Real-world prostate-specific antigen response and progression to castration-resistant prostate cancer among men with metastatic castration-sensitive prostate cancer treated with apalutamide: a multi-institutional study in the Chu-shikoku Japan Urological Consortium.

BACKGROUND: Japanese men receiving apalutamide often experience skin-adverse events (AEs), possibly requiring treatment interruption or dose reduction. However, concerns have arisen regarding the impact of these adjustments on the efficacy of apalutamide. Our study evaluated the efficacy, safety, and persistence of apalutamide in men with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: We retrospectively reviewed the medical records of 108 men with mCSPC from 14 Japanese institutions. The primary outcomes were the efficacy of apalutamide: prostate-specific antigen (PSA) response (50%, 90% and < 0.2 decline) and progression to castration-resistant prostate cancer (CRPC). The secondary outcomes were the skin-AE and compliance of apalutamide. RESULTS: PSA50%, PSA90% and PSA < 0.2 declines were observed in 89.8, 84.3 and 65.7%, and the median time to CRPC progression was not reached. PSA < 0.2 decline and an initial full dose of apalutamide were significantly associated with a longer time to CRPC. The most common AE was skin-AE (50.9%), and there was no association between the occurrence of skin-AE and the time to CRPC (P = 0.72). The median apalutamide persistence was 29 months, which was longer in the initial full dose recipients than in the reduced dose recipients. The dosage is reduced in about 60% of patients within the first year of treatment in the initial full dose recipients. CONCLUSIONS: Our findings indicate the effectiveness of apalutamide in Japanese men with mCSPC, despite a substantial portion requiring dose reduction within a year among the initial full dose recipients.

Peripheral neuropathy and nerve electrophysiological changes with enfortumab vedotin in patients with advanced urothelial carcinoma: a prospective multicenter cohort study.

BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.

Enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment in Japan (Japanese research for patients with non-metastatic castration-resistant prostate cancer-enzalutamide: JCASTRE-zero)-a prospective single-arm interventional study.

BACKGROUND: The effect of enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade, which represents a patient profile similar to real-world clinical practice in Japan, remains unknown. Therefore, we investigate the efficacy and safety of enzalutamide after combined androgen blockade for recurrence following radical treatment in Japanese patients with non-metastatic castration-resistant prostate cancer. METHODS: We analyzed 66 patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical prostatectomy or radiation therapy who were prospectively enrolled from October 2015 to March 2018. They received enzalutamide 160 mg orally once daily until the protocol treatment discontinuation criteria were met. The primary endpoint was prostate-specific antigen-progression-free survival, defined as the time from enrollment to prostate-specific antigen-based progression or death from any cause. The secondary endpoints included overall survival, progression-free survival, metastasis-free survival, time to prostate-specific antigen progression, prostate-specific antigen response rate, chemotherapy-free survival, and safety assessment. RESULTS: The median observation period was 27.3 months. The median prostate-specific antigen-progression-free survival was 35.0 months (95% confidence interval, 17.5 to not reached). The median overall survival, median progression-free survival, median metastasis-free survival, and chemotherapy-free survival were not reached, with the corresponding 2-year rates being 91.6%, 67.1%, 72.4%, and 85.8%, respectively. The 50% prostate-specific antigen response rate was 88.9%, with the median time being 2.8 months. In total, 42.2% of the patients experienced adverse events, with malaise being the most common. CONCLUSIONS: Enzalutamide effectively manages non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment. TRIAL REGISTRATION:  UMIN000018964, CRB6180007.

Real-world analysis of apalutamide-associated skin adverse events in Japanese patients with advanced prostate cancer: a multi-institutional study in the Chu-shikoku Japan Urological Consortium.

