Yonsei nomogram: A predictive model of new‐onset chronic kidney disease after on‐clamp partial nephrectomy in patients with T1 renal tumors

Objectives

To develop a predictive nomogram for chronic kidney disease‐free survival probability in the long term after partial nephrectomy.

Methods

A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end‐points were to identify independent risk factors for new‐onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease‐free survival probability after partial nephrectomy.

Results

The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new‐onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease‐free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new‐onset chronic kidney disease. The C‐index for chronic kidney disease‐free survival was 0.853 (95% confidence interval 0.815–0.895).

Conclusion

We developed a novel nomogram for predicting the 5‐year chronic kidney disease‐free survival probability after on‐clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision‐making and follow‐up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered.

     

Purely off‐clamp robotic partial nephrectomy: Preliminary 3‐year oncological and functional outcomes

Objectives

To describe our surgical technique and to report perioperative, 3‐year oncological and functional outcomes of a single‐center series of purely off‐clamp robotic partial nephrectomy.

Methods

A prospective renal cancer institutional database was queried, and data of consecutive patients treated with purely off‐clamp robotic partial nephrectomy between 2010 and 2015 in a high‐volume center were collected. Perioperative complications, and 3‐year oncological and functional outcomes were assessed. Univariable and multivariable analyses were carried out to identify independent predictors of renal function deterioration.

Results

Out of 308 patients treated, 41 (13.3%) experienced perioperative complications, 2.9% of which were Clavien grade ≥3. The 3‐year local recurrence‐free survival and renal cell carcinoma‐specific survival rates were 99.5% and 97.9%, respectively. No patient with preoperative chronic kidney disease stage ≤3B developed severe renal function deterioration (chronic kidney disease stage 4) at 1‐year follow up. At multivariable analysis, preoperative estimated glomerular filtration rate (P = 0.005) was the only independent predictor of a new‐onset chronic kidney disease stage ≥3 in patients with preoperative chronic kidney disease stages 1 or 2.

Conclusions

Off‐clamp robotic partial nephrectomy is a safe surgical approach in tertiary referral centers, with adequate oncological outcomes and negligible impact on renal function.

     

Partial nephrectomy for small children: Robot‐assisted versus open surgery

Objectives

To compare the outcomes of robot‐assisted heminephrectomy for duplex kidney in children with those of open heminephrectomy.

Methods

The present retrospective multicentric analysis reviewed the records of robot‐assisted versus open heminephrectomy carried out for duplex kidney in children from 2007 to 2014. Demographic data, weight, surgical time, hospital stay, complications and outcome were recorded. Follow up was based on a clinical review, renal sonography and dimercaptosuccinic acid renal scintigraphy.

Results

A total of 15 patients underwent robot‐assisted heminephrectomy, and 13 patients underwent retroperitoneal heminephrectomy by open approach. All patients weighed <15 kg. The mean age at the time of surgery was 20.2 months (range 7–39 months) in the robotic group, and 18.4 months (range 6–41 months) in the open group. The mean hospital stay was statistically longer for the open surgery group (6.3 days, range 5–8 days vs 3.4 days, range 1–7 days; P < 0.001). Regarding postoperative pain control, total morphine equivalent intake was statistically greater for the open group (0.52 mg/kg/day vs 1.08 mg/kg/day; P < 0.001). No patient lost the remaining healthy moiety. There was no significant difference in terms of operating time, complication rate or renal outcomes.

Conclusions

Robot‐assisted heminephrectomy in small children seems to offer comparable renal outcomes with those of its standard open surgery counterpart. Specific technical adjustments are necessary, which typically increase the set‐up time.

     

Glutamatergic cells in the periaqueductal gray matter mediate sensory inputs after bladder stimulation in freely moving rats

Objectives

To determine the phenotype of the ventrolateral part of the periaqueductal gray matter neurons after bladder stimulation.

