate urine leakage persisting more than 1 year after prostatectomy, in spite of behavioral and pharmacological therapies. The primary endpoint is the rate of patients at 52 weeks with improvement of urine leakage volume defined as a reduction from baseline greater than 50% by 24-h pad test. Our specific hypothesis is that the primary endpoint result will be higher than a pre-specified threshold of 10%. DISCUSSION: The ADRESU study is the first clinical trial of regenerative treatment for stress urinary incontinence by adipose-derived regenerative cells using the Celution® system based on the Japanese Pharmaceutical Affaires Act. We will evaluate the efficacy and safety in this trial to provide an adequate basis for marketing approval with the final objective of making this novel therapy widely available for Japanese patients. TRIAL REGISTRATION: This trial was registered at the University Hospital Medical information Network Clinical Trial Registry (UMIN-CTR Unique ID: UMIN000017901 ; Registered July 1, 2015) and at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT02529865 ; Registered August 18, 2015).

Changes in penile length after radical prostatectomy: investigation of the underlying anatomical mechanism.

OBJECTIVE: To measure changes in penile length (PL) over time before and after radical prostatectomy (RP), and to investigate the underlying mechanisms for these changes. PATIENTS AND METHODS: The stretched PL (SPL) of 102 patients was measured before, 10 days after, and at 1, 3, 6, 9, 12, 18 and 24 months after RP. The perpendicular distance from the distal end of the membranous urethra to the midline of the pelvic outlet was measured on mid-sagittal magnetic resonance imaging (MRI) slice at three time points: preoperatively; 10 days after RP; and 12 months after RP. Pre- and postoperative SPLs were compared using paired Student's t-test. Predictors of PL shortening at 10 days and at 12 months after RP were evaluated on univariate and multivariate analyses. RESULTS: The SPL was shortest 10 days after RP (mean PL shortening from preoperative level: 19.9 mm), and gradually recovered thereafter. SPL at 12 months after RP was not significantly different from preoperative SPL. On MRI examination, the distal end of membranous urethra was found to have moved proximally (mean proximal displacement: 3.9 mm) at 10 days after RP, and to have returned to the preoperative position at 12 months after RP. On univariate analysis, only the volume of the removed prostate was a predictor of SPL change at 10 days after surgery; on multivariate analysis, the association was not statistically significant. No predictor of SPL change was found at 12 months after RP. CONCLUSION: The SPL was shortest at 10 days after RP and gradually recovered thereafter in the present study. Anatomically, the glans and corpus spongiosum surrounding the urethra are an integral structure, and the proximal urethra is drawn into the pelvis during urethrovesical anastomosis. This is the first report showing that slight vertical repositioning of the membranous urethra after RP causes changes in SPL over time. These results can help inform patients about changes in penile appearance after RP.

Tumor-associated macrophages promote prostate cancer migration through activation of the CCL22-CCR4 axis.

Previous studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported that TAMs promote prostate cancer metastasis via activation of the CCL2-CCR2 axis. The CCR4 (receptor of CCL17 and CCL22) expression level in breast cancer was reported to be associated with lung metastasis. The aim of this study was to elucidate the role of CCR2 and CCR4 in prostate cancer progression. CCR2 and CCR4 were expressed in human prostate cancer cell lines and prostate cancer tissues. In vitro co-culture of prostate cancer cells and macrophages resulted in increased CCL2 and CCR2 levels in prostate cancer cells. The addition of CCL2 induced CCL22 and CCR4 production in prostate cancer cells. The migration and invasion of prostate cancer cells via enhanced phosphorylation of Akt were promoted by CCL17 and CCL22. CCR4 may be a potential candidate for molecular-targeted therapy.

Understanding prostate-specific antigen dynamics in monitoring metastatic castration-resistant prostate cancer: implications for clinical practice.

Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer (CRPC) has changed the outlook for this group of patients with improvements in progression-free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate-specific antigen (PSA). However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC.