Molecular mechanism of formation and destruction of a pseudo­capsule in clear cell renal cell carcinoma.

The process and molecular mechanisms underlying the formation and destruction of a pseudo-capsule (PC) in clear cell renal cell carcinoma (ccRCC) are poorly understood. In the present study, the PCs of surgical specimens from primary tumors and metastatic lesions in 169 patients with ccRCC, and carcinogen-induced ccRCC rat models were semi-quantified using the invasion of PC (i-Cap) score system. This was based on the relationship among the tumor, PC and adjacent normal tissue (NT) as follows: i-Cap 0, tumor has no PC and does not invade NT; i-Cap 1, tumor has a complete PC and does not invade into the PC; i-Cap 2, tumor with focal absences in the PC, which partially invades the PC but not completely through the PC; i-Cap 3, tumor crosses the PC and invades the NT; i-Cap 4, tumor directly invades the NT without a PC. The study suggested that PC formation was not observed without physical compression, and also revealed that tumor invasion into the PC was a prognostic factor for postoperative oncological outcomes. Higher i-Cap, Fuhrman grade and tumor size were independent poor prognostic factors for postoperative disease-free survival. mRNA expression arrays generated from carcinogen-induced ccRCC rat models were used to explore genes potentially associated with the formation and destruction of a PC. Subsequently, human ccRCC specimens were validated for four genes identified via expression array; the results revealed that collagen type 4A2, matrix metalloproteinase-7 and l-selectin were upregulated alongside the progression of i-Cap score. Conversely, endoglin was downregulated. In conclusion, the present study provides insights into the formation and destruction of a PC, and the results may aid the treatment and management of patients with ccRCC.

Impact of Complete Surgical Resection of Metastatic Lesions in Patients with Advanced Renal Cell Carcinoma in the Era of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.

Complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) has demonstrated efficacy in the cytokine era, but its effectiveness in the era of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) remains unclear. A multi-institutional database included clinicopathological data of 367 patients with mRCC. Patients were divided into two groups: the CM group and the non-CM group. These two groups were compared before and after propensity score matching (PSM). Cox proportional hazard models were used to detect factors associated with disease-free survival (DFS) and overall survival (OS) from mRCC diagnosis. The CM group showed a significant association with longer overall survival compared to the non-CM group in the PSM-unadjusted cohorts (p < 0.001, hazard ratio 0.49, 95% confidence interval 0.35-0.69), but no superiority was noted in the adjusted cohorts. The median DFS after CM was 24 months, with no significant differences based on relapse timing. Notably, the international metastatic RCC database consortium risk categories and metastatic burden were associated with DFS. This study supports the potential of CM in mRCC management during the TKI/ICI era, although limitations including sample size and selection bias need to be considered.

Comprehensive Analysis of Donor Factors for Allograft Survival in Living Kidney Transplantation: A Single-Center Study in Japan.

BACKGROUND: Various donor characteristics have been reported as predictive factors for graft survival in kidney transplantations. The living kidney donor profile index (LKDPI) was established in 2016 to evaluate the quality of living donor kidneys. Herein, we verified whether the index score was associated with graft survival and analyzed various donor factors to identify predictors of graft survival in living donor kidney transplantations. METHODS: This retrospective study included 130 patients who received a living donor kidney between 2006 and 2019 at our hospital. Clinical and laboratory data were obtained from the medical records. Living donor kidneys were categorized into 3 groups by LKDPI score, and the death-censored graft survival and predictors of graft survival were evaluated. RESULTS: The median LKDPI score was 35 (IQR: 17-53). The index scores of the living donor kidneys in this study were higher than in previous studies. The groups with the highest scores (LKDPI >40) had significantly shorter death-censored graft survival compared with the group with the lowest scores (LKDPI <20; hazard ratio = 4.0, P = .005). There were no significant differences between the group with the middle scores (LKDPI, 20-40) and the other 2 groups. Donor/recipient weight ratio <0.9, ABO incompatibility, and 2 HLA-DR mismatches were identified as independent predictive factors for shorter graft survival. CONCLUSION: The LKDPI was correlated with death-censored graft survival in this study. However, more studies are required to establish a modified index that is more accurate for Japanese patients.

