Clinical questions in the Japanese Urological Association's 2024 clinical practice guidelines for urethral strictures.

Transurethral procedures such as direct vision internal urethrotomy and urethral dilation have been the traditional treatments for urethral strictures. However, transurethral procedures are associated with high recurrence rates, resulting in many uncured cases and prompting major international urological societies to recommend urethroplasty as the standard treatment owing to its high success rate. In contrast, many Japanese general urologists have little doubts about treating urethral strictures with transurethral treatment. Therefore, urethral stricture treatments in Japan are not in line with those used in other countries. To address this, the Trauma, Emergency Medicine, and Reconstruction Subcommittee of the Japanese Urological Association has developed guidelines to offer standardized treatment protocols for urethral stricture, based on international evidence and tailored to Japan's medical landscape. These guidelines target patients with a clinically suspected urethral stricture and are intended for urologists and general practitioners involved in its diagnosis and treatment. Following the Minds Clinical Practice Guideline Development Manual 2020, the committee identified eight critical clinical issues and formulated eight clinical questions using the "patient, intervention, comparison, and outcome" format. A comprehensive literature search was conducted. For six clinical questions addressed by the existing guidelines or systematic reviews, the level of evidence was determined by qualitative systematic reviews. Quantitative systematic reviews and meta-analyses were performed for the two unique clinical questions. The recommendation grades were determined using the Delphi method and consensus by the committee. These guidelines will be useful to clinicians in daily practice, especially those involved in the care of urethral strictures.

The Japanese Urological Association's clinical practice guidelines for urotrauma 2023.

The Japanese Urological Association's guidelines for the treatment of renal trauma were published in 2016. In conjunction with its revision, herein, we present the new guidelines for overall urotrauma. Its purpose is to provide standard diagnostic and treatment recommendations for urotrauma, including iatrogenic trauma, to preserve organ function and minimize complications and fatality. The guidelines committee comprised urologists with experience in urotrauma care, selected by the Trauma and Emergency Medicine Subcommittee of the Specialty Area Committee of the Japanese Urological Association, and specialists recommended by the Japanese Association for the Surgery of Trauma and the Japanese Society of Interventional Radiology. The guidelines committee established the domains of renal and ureteral, bladder, urethral, and genital trauma, and determined the lead person for each domain. A total of 30 clinical questions (CQs) were established for all domains; 15 for renal and ureteral trauma and five each for the other domains. An extensive literature search was conducted for studies published between January 1, 1983 and July 16, 2020, based on the preset keywords for each CQ. Since only few randomized controlled trials or meta-analyses were found on urotrauma clinical practice, conducting a systematic review and summarizing the evidence proved challenging; hence, the grade of recommendation was determined according to the 2007 "Minds Handbook for Clinical Practice Guidelines" based on a consensus reached by the guidelines committee. We hope that these guidelines will be useful for clinicians in their daily practice, especially those involved in urotrauma care.

Distribution analysis of hydrogel spacer and evaluation of rectal dose reduction in Japanese prostate cancer patients undergoing stereotactic body radiation therapy.

BACKGROUND: To report on our primary experience with the placement of a hydrogel spacer following stereotactic body radiation therapy (SBRT) in low- and intermediate-risk prostate cancer patients and assess its impact on dosimetry as well as acute toxicity. METHODS: A total of 70 patients treated with SBRT (total dose of 36.25 Gy) in 5 fractions were included. Hydrogel spacers were inserted in 53 patients along with gold fiducial markers. For dosimetry, we trisected the rectum on the sagittal image of magnetic resonance imaging and defined it as the upper rectum (UR), middle rectum (MR), and lower rectum (LR). We compared the dose to each part of the rectum with and without hydrogel spacer using dose volume histograms. Genitourinary (GU) and gastrointestinal (GI) toxicity assessments were conducted until 6 months of follow-up visits. RESULTS: The median volume of the hydrogel spacer was 12.3 mL. Overall, the hydrogel spacer could significantly reduce the rectal dose in the middle-to-high-dose region (V20-V35). The rectum doses at the UR and MR were significantly lower in the spacer group in the middle to high dose region (V20-V35); the dose at the LR was significantly lower in the spacer group in the high-dose region (V30-V35). There was no grade ≥ 3 toxicity observed, but grade 2 toxicity of GU and GI occurred in 17.1% and 1.4% of the patients, respectively. CONCLUSION: Hydrogel spacers could contribute to rectal dose reduction, especially in high dose regions, by creating a prostate-rectum distance.