BACKGROUND: Apalutamide-associated skin adverse events are more common in the Japanese than in the global population. However, limited clinical data have hampered further understanding. This real-world study investigated the clinical characteristics of skin adverse events in patients with advanced prostate cancer. METHODS: We retrospectively reviewed 119 patient records from 16 institutions in Japan. Skin adverse events were graded according to the Common Terminology Criteria for Adverse Events (v5.0). The incidence and characteristics of skin adverse events (along with the clinical risk factors for their incidence, worsening, and recurrence) were evaluated. RESULTS: Fifty-five patients (46.2%) experienced skin adverse events. The median times to the incidence and remission of skin adverse events were 62 and 30 days, respectively. Grade 3 skin adverse events were observed in 15 patients (12.6%). The median time from the first incidence to apalutamide interruption was significantly longer in patients with progression to grade 3 skin adverse events than in those without such a progression (8 vs. 0 days, p = 0.005). Skin adverse events were observed in 45.2% of patients who resumed apalutamide treatment (median treatment interruption time: 31.5 days). Sixteen patients (13.4%) permanently discontinued apalutamide due to skin adverse events. No significant clinical risk factors for the incidence, worsening and recurrence of apalutamide-associated skin adverse events were observed. CONCLUSIONS: Nearly half of the Japanese patients in this study experienced skin adverse events following apalutamide administration. The time to apalutamide discontinuation after the incidence of skin adverse events was positively correlated with the worsening of these events.

Health-related quality of life in Japanese low-risk prostate cancer patients choosing active surveillance: 3-year follow-up from PRIAS-JAPAN.

PURPOSE: To evaluate the health-related quality of life (HRQoL) of Japanese men on active surveillance (AS) in the Prostate cancer Research International Active Surveillance study in Japan (PRIAS-JAPAN). METHODS: Participants were included in the PRIAS-JAPAN HRQoL study between January 2010 and March 2016. Their general HRQoL was assessed using a validated Japanese version of the Short-Form 8 Health Survey (SF-8) at enrolment and annually thereafter until discontinuation of AS. The SF-8 mental component summary (MCS) and physical component summary (PCS) of men on AS were compared with scores of the general population (norm-based score [NBS]: 50) and MCS and PCS scores for men following AS were analysed over time. We tested whether MCS and PCS scores over time explained discontinuation of AS. RESULTS: Five hundred and twenty-five patients enrolled, and the median age at baseline was 68 years. At enrolment and after 1-, 2-, and 3-year follow-ups, the PCS and MCS scores were significantly higher than the NBS of the general Japanese population except for the median PCS at 3 years. We found that age at diagnosis and time on AS negatively affected the PCS score of men on AS, while every additional year on AS led to a 0.27 point increase in MCS scores. Neither PCS nor MCS were predictors for discontinuation of AS. CONCLUSION: Japanese men following an AS strategy for 3 years reported better HRQoL compared with the general population, indicating that monitoring Japanese low-risk prostate cancer patients can be an effective treatment strategy. STUDY REGISTRATION: Clinical trial registry-UMIN (University Hospital Medical Information Network); UMIN000002874 (2009/12/11).

Diagnostic Impacts of Clinical Laboratory Based p2PSA Indexes on any Grade, Gleason Grade Group 2 or Greater, or 3 or Greater Prostate Cancer and Prostate Specific Antigen below 10 ng/ml.

PURPOSE: The PROPHET (Prostate Cancer: Prostate Health Index Trial) is a prospective study to clarify the diagnostic impact of laboratory based and prostate volume adjusted p2PSA ([-2] proenzyme prostate specific antigen) related indexes on prostate cancer and clinically significant prostate cancer with prostate specific antigen less than 10 ng/ml. MATERIALS AND METHODS: Between April 2015 and March 2017, 421 men 50 to 79 years old in the prostate specific antigen range above age specific cutoffs and below 10 ng/ml were registered in the PROPHET. We investigated the diagnostic impacts of various clinical laboratory based free prostate specific antigen related and p2PSA related indexes on any grade and high Gleason grade group prostate cancer. RESULTS: Of the 363 eligible participants 179, 141 and 80 were diagnosed with any grade, and Gleason Grade Group 2-5 and 3-5 prostate cancer, respectively. The AUC-ROCs distinguishing nonprostate cancer vs prostate cancer, nonprostate cancer plus low Gleason Grade Group and low volume vs remaining prostate cancer with a higher Gleason Grade group or a higher volume on the PHI (Prostate Health Index) were significantly superior to the AUC-ROCs of prostate specific antigen and free-to-total prostate specific antigen. At 90% sensitivity in all investigated p2PSA related indexes the false-positive rate was superior to that of prostate specific antigen and free-to-total prostate specific antigen in any group comparison in terms of the Gleason Grade Group and positive biopsy cores. In 35% to 42% of men without prostate cancer and/or those with less aggressive prostate cancer the PHI would avoid unnecessary biopsy. CONCLUSIONS: Laboratory based p2PSA related indexes were significantly superior for detecting clinically significant prostate cancer compared to free-to-total prostate specific antigen. The indexes those would avoid up to 42% of prostate biopsies in men without aggressive cancer while maintaining 90% sensitivity.

