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.

     

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.

     

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.

     

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.

     

Prognostic impact of the pretreatment aspartate transaminase/alanine transaminase ratio in patients treated with first‐line systemic tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma

Objectives

To examine the prognostic role of the pretreatment aspartate transaminase/alanine transaminase or De Ritis ratio in patients with metastatic renal cell carcinoma receiving first‐line systemic tyrosine kinase inhibitor therapy.

Methods

We retrospectively searched the medical records of 579 patients with metastatic renal cell carcinoma who visited Samsung Medical Center, Seoul, Korea, from January 2001 through August 2016. After excluding 210 patients, we analyzed 360 patients who received first‐line tyrosine kinase inhibitor therapy. Cancer‐specific survival and overall survival were defined as the primary and secondary end‐points, respectively. A multivariate Cox proportional hazards regression model was used to identify independent prognosticators of survival outcomes.

Results

The overall population was divided into two groups according to the pretreatment De Ritis ratio as an optimal cut‐off value of 1.2, which was determined by a time‐dependent receiver operating characteristic curve analysis. Patients with a higher pretreatment De Ritis ratio (≥1.2) had worse cancer‐specific survival and overall survival outcomes, compared with those with a lower De Ritis ratio (<1.2). Notably, a higher De Ritis ratio (≥1.2) was found to be an independent predictor of both cancer‐specific survival (hazard ratio 1.61, 95% confidence interval 1.13–2.30) and overall survival outcomes (hazard ratio 1.69, 95% confidence interval 1.19–2.39), along with male sex, multiple metastasis (≥2), non‐clear cell histology, advanced pT stage (≥3), previous metastasectomy and the Memorial Sloan Kettering Cancer Center risk classification.

Conclusion

Our findings show that the pretreatment De Ritis ratio can provide valuable information about the survival outcomes of metastatic renal cell carcinoma patients receiving first‐line tyrosine kinase inhibitor therapy.

     

Robotic partial nephrectomy using robotic bulldog clamps

Background and Objectives:

The need for a skilled assistant to perform hilar clamping during robotic partial nephrectomy is a potential limitation of the technique. We describe our experience using robotic bulldog clamps applied by the console surgeon for hilar clamping.

Methods:

A total of 60 consecutive patients underwent robotic partial nephrectomy, 30 using laparoscopic bulldog clamps applied by the assistant and 30 using robotic bulldog clamps applied with the robotic Prograsp instrument. Perioperative outcomes were compared between groups.

Results:

All 30 patients underwent successful hilar clamping during robotic partial nephrectomy using robotic bulldog clamps with no intraoperative complications and without the need for readjustment/reclamping. Robotic bulldog clamps provided adequate ischemia even for tumors >4 cm, hilar, endophytic, multiple tumors, and multiple renal arteries. Both groups had similar baseline characteristics. Perioperative outcomes with robotic bulldog clamps were at least comparable to the laparoscopic bulldog group, with a trend to lower console time, warm ischemia time, and estimated blood loss.

Conclusions:

Use of robotically applied bulldog clamps is a safe and feasible method of hilar occlusion during robotic partial nephrectomy; they perform at least as well as laparoscopic bulldog clamps while allowing the console surgeon greater autonomy and precision for hilar clamping.     

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.

     

Intensity ratio curve analysis of small renal masses on T2‐weighted magnetic resonance imaging: Differentiation of fat‐poor angiomyolipoma from renal cell carcinoma

Objectives

To assess the diagnostic ability of a pixel intensity‐based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat‐poor angiomyolipoma from renal cell carcinoma.

Methods

T2‐weighted images from 121 solid small renal masses (<4 cm) without visible fat (14 fat‐poor angiomyolipomas, 92 clear cell renal cell carcinomas, six chromophobe renal cell carcinomas and nine papillary renal cell carcinomas) were retrospectively evaluated. An intensity ratio curve was plotted using intensity ratios, which were ratios of signal intensities of tumor pixels (each pixel along a linear region of interest drawn across the renal tumor on T2‐weighted image) to the signal intensity of a normal renal cortex. The diagnostic ability of the intensity ratio curve analysis was evaluated.

Results

The tumors were classified into three types: intensity ratio fat‐poor angiomyolipoma (n = 19) with no pseudocapsule, iso‐low intensity and no heterogeneity; intensity ratio clear cell renal cell carcinoma (n = 76) with a pseudocapsule, iso‐high intensity and heterogeneity; and other type of intensity ratio (n = 26), including tumors that did not fall into the above two categories. The sensitivity/specificity/accuracy of the intensity ratio curve analysis in diagnosing fat‐poor angiomyolipoma was 93%/94%/94%, respectively. When the intensity ratio curve analysis was applied only to the tumor with undetermined radiological diagnosis, the sensitivity for diagnosing fat‐poor angiomyolipoma compared with subjective reading alone significantly improved (93% vs 50%; P = 0.014).

