Focal brachytherapy for localized prostate cancer: 5.7-year clinical outcomes and a pair-matched study with radical prostatectomy.

OBJECTIVES: To report experience with focal brachytherapy (FB) and compare its clinical outcomes with those of radical prostatectomy (RP) in localized prostate cancer. METHODS: Fifty-one patients with low- to intermediate-risk prostate cancer underwent low-dose-rate FB. Survival rates free from biochemical failure (BF), additional treatment (AT) including re-FB, and whole-gland or systemic salvage therapy (ST) were calculated and oncological risk factors were investigated. Patient-reported outcomes on genitourinary function were also assessed. Using propensity scoring, 51 pair-matched RP patients were selected. Oncological control, urinary continence, and ejaculation status after FB and RP were compared. RESULTS: During a median 5.7-year follow-up, BF, AT, and ST occurred in 12 (24%), 10 (20%), and 4 FB patients (8%), respectively. 6 of 10 AT patients were managed with re-FB alone. In the RP cohort, 3 patients (6%) underwent ST. 5-year BF-free survival rate after FB was 79%. Compared to 5-year ST-free survival rate of 94% after RP, ST-free and AT-free survival rates after FB were 93% (P = 0.813) and 87% (P = 0.049), respectively. Multivariate analyses of FB-treated patients showed that time to PSA nadir was negatively associated with BF and AT (hazard ratio 0.84 and 0.83, respectively, P <0.001 for each). The difference in oncological outcomes between low- and intermediate-risk categories was not significant. At 2 years after FB and RP, pad-free continence rates were 100% and 81%, respectively (P = 0.001). Ejaculation was preserved in 67% and 0% of patients who had been capable of ejaculation at baseline, respectively (P <0.001). CONCLUSION: In low- to intermediate-risk prostate cancer, FB-treated patients achieved superior genitourinary function compared to pair-matched RP patients. The need for ST was not substantially different between the 2 treatment cohorts. Over half of patients requiring AT could be managed by re-focal treatment rather than whole-gland ST. Early PSA nadir may predict poor oncological control after FB.

Nonuse of antimicrobial prophylaxis in clean surgeries for adrenal and renal tumors: Results of the risk-based strategy in 1362 consecutive patients.

OBJECTIVES: To evaluate the incidence of perioperative infections without antimicrobial prophylaxis in patients undergoing clean surgeries for adrenal and renal tumors. METHODS: We prospectively enrolled 1362 consecutive patients who underwent minimally invasive adrenalectomy (n = 303), radical nephrectomy (n = 499), and partial nephrectomy (n = 560) using the gasless laparoendoscopic single-port surgery technique between 2005 and 2019. In 1059 patients, antimicrobial prophylaxis was not administered. The remaining 303 patients were considered at high risk for infection and received single-dose antimicrobial prophylaxis. The endpoint was the incidence of perioperative infections within 1 month from the surgery date. Perioperative infections were classified into surgical site infections, urinary tract infections, and remote infections. RESULTS: Seventy-four patients whose collecting systems were opened during partial nephrectomy were excluded, and the remaining 1013 patients with nonuse of antimicrobial prophylaxis and 275 patients with single-dose antimicrobial prophylaxis were retrospectively analyzed. The incidence of superficial surgical site infections, deep/organ-space surgical site infections, urinary tract infections, and remote infections was 1.6%, 0.7%, 2.8%, and 1.3%, respectively, in patients with nonuse of antimicrobial prophylaxis and 0.4%, 1.8%, 1.5%, and 1.5%, respectively, in patients with single-dose antimicrobial prophylaxis. All patients who developed perioperative infections were successfully treated. No clinical or surgical variables were significantly associated with the incidence of surgical site infections. One limitation of the present study was its nonrandomized and noncontrolled design. CONCLUSIONS: In minimally invasive clean surgeries for adrenal and renal tumors, antimicrobial prophylaxis is not necessary when individual risk of infection is considered low.

Medium-term oncological and functional outcomes of hemi-gland brachytherapy using iodine-125 seeds for intermediate-risk unilateral prostate cancer.

PURPOSE: To examine medium-term outcomes of hemi-gland low-dose-rate brachytherapy as a primary treatment for intermediate-risk prostate cancer. METHODS: We recruited intermediate-risk unilateral prostate cancer patients for a prospective trial of hemi-gland brachytherapy. Twenty-four patients underwent hemi-gland iodine-125 seed implantation with a prescribed dose of 160 Gy. Serum prostate-specific antigen (PSA) was measured regularly and follow-up biopsy was scheduled after 2-3 years of treatment. When clinically needed afterward, for-cause biopsy was performed to confirm pathology. Treatment failure (TF)-free survival, which was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality, was assessed, as was biochemical failure (BF)-free survival. Urinary and sexual functions were also evaluated. RESULTS: Median follow-up duration was 61 months. Twenty-two patients (92%) exhibited a declining trend or decreased value of PSA for 12 months or longer after the treatment. Follow-up biopsy in the initial triennium and for-cause biopsy in the subsequent triennium were performed in 16 and four patients, respectively, and cancer was found from the treated lobe in one patient (4% of the cohort) and significant cancer was found from untreated lobes in four patients (17%) in total. Secondary treatments were performed in six patients successfully. Five-year freedom from BF, TF, and metastasis was 71%, 90%, and 100%, respectively. The International Prostate Symptom Score significantly deteriorated at 3 months and reversed itself afterward. The International Index of Erectile Function 5 had no significant decrease. CONCLUSIONS: Hemi-gland low-dose-rate brachytherapy provides favorable medium-term oncological outcomes with genito-urinary functional preservation for men with intermediate-risk unilateral prostate cancer.