Methods

In the experimental group, electrical stimulation of the bladder was carried out under freely moving condition by a bipolar stimulation electrode implanted in the bladder wall. Thereafter, the brain sections were processed for immunohistochemical analysis using antibodies against c‐Fos (neuronal activation marker) together with one of the following: tyrosine hydroxylase (dopaminergic cell marker), vesicular glutamate transporter (glutamatergic cell marker), serotonin, glutamate decarboxylase (glutamate decarboxylase 67, gamma‐aminobutyric acid cell marker) and neuronal nitric oxide synthase. We used design‐based confocal stereological analysis to quantify the immunohistochemically stained sections.

Results

A significant increase in the number of c‐Fos‐positive cells in the ventrolateral part of the periaqueductal gray matter after stimulation was found. Furthermore, the ratio of c‐Fos cells double labeled with vesicular glutamate transporter was significantly higher in the ventrolateral part of the periaqueductal gray matter region in the stimulated compared with the sham group. Quantitative analysis of the other four cell types did not show any significant difference.

Conclusion

These findings suggest that glutamatergic neurotransmission in the ventrolateral part of the periaqueductal gray matter is seemingly the main pathway to be activated after receiving sensory signals from the bladder.

     

Premenopausal women with recurrent urinary tract infections have lower quality of life

Objectives

To examine the impact on quality of life of recurrent acute uncomplicated urinary tract infection among premenopausal Singaporean women, and to determine the risk factors for lower quality of life among these patients.

Methods

A total of 85 patients with recurrent acute uncomplicated urinary tract infection who were referred to the Urology Department at the National University Hospital, Singapore, were prospectively recruited over a 3‐year period to complete the validated Short Form 36 Health Survey version 1. In addition, demographic and clinical details including symptomology and medical history were analyzed for factors impacting quality of life. Short Form 36 Health Survey version 1 results were compared with published population norms.

Results

After adjusting for age, gender and race, recurrent acute uncomplicated urinary tract infection patients had significantly lower quality of life on seven out of eight Short Form 36 Health Survey version 1 domains when compared with age‐, gender‐ and race‐adjusted population norms for Singapore. Among those with recurrent acute uncomplicated urinary tract infection, those who also reported caffeine consumption had significantly lower Short Form 36 Health Survey version 1 scores than those who did not. Those who reported chronic constipation also had consistently lower Short Form 36 Health Survey version 1 scores across all domains.

Conclusions

Recurrent acute uncomplicated urinary tract infection has a negative impact on the quality of life of premenopausal, otherwise healthy women. Recurrent acute uncomplicated urinary tract infection patients who also have chronic constipation or consume caffeine have lower quality of life than those who do not. More studies are required to understand the relationships between these common problems and risk factors.

     

Combination of solifenacin with tamsulosin reduces prostate volume and vascularity as opposed to tamsulosin monotherapy in patients with benign prostate enlargement and overactive bladder symptoms: Results from a randomized pilot study

Objectives

To identify the potential influence of antimuscarinics on morphometric parameters of the prostate in patients with benign prostatic enlargement and overactive bladder.

Methods

Non‐neurological patients with prostate volume >30 mL, predominately storage lower urinary tract symptoms, three or more urgency episodes per 24 h, maximum flow rate ≥10 mL/s and post‐void residual ≤100 mL were recruited for this study. They were randomized to receive either tamsulosin or tamsulosin + solifenacin. Patients were submitted to transrectal and transvesical ultrasonography, pressure‐flow study and prostate‐specific antigen test, and completed the International Prostate Symptom Score, bladder diary and overactive bladder questionnaire at induction and at 6 months. End‐study changes in morphometric prostate parameters (total prostate and adenoma volumes, prostate vascularity), as measured by transrectal ultrasound, were the principal outcomes.