Clinical significance of limited and extended pelvic lymph node dissection during robot-assisted radical prostatectomy for patients with localized prostate cancer: A retrospective, propensity score matching analysis.

OBJECTIVES: We investigated the diagnostic and therapeutic benefits of limited or extended pelvic lymph node dissection during a robot-assisted radical prostatectomy for localized prostate cancer. METHODS: Diagnostic and therapeutic benefits were assessed according to the rates of pN1 and biochemical recurrence, respectively. The primary outcome was the biochemical recurrence-free rate, and secondary outcomes included the diagnostic and therapeutic benefits of pelvic lymph node dissection. RESULTS: A total of 534 patients were analyzed. Out of the 534 patients, 207 (38.8%) received limited pelvic lymph node dissection while 134 (25.1%) received extended dissection. There were 297 patients with a Briganti index ≥5%. Extended dissections yielded significantly more resected lymph nodes (p < 0.0001), and 72.2% of cases of pN1 were located outside the obturator. The incidence rate of pN1 was 6.1%, and performance of extended lymph node dissection was an independent predictor for pN1 (odds ratio 9.0, 95% confidence interval 2.5-33.1). The rate of biochemical recurrence was 14.9%, and Cox proportional hazards regression analysis of the propensity score matched population revealed that patients with high or very-high risk tended to benefit from limited lymph node dissection (hazard ratio 8.4, 95% confidence interval 0.8-82.3) while the therapeutic benefit of extended dissection was unclear by comparison. CONCLUSIONS: Extended pelvic lymph node dissection significantly improves diagnostic accuracy; however, the therapeutic benefit of pelvic lymph node dissection was not observed in this study.

Mortality differences in disabled older adults by place of care in Japan: nationwide 10-year results.

This longitudinal study aimed to compare 1-year mortality between users of home- and community-based services (HCBS) and residential facilities (nursing homes, group homes, and geriatric apartments) among non-hospitalized frail older adults in Japan. Using three nationwide data sources, we conducted a nationwide pooled cohort study of 1-year follow-up among certified users of long-term care insurance (LTCI) aged 65 years and older from 2007 through 2016 to compare 1-year mortality using a logistic regression model. Overall, compared to HCBS users, mortality was higher in residents in nursing homes and geriatric apartments but lower in group home residents. While mortality gradually increased over time among those in residential facilities, it remained at a level similar to that of HCBS users. Since 2006, Japan's public health policy has been to increase end-of-life care in residential facilities. Our results indicate that this policy resulted in an increase in mortality in residential facilities, possibly due to accommodation of more severely ill people there, or a shift in their focus from transferring dying residents to hospitals to preserve the dignity of residents.

First-line pembrolizumab for patients with early relapsing urothelial carcinoma after perioperative chemotherapy: a retrospective analysis of bladder cancer and upper urinary tract cancer.

BACKGROUND: First-line pembrolizumab is available for recurrent disease within 12 months after the receipt of platinum-based perioperative chemotherapy. However, the benefit of first-line pembrolizumab is unclear. This study evaluated the oncological outcome of patients treated with pembrolizumab compared with chemotherapy as first-line therapy for early relapsing disease after the receipt of platinum-based perioperative chemotherapy. METHODS: Data from a multicenter study included 454 patients diagnosed with unresectable or metastatic UC from November 2006 to July 2021. We identified patients with early and non-early relapsing disease. Oncological outcomes were evaluated using progression-free survival, overall survival, and survival with disease control. RESULTS: Fifty-three patients with early relapsing disease and 15 patients with non-early relapsing disease were identified. Of 53 patients with early relapsing disease, 26 (49.1%) were treated with pembrolizumab and 27 (50.9%) were treated with chemotherapy as first-line therapy. Fifteen patients with non-early relapsing disease were treated with chemotherapy. Early relapsing disease was associated with shorter progression-free survival and overall survival than non-early relapsing disease. Pembrolizumab was associated with longer progression-free survival and survival with disease control than chemotherapy in patients with early relapsing disease. There was no significant difference in overall survival between pembrolizumab and chemotherapy, but overall survival plateau with a long tail was observed in pembrolizumab. CONCLUSIONS: First-line pembrolizumab in earlier clinical settings for highly malignant tumors might improve the prognosis of patients with early relapsing disease after the receipt of platinum-based perioperative chemotherapy.

