Poor performance status is a risk factor for higher detection of Gram positive coccus in stone-related pyelonephritis.

INTRODUCTION: We aimed to investigate the detection rate of causative organisms in stone-related pyelonephritis and to compare their distribution according to patient backgrounds. METHODS: We retrospectively identified patients with stone-related pyelonephritis. Clinical data were collected between November 2012 and August 2020 at Wakayama Medical University Hospital, including on patient backgrounds and causative organisms. Patients were categorized by Eastern Cooperative Oncology Group performance status (PS) as the good PS group (0, 1) and the poor PS group (2-4). Bacteria were divided into Gram-positive cocci (GPC) or non-GPC groups and logistic regression analysis was used to examine factors that predict detection of GPC. RESULTS: Seventy-nine patients had stone-related pyelonephritis, 54 (68.4 %) in the good PS group and 25 (31.6 %) in the poor PS group. In the good PS group, Escherichia coli (67 %) was followed by Klebsiella species (9 %), while in the poor PS group, Escherichia coli (20 %) was followed by Enterococci and Staphylococci (12 %). GPC detection rate was significantly higher in the poor PS group than in the good PS group (40.0 % vs 14.8 %, p = 0.016), and multivariate logistic regression analysis showed that poor PS was an independent factor predicting detection of GPC (OR = 6.54, p = 0.02). CONCLUSIONS: The distribution of the causative organisms in stone pyelonephritis was similar to that in common complicated urinary tract infections. Poor PS may be an independent predictor of GPC detection in patients with stone pyelonephritis.

Myosteatosis as a novel predictor of new-onset diabetes mellitus after kidney transplantation.

OBJECTIVES: We evaluate the effect of myosteatosis on new-onset diabetes mellitus after kidney transplantation. METHODS: Consecutive patients who had renal transplant between 2006 and 2021 were reviewed, and 219 patients were finally included. Psoas muscle index was used to evaluate sarcopenia and average total psoas density (calculated by computed tomography before surgery) for myosteatosis. We used Cox proportional regression analyses in investigation of whether skeletal muscle depletion before surgery inclusive of sarcopenia and myosteatosis is a new additional predictor of new-onset diabetes mellitus. RESULTS: Median recipient age and body mass index were 45 years and 21.1 kg/m2 , respectively, and 123 patients (56%) were male. Preoperative impaired glucose tolerance was present in 58 patients (27%) and new-onset diabetes mellitus in 30 patients (14%), with median psoas muscle index of 6 cm2 /m2 and average total psoas density of 41 Hounsfield Unit. In multivariate analysis, significant risk factors were body mass index ≥25 kg/m2 (p < 0.01), impaired glucose tolerance (p < 0.01), and average total psoas density < 41.9 Hounsfield Unit (p = 0.03). New-onset diabetes mellitus had incidence rates of 3.7% without risk factors, 10% with a single risk factor, 33% with two, and 60% with three. Patients with new-onset diabetes mellitus were effectively stratified by the number of risk factors (p < 0.01). CONCLUSIONS: Myosteatosis could be a new risk factor used to predict new-onset diabetes mellitus.

High aldehyde dehydrogenase 1 activity is related to radiation resistance due to activation of AKT signaling after insulin stimulation in prostate cancer.