Outcomes of gasless laparoendoscopic single-port partial nephrectomy in 356 consecutive patients: Feasibility of a clampless and sutureless technique.

OBJECTIVES: To investigate the outcomes and feasibilities of gasless laparoendoscopic single-port clampless sutureless partial nephrectomy. METHODS: We reviewed 356 consecutive patients with primary unilateral non-metastatic renal masses who underwent gasless laparoendoscopic single-port partial nephrectomy (2011-2018), which was performed retroperitoneally using a three-dimensional flexible endoscope, without vascular clamping or renorrhaphy in principle. RESULTS: The median tumor size was 2.5 cm, and 213 (60%), 105 (29%), and 38 (11%) patients had peripheral, central, and hilar tumors, respectively. Clampless and sutureless partial nephrectomy was accomplished in 337 patients (95%), while eight (2%) and 16 (4%) patients required vascular clamping and renorrhaphy, respectively. The median operative time and blood loss were 220 min and 266 mL, respectively; eight patients (2%) received blood transfusion. Clavien-Dindo grade 3a complications occurred in 27 patients (8%); all these patients had urinary leakage treated with ureteral stent placement, one of whom also developed a postoperative pseudoaneurysm. Among 324 patients diagnosed with renal cell carcinoma, six (2%) had positive surgical margins, and one (0.3%) and seven (2%) developed metastatic and local recurrences, respectively. During a median follow-up of 54 months, no patient died from kidney cancer. The median percent decrease in estimated glomerular filtration rate at 3 months after surgery was 5.7%. No patient experienced postoperative acute renal failure, while one patient with preexisting renal impairment started dialysis at 70 months after surgery. CONCLUSIONS: Clampless and sutureless partial nephrectomy can be safely accomplished in most patients undergoing gasless laparoendoscopic single-port surgery, yielding favorable oncological and functional outcomes.

Clinical Outcomes of Patients With Histologic Variants of Urothelial Carcinoma Treated With Selective Tetramodal Bladder-preservation Therapy Incorporating Consolidative Partial Cystectomy.

BACKGROUND: Tetramodal bladder-preservation therapy includes maximal transurethral resection (TUR), induction chemoradiotherapy (CRT), and consolidative partial cystectomy with pelvic lymph node dissection. Tetramodal bladder-preservation therapy theoretically provides surgical consolidation of chemotherapy- and radioresistant cells. However, its efficacy in providing optimal cancer control for patients with histologic variants of urothelial carcinoma (VUCs) is currently unknown. We compared the oncologic outcomes between patients with muscle-invasive bladder cancer (MIBC) and pure urothelial carcinoma (PUC) and those with MIBC and VUCs after selective tetramodal bladder-preservation therapy. PATIENTS AND METHODS: We prospectively enrolled 154 patients. After maximal TUR and induction CRT, patients with a clinical complete response were offered consolidative partial cystectomy to achieve bladder preservation, with radical cystectomy recommended for the others. The VUCs identified in the maximal TUR samples were categorized according to the 2004 World Health Organization classification. The primary endpoint was cancer-specific survival. The secondary endpoints included the clinical and pathologic response rates to induction CRT and MIBC recurrence-free survival. RESULTS: A VUC was identified in 37 patients (24%). The most frequent variants involved glandular differentiation (n = 13), squamous differentiation (n = 11), and micropapillary (n = 8). No difference was found in the clinical complete response rate to CRT between PUC and VUCs (P = .81). On an intention-to-treat basis, the 5-year cancer-specific survival rates for those with PUC (n = 116) and VUC (n = 37) were 82% and 81% (P = .86), respectively. CONCLUSION: Tetramodal bladder-preservation therapy incorporating partial cystectomy could provide favorable locoregional control and survival for patients with VUC. Thus, patients with MIBC need not be excluded from the bladder-preservation approach because of the presence of a variant histologic type.

Impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma.