History of Non-Muscle-Invasive Bladder Cancer May Have a Worse Prognostic Impact in cT2-4aN0M0 Bladder Cancer Patients Treated With Radical Cystectomy.

PURPOSE: To investigate whether a history of non-muscle-invasive bladder cancer (NMIBC) plays a prognostic role in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy in the era when neoadjuvant chemotherapy was established as standard therapy for MIBC. PATIENTS AND METHODS: A total of 282 patients who were diagnosed with cT2-T4aN0M0 bladder cancer treated with open radical cystectomy at our institutions were included. Initially diagnosed MIBC without a history of NMIBC was defined as primary MIBC group (n = 231), and MIBC that progressed from NMIBC was defined as progressive MIBC (n = 51). RESULTS: The rate of cT3/4a tumors was significantly higher in the primary MIBC group than in the progressive MIBC group (P = .004). Five-year recurrence-free survival and cancer-specific survival (CSS) rates for the primary MIBC group versus progressive MIBC group were 68.2% versus 55.9% (P = .039) and 76.1% versus 61.6% (P = .005), respectively. Progressive MIBC (hazard ratio, 2.170; P = .008) was independently associated with cancer death. In the primary MIBC group, the 5-year CSS rate in patients treated with neoadjuvant chemotherapy was 85.4%, which was significantly higher than that in patients without (71.5%, P = .023). In the progressive MIBC group, no significant differences were observed in CSS between patients treated with and without neoadjuvant chemotherapy. CONCLUSION: MIBC that progressed from NMIBC had a significantly worse clinical outcome than MIBC without a history of NMIBC and may not respond as well to neoadjuvant chemotherapy. These results are informative, even for NMIBC patients treated with conservative intravesical therapy.

Significance of a frozen section analysis of the ureteral margin in bladder cancer patients treated with radical cystectomy and neoadjuvant chemotherapy.

Although the clinical utility of a frozen section analysis (FSA) at the time of radical cystectomy (RC) has already been established, its significance and utility in bladder cancer patients receiving neoadjuvant chemotherapy (NAC) have not yet been fully evaluated. We identified 458 patients (937 ureters) who underwent open RC for bladder cancer at our 7 Japanese institutions between 2004 and 2015. Among these patients, 139 (284 ureters) received NAC before RC (NAC group), while 319 (653 ureters) underwent RC alone (non-NAC group). FSA was performed on 356 out of 937 (38.0%) ureters and 179 out of 458 (39.1%) patients. FSA was positive in 30 out of 356 (8.4%) ureters and its sensitivity, specificity, and accuracy were 89.3, 98.5, and 97.8%, respectively. In the NAC group, FSA was performed on 138 out of 284 (48.6%) ureters and 68 out of 139 (48.9%) patients. FSA was positive in 8 out of 138 ureters (5.8%), and its sensitivity, specificity, and accuracy were 77.8, 99.2, and 97.8%, respectively. In the non-NAC group, FSA was performed on 218 out of 653 (33.4%) ureters and 111 out of 319 (34.8%) patients. FSA was positive in 22 out of 218 (10.1%) ureters, and its sensitivity, specificity, and accuracy were 94.7, 98.0, and 97.7%, respectively. No correlation was observed between preoperative clinical factors and FSA positivity in the NAC group; however, in the non-NAC group, the incidence of FSA positivity in the ureters of patients with concomitant CIS in TUR-BT specimens was 8/41 (19.5%), which was significantly higher than that in their counterpart (14/177, 7.9%, p = 0.033). Even in the era of NAC in the management of bladder cancer patients, the performance of FSA does not change and FSA at the time of RC may provide useful diagnostic information.