Results

A reduction in total prostate volume (mean ?9.5%) was noted in the combination group, as opposed to an increase in the monotherapy group (+9.2%; P < 0.001). Similar changes were reflected in adenoma volume (monotherapy +17.4% vs combination ?12.5%, P = 0.001) and in prostate vascularity (monotherapy +149.3% vs combination ?19.8%, P = 0.001). Both treatment regimens improved the International Prostate Symptom Score (P = 0.001); monotherapy improved the voiding subscale (P = 0.01) more, whereas combination therapy improved the storage subscale (P = 0.024). Cystometric capacity improved in the combination group (P < 0.001). Post‐void residual was increased in the combination group (+34.79%), as opposed to a decrease in the monotherapy group (?17.05%; P = 0.001).

Conclusions

The results of this pilot study suggest that solifenacin might affect morphometric properties of the prostate, decreasing total prostate and adenoma volume, as well as vascularity. A molecular effect of antimuscarinics on the prostate, in parallel with their expected bladder effect, warrants further investigation.

     

Laser prostate ablation and enucleation: Analysis of a national cohort

Objective

To compare characteristics and outcomes of benign prostatic hyperplasia patients undergoing prostate laser ablation with those undergoing laser enucleation using a nationwide cohort.

Methods

Men who underwent prostate laser ablation (n=10054) or laser enucleation (n=1705) between 2011 and 2015 were identified by the common procedural terminology code as recorded in the National Surgical Quality Improvement Program database. Preoperative, intraoperative and postoperative parameters were compared between the groups using univariate and multivariate analysis.

Results

Prostate laser ablation patients were older, had more comorbidities and were more likely to have abnormal laboratory values. Enucleations were significantly longer and more likely to result in a hospital stay >1day. Enucleation patients were also more likely to require a blood transfusion postoperatively, but less likely to experience urinary tract infection and sepsis on both univariate and multivariate analysis adjusted for preoperative and intraoperative factors.

Conclusions

Although laser enucleation and prostate laser ablation are both considered minimally invasive techniques, significant differences in patient selection, intraoperative factors and postoperative complications are identified in this national cohort. The present study shows that despite similar outcomes in prospective single‐center studies, prostate laser ablation and laser enucleation have distinct practice patterns in a broader national context.

     

Clinical complications in renal biopsy using two different needle gauges: The impact of large hematomas,a random clinical trial study

Objective

To compare complications of ultrasound‐guided percutaneous renal biopsy using two needle gauges (16‐G and 18‐G).

Methods

A total of 238 individuals with renal biopsy indication were included and randomly separated into two groups: ultrasound‐guided percutaneous renal biopsy procedure carried out with a 16‐G or 18‐G needle. The adequacy of biopsy samples and post‐procedure complications were compared between the two groups.

Results

The procedures carried out with a 16‐G needle collected fragments with a mean of 22.1 ± 10.8 glomeruli, and those carried out with an 18‐G needle had a mean of 17.5 ± 9.4 glomeruli. Patients submitted to renal biopsies with a 16‐G needle had a higher likelihood of having a complication (OR5.1, 95% CI 1.7–15.4, P = 0.001). The overall mean volume of post‐biopsy hematoma in patients with complications was significantly larger than those without complications (44 ± 56.1 mL vs 5.9 ± 6.6 mL; P < 0.001).

Conclusions

Renal biopsies carried out by ultrasonography using an 18‐G needle provide adequate histological analysis, showing a lower amount of glomeruli but with similar clinical quality as a 16‐G needle. Furthermore, it is associated with a lower risk of procedure‐related complications.

     

Impact of a novel biopsy instrument with a 25‐mm side‐notch needle on the detection of prostate cancer in transrectal biopsy

Objectives

To evaluate the impact of a novel biopsy instrument that extends the length of the side‐notch on the detection of prostate cancer in transrectal needle biopsy.

Methods

We collaborated with a biopsy needle manufacturer and developed a novel biopsy instrument (PRIMECUT II long‐notch type) with a 25‐mm side‐notch length and 28‐mm stroke length to take longer tissue cores. The sampled core length, cancer detection rate, pain and complications of 489 patients who underwent transrectal biopsy using the long‐notch needle were compared with those of 469 patients who underwent biopsy using a normal instrument with a 19‐mm side‐notch length and 22‐mm stroke length.