The efficacy and toxicity of cabazitaxel for treatment of docetaxel-resistant prostate cancer correlating with the initial doses in Japanese patients.

BACKGROUND: We analyzed the efficacy and toxicity of cabazitaxel (CBZ) at high and low initial doses in Japanese patients with docetaxel-resistant castration-resistant prostate cancer (CRPC). METHODS: We retrospectively evaluated 118 patients who received CBZ for docetaxel-resistant CRPC in 10 university hospitals in Japan between 2014 and 2016. The rate of decrease of prostate-specific antigen (PSA), adverse events, progression-free survival (PFS), and overall survival (OS) were compared between patients receiving initially high (≥22.5 mg/m2, n = 36) and low (≤20 mg/m2, n = 80) CBZ doses. Factors associated with survival and grade 4 neutropenia were evaluated. RESULTS: PSA values decreased by > 50% in 22 patients (19%), with a higher frequency in the high-dose group than in the low-dose group (29 and 14%, P = 0.073). The median PFS time for the all-patient, high- and low-dose groups was 2.8 months (95% confidence interval [CI] 1.9-4.4), 2.1 months (1.2-5.5), and 3.0 months (2.0-4.4), respectively (P = 0.904). The median OS times were 16.3 months (95% CI 9.7-30.9), 30.9 months (11.8-47.4), and 10.2 months (8.6-20), respectively (P = 0.020). In multivariate analyses, PFS was significantly associated with existing bone metastasis at diagnosis (P = 0.005) and OS with PSA > 100 ng/ml (P = 0.007), hemoglobin < 12 g/dl (P = 0.030), and low initial CBZ dose (P = 0.030). Grade 4 neutropenia occurred in 53 patients (45%) and was associated with a low CBZ dose (hazard ratio 0.21, 95% CI 0.08-0.59, P = 0.002). CONCLUSIONS: CBZ at a higher initial dose may have similar response rate and response duration, but longer survival duration after treatment with higher toxicity than a lower initial dose for docetaxel-resistant CRPC in Japanese patients.

A phosphodiesterase 5 inhibitor, tadalafil, suppresses stromal predominance and inflammation in a rat model of nonbacterial prostatitis.

BACKGROUND: Chronic inflammation is thought to be a major causative factor for the development of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Tadalafil, a phosphodiesterase type 5 inhibitor (PDE5-I), which has been used for the treatment of BPH-LUTS in daily practice, is known to act at several urinary organs. In this study, focused on the prostate, we examined the effect of tadalafil on the pathological changes and inflammatory factors in a rat nonbacterial prostatitis (NBP) model. METHODS: Forty ten-month-old male Wistar rats were divided into nonbacterial prostatitis (NBP), NBP with tadalafil treatment (NBP-tadalafil), control, and control treated with tadalafil (control-tadalafil) groups (n = 10 per group). The NBP and NBP-tadalafil groups were castrated and then received daily subcutaneous 17ß-estradiol for 30 days. The control-tadalafil and NBP-tadalafil groups were administered daily oral tadalafil for 30 days. All rats were then sacrificed and pathological changes and inflammatory factors were assessed in the prostatic tissues. RESULTS: In the NBP group, the stroma-to-epithelium (S/E) ratio in the ventral prostate was significantly higher than in the control group (P < 0.001). In the NBP-tadalafil group, the S/E ratio was significantly lower than in the NBP group (P < 0.001). The macrophage levels and the extent of T-cell infiltration in the NBP-tadalafil group were significantly lower than in the NBP group (P < 0.005; P < 0.001, respectively). Compared with the NBP group, tissue concentrations of inflammatory cytokines, such as tumor necrosis factor-α, interleukin-8, and interleukin-1ß, were significantly downregulated in the NBP-tadalafil group (P < 0.01; P < 0.05; P < 0.005, respectively). CONCLUSIONS: Tadalafil suppressed stromal predominance and showed anti-inflammatory effects in a rat NBP model in association with downregulation of inflammatory cytokines.

Retroperitoneal liposarcoma excreting insulin-like growth factor 2 that induced severe hypoglycemia.