The association between type 2 diabetes mellitus and prostate cancer is still under investigation, and the relationship between hyperinsulinemia and prostate cancer stem-like cells (CSCs) is elusive. Here, we investigated the function of insulin/AKT signaling in prostate CSCs. We isolated prostate CSCs as aldehyde dehydrogenase 1-high (ALDH1high) cells from the human prostate cancer 22Rv1 cell line using an ALDEFLUOR assay and established several ALDH1high and ALDH1low clones. ALDH1high clones showed high ALDH1 expression which is a putative CSC marker; however, they showed heterogeneity regarding tumorigenicity and resistance to radiation and chemotherapy. Interestingly, all ALDH1high clones showed lower phosphorylated AKT (Ser473) (pAKT) levels than the ALDH1low clones. PI3K/AKT signaling is a key cell survival pathway and we analyzed radiation resistance under AKT signaling activation by insulin. Insulin increased pAKT levels in ALDH1high and ALDH1low cells; the fold increase rate of pAKT was higher in ALDH1high cells than in ALDH1low cells. Insulin induced resistance to radiation and chemotherapy in ALDH1high cells, and the increased levels of pAKT induced by insulin were significantly related to radiation resistance. These results suggest that ALDH1 suppresses baseline pAKT levels, but AKT can be activated by insulin, leading to treatment resistance.

[Usefulness of Immunostaining Scoring for Predicting Response to Single-Agent Nivolumab in Patients with Metastatic Renal Cell Carcinoma].

Although several biomarkers have been identified to predict prognosis in renal cell carcinoma (RCC), there are no evidence-based biomarkers to predict the response to immune checkpoint inhibitors. In this study, we focused on lymphocytes and tumor cells in the tumor microenvironment and investigated whether immunostaining scoring could predict the best overall response. We evaluated 32 patients with metastatic RCC (mRCC) who were treated with nivolumab monotherapy between August 2016 and July 2020. We performed immunostaining for CD8 T cells, TIA-1, PD-L1, and HLA class 1 in RCC tissues and assigned a score with a maximum of 4 points each, which we defined as histological score. The best overall response of nivolumab was observed in 4 patients (12.5%) with complete response (CR), 10 patients (31.3%) with partial response (PR), 5 patients (15.6%) with stable disease (SD), and 13 patients (40.6%) with progressive disease (PD). There was no significant difference in patient background between the CR＋PR＋SD group (19 patients) and the PD group (13 patients), but CD8 T cells were significantly higher and TIA-1 positive cells tended to be higher in the CR＋PR＋SD group (CD8 T cell : p＝0.03, TIA-1 : p＝0.07, PD-L1 : p＝0.67, HLA class 1 : p＝1.00). In univariate analysis, histological score ≥3 tended to contribute to the best overall response of nivolumab (p＝0.05). There was no significant difference in overall survival or cancer-specific survival after nivolumab administration between the two groups of patients with histological score ≥3 and those with histological score ＜3. In conclusion, immunostaining scoring based on CD8 T cells may be able to predict the efficacy of single-agent nivolumab in patients with mRCC.

Inverse planning in high-dose rate brachytherapy improves quality of life of prostate cancer patients compared with forward planning.

OBJECTIVES: To understand differences in quality of life outcomes between cases with forward planning and cases with inverse planning, we examine patients undergoing high-dose rate brachytherapy combined with external beam radiotherapy for localized prostate cancer. METHODS: We prospectively identified 283 patients with localized prostate cancer and divided them into forward planning and inverse planning groups. We extracted data on doses to the prostate, rectum and urethra that could potentially affect quality of life. We also evaluated quality of life using the Japanese version of Medical Outcome Study 8-Items Short Form Health Survey and Expanded Prostate Cancer Index Composite at pre-treatment and at 3, 6, 12 and 24 months after treatment. Wilcoxon signed rank test and Bonferroni correction were used to analyze the irradiation dose and any change in quality of life. RESULTS: Doses to the prostate and rectum were not significantly different between the two groups. Notably, however, doses to the urethra were significantly lower in the inverse planning group than in the forward planning group. Patients in the forward planning group had significantly poorer physical component summary scores at 3 months according to survey results. In Expanded Prostate Cancer Index Composite, patients in the forward planning group had statistically significant poorer urinary, bowel and sexual scores than those in the inverse planning group. Quality of life related to decline in sexual function was significantly reduced in the inverse planning group. CONCLUSIONS: Inverse planning in high-dose rate brachytherapy could significantly improve quality of life of patients with prostate cancer.