Results

The mean length of tissue taken by the long‐notch needle was significantly longer than that of tissue taken by the normal‐notch needle (16.3 vs 22.4 mm, P < 0.001). The overall cancer detection rate was 42.0% for the normal‐notch needle and 51.1% for the long‐notch needle (P = 0.005). In patients with a prostate volume of 20–40 mL, the cancer detection rate for the long‐notch needle was especially higher than that for the normal‐notch needle (74.2% vs 47.5%, P < 0.001). Multivariate analysis showed that the long‐notch needle improved cancer detection significantly (odds ratio 1.702, P < 0.001). There were no differences of pain during biopsy and complication between the two groups.

Conclusions

The novel biopsy instrument with a 25‐mm side‐notch can take longer tissue samples safely and has a significantly higher rate of prostate cancer detection in transrectal biopsy.

     

Oral administration of cernitin pollen extract (Cernilton®) for 30 days might be useful to avoid unnecessary biopsy in prostate biopsy candidates: A preliminary study

Objectives

To assess the effect of cernitin pollen extract on serum prostate‐specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure.

Methods

A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate‐specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate‐specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer.

Results

The mean change in serum prostate‐specific antigen and rate of change after administration of cernitin pollen extract in all patients were ?0.6 ± 1.4 ng/mL and ?7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate‐specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively).

Conclusions

The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate‐specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.

     

Prostate‐specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer

Objective

To clarify the impact of prostate‐specific antigen screening on surgical outcomes of prostate cancer.

Methods

Patients who underwent radical prostatectomy were divided into two groups according to prostate‐specific antigen testing opportunity (group 1, prostate‐specific antigen screening; group 2, non‐prostate‐specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank‐sum and χ²‐tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence‐free survival.

Results

In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate‐specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5‐year biochemical recurrence‐free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate‐specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate‐specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate‐specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study.

Conclusions

Detection by screening results in favorable outcomes after surgery. Prostate‐specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer.

     

Contralateral adrenal width predicts the duration of prolonged post‐surgical steroid replacement for subclinical Cushing syndrome

Objectives

To identify pre‐treatment factors affecting the duration of post‐surgical steroid replacement in patients undergoing adrenalectomy for subclinical Cushing syndrome.

Methods

The present retrospective analysis included 64 patients who underwent unilateral laparoscopic adrenalectomy for subclinical Cushing syndrome. Adrenal tumor and contralateral adrenal sizes together with various clinical factors were studied in association with the duration of post‐surgical steroid replacement. Adrenal tumor and contralateral adrenal size were measured at the level of the maximum transverse plane of the adrenal glands using computed tomography scan or magnetic resonance imaging. Cox's proportional hazards model was used for the statistical analysis.

Results

All 64 patients were treated with post‐surgical steroid replacement after adrenalectomy. The median duration of the steroid treatment was 6 months. When assessing the duration of post‐surgical steroid replacement, contralateral adrenal volume <0.745 cm³, contralateral adrenal width <6.15 mm and serum cortisol after a 1‐mg dexamethasone suppression test >2.65 μg/dL were significant predictors of prolonged post‐surgical steroid treatment on univariate analysis. On multivariate analysis, contralateral adrenal width <6.15 mm was the only independent predictive factor for the prolonged post‐surgical steroid replacement.

Conclusions

Contralateral adrenal width seems to represent a significant predictive factor for the duration of post‐surgical steroid replacement in subclinical Cushing syndrome patients. Pre‐surgical assessment of image findings might help clinicians determine the total duration of steroid therapy after adrenalectomy.

     

Laparoscopic adrenalectomy using the lateral retroperitoneal approach: Is it a safe and feasible treatment option for pheochromocytomas larger than 6 cm?