[Validation of using disqualification from long-term care insurance registry as a proxy of death].

Objectives　The national database for long-term care insurance (LTCI) of Japan (Kaigo DB) enables researchers to access comprehensive data from its LTCI registry, eligibility assessment records, claims for service usage, and information about service providers. However, studies regarding the death or mortality of beneficiaries cannot be conducted because Kaigo DB does not contain death records, and researchers are not allowed to link Kaigo DB to other databases, such as national death records. Therefore, we aimed to assess the validity of using an insurer's disqualification from an LTCI beneficiary as a proxy of death.Methods　We used 510,751,798 monthly beneficiary records between April 2007 and March 2017 from the LTCI registry, while excluding data for ineligible persons for LTCI benefit or those younger than 65 years. We identified insurer cases disqualified from LTCI beneficiaries and linked them to national death records using deterministic linkage methods by dates of birth and death, sex, and residence. We considered the cases as positive if they were disqualified and their record was linked to a death. We used sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) as validity indices.Results　We identified 5,986,991 (1.17%) disqualified and 5,295,961 death cases. Sensitivity, specificity, PPV, and NPV of disqualification for death were 100%, 99.86%, 88.46%, and 100%, respectively. After stratification, PPV of disqualification was between 85% and 88% before 2012, 91% after 2012, 91.9% in men, and 85.9% in women. PPV increased with age (65-69 years: 80.6%, 70-74 years: 86.7%, 75-79 years: 86.4%, 80-84 years: 86.7%, 85-89 years: 88.0%, 90-94 years: 90.6%, and 95+ years: 93.4%) and level of care needed (support level: 72.2%, care level (CL) 1: 79.7%, CL2: 85.9%, CL3: 89.3%, CL4: 92.3%, and CL5: 94.0%).Conclusions　Disqualification from the LTCI registry is an inappropriate measure to estimate mortality accurately because it has a 10% false-positive rate. However, it appears sufficiently valid to use disqualification as a proxy outcome of death, although the main effect or confounding of a possible predictor of death could be slightly underestimated.

Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study.

To investigate the organ-specific response and clinical outcomes of mixed responses (MRs) to immune checkpoint inhibitors (ICIs) for unresectable or metastatic urothelial carcinoma (ur/mUC), we retrospectively analyzed 136 patients who received pembrolizumab. The total objective response rate (ORR) and organ-specific ORR were determined for each lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 as follows: (i) complete response (CR), (ii) partial response (PR), (iii) stable disease (SD), and (iv) progressive disease (PD). Most of the organ-specific ORR was 30−40%, but bone metastasis was only 5%. There was a significant difference in overall survival (OS) between responders and non-responders with locally advanced lesions and lymph node, lung, or liver metastases (HR 9.02 (3.63−22.4) p < 0.0001; HR 3.63 (1.97−6.69), p < 0.0001; HR 2.75 (1.35−5.59), p = 0.0053; and HR 3.17 (1.00−10.0), p = 0.049, respectively). MR was defined as occurring when PD happened in one lesion plus either CR or PR occurred in another lesion simultaneously, and 12 cases were applicable. MR was significantly associated with a poorer prognosis than that of the responder group (CR or PR; HR 0.09 (0.02−0.35), p = 0.004). Patients with bone metastases benefitted less. Care may be needed to treat patients with MR as well as patients with pure PD. Further studies should be conducted in the future.