Impact of preoperative sarcopenia and myosteatosis on prognosis after radical cystectomy in patients with bladder cancer.

OBJECTIVE: To evaluate the prognostic impact of sarcopenia and myosteatosis on survival after radical cystectomy for bladder cancer. METHODS: We retrospectively reviewed consecutive patients who underwent radical cystectomy for bladder cancer between 2010 and 2019, and 123 patients were finally included in this single-center study. Pretreatment computed tomography images at the L3 level were used to calculate skeletal muscle index and skeletal muscle density. Sarcopenia and myosteatosis were diagnosed according to the gender-specific cutoff values of skeletal muscle index and skeletal muscle density used in a previous study. We compared overall survival and cancer-specific survival between patients with and without sarcopenia/myosteatosis. We also performed Cox proportional regression analyses to identify the predictors of overall survival and cancer-specific survival. RESULTS: The median patient age was 74 years, and 20 patients (16%) were female. Thirty-eight patients (31%) died from bladder cancer and 13 (11%) died from other causes. The patients with sarcopenia (n = 48, 39%) and those with myosteatosis (n = 101, 82%) had significantly lower overall survival and cancer-specific survival rates than those without sarcopenia and those without myosteatosis, respectively. In multivariable analysis, in addition to the number of pathological risk factors, both sarcopenia (P < 0.01) and myosteatosis (P = 0.04) were independent significant predictors of poor cancer-specific survival. CONCLUSIONS: In our experience, sarcopenia and myosteatosis are independent predictors of poor cancer-specific survival in patients undergoing radical cystectomy for bladder cancer. Sarcopenia is also associated with poor overall survival.

Identification of antigenic peptides from novel renal cancer stem-like cell antigen, DNAJB8.

OBJECTIVES: To identify antigenic peptides of cancer stem-like cells (CSCs) antigen, DNAJB8, and establish a mouse CSCs-targeting immunotherapy model. MATERIALS AND METHODS: To induce DNAJB8-specific immune reaction, we stimulated human CD8+ lymphocytes with antigen-presenting cells pulsed with a cocktail of three candidate HLA-A*24:02 restricted peptides and assessed peptide specific human cytotoxic T lymphocytes (CTLs) induction. One of the antigenic peptides showed identical amino acid sequence as corresponding mouse DNAJB8. We evaluated CTL induction with the peptide immunization in mouse model. RESULTS: We confirmed peptide-specific interferon-γ secretions and cytotoxic activities of induced human CTLs. In vivo immunization with the peptide to mice, peptide-specific CTL response could be observed in mouse CD8+ T cells. Furthermore, immunization with the peptide showed significant anti-tumor effects compared with negative controls. CONCLUSION: DNAJB8-derived peptide is a novel candidate for CSCs-targeting immunotherapy, and mouse models can be used to evaluate CSCs-targeting immunotherapy.

Upper urinary tract stone disease in patients with poor performance status: active stone removal or conservative management?

BACKGROUND: It remains controversial as to whether active stone removal should be performed in patients with poor performance status because of their short life expectancy and perioperative risks. Our objectives were to evaluate treatment outcomes of active stone removal in patients with poor performance status and to compare life prognosis with those managed conservatively. METHODS: We retrospectively reviewed 74 patients with Eastern Cooperative Oncology Group performance status 3 or 4 treated for upper urinary tract calculi at our four hospitals between January 2009 and March 2016. Patients were classified into either surgical treatment group or conservative management group based on the presence of active stone removal. Stone-free rate and perioperative complications in surgical treatment group were reviewed. In addition, we compared overall survival and stone-specific survival between the two groups. Cox proportional hazards analysis was performed to investigate predictors of overall survival and stone-specific survival. RESULTS: Fifty-two patients (70.3%) underwent active stone removal (surgical treatment group) by extracorporeal shock wave lithotripsy (n = 6), ureteroscopy (n = 39), percutaneous nephrolithotomy (n = 6) or nephrectomy (n = 1). The overall stone-free rate was 78.8% and perioperative complication was observed in nine patients (17.3%). Conservative treatment was undergone by 22 patients (29.7%) (conservative management group). Two-year overall survival rates in surgical treatment and conservative management groups were 88.0% and 38.4%, respectively (p < 0.01) and two-year stone-specific survival rates in the two groups were 100.0% and 61.3%, respectively (p < 0.01). On multivariate analysis, stone removal was not significant, but was considered a possible favorable predictor for overall survival (p = 0.07). Moreover, stone removal was the only independent predictor of stone-specific survival (p < 0.01). CONCLUSIONS: Active stone removal for patients with poor performance status could be performed safely and effectively. Compared to conservative management, surgical stone treatment achieved longer overall survival and stone-specific survival.