Patient age was an independent predictor of cancer-specific survival in male patients with upper tract urothelial carcinoma treated by radical nephroureterectomy.

OBJECTIVE: We hypothesized that there may be a prognostic difference in age between the genders and evaluated the influence of gender-adjusted age on prognosis in upper tract urothelial carcinoma patients. METHODS: A total of 839 patients with upper tract urothelial carcinoma from a retrospective multi-institutional cohort were included. The patients were divided into four groups consisting of males (N = 610) and females (N = 229) according to age ((i) <60 years, (ii) 60-69.9 years, (iii) 70-79.9 years and (iv) ≥80 years), and we evaluated the associations of patient age and gender with clinicopathological features and oncological outcomes following radical nephroureterectomy. The median follow-up duration was 34 months. RESULTS: Disease recurrence occurred in 249 patients and 192 patients died of upper tract urothelial carcinoma. The 3-year cancer-specific survival rates were (i) 84.3%, (ii) 80.2%, (iii) 77.1% and (iv) 71.5% in the entire patient population (P = 0.001); (i) 84.5%, (ii) 81.1%, (iii) 76.8% and (iv) 69.7% in males (P = 0.010); and (i) 83.3%, (ii) 76.9%, (iii) 77.7% and (iv) 72.9% in females (P = 0.287), respectively. No significant differences between disease recurrence and age were found in the male or female population. In multivariate analysis, older age was an independent predictor of cancer-specific survival, in addition to advanced pT stage, the presence of lymphovascular invasion and lymph node involvement in males. In contrast, age was not associated with cancer-specific survival in females, while high grade, advanced pT stage, the presence of lymph node involvement and multifocal tumor were independent predictors. CONCLUSION: The results indicate that gender-adjusted age might be a new prognostic factor in upper tract urothelial carcinoma patients.

PREDICTIVE FACTORS OF THE INITIAL TREATMENT FOR 207 BLUNT RENAL TRAUMA CASES BASED ON THE CLASSIFICATION FOR RENAL INJURY OF JAPANESE ASSOCIATION FOR THE SURGERY OF TRAUMA 2008's VERSION.

(Objective) We retrospectively investigated the applicability of the Japanese Association for the Surgery of Trauma (JAST) classification version 2008 for renal injuries as predictive factors of the initial treatment for 207 blunt renal injury cases. (Materials and methods) We reviewed 207 patients between 1982 and 2013 who were admitted to our institution with blunt renal trauma. Patients were classified as conservative management group, immediate transcatheter arterial embolization (TAE) group, and immediate nephrectomy group by initial treatment. We retrospectively assessed several parameters including JAST criteria version 2008 type of renal injury (type), severity of hematoma (H factor) and extravasation of urine (U factor), the shock on arrival, associated abdominal injuries, serum hemoglobin levels, and macrohematuria as predicting factors of initial treatment of blunt renal trauma. (Result) TypeIII and PV injuries, H2 factor and associated non-renal abdominal injuries were predictive factors of immediate nephrectomy (p=0.001, p=0.000, p=0.003). TypeIII and PV injuries and H2 factor were predictive factors of immediate TAE. Both of H2 and U2 factors were significant predictors of immediate nephrectomy in patients with typeIII injury. H factor was a significantly predictive factor of immediate TAE in patients with typeI/II injuries (p=0.040). The rate of immediate TAE has been increasing but the rate of partial nephrectomy except for nephrectomy has been decreasing since the year 2007 when TAE was immediately available in our hospital. (Conclusion) The type category and severity of hematoma of JAST classification version 2008 would be predictive factors of initial management of blunt renal injuries. Patients with typeIII injuries and both of H2 and U2 factors, can be adapted to immediate nephrectomy. Patients with typeI/II and H2 factors can be adapted to immediate TAE.