Objectives

To evaluate the surgical feasibility of laparoscopic adrenalectomy using the lateral retroperitoneal approach for the treatment of large pheochromocytomas, and to identify the preoperative risk factors for intraoperative hypertension.

Methods

We retrospectively reviewed 51 patients who underwent laparoscopic adrenalectomy using the lateral retroperitoneal approach for the treatment of pheochromocytomas. Patient characteristics and perioperative outcomes were analyzed and compared between the two study groups based on tumor size: group A (n = 27, ≤6 cm) and group B (n = 24, ?6 cm).

Results

There was no significant difference in preoperative characteristics between the two groups except for tumor size (P = 0.001) and urinary metanephrine (P = 0.011). Group B patients required longer operating time (P = 0.008), had a greater estimated blood loss (P = 0.001) and hemoglobin change (P = 0.002). However, no significant differences were observed in perioperative complications and mortality. Multivariate analysis showed that symptomatic pheochromocytomas (P = 0.004) and tumor size (P = 0.007) were significant risk factors for intraoperative hypertension.

Conclusions

Laparoscopic adrenalectomy using the lateral retroperitoneal approach for pheochromocytomas can be regarded as a treatment option, even for tumors measuring >6 cm. Symptomatic pheochromocytomas and large tumor size seem to represent risk factors for intraoperative hypertension.

     

Prospective study of robotic partial nephrectomy for renal cancer in Japan: Comparison with a historical control undergoing laparoscopic partial nephrectomy

Objectives

To evaluate the outcomes of robotic partial nephrectomy compared with those of laparoscopic partial nephrectomy for T1 renal tumors in Japanese centers.

Methods

Patients with a T1 renal tumor who underwent robotic partial nephrectomy were eligible for inclusion in the present study. The primary end‐point consisted of three components: a negative surgical margin, no conversion to open or laparoscopic surgery and a warm ischemia time ≤25 min. We compared data from these patients with the data from a retrospective study of laparoscopic partial nephrectomy carried out in Japan.

Results

A total of 108 patients were registered in the present study; 105 underwent robotic partial nephrectomy. The proportion of patients who met the primary end‐point was 91.3% (95% confidence interval 84.1–95.9%), which was significantly higher than 23.3% in the historical data. Major complications were seen in 19 patients (18.1%). The mean change in the estimated glomerular filtration rate in the operated kidney, 180 days postoperatively, was ?10.8 mL/min/1.73 m² (95% confidence interval ?12.3–9.4%).

Conclusions

Robotic partial nephrectomy for patients with a T1 renal tumor is a safe, feasible and more effective operative method compared with laparoscopic partial nephrectomy. It can be anticipated that robotic partial nephrectomy will become more widely used in Japan in the future.

     

Radiotherapy for the treatment of distant nodes metastases from oligometastatic urothelial cancer: A retrospective case series

Objectives

To investigate the efficacy of stereotactic body radiotherapy in oligometastatic urothelial carcinoma with node‐only involvement.

Methods

We retrospectively collected data on the outcomes of patients who underwent stereotactic body radiotherapy for metastatic node lesions from oligometastatic urothelial carcinoma at Radiotherapy Unit of University Hospital of Parma, Parma, Italy. The investigated outcomes were lesion size, standardized uptake value, overall response rate, lesion control rate, lesion progression‐free interval, progression‐free survival and overall survival.

Results

Among seven patients included in the study, a total of 14 node metastatic lesions were treated with stereotactic body radiotherapy. The mean total dose of stereotactic body radiotherapy was 32 Gy (range 25–40 Gy). At first imaging evaluation, a mean variation of ?4% (P = 0.427) in major diameter, ?16% (P = 0.048) in minor diameter and –76% in standardized uptake value (P < 0.001) were documented. The overall response rate and lesion control rate were 43% and 100%, respectively. Median lesion progression‐free interval, progression‐free survival and overall survival were 11.4 months (95% CI 3.4–19.4), 2.9 months (95% CI 2.6–3.1) and 14.9 months (95% CI 12.3–17.5), respectively. Stereotactic body radiotherapy was effective in delaying the beginning of a systemic chemotherapy in four patients.