Insulin-like growth factor 2 is overexpressed in various cancers, and is associated with a poor prognosis. Also, it is known that insulin-like growth factor 2 is an etiology of non-islet cell tumor hypoglycemia. In this report, we describe a case of unexpected hypoglycemia caused by a dedifferentiated liposarcoma producing insulin-like growth factor 2. A large mass in the retroperitoneum was detected in a 61-year-old man who complained of appetite loss. Despite having no history of diabetes mellitus, hypoglycemia suddenly occurred after admission, but oral glucose therapy was ineffective. After total parenteral nutrition, tumor resection was attempted, but failed as a result of rigid adhesion to the surrounding organs. The patient died of the disease 21 days after surgery. Pathological diagnosis at autopsy revealed dedifferentiated liposarcoma, and immunohistochemical staining showed that the tumor excreted insulin-like growth factor 2. The possibility of an insulin-like growth factor 2-producing tumor should be taken into consideration when we encounter a patient with spontaneous hypoglycemia resistant to glucose substitution therapy.

Should inclusion criteria for active surveillance for low-risk prostate cancer be more stringent? From an interim analysis of PRIAS-JAPAN.

PURPOSE: To define clinical and pathological factors predicting reclassification at the time of 1-year repeat biopsy (re-Bx) based on a Japanese cohort forming part of the Prostate Research International: Active Surveillance (PRIAS) study. PATIENTS AND METHODS: The inclusion criteria for the PRIAS study are as follows: clinical stage T1c/T2, PSA ≤ 10 ng/ml, PSA density (PSAD) < 0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score (GS) ≤ 6 at initial diagnostic biopsy. Baseline clinical characteristics and prostate-specific antigen doubling time (PSADT) at the time of re-Bx were analyzed via multivariate logistic regression with respect to reclassification and 'no cancer' status on the 1-year re-Bx. RESULTS: A total of 386 patients were enrolled in PRIAS-JAPAN by the end of 2013. Of these, 216 underwent re-Bx at 1 year. A total of 73 patients (33.8 %) were reclassified, whereas 74 (34.3 %) had no cancer. Older age, a higher PSAD, a higher positive core rate, and a shorter PSADT were significant predictors of reclassification. The positive core rate was the predictor common to reclassification, no cancer, and high GS, upon re-Bx. CONCLUSIONS: An interim analysis of a Japanese AS cohort participating in PRIAS revealed that the positive core rate was strongly associated with reclassification at the 1-year re-Bx. However, although amendment of the PRIAS inclusion criteria to incorporate a positive core might reduce any concern about underestimation, this would also reduce the number of patients undergoing AS.

Case of vascular air embolism during holmium laser enucleation of the prostate.

Vascular air embolism is a rare complication during transurethral surgery. A case of air embolism during holmium laser enucleation of the prostate in a 76-year-old man is presented. During the step of morcellation, the patient's blood pressure suddenly oscillated up and down, and end-tidal CO2 and arterial saturation decreased. Transesophageal and transthoracic echocardiography showed air collection in the right atrium. It was also discovered that incorrect assembly of the tube from the morcellator caused rapid entrainment of air into the vein. Computed tomography and abdominal X-ray showed niveau formation in the femoral vein and air collection in the pelvic retroperitoneal space. The patient recovered with careful observation and was discharged 7 days after the operation with no sequelae. This report is presented to remind urologists of this unusual complication that can occur during holmium laser enucleation of the prostate procedures.

Reclassification prediction of first-year protocol biopsy on active surveillance of prostate cancer by p2PSA-related parameters: from PRIAS-JAPAN.