Conclusions

Our novel semiquantitative model for combined assessment of key features of fat‐poor angiomyolipoma, including low intensity, homogeneity and absence of a pseudocapsule on T2‐weighted image, might make diagnosis of fat‐poor angiomyolipoma more accurate.

     

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.

     

Erectile dysfunction and atrial fibrillation: A systematic review and meta‐analysis

Objective

To investigate the pooled incidence or the prevalence of erectile dysfunction, and to assess the risk of erectile dysfunction in patients with atrial fibrillation.

Methods

A systematic review was carried out in the MEDLINE, EMBASE and Cochrane databases from inception through January 2018 to identify: (i) studies that reported the incidence and/or prevalence of erectile dysfunction in atrial fibrillation patients; or (ii) studies that assessed the association between atrial fibrillation and erectile dysfunction. Pooled odds ratios and 95% confidence intervals were calculated using a random effects model.

Results

Five observational studies (27 841 patients) were enrolled. The pooled estimated prevalence of erectile dysfunction in atrial fibrillation patients was 57% (95% confidence interval 50–64, I² = 0). A study showed an incidence of newly diagnosed erectile dysfunction in atrial fibrillation patients of 0.96% during the mean follow‐up duration of 4.67 ± 3.20 years. There was a significant association of atrial fibrillation with an increased risk of erectile dysfunction, with a pooled odds ratio of 1.79 (95% confidence interval 1.44–2.23, I² = 0%). The data on the risk of atrial fibrillation development in patients with erectile dysfunction were limited. A study showed the comparable risk of atrial fibrillation in patients with erectile dysfunction (odds ratio 1.03, 95% confidence interval 0.67–1.5), when compared with those without erectile dysfunction.

Conclusions

The present study suggests a significant association between erectile dysfunction and atrial fibrillation. The overall estimated prevalence of erectile dysfunction among atrial fibrillation patients is 57%. However, despite limited data, the current evidence suggests a low incidence of new erectile dysfunction in atrial fibrillation patients.

     

Therapy‐related acute myeloid leukemia and myelodysplastic syndrome among refractory germ cell tumor patients

Objectives

To analyze cases of therapy‐related acute myeloid leukemia and myelodysplastic syndrome diagnosed after chemotherapy for refractory testicular and extragonadal germ cell tumor in our experience.

Methods

A total of 171 consecutive patients who were diagnosed and treated as refractory germ cell tumor and had records of detailed chemotherapy doses between April 1998 and December 2015 were retrospectively reviewed.

Results

Four testicular tumor patients (4/171, 2.3%) developed therapy‐related acute myeloid leukemia and myelodysplastic syndrome. Three of them were affected after complete remission of the primary testicular tumor. A median time interval from a start of chemotherapy to a secondary tumor development was 6.8 years (range 3.7–11.5 years). The median total dose of etoposide, ifosfamide, cisplatin and nedaplatin were 3640 mg/m² (range 2906–4000 mg/m²), 42.7 g (range 19.5–54.0 g), 1100 mg/m² (range 600–1500 mg/m²) and 500 mg/m² (range 300–1600 mg/m²), respectively. Etoposide had the only significant relationship between a cumulative dose and leukemogenesis in univariate analysis (P < 0.05). One patient had complete remission, but the other three patients died.

Conclusions

The present findings show that refractory germ cell tumor patients have an increased risk of therapy‐related acute myeloid leukemia and myelodysplastic syndrome. A cumulative dose of etoposide is a significant risk of leukemogenesis. As therapy‐related acute myeloid leukemia and myelodysplastic syndrome has a poor prognosis, close follow up is required for refractory germ cell tumor patients.

     

Laparoscopic radical nephrectomy in the elderly

Authors from Innsbruck present their work in laparoscopic radical nephrectomy in elderly patients. They evaluated the outcome of this technique in patients over 75 years old and compared the results with a similar number of patients aged less than 75 years who had the same procedure. Despite more comorbid conditions in the older group the final outcome was equally as good as in the younger patients. Hormone‐refractory prostate cancer is becoming a matter of great concern, and authors from Paris describe their experience with a combination of docetaxel and zoledronic acid in this condition. In this early report, they found the use of these agents to be promising, and recommend the setting up of a prospective randomized trial.

OBJECTIVE

To evaluate the efficacy and outcome of laparoscopic radical nephrectomy (LRN) in patients aged >75 years, and to compare the results with those obtained from patients younger than this undergoing laparoscopic surgery for the same indication.