Conclusions

The present findings generate the hypothesis of a possible role for the use of stereotactic body radiotherapy in selected patients with distant node metastases from oligometastatic urothelial carcinoma.

     

Transurethral seminal vesiculoscopy acts as a therapeutic investigation for intractable hemospermia: Step‐by‐step illustrations and single‐surgeon experience

Objective

To describe the methodology of transurethral seminal vesiculoscopy and the anatomy of the seminal tract, and to report a single‐surgeon experience with this procedure.

Methods

A total of 38 consecutive patients with intractable macroscopic hemospermia were enrolled from January 2010 to July 2016. A 6/7.5‐Fr semirigid ureteroscope was used to enter the seminal tract by one of these two approaches: through either a trans‐ejaculatory duct opening or a trans‐utricle fenestration. Patient characteristics and their preoperative and postoperative measurements were analyzed retrospectively.

Results

The success rate of transurethral seminal vesiculoscopy was 92.1%, whereas the approaching method in most patients was the trans‐utricle fenestration (88.89%). A total of 34 (94.4%) transurethral seminal vesiculoscopy inspections ended with complete remission, even though nearly half of them (47.2%) only disclosed negative perioperative findings. The median period to complete remission was 4 weeks (interquartile range 4–6 weeks) after the procedure. Four patients had recurrent hemospermia, and the median time to recurrence was 21.5 (range 13–48.5) months.

Conclusions

Transurethral seminal vesiculoscopy is a valuable diagnostic tool for intractable hemospermia, and also plays a therapeutic role by blocking the vicious cycle of stasis, calculi and seminal vesiculitis. More familiarity of the anatomy and enough practice would make the learning curve less steep.

     

Protease activated‐receptor 4 activation as a model of persistent bladder pain: Essential role of macrophage migration inhibitory factor and high mobility group box 1

Objectives

To develop a rodent model of persistent non‐inflammatory bladder pain and to test macrophage migration inhibitory factor and high mobility box group 1 as mediators of bladder pain.

Methods

Female C57BL/6 mice received intravesical instillations of protease activated receptor 4 (100 μmol/L, for 1 h) three times every other day and abdominal mechanical hypersensitivity (50% mechanical threshold) was tested on day 0 (baseline), and at days 1, 2, 3, 4, 7 and 9 after the first protease‐activated receptor 4 injection. At the end of the experiment, micturition changes were measured and bladders were examined for histological changes. Macrophage migration inhibitory factor antagonist (MIF098; 40 mg/kg i.p. b.i.d.) or high mobility group box 1 inhibitor (glycyrrhizin; 50 mg/kg i.p. daily) was administered from day 2 until day 8.

Results

There was a significant and persistent decrease in abdominal mechanical threshold starting from day 3 in the protease‐activated receptor 4‐treated group that persisted until day 9 (5 days post‐last instillation), but not in the control group. Glycyrrhizin fully reversed while MIF098 partially reversed abdominal mechanical hypersensitivity in protease‐activated receptor 4‐treated mice. The changes started on day 3 after the first protease‐activated receptor 4 instillation, and analgesic effects lasted throughout the rest of the testing period. None of the groups had significant micturition changes or overt bladder histological changes.

Conclusions

Repeated intravesical protease activated receptor 4 instillations produce persistent bladder pain without inflammation. Macrophage migration inhibitory factor and high mobility group box 1 are possible effective target molecules for bladder pain alleviation.

     

Primary whole‐gland ablation for localized prostate cancer with high‐intensity focused ultrasound: The important predictors of biochemical recurrence

Objectives

To identify predictive factors of biochemical recurrence for patients undergoing high‐intensity focused ultrasound treatment for localized prostate cancer.