Impact of an adjuvant chemotherapeutic regimen on the clinical outcome in high risk patients with upper tract urothelial carcinoma: a Japanese multi-institution experience.

PURPOSE: Current guidelines do not yet provide any recommendations for adjuvant chemotherapy in patients with upper tract urothelial carcinoma managed with radical nephroureterectomy. We evaluated whether an adjuvant chemotherapeutic regimen would affect the clinical outcome in patients with high risk upper tract urothelial carcinoma. MATERIALS AND METHODS: We identified 873 patients who had undergone radical nephrouretectomy for localized upper tract urothelial carcinoma at 14 Japanese institutions between 1993 and 2011. We assessed whether the type of regimen, such as methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and cisplatin, in an adjuvant setting, could affect the subsequent clinical outcome of patients with upper tract urothelial carcinoma. RESULTS: On multivariate analysis pathological T stage, tumor grade, lymphovascular invasion and lymph node involvement were prognostic factors for recurrence-free survival and cancer specific survival. We defined 229 patients with 3 or more of these factors as the high risk group. In an analysis according to adjuvant regimen, Kaplan-Meier curves showed that the 1 and 2-year recurrence-free survival rates in the methotrexate, vinblastine, doxorubicin and cisplatin treated group were 71.4% and 47.9%, which were significantly higher than in the gemcitabine and cisplatin treated group (48.2% and not reached, p=0.022) or those not treated with adjuvant chemotherapy (53.4% and 39.6%, p=0.039). Similar results were observed in terms of cancer specific survival. CONCLUSIONS: Our study showed that pT3-4, tumor grade 3, positive lymphovascular invasion and lymph node involvement were independent risk factors for disease mortality in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. In the high risk group methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy contributed to improve subsequent mortality compared to gemcitabine and cisplatin or no adjuvant chemotherapy.

Optimal timing of hormonal therapy for prostate-specific antigen recurrence after radical prostatectomy.

The present study was undertaken to examine biochemical progression in patients who received salvage hormonal therapy (HT) for biochemical disease recurrence (BCR) after radical prostatectomy (RP), and to determine the optimal timing for the administration of HT. The study population consisted of 156 patients who underwent RP and received salvage HT for BCR. The starting point of this study was the timing of RP, and the endpoint was biochemical prostate-specific antigen (PSA) progression (castration-resistance) after HT. The mean follow-up period after surgery was 8.1 years. First, we excluded 18 patients with persistent PSA (≥ 0.2 ng/mL) after RP from an analysis below because their prognoses were significantly poorer compared with 138 patients whose PSA nadirs had reached <0.2 ng/mL. Multivariate analysis demonstrated that Gleason score ≥ 8 (p = 0.010, hazard ratio (HR) 3.02), and PSA doubling time (PSA-DT) <6 months (p = 0.001, HR 7.39) was independently associated with subsequent biochemical progression after HT. Using these two variables (Gleason score and PSA-DT), we could stratify patients into three risk groups for BCR after salvage HT. Regarding the optimal timing for HT administration for these high-risk patients with both risk factors (relative risk = 22.3), the PSA cutpoint of 1.0 ng/mL at the initiation of HT showed a significant difference in progression-free survival rates (p = 0.023). The findings indicated that for high-risk patients, salvage HT for BCR after PSA nadir (<0.2 ng/mL) should be started before the PSA level exceeds 1.0 ng/mL; otherwise, there is a significant risk of subsequent biochemical progression after HT.

A multi-institutional validation of the prognostic value of the neutrophil-to-lymphocyte ratio for upper tract urothelial carcinoma treated with radical nephroureterectomy.