BACKGROUND: There is no useful predictive marker for reclassification on active surveillance. Thus, we aimed to investigate thresholds of [-2] proPSA (p2PSA)-related parameters to predict reclassification of the first-year protocol biopsy (1-year PBx) and evaluate the influence of clinical decision-making. METHODS: This was an observational, prospective cohort study conducted at 19 Japanese institutes. The inclusion criteria included clinical stage T1c/T2, prostate-specific antigen (PSA) levels ≤10 ng/mL, PSA density <0.2 ng/ml/cc, one or two positive biopsy cores, and Gleason score (GS) ≤6 (GS ≦7 for patients aged ≥70 years) at diagnostic biopsy. All participants were required to receive a blood-sampling test on a protocol visit at inclusion and at the 1-year PBx. PSA and PSA isoforms (free PSA, p2PSA) were measured, and parameters (%free PSA, %p2PSA, phi) were calculated. Multivariable logistic regression models were used to predict the reclassification risk. To assess the predictive power and thresholds for reclassification, we plotted Receiver Operating Characteristic (ROC) curves. Decision curve analysis (DCA) was used to evaluate the variables that yielded a net clinical benefit. RESULTS: A total of 135 patients were included, and 36 patients were reclassified on the 1-year PBx. Multivariate analyses showed that %p2PSA and phi at inclusion and p2PSA, %p2PSA, and phi before the 1-year PBx were significant predictors of reclassification at the 1-year PBx. The ROC analysis showed an optimal cutoff point, sensitivity, and specificity of %p2PSA and phi before the 1-year PBx of 1.64, 86%, 49% and 35.92, 89%, 47%, respectively. The DCA showed that phi before the 1-year PBx had the highest net benefit. The study limitation was its single-arm observational design. CONCLUSIONS: %p2PSA and phi before the 1-year PBx had a good prediction power. phi is the most useful indicator for clinical decision-making on active surveillance. TRIAL REGISTRATION: This study is registered atthe Japan Trial Register with ID UMIN000009876 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011573 ).

[A case with hepatitis and interstitial pneumonitis caused by intravesical bacillus Calmette-Guérin (BCG) instillation].

A 49-year man, with past history of right total nephroureterectomy due to urothelial carcinoma of the right renal pelvis in September 2006 and left partial ureterectomy due to contralateral ureteral recurrence in October 2007, underwent TUR-BT due to superficial high-grade recurrent bladder cancer. After TUR-Bt, he was treated with intravesical Bacillus Calmette-Guérin (BCG) instillation at weekly intervals. Just after 5th instillation, he suffered a continuous high fever up to 38 degrees C and complained of general fatigue. Chest CT showed diffuse micronodular shadows in both lungs, and serum liver enzyme was markedly elevated. All cultures from his sputum and urine were negative for mycobacterium tuberculosis. TB-PCR test and quantiferon were also negative. These findings together with no improvement of the symptoms with anti-tuberculous treatment finally made us to judge that this was due to a hypersensitivity reaction to BCG. Soon after pulse steroid therapy, body temperature was normalized and the abnormal findings of the lung and liver disappeared.

Retinal Nerve Fiber Layer Thickness Progression after Robotic-Assisted Laparoscopic Radical Prostatectomy in Glaucoma Patients.

PURPOSE: To investigate the effect of the steep Trendelenburg position surgical procedure on the retinal structure and function during robotic-assisted laparoscopic radical prostatectomy (RALP) in glaucoma patients. METHODS: At 1 month and 1 day before and at 1 and 2 months after the RALP operation, 10 glaucoma patients underwent standard automated perimetry and optical coherence tomography. After placing patients in a supine position, intraocular pressure (IOP) was measured at 5 min after intubation under general anesthesia (T1), at 5 discrete time points (5, 30, 60, 120, and 180 min; T2-6) and at 5 min after returning to a horizontal supine position (T7). The Guided Progression Analysis software program was used to assess serial retinal nerve fiber layer (RNFL) thicknesses and visual field progression. RESULTS: Eight additional patients were newly diagnosed in addition to the two previous glaucoma patients. Average IOP (mmHg) at each time point was as follows: T1 = 11.2 ± 3.8, T2 = 19.0 ± 4.4, T3 = 23.3 ± 6.3, T4 = 25.1 ± 4.3, T5 = 25.5 ± 5.1, T6 = 28.3 ± 4.8, and T7 = 22.6 ± 5.4. IOP significantly increased during RALP. RNFL thickness progressed in two eyes of two patients after the surgery, even though there was no progression of the visual field. CONCLUSIONS: Two eyes of two patients exhibited significant RNFL thickness progression. Since an increased IOP during the surgery was the probable cause of the changes, ophthalmologic examinations should be performed before and after RALP, especially in glaucoma patients.

The Effect of Steep Trendelenburg Positioning on Retinal Structure and Function during Robotic-Assisted Laparoscopic Procedures.