[IMPACT OF THE SPREAD OF COVID-19 ON THE UROLOGY PRACTICE IN OUR HOSPITAL].

(Purpose) Our hospital plays the role of a prefectural core hospital for COVID-19 and mainly accepts moderate and severely ill patients. In addition, our hospital is also actively responsible for regional emergency medical care, and is designated as a cancer treatment cooperation base hospital. We started accepting patients with COVID-19 in April 2020, and 2 out of 10 wards of our hospital are in operation as exclusive wards for COVID-19 at the time of May 31, 2021. In this study, we compared the effects of the spread of COVID-19 on our urological practice with those before the spread. (Materials and methods) The number of urological operations, their types and average length of stay, the number of outpatients / inpatients, the unit cost of medical treatment income, the referral rate, and the reverse referral rate were calculated based on the in-hospital clinical statistics. (Results) The number of urological operations decreased to 847, 862, and 768 in fiscal year 2018, 2019, and 2020, respectively. There was no significant change in the number of surgeries for malignant tumors in fiscal year 2020, but the number of surgeries for benign diseases decreased. The number of emergency operations tended to increase in fiscal year 2020. The number of urological hospitalized patients in fiscal year 2018, 2019, and 2020 decreased to 653, 690, and 533, and the average length of stay was shortened to 8.4, 8.8, and 8.1 days, respectively. The outpatient and inpatient unit prices per patient when fiscal year 2018 was set to 100 were increasing to 119.5 and 104.9, 133.7 and 119.1 in fiscal year 2019 and 2020, respectively. (Conclusion) It is thought that the spread of COVID-19 has clarified the function and characteristics of our hospital in community medicine.

[A Case Report of Severe Ischemic Priapism Treated Aggressively by Proximal Shunt].

Priapism is defined as a full or partial erection for >4 hours without sexual stimulation or orgasm. Ischemic priapism is an emergency disease that urgently requires surgery to reduce pressure in the corpora cavernosa. We encountered a case of severe ischemic priapism that required a proximal shunt. The patient was a 71-year-old man who had been diagnosed with benign prostatic hyperplasia ; hence, oral administration of tamsulosin had been initiated at a local hospital. His penis became gradually rigid and presented with prolonged erection. Then he consulted our hospital. Penile aspiration was impossible, and phenylephrine injection was not effective. He was subsequently transferred to our hospital. He did not have severe pain but had complete erection. We could not correctly evaluate blood gas from the corpora cavernosa and color Doppler ultrasonography showed little blood flow in the corpora cavernosa. We judged that the patient had ischemic priapism. The erection could not be controlled by distal shunt plastic surgery performed using the T shunt and Al-Ghorab methods. Therefore, a proximal shunt plastic surgery as described by Sacher was performed. The surgery was effective, but it caused erectile dysfunction.

Living-donor kidney transplantation for a patient with hypoparathyroidism, deafness, and renal dysplasia syndrome.

INTRODUCTION: Hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome is an autosomal dominant rare genetic disease. Some patients with hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome may present with renal calcification (nephrocalcinosis) and disorder. We report the first case of living-donor kidney transplantation for a patient with hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome. CASE PRESENTATION: This case pertains to a 26-year-old woman who was diagnosed with congenital hypoparathyroidism 1 month after birth, following which vitamin D supplementation was initiated. In 20XX, she developed nephrocalcinosis and was confirmed to have a GATA3 mutation; hence, she was diagnosed with hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome. In 20XX + 7, ABO-incompatible living-donor kidney transplantation was performed. Her renal function improved, and graft calcification was not observed. CONCLUSION: Over intake of vitamin D caused nephrocalcinosis. The renal function was improved after living-donor kidney transplantation and the patient's serum calcium levels normalized without vitamin D supplementation. Therefore, kidney transplantation should be considered a treatment option for patients with hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome.