BACKGROUND: To externally validate the prognostic impact of preoperative neutrophil-lymphocyte ratio (pre-NLR) in patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). METHODS: A total of 665 patients from 12 institutions were included. The median follow-up was 28 months. Associations between pre-NLR level and outcome were assessed using multivariate analysis. A pre-NLR level of >3.0 was defined as elevated. RESULTS: Pre-NLR levels were elevated in 184 patients (27.7 %), and pre-NLR elevation was significantly associated with worse pathological features such as tumor grade 3, advanced pT stage, positive lymphovascular invasion (LVI), and lymph node involvement in RNU specimens. The 5-year recurrence-free and cancer-specific survival rates were 57.0 % (p < 0.001) and 60.2 % (p < 0.001), respectively, in patients with elevated pre-NLR, and 69.2 and 77.3 %, respectively, in their counterparts. Multivariate analysis showed that elevated pre-NLR was an independent risk factor for predicting subsequent disease recurrence (p = 0.037; hazard ratio (HR) 1.38) and cancer-specific mortality (p = 0.036;, HR 1.47), although the addition of pre-NLR slightly improved the accuracies of the base model for predicting both disease recurrence and cancer-specific mortality to 79.8 % (p = 0.041) and 83.0 % (p = 0.039), respectively (gain in predictive accuracy: 0.2 and 0.1 %, respectively). CONCLUSION: This multi-institutional study revealed that elevated pre-NLR was significantly associated with worse pathological features such as tumor grade 3, advanced pT stage, positive LVI, and lymph node involvement in RNU specimens, and elevated pre-NLR was an independent risk factor of disease recurrence and cancer-specific mortality in UTUC patients treated with RNU.

Survival following primary androgen deprivation therapy for localized intermediate- or high-risk prostate cancer: comparison with the life expectancy of the age-matched normal population.

The representative guidelines do not recommend androgen deprivation therapy (ADT) as a primary treatment for localized prostate cancer. However, in clinical practice, the use of primary ADT for localized prostate cancer has been widespread, especially among older patients. We performed a retrospective review of the efficacy of primary ADT for localized prostate cancer and compared their outcomes with the life expectancy of the normal population. The study cohort consisted of 410 men diagnosed with localized intermediate- or high-risk prostate cancer over the period 1992-2012 at five institutions. All patients underwent ADT as a primary cancer therapy, and mean follow-up was 6.0 years. Their progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) rates were calculated. Patients' expected survival rates were estimated by the Hakulinen method. Multivariate analysis demonstrated that Gleason score ≥8 and cT3a were independent risk factors for all of PFS, CSS, and OS. In patients who have none or one of these risk factors, minimum OS rates were not inferior to the expected survival curves of the normal population. Meanwhile, in patients with both risk factors, the OS curve fell below the expected survival rates, especially after 6 years of follow-up. We conclude that primary ADT might be one of the therapeutic options for localized intermediate- and high-risk prostate cancer. However, for high-risk cases with Gleason score ≥8 and cT3a, the choice of primary ADT should be deliberated carefully because the OS of these cases was inferior to the expected survival, especially at a late time point.

Independent predictors for bladder outcomes after treatment of intravesical recurrence following radical nephroureterectomy in patients with primary upper tract urothelial carcinoma.

BACKGROUND: Few studies have described the clinical courses and outcomes in the bladder after treatment of intravesical recurrence after radical nephroureterectomy (RNU) in patients with primary upper tract urothelial carcinoma (UTUC). We investigated the indicators for predicting subsequent bladder outcomes after treatment of intravesical recurrence after RNU. METHODS: A total of 241 patients with primary UTUC (pTa-4N0M0) who experienced intravesical recurrence after RNU were included. Of these patients, 101 (41.9 %) underwent Bacillus Calmette-Guérin treatments, whereas 49 (20.3 %) underwent intravesical chemotherapy. The median follow-up period after initial transurethral resection of the bladder tumor was 33 months. Relationships with bladder outcomes were analyzed by using multivariable analysis. RESULTS: Ninety-six patients experienced intravesical recurrence, and bladder progression was observed in 13. Cumulative incidence rates of intravesical recurrence at 1 and 5 years after treatment of the first intravesical recurrence were 31.0 and 48.4 %, whereas those of bladder progression at 1 and 5 years thereafter were 2.4 and 8.0 %. Multivariate analysis showed that the number of recurrent tumors and pT1 tumors at the time of the first intravesical relapse were independent risk factors for subsequent intravesical recurrence. With respect to bladder progression, multivariate analysis showed that pT1 tumors, the appearance of concomitant carcinoma-in situ at the time of the first intravesical relapse, and the absence of the Bacillus Calmette-Guérin treatment were independent risk factors. CONCLUSIONS: This retrospective study presents a detailed picture of further bladder outcomes after intravesical recurrence after RNU in primary UTUC patients. The results may assist physicians to develop a more rational protocol in bladder surveillance.