[Two Cases of Spontaneous Rupture of the Urinary Bladder Associated with Radiation Cystitis, Repaired with Omentum Covering].

We experienced two cases of spontaneous rupture of the urinary bladder associated with radiation cystitis. Case 1 and Case 2 were a 45-year-old female and a 71-year-old female, respectively. Both of them were admitted to our hospital with complaints of high grade fever and severe lower abdominal pain. They had a past history of total hysterectomy followed by radiationtherapy more than10 years ago. The cystography and the subsequent computed tomography revealed spontaneous rupture of the urinary bladder. We performed the operationto repair the perforationsite with omentum covering. Case 1 had a good postoperative course with intermittent self-catheterization after removal of urethral catheter. However, she died of cerebral hemorrhage during hospitalization. Although case 2 needed an indwelling urethral catheter due to the difficulty of intermittent self-catheterization, she had no recurrence of rupture for six months after the operation. Inthis way, total hysterectomy followed by radiationtherapy seems to be a risk factor for the spontaneous rupture of the urinary bladder. When we see a patient with acute abdomen, who has a history of hysterectomy followed by radiation, rupture of the urinary bladder can be a differential diagnosis.

Area of hydronephrosis is a useful predictive factor of impacted ureteral stones.

Ureteroscopic lithotripsy for impacted stones is challenging, but it is important to predict impacted stones preoperatively. Hydronephrosis, which is evaluated by a grading system, is often apparent in impacted stones. However, the currently used grading system is a qualitative evaluation. We, therefore, focused on a quantitative evaluation: the area of hydronephrosis. The aim of this study was to investigate whether the area of hydronephrosis could predict impacted stones more accurately than Society for Fetal Urology grade. We retrospectively identified 160 patients who underwent ureteroscopic lithotripsy for ureteral stones at our hospital between January 2014 and April 2022. Impacted stones were defined as stones fixed to the ureteral wall that could not be moved by means of ureteroscopic manipulation or water pressure. Of the 160 patients, 54 (33.8%) had impacted stones. Comparing patient characteristics, there were significant differences in stone size, ureteral wall thickness, Society for Fetal Urology grade, renal pelvic width and area of hydronephrosis (all P < 0.01). Receiver operating characteristic analysis showed that area of hydronephrosis was the more significant predictive value (area under the curve 0.781) compared with Society for Fetal Urology grade (area under the curve 0.676, P < 0.01). Multivariate analysis revealed that significant independent predictive factors of impacted stones were thicker ureteral wall thickness and larger area of hydronephrosis (both P < 0.01). The area of hydronephrosis and ureteral wall thickness were significant predictors of impacted stones in patients undergoing ureteroscopic lithotripsy for ureteral stones. These factors may be useful for selecting the treatment and preoperative settings.

hinotoriTM vs. da Vinci®: propensity score-matched analysis of surgical outcomes of robot-assisted radical prostatectomy.