PURPOSE: Robotic-assisted laparoscopic radical prostatectomy (RALP) has become a standard treatment choice for localized prostate cancer. RALP requires a steep Trendelenburg position, which leads to a significant increase in intraocular pressure (IOP). This study evaluated the effect on the retinal structure and function in patients undergoing RALP. METHODS: Standard automated perimetry (SAP) and optical coherence tomography (OCT) were performed in 20 males scheduled for RALP at 1 month and 1 day before the operation and at 1 and 3 months after the operation. IOP measurements were made in the supine position at 5 min after intubation under general anesthesia (T1), at 6 discrete time points (5, 30, 60, 120, 180, and 240 min; T2-7), and at 5 min after returning to a horizontal supine position (T8). Serial retinal nerve fiber layer (RNFL) thicknesses and visual field progression were assessed using the guided progression analysis software program. RNFL thickness progression and visual field progression were evaluated by event analysis. RESULTS: Average IOP (mmHg) for each time point was as follows: T1 = 12.3 ± 2.6, T2 = 20.4 ± 4.2, T3 = 23.3 ± 3.8, T4 = 24.0 ± 3.2, T5 = 24.3 ± 3.4, T6 = 27.1 ± 7.2, T7 = 29.8 ± 8.7, and T8 = 20.1 ± 4.4. During RALP, IOP significantly increased. There was no progression of the visual field and RNFL thickness after surgery or any other ocular complications found. CONCLUSIONS: Although IOP significantly increased during RALP, there were no significant changes in the retinal structure and function between the pre- and postoperation observations.

The impact of baseline [-2]proPSA-related indices on the prediction of pathological reclassification at 1 year during active surveillance for low-risk prostate cancer: the Japanese multicenter study cohort.

PURPOSE: Active surveillance (AS) is one potential solution to avoiding the overtreatment of favorable prostate cancer. By handling the AS strategy more safely, tumor aggressiveness may be evaluated more accurately. The aim of the present study was to evaluate the predictive impact of baseline prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA)-related indices on the pathological reclassification at 1 year during an AS program. METHODS: Between 2002 and 2003, 134 males diagnosed with low-risk prostate cancer were registered in the Japanese multicenter study cohort as candidates for AS, and 118 (88 %) males actually proceeded to AS. Of the 118 patients, the 67 that underwent protocol biopsy at 1 year after beginning AS were enrolled in the present study. The predictive significance of various baseline clinicopathological features and p2PSA-related indices on pathological reclassification at 1 year after beginning AS were investigated. RESULTS: The pathological reclassification rate was 37.3 %. According to the univariate analysis, prostate volume (p = 0.049), number of biopsy cores (p = 0.047), percentage of positive biopsy cores (p = 0.023), p2PSA to free PSA ratio (%p2PSA) (p = 0.003) and prostate health index (phi) (p = 0.010) at baseline were significantly different between the reclassification and non-reclassification groups. By multivariate logistic regression analysis, baseline %p2PSA (p = 0.008) and phi (p = 0.008) were the only independent predictive factors for pathological upgrade at 1 year after AS commencement. CONCLUSIONS: Baseline %p2PSA and phi may predict the pathological reclassification at 1 year after starting AS, which could be due to the under detection of clinically significant prostate cancer at AS enrollment.

Cellular intermingling between adrenal gland and liver: an infrequent cause of incomplete resection at right adrenalectomy.

PURPOSE: To assess the incidence of difficulty in complete dissection between the right adrenal gland and the liver at the time of laparoscopic surgery for adrenal tumor and to elucidate its cause histopathologically. PATIENTS AND METHODS: Thirty-six patients underwent laparoscopic right adrenalectomy between 2004 and 2011 at our institution. Two reviewers independently assessed difficulty in dissection for the 36 nonedited video records of laparoscopic right adrenalectomy in blinded fashion. Twenty-seven records were evaluable for the judgment of difficulty in dissection between the lower surface of the liver and the right adrenal gland. On the other hand, the gross and microscopic relationship between the right adrenal gland and the surface of the liver was investigated in 32 cadavers. RESULTS: Incomplete resection of the adrenal gland was found in 11 of 27 (40.7%) patients. Difficulties in dissection because of adhesions between the liver and the adrenal gland were apparently recognized in 5 of 27 (18.5%) patients. Pathologic assessment for cadavers revealed that capsules between these two organs are partially fused in 10 of 32 (31.3%) cases. Histopathologically, intermingling of parenchymal cells (infiltration through the fibrous capsules) was observed in nine (28.1%) cases. CONCLUSIONS: The tight adhesion between the lower surface of the liver and the adrenal gland because of intermingling of parenchymal cells of both organs is a major cause of incomplete resection of right adrenalectomy. Surgeons have to keep this fact in mind during right adrenalectomy to avoid unnecessary adverse events.