SIU/ICUD Consultation on Urethral Strictures: The management of anterior urethral stricture disease using substitution urethroplasty.

In this systematic review of the literature, a search of the PubMed database was conducted to identify articles dealing with augmentation/substitution urethral reconstruction of the anterior urethral stricture. The evidence was categorized by stricture site, surgical technique, and the type of tissue used. The committee appointed by the International Consultation on Urological Disease reviewed this data and produced a consensus statement relating to the augmentation and substitution of the anterior urethra. In this review article, the background pathophysiology is discussed. Most cases of urethral stricture disease in the anterior urethra are consequent on an ischemic spongiofibrosis. The choice of technique and the surgical approach are discussed along with the potential pros and cons of the use of a graft vs a flap. There is research potential for tissue engineering. The efficacy of the surgical approach to the urethra is reviewed. Whenever possible, a 1-stage approach is preferable from the patient's perspective. In some cases, with complex penile urethral strictures, a 2-stage procedure might be appropriate, and there is an important potential role for the use of a perineal urethrostomy in cases where there is an extensive anterior urethral stricture or where the patient does not wish to undergo complex surgery, or medical contraindications make this hazardous. It is important to have accurate outcome measures for the follow-up of patients, and in this context, a full account needs to be taken of patients' perspectives by the use of appropriate patient-reported outcome measures. The use of symptoms and a flow rate can be misleading. It is well established that with a normally functioning bladder, the flow rate does not diminish until the caliber of the urethra falls below 10F. The most accurate means of following up patients after stricture surgery are by the use of endoscopy or visualization by urethrography. Careful consideration needs to be made of the outcomes reported in the world literature, bearing in mind these aforementioned points. The article concludes with an overview of the key recommendations provided by the committee.

Metastatic behavior of upper tract urothelial carcinoma after radical nephroureterectomy: association with primary tumor location.

PURPOSE: To investigate the site-specific pattern of disease recurrence and/or metastasis and the associated patient outcomes after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). METHODS: A total of 733 patients with UTUC from a retrospective multi-institutional cohort were included, with a median follow-up of 34 months. Associated patient outcomes were analyzed by multivariate analysis. To evaluate the influence of primary tumor location, we divided it into four areas: renal pelvis, and upper, middle, and lower ureter. RESULTS: A total of 218 patients experienced disease recurrence, with the majority of relapses occurring within the first 3 years. Cumulative incidence rates of first disease recurrence at 1 and 3 years were 18.9 and 29.8 %, respectively. Of these patients, 38.5 % developed distant recurrence; 17.4 % experienced both local and distant recurrences; and 44.0 % developed isolated local recurrence. The predominant sites of distant metastasis were lung, liver, and bone. Multivariate analysis revealed that the prevalence of local recurrence and lung metastasis was significantly associated, with primary tumor location being independent of other clinicopathological variables. Lower/middle ureter tumors had a higher rate of local recurrence in the pelvic cavity, and renal pelvic tumors had a higher prevalence of distant relapse in the lungs. Similar results were obtained when rerunning the data set by excluding patients who received adjuvant chemotherapy (n = 131). CONCLUSIONS: This multi-institutional study provided a detailed picture of metastatic behavior after RNU, and primary tumor locations were associated with unique patterns of metastatic spread in UTUC patients.

The predictive value of positive urine cytology for outcomes following radical nephroureterectomy in patients with primary upper tract urothelial carcinoma: a multi-institutional study.