hinotori™ is a recently developed surgical robot system. The present study aims to compare intraoperative and postoperative outcomes of robot-assisted radical prostatectomy (RARP) by the hinotori™ system compared with those of the longer-established da Vinci® system. This study includes 100 consecutive patients who underwent RARP by da Vinci® and 60 patients who underwent RARP by hinotori™. To minimize imbalances of patient demographics between the two groups, 1:1 propensity score-matching was performed, and 43 patients each were assigned to the da Vinci® and hinotori™ groups after matching. In the propensity score-matched cohort, we could not find significant differences in patient demographics between the two groups. Surgical outcomes, operative time, and console time in the hinotori™ group were significantly longer than those in the da Vinci® group. Meanwhile, we could not find significant differences in other outcomes between the two groups, such as estimated blood loss, intraoperative complications, major postoperative complications (Clavien-Dindo grade 3 or 4) or length of hospital stay after surgery. The rate of positive cancer margin in the hinotori™ group was higher than that in the da Vinci® group, but significant difference could not be found between the two groups. Moreover, we could not find significant differences in urinary continence rates after surgery between the da Vinci® and hinotori™ groups. Our results suggest that the hinotori™ surgical robot system could provide comparable surgical outcomes to that of the da Vinci® system for patients undergoing RARP.

Efficacy of Bisphosphonate for Urolithiasis Complicated by Osteogenesis Imperfecta.

A 44-year-old man with osteogenesis imperfecta presented with left renal colic. Non-contrast computed tomography revealed a stone (10×9 mm) in the left upper ureter. Ureteroscopic lithotripsy was performed twice and stone-free status was achieved. An analysis of the stone revealed a mixed composition including calcium oxalate and calcium phosphate. Postoperatively, we administered bisphosphonates to prevent recurrence of urolithiasis, as 24-hour urine collection revealed marked hypercalciuria. Eighteen months after surgery, the urinary calcium levels had normalized, and there was no recurrence of urolithiasis. Osteogenesis imperfecta can be complicated by urolithiasis, but bisphosphonates may be useful in preventing recurrence of this disease.

Prognostic Impact of Lymphatic Invasion in Patients with High-Risk Prostate Cancer after Robot-Assisted Radical Prostatectomy and Extended Lymph Node Dissection: A Single-Institution Prospective Cohort Study.

The prognostic impact of lymphatic invasion in patients with high-risk prostate cancer (PC) remains unclear. The aim of our single-institution prospective cohort study was to examine the impact of lymphatic invasion on biochemical recurrence (BCR) in patients with high-risk PC according to National Comprehensive Cancer Network (NCCN) criteria who underwent robot-assisted radical prostatectomy (RARP) and extended lymph node dissection (eLND). A total of 183 patients were included who underwent RARP and eLND for NCCN high-risk PC between June 2014 and August 2019. Lymphatic invasion in resected specimens was observed in 47 patients (26%), whereas lymph node metastasis was observed in 17 patients (9%). During follow-up, BCR was observed in 48 patients (26%). The BCR rate in patients with lymphatic invasion was significantly higher than that in patients without lymphatic invasion (p < 0.01). According to multivariable Cox proportional hazards regression analyses, lymphatic invasion was a significant independent predictor of BCR in the overall patient group and was independently associated with BCR, even in patients without lymph node metastasis. In conclusion, evaluation of lymphatic invasion could be useful in predicting BCR in patients undergoing RARP and eLND for high-risk PC.

Disseminated carcinomatosis of the bone marrow caused by prostate cancer diagnosed with only bone marrow biopsy.

INTRODUCTION: Disseminated carcinomatosis of the bone marrow caused by prostate cancer is a rare condition with poor prognosis. Diagnosis has mostly been by primary prostate biopsy. CASE PRESENTATION: A 60-year-old man had malaise, low platelet count (9000/µL), and high prostate-specific antigen (1382 ng/mL). Bone marrow biopsy showed strongly positive immunostaining NKX3.1, leading to diagnosis of prostate cancer bone marrow metastasis, cT3aN1M1b. Definitive diagnosis by prostate biopsy was difficult because of the sparsity of atypical glands. He had progression to castration-resistant prostate cancer after 3 months of hormonal therapy, and received 27 courses of docetaxel and six courses of cabazitaxel as chemotherapy, but finally died of respiratory failure 33 months after the start of treatment. CONCLUSION: Aggressive biopsy of the metastatic sites should be considered if a prostate biopsy at the primary site cannot be diagnosed definitively.