Clinical Impact of Sarcopenia and Inflammatory/Nutritional Markers in Patients with Unresectable Metastatic Urothelial Carcinoma Treated with Pembrolizumab.

Sarcopenia is a muscle loss syndrome known as a risk factor of various carcinomas. The impact of sarcopenia and sarcopenia-related inflammatory/nutritional markers in metastatic urothelial carcinoma (mUC) treated with pembrolizumab was unknown, so this retrospective study of 27 patients was performed. Psoas muscle mass index (PMI) was calculated by bilateral psoas major muscle area at the L3 with computed tomography. The cut-off PMI value for sarcopenia was defined as ≤6.36 cm2/m2 for men and ≤3.92 cm2/m2 for women. Neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 and sarcopenia correlated with significantly shorter progression-free survival (PFS) (hazard ratio (HR) 3.81, p = 0.020; and HR 2.99, p = 0.027, respectively). Multivariate analyses identified NLR ≥ 4.0 and sarcopenia as independent predictors for PFS (HR 2.89, p = 0.025; and HR 2.79, p = 0.030, respectively). Prognostic nutrition index < 45, NLR ≥ 4.0 and sarcopenia were correlated with significantly worse for overall survival (OS) (HR 3.44, p = 0.046; HR 4.26, p = 0.024; and HR 3.92, p = 0.012, respectively). Multivariate analyses identified sarcopenia as an independent predictor for OS (HR 4.00, p = 0.026). Furthermore, a decrease in PMI ≥ 5% in a month was an independent predictor of PFS and OS (HR 12.8, p = 0.008; and HR 6.21, p = 0.036, respectively). Evaluation of sarcopenia and inflammatory/nutritional markers may help in the management of mUC with pembrolizumab.

Arterial reconstruction using the donor's gonadal vein in living renal transplantation with multiple renal arteries: a case report and a literature review.

BACKGROUND: Arterial reconstruction is one of the paramount procedures in kidney transplantation (KT) and greatly important if the procured kidney has multiple renal arteries (MRA). Despite various established techniques for arterial reconstruction, sometimes, the surgeon finds performing arterial anastomoses challenging in case of MRA. In our case, the donor's gonadal vein and recipient's internal iliac artery graft were used for arterial anastomoses, and 3 years after KT, the allograft did not present vascular complications. CASE PRESENTATION: A 34-year-old man underwent ABO-incompatible preemptive living KT. The allograft had three renal arteries and four renal veins. After donor nephrectomy, arterial reconstruction was performed on a back table. These arteries were reconstructed into one piece using the recipient's internal iliac artery graft. The two arteries at the middle of the renal hilum were reconstructed using the conjoined method. As the superior renal artery was too short to anastomose, the donor's gonadal vein was used for extension. The internal iliac artery graft was anastomosed to the original internal iliac artery. Intraoperative Doppler ultrasonography revealed that the blood flow in each renal artery was adequate, resulting in sufficient blood flow throughout the allograft. The allograft function was maintained with a serum creatinine level of approximately 0.9 mg/dL without vascular complications 3 years after KT. CONCLUSIONS: The donor's gonadal vein can be a candidate for extension of the renal artery in the allograft with MRA. Further follow-up is needed for the assessment of long-term outcomes.

[A Case of Small Cell Carcinoma of the Renal Pelvis].

A 84-year-old female visited our hospital with the chief complaint of asymptomatic gross hematuria. The computed tomography and magnetic resonance imaging revealed a large invasive tumor in the right renal pelvis. Metastatic workup was negative. On imaging studies and voided urine cytology, diagnosis of right renal pelvic cancer (cT3N0M0) was made. Laparoscopic right nephroureterectomy was performed. Histopathological examinations revealed a small cell carcinoma of the renal pelvis. The patient declined adjuvant chemotherapy and died 5 months after surgery. Primary small cell carcinoma of the renal pelvis is a rare disease. To our knowledge, this is the 29th case of primary small cell carcinoma of the renal pelvis in the world literature.