BACKGROUND AND OBJECTIVE: Few studies have addressed the predictive value of positive urine cytology for prognosis in patients with upper tract urothelial carcinoma (UTUC). We investigated whether the status of preoperative urine cytology could provide additional prognostic information following radical nephroureterectomy (RNU). MATERIALS AND METHODS: The study included 474 patients with primary nonmetastatic UTUC (pTa-4N0M0) from a retrospective multi-institutional cohort. The median follow-up period was 35 months. Associations between the status of urine cytologic evaluation and outcomes were analyzed using multivariate Cox regression models. Urine cytology was evaluated preoperatively using voided samples. Disease recurrence was defined as any relapse in nonbladder lesions and was coded separately from intravesical recurrence. RESULTS: Positive urine cytology was detected in 184 patients (38.8%) preoperatively. Disease recurrence occurred in 127 patients, while intravesical recurrence occurred in 219 patients; 83 patients died of UTUC during follow-up. Kaplan-Meier analysis revealed that only the incidence of intravesical recurrence was significantly associated with the status of urine cytologic evaluation (P = 0.024); the intravesical recurrence-free survival rates at 1 and 3 years following RNU were 61.4% and 46.2% in patients with positive urine cytology and 71.1% and 51.6% in their counterparts, respectively. Multivariate analysis showed that gender (hazard ratio [HR] = 1.74, 95% confidence interval [CI]; 1.28-2.43), tumor multifocality in RNU specimens (HR = 1.64, 95% CI; 1.09-2.47), and positive urine cytology (HR = 1.41, 95% CI; 1.08-1.85) were independent risk factors for subsequent intravesical recurrence. CONCLUSIONS: The results showed the prognostic value of positive urine cytology in patients with primary UTUC, and preoperative positive urine cytology may be associated with a significant increase in the prevalence of intravesical recurrence following RNU.

[Three cases of IgG4-related disease associated with urinary tract obstruction].

IgG4-related disease (IgG4RD) is a novel clinical entity characterized by tissue infiltration of IgG4-positive plasma cells. We report here 3 cases of IgG4RD associated with urinary tract obstruction. Patient 1 was a 59-year-old male who complained of difficulty on urination. A CT scan showed bilateral ureteral wall thickness, hydronephrosis, and an enlarged prostate. His serum IgG4 was 817 mg/dl. We made a diagnosis of IgG4RD and performed bilateral ureteral stenting and steroid therapy. A significant reduction in the size of the lesion was detected, and IgG4 was decreased to 272 mg/dl. He was doing well after removal of the ureteral stent. Patient 2 was a 51-year-old female who complained of bilateral swelling of the submaxillary gland. A CT scan showed left ureteral wall thickness and hydronephrosis. Her serum IgG4 was 1,020 mg/dl. We made a diagnosis of IgG4RD and performed left ureteral stenting and steroid therapy. A significant reduction in the size of the lesion was detected, and IgG4 was decreased to 337 mg/dl. She was doing well after removal of the ureteral stent. Patient 3 was a 64-year-old male who underwent evaluation for autoimmune pancreatitis. He complained of back pain and bilateral hydronephrosis was detected. His serum IgG4 level was 649 mg/dl. Bilateral ureteral stenting was performed based on a diagnosis of IgG4RD. He did not receive steroid therapy because of poorly-controlled diabetes mellitus. After insertion of the ureteral stent, hydronephrosis and back pain were relieved. We could only find a few case reports in the literature on IgG4RD associated with urinary tract obstruction. It is important for clinicians to bear in mind that IgG4RD sometimes causes urinary tract obstruction.

Patient characteristics and outcomes in metastatic upper tract urothelial carcinoma after radical nephroureterectomy: the experience of Japanese multi-institutions.