Reduction of toxicity in brachytherapy using a new technique.

PURPOSE: The purpose of the study was to elucidate the usefulness of a dose evaluation method for reducing late genitourinary (GU) toxicity in high-dose-rate brachytherapy (HDR-BT) of prostate cancer. METHODS AND MATERIALS: GU toxicity was scored in accordance with the Common Terminology Criteria for Adverse Events version 4.0. The prostatic urethra was divided into three segments (base = B, midgland = M, apex = A), which were subclassified into seven subgroups (B, M, A, BM, BA, MA, BMA) using a D10% color map of the urethra. Significance testing was conducted on urethral D0.1% and D10% among the seven subgroups. Grade < 2 GU toxicity was also implemented. RESULTS: Data of 174 patients with localized prostate cancer treated with HDR-BT combined with external beam radiotherapy between November 2011 and July 2014 were analyzed retrospectively. Median age was 74 (53-84) years, and median followup period was 44 (6-69) months. The number of Grade < 2 and Grade ≥ 2 toxicity was significantly different in the M subgroup than in the other subgroups (p < 0.05), suggesting increased radioresistance in the midgland urethra. CONCLUSIONS: A high-dose-area evaluation method using a urethral D10% color map may be helpful in reducing late GU toxicity in HDR-BT for prostate cancer.

[GIANT CELL CARCINOMA OF THE RENAL PELVIS AND URETER WITH GIANT HYDRONEPHROSIS; A CASE REPORT].

A 78-year-old woman presented with macroscopic hematuria. We diagnosed giant hydronephrosis with a left ureteral stone and multiple renal pelvic carcinoma cT3N0M0 tumors.Open nephroureterectomy proceeded via a peritoneal approach, and 8,600 mL of urine were collected from the renal pelvis. The pelvic carcinoma was histologically confirmed as a rare giant cell variant with high malignant potential. The same variant was found in the upper ureter where a 15-mm stone had lodged. We considered that this was due to rapid progression of the renal pelvic giant cell carcinoma and hydronephrosis during the month before surgery.Multiple lung and bone metastases occurred after three courses of gemcitabine/cisplatin combination chemotherapy as postoperative adjuvant therapy. Therefore, radiotherapy for bone metastasis and gemcitabine/paclitaxel combination chemotherapy were performed concurrently.

Transplantation of Horseshoe Kidney from Living, Genetically Unrelated Donor.

We report a case of renal transplantation using a horseshoe kidney from a living, genetically unrelated donor. The recipient was a 60-year-old man with diabetic nephropathy, and the donor was the 63-year-old wife of the recipient with a horseshoe kidney free of complications. Computed tomography showed two renal arteries and one renal vein on the left side, and the isthmus was perfused by several accessory arteries and veins. To demarcate the boundary of the isthmus, the left renal artery was ligated and cannulated for in situ perfusion. Furthermore, the isthmus was clamped, and the boundary of the isthmus was confirmed. The kidney was divided at the left margin of the perfused boundary. The cut ends of the isthmus were closed by sutures. The left kidney was transplanted into the right iliac fossa of the recipient. Asymptomatic fluid collection occurred on the cut surface at the isthmus of the donor, and this fluid decreased in due course. On the other hand, the recipient experienced no surgical complication or rejection, while maintaining serum creatinine levels of 2.00-2.20 mg/dL over a 22-month follow-up period. Horseshoe kidneys may be used for transplantation in selected cases after a detailed preoperative evaluation.