PATIENTS AND METHODS

From a retrospective review of 33 patients aged >75 years undergoing LRN, 28 were for tumour. A group of 28 consecutive patients aged <75 years undergoing laparoscopy for the same indication were used for comparison. The two groups were compared for American Society of Anesthesiology (ASA) physical status score, comorbidity, previous surgical history, operative duration, estimated blood loss, tumour size, complications during and after surgery, conversion rates, time to oral intake and drain removal, perioperative mortality and hospital stay.

RESULTS

Only the initial ASA score was significantly higher for the older patients. All other variables before, during and after surgery were similar for both groups.

CONCLUSIONS

The final outcome of laparoscopic surgery in elderly patients was as promising as in their younger counterparts. Therefore, elderly patients should not be excluded from LRN, even though they usually present with more comorbidities.

     

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.

     

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.

     

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.

     

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.

     

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.

     

Prognostic role of the preoperative serum albumin : globulin ratio after radical nephroureterectomy for upper tract urothelial carcinoma

Objectives

To elucidate the effects of the preoperative albumin : globulin ratio on the survival of patients with upper tract urothelial carcinoma after radical nephroureterectomy.

Methods

We retrospectively reviewed 124 consecutive patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy at Chiba Cancer Center, Chiba, Japan between 2002 and 2015. The albumin : globulin ratio was defined: albumin / (total protein ? albumin). Associations between preoperative clinicopathological factors, including the albumin : globulin ratio, and recurrence‐free survival, cancer‐specific survival and overall survival were assessed. The log–rank test and Cox proportional hazards models were used for univariate and multivariable analyses, respectively. The study cohort was separated into two groups based on the optimal albumin : globulin ratio cut‐off value determined using receiver operating characteristic curve analysis.

Results

The median survival time was 55 months (interquartile range 28–76 months), and 31 patients died during follow up. A low preoperative albumin : globulin ratio <1.40 was associated with tumor grade and surgical margin status. Kaplan–Meier analyses showed that a low albumin : globulin ratio was more significantly correlated with worse recurrence‐free survival, cancer‐specific survival and overall survival. Multivariate analyses showed that a low albumin : globulin ratio was an independent predictive factor associated with poor recurrence‐free survival (hazard ratio 3.758; P = 0.0028), cancer‐specific survival (hazard ratio 5.687; P = 0.0044) and overall survival (hazard ratio 3.124; P = 0.0030).

Conclusions

A low albumin : globulin ratio is an independent predictive factor associated with poor prognosis in upper tract urothelial carcinoma patients treated with radical nephroureterectomy.

     

Chemotherapy for metastatic testicular cancer: The first nationwide multi‐institutional study by the Cancer Registration Committee of the Japanese Urological Association

Objectives

To assess clinicopathological data and oncological outcomes focused on metastatic testicular cancer patients, who received chemotherapy as the initial treatment, in the nationwide multi‐institutional study by the Cancer Registration Committee of the Japanese Urological Association.

Methods

A testicular cancer survey was carried out by the Japanese Urological Association in 2011 to register newly diagnosed testicular cancers in 2005 and 2008. Among 1121 registered patients, 278 patients with metastases who received chemotherapy as the initial treatment and could be categorized by the Japanese Urological Association classification were eligible for the analysis.

Results

As first‐line chemotherapy, bleomycin, etoposide and cisplatin, and etoposide and cisplatin therapies were chosen for 260 patients (93.5%). As second‐line therapy, vinblastine, ifosfamide and cisplatin/etoposide, ifosfamide and cisplatin; and paclitaxel, ifosfamide and cisplatin/paclitaxel, ifosfamide and nedaplatin therapies were carried out in 23 out of 63 (36.5%) and 29 out of 63 (46.0%) patients, respectively. The response rate and serum tumor marker normalization rate were 93.4% and 81.3% at first line, 75.4% and 60.7% at second line, and 41.7% and 16.7% at third line, respectively. The Japanese Urological Association classification (≥IIIB2 vs ≤IIIB1) and choriocarcinoma component in primary histology were independent prognostic factors of overall survival before starting chemotherapy. Furthermore, in patients with non‐seminomatous germ cell tumors, serum tumor marker normalization was an independent factor that was associated with better outcome of overall survival after completion of the initial series of chemotherapies.

Conclusions

The initial accurate diagnosis and risk stratification is an important prognostic factor to achieve better oncological outcomes. In patients with non‐seminomatous germ cell tumors, aiming for serum tumor marker normalization with continuous sequential chemotherapy could improve overall survival.

     

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.