Clinical benefit of early treatment with bone-modifying agents for preventing skeletal-related events in patients with genitourinary cancer with bone metastasis: A multi-institutional retrospective study.

OBJECTIVES: To evaluate the clinical benefit of bone-modifying agents and identify the risk factors of skeletal-related events in patients with genitourinary cancer with newly diagnosed bone metastasis. METHODS: This was a multicenter retrospective study including a total of 650 patients with bone metastasis of the following cancer types: hormone-sensitive prostate cancer (n = 443), castration-resistant prostate cancer (n = 50), renal cell carcinoma (n = 80) and urothelial carcinoma (n = 77). Clinical factors at the time of diagnosis of bone metastasis were analyzed. Early treatment with bone-modifying agents was defined as follows: administration of bone-modifying agents before the development of skeletal-related events and within 6 months from the diagnosis of bone metastasis. RESULTS: During the follow-up period (median 19.0 months, interquartile range 6.0-43.8 months), skeletal-related events were reported in 88 (20%) patients with hormone-sensitive prostate cancer, 17 (34%) patients with castration-resistant prostate cancer, 58 (73%) patients with renal cell carcinoma and 34 (44%) patients with urothelial carcinoma. Early treatment with bone-modifying agents significantly prolonged the time to the first skeletal-related event in castration-resistant prostate cancer, renal cell carcinoma and urothelial carcinoma, but not in hormone-sensitive prostate cancer. Bone pain and elevated alkaline phosphatase levels were independent predictive risk factors of the first skeletal-related event. The subgroup analysis showed that early treatment with bone-modifying agents was associated with prolonged time to the first skeletal-related events in patients with bone pain or elevated alkaline phosphatase levels. CONCLUSIONS: Early treatment with bone-modifying agents should be considered, especially for patients with bone pain and elevated alkaline phosphatase levels, to prevent skeletal-related events in patients with genitourinary cancer with bone metastasis.

[THE RISK FACTORS AND CHEMOPREVENTION OF FEBRILE URINARY TRACT INFECTION AFTER TRANSURETHRAL URETEROLITHOTRIPSY].

(Objectives) Transurethral Ureterolithotripsy (TUL) has become an increasingly more common treatment for ureteric stones since the reduction in ureteroscope diameter and other device improvements. At the same time, TUL sometimes shows postoperative febrile urinary tract infection (fUTI) with severe complications. Therefore we investigated the occurrence and risk factors of fUTI in our hospital, and assessed the effect of antibiotic prophylaxis prior to TUL. (Materials and methods) The subjects were 260 patients who underwent TUL in our department during the period from January 2011 to October 2014. We retrospectively reviewed the data of those who developed postoperative fUTI and identified the risk factors of postoperative fUTI. From November 2014 to August 2016, we enrolled 110 patients undergoing TUL with one or more risk factors in a prospective clinical trial of prophylactic oral levofloxacin (500 mg) for 1 week before TUL. The chi-squared test, Mann-Whitney U-test, and logistic regression analysis were used for data analysis (significance level of 0.05). (Results) Postoperative fUTI occurred in 43 (16.5%) of 260 patients. The risk factors of postoperative fUTI included preoperative pyelonephritis (P=0.02), preoperative ureteral stent placement (P=0.017), and operative time >90 min (P=0.005). Operative time was correlated with and could be substituted for pre-TUL stone size (P<0.0001). Chemopreventive therapy before TUL in patients with preoperative pyelonephritis, preoperative ureteral stent placement, or stones of >20 mm significantly reduced their risk of fUTI (P=0.012). (Conclusions) The use of antibiotic prophylaxis significantly reduces the risk of postoperative fUTI in patients with preoperative pyelonephritis, preoperative ureteral stent placement, or stones of >20 mm.