OBJECTIVES: To investigate oncological outcomes and prognostic factors in patients with upper tract urothelial carcinoma (UTUC) who experienced disease recurrence after radical nephroureterectomy (RNU). Few studies have focused on the clinical courses of patients who experienced disease recurrence after RNU. PATIENTS AND METHODS: A total of 204 UTUC patients who experienced disease recurrence from a retrospective multi-institutional cohort were included in the present study. Associated patient outcomes were analyzed using multivariate analysis. RESULTS: The mean time from RNU to first disease recurrence was 15.0 months and ≈90% of patients experienced disease recurrence within the first 3 years after RNU. During a median follow-up of 8.1 month after disease recurrence, 165 patients died from UTUC and five patients died from other causes. In the 204 cohorts, 1- and 3-year cancer-specific survival rates were 40.2% and 9.7%, respectively, and 1- and 3-year overall survival rates were 39.5% and 9.4%, respectively. After disease recurrence, 132 patients underwent systemic chemotherapy, and a subgroup analysis of patients who underwent systemic chemotherapy multivariate analysis showed that performance status, the presence of liver metastasis and the number of recurrence sites were independently prognostic of cancer-specific and overall survival after relapsing. According to three significant variables, 1- and 3-year cancer-specific survival rates were 72.7% and 20.8% in patients with no risk factors, 46.5% and 7.5% in patients with one risk factor, and 26.4% and 4.4% in patients with two or three risk factors, respectively (P < 0.001). CONCLUSIONS: Most patients died from UTUC within 3 years, even though systemic chemotherapies were administered after relapsing. Multivariate analysis showed that performance status, the presence of liver metastasis and the number of recurrence sites were independently related to poor survival after systemic chemotherapy.

Rectal injury during permanent seed implantation for prostate brachytherapy.

Serious complications have not been previously reported during seed implantation for prostate brachytherapy. We present an unreported case of rectal injury caused by an ultrasound probe. A 67-year-old male presented with a serum prostate-specific antigen level of 5.50 ng/ml, a Gleason score of 7 (3 + 4) and clinical T2a adenocarcinoma of the prostate. A transperineal permanent prostate brachytherapy implantation was performed. The patient subsequently complained of abdominal pain postoperatively. A gastrointestinal perforation was suspected based on an abdominal X-ray obtained on the day after the brachytherapy. Rectal injury was recognized during an exploratory laparotomy, and a primary closure and temporary diversion ileostomy were performed. The healing of the injury was confirmed by colonoscopy and an ileostomy closure was performed 2 months after the temporary diversion. The investigating committee for this accident concluded that the ultrasound probe had perforated the rectum. This is the first case of a rectal injury during seed implantation for prostate brachytherapy.

Effect of unsaturated alkyl chains on transfection activity of poly(amidoamine) dendron-bearing lipids.

In an earlier study, we developed a new type of gene vector using poly(amidoamine) (PAMAM) dendron-bearing lipids and reported that their transfection activity was affected by their structures, such as dendron generation and alkyl chain length. In this study, for improvement of their performance as gene vectors, we examined the effect of unsaturated chains of the dendron-bearing lipids using DL-G1-2C(18), which consists of PAMAM G1 dendron moiety and two octadecyl chains, and achieved the most efficient transfection activity among the dendron-bearing lipids having saturated alkyl chains, and DL-G1-2C(18)-U2, which consists of the same dendron-moiety and two octadecenyl chains. DL-G1-2C(18)-U2 showed a higher ability to form lipoplexes with plasmid DNA than DL-G1-2C(18). The DL-G1-2C(18)-U2 lipoplexes exhibited much smaller particle sizes than the DL-G1-2C(18). In addition, the DL-G1-2C(18)-U2 lipoplexes exhibited more efficient transfection of HeLa cells than DL-G1-2C(18) did. Results demonstrate the importance of unsaturated chains for the production of the dendron-bearing lipids having excellent gene transfection performance. Without the help of additional fusogenic lipids such as dioleoylphosphatidylethanolamine, DL-G1-2C(18)-U2 lipoplexes achieved the highly efficient transfection of the cells without marked cellular toxicity, in the presence of serum. Therefore, DL-G1-2C(18)-U2 might be promising as a potent gene vector.