Methods

We retrospectively identified patients receiving whole‐gland prostate ablation with high‐intensity focused ultrasound for localized prostate cancer from 2009 to 2015. All the patients received pre‐high‐intensity focused ultrasound radical transurethral resection of the prostate. We included perioperative parameters as follows: age, preoperative prostate volume, stage of operation, initial prostate‐specific antigen, T stage, postoperative prostate‐specific antigen nadir, Gleason score, time to prostate‐specific antigen nadir and the presence of prostate‐specific antigen biochemical recurrence. Multivariable Cox regression and Kaplan–Meier analysis were used for investigating predictors of recurrence, and receiver operating characteristic analysis was used for the cut‐off values of prostate‐specific antigen nadir.

Results

Among 182 patients, 26.9% had prostate‐specific antigen biochemical recurrence after high‐intensity focused ultrasound during the median follow‐up period of 32.21 months. Gleason score ≥7 (Gleason score 7, hazard ratio 2.877, P = 0.027), stage ≥T2b (T2b, hazard ratio 3.16, P = 0.027) and prostate‐specific antigen nadir (hazard ratio 1.11, P < 0.001) were statistically significant, whereas there was no significance in prostate volume and initial prostate‐specific antigen. We posit that a cut‐off level of prostate‐specific antigen nadir 0.43 ng/mL might be considered as an independent predictive factor for prostate‐specific antigen biochemical recurrence in high‐intensity focused ultrasound patients in multivariate analysis (P < 0.001, hazard ratio 7.39, 95% confidence interval 3.56–15.37), and created a new nadir‐related prediction model for biochemical recurrence prediction.

Conclusions

Postoperative prostate‐specific antigen nadir of 0.43 ng/mL can be considered an important predictive factor for biochemical recurrence in primary whole‐prostate gland high‐intensity focused ultrasound treatment, and the nadir‐related prediction model might provide a reference for early salvage treatment. Furthermore, Gleason score ≥7, stage ≥T2b might be associated with unfavorable outcomes, although prostate volume and higher initial prostate‐specific antigen appear not to be associated with biochemical recurrence for the high‐intensity focused ultrasound treatment.

     

Evaluating the predictive accuracy and the clinical benefit of a nomogram aimed to predict survival in node‐positive prostate cancer patients: External validation on a multi‐institutional database

Objectives

To assess the predictive accuracy and the clinical value of a recent nomogram predicting cancer‐specific mortality‐free survival after surgery in pN1 prostate cancer patients through an external validation.

Methods

We evaluated 518 prostate cancer patients treated with radical prostatectomy and pelvic lymph node dissection with evidence of nodal metastases at final pathology, at 10 tertiary centers. External validation was carried out using regression coefficients of the previously published nomogram. The performance characteristics of the model were assessed by quantifying predictive accuracy, according to the area under the curve in the receiver operating characteristic curve and model calibration. Furthermore, we systematically analyzed the specificity, sensitivity, positive predictive value and negative predictive value for each nomogram‐derived probability cut‐off. Finally, we implemented decision curve analysis, in order to quantify the nomogram's clinical value in routine practice.

Results

External validation showed inferior predictive accuracy as referred to in the internal validation (65.8% vs 83.3%, respectively). The discrimination (area under the curve) of the multivariable model was 66.7% (95% CI 60.1–73.0%) by testing with receiver operating characteristic curve analysis. The calibration plot showed an overestimation throughout the range of predicted cancer‐specific mortality‐free survival rates probabilities. However, in decision curve analysis, the nomogram's use showed a net benefit when compared with the scenarios of treating all patients or none.

Conclusions

In an external setting, the nomogram showed inferior predictive accuracy and suboptimal calibration characteristics as compared to that reported in the original population. However, decision curve analysis showed a clinical net benefit, suggesting a clinical implication to correctly manage pN1 prostate cancer patients after surgery.