OBJECTIVES: To evaluate the impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma. METHODS: The present study assessed 51 metastatic urothelial carcinoma patients undergoing fluorodeoxyglucose positron emission tomography/computed tomography before first-line systemic chemotherapy. Fluorodeoxyglucose uptake in metastases was evaluated using the maximum standardized uptake value, which was measured for all eligible lesions, and the highest value among the maximum standardized uptake value measurements in each case was defined as the highest maximum standardized uptake value. The associations between the highest maximum standardized uptake value and objective response rate to chemotherapy, progression-free survival or cancer-specific survival were analyzed. For cancer-specific survival, the C-index was compared between multivariate models that incorporated predictors in the Bajorin model including the Karnofsky performance status and the presence of visceral metastasis, and the Apolo model additionally including hemoglobin and albumin levels, with/without the highest maximum standardized uptake value. RESULTS: The median age was 69 years. The Karnofsky performance status was ≥80% for all patients. Visceral metastasis was observed in 12 patients (24%). The objective response rate, median progression-free survival and median cancer-specific survival were 61%, 9 and 26 months in the entire cohort, respectively. The higher highest maximum standardized uptake value was significantly associated with a lower objective response rate, shorter progression-free survival and shorter cancer-specific survival (P = 0.01, <0.001 and 0.004, respectively). On multivariate analyses, the highest maximum standardized uptake value was an independent predictor for all end-points. In the multivariate models for cancer-specific survival, the C-index improved from 0.559 to 0.601 and from 0.604 to 0.652 by adding the highest maximum standardized uptake value to the parameter set of the Bajorin model and Apolo model, respectively. CONCLUSIONS: Higher fluorodeoxyglucose uptake in metastases was significantly and independently associated with poor chemosensitivity and worse survival outcomes. Fluorodeoxyglucose positron emission tomography/computed tomography might aid in patient counseling and treatment decisions for metastatic urothelial carcinoma patients.

Usefulness of the inchworm sign on DWI for predicting pT1 bladder cancer progression.

OBJECTIVE: To evaluate the significance of the presence or absence of an "inchworm sign" on DWI for the recurrence and progression of T1 bladder cancer. MATERIALS AND METHODS: We retrospectively analyzed 91 patients with pT1 urothelial carcinoma who underwent DWI prior to transurethral resection between 2007 and 2016. DWI of the dominant tumors was scrutinized for inchworm signs at b = 1000 s/mm2. The association of the presence of the inchworm sign with progression and recurrence was analyzed; progression was defined as recurrence to stage T2 or higher and/or N+, and/or M1. RESULTS: An inchworm sign was seen in 65 cases (71%), while it was absent in 26 cases. Among the 65, 25 (38%) had confirmed tumor recurrence, while in the remaining 26, 14 (54%) had confirmed recurrence (median time post TURB = 7.9 and 10.1 months for each). At the time of recurrence, the tumor had progressed in one (2%) inchworm-sign-positive and seven (27%) inchworm-sign-negative cases. The progression rate of inchworm-sign-negative cases was significantly higher than that of inchworm-sign-positive cases (hazard ratio = 17.2, p = 0.0017), whereas there was no significant difference in the recurrence rate between two groups. The absence of an inchworm sign and histological grade 3 were independent risk factors for progression (p < 0.001 and 0.010, respectively). CONCLUSIONS: The absence of an inchworm sign on DWI was a significant prognostic factor for progression of T1 bladder cancer. Morphological evaluation of DWI signals may therefore be a useful adjunct to preoperative assessment of biological aggressiveness. KEY POINTS: • An inchworm sign is a simple diagnostic criterion that characterizes only the shape of the tumor signal on DWI, and potentially serves as an imaging biomarker to predict clinical aggressiveness. • The absence of an inchworm sign on DWI is a significant indicator of progression of T1 bladder cancer.

Selective tetramodal bladder-preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle-invasive bladder cancer: oncological and functional outcomes of 107 patients.

OBJECTIVES: To evaluate the oncological and functional outcomes associated with selective tetramodal bladder-sparing therapy, comprising maximal transurethral resection of bladder tumour (TURBT), induction chemoradiotherapy (CRT), and consolidative partial cystectomy (PC) with pelvic lymph node dissection (PLND). MATERIALS AND METHODS: In the present study, 154 patients with non-metastatic muscle-invasive bladder cancer (MIBC), prospectively enrolled in the tetramodal bladder-preservation protocol, were analysed. After TURBT and induction CRT, patients showing complete remission were offered consolidative PC with PLND for the achievement of bladder preservation. Pathological response to induction CRT was evaluated using PC specimens. Oncological and functional outcomes after bladder preservation were evaluated using the following endpoints: MIBC-recurrence-free survival (RFS); cancer-specific survival (CSS); overall survival (OS), and cross-sectional assessments of preserved bladder function and quality of life (QoL) including uroflowmetry, bladder diary, International Prostate Symptom Score, Overactive Bladder Symptom Score and the 36-item Short-Form Health Survey (SF-36) score. RESULTS: The median follow-up period was 48 months. Complete MIBC remission was achieved in 121 patients (79%) after CRT, and 107 patients (69%) completed the tetramodal bladder-preservation protocol comprising consolidative PC with PLND. Pathological examination in these 107 patients revealed residual invasive cancer (≥pT1) that was surgically removed in 11 patients (10%) and lymph node metastases in two patients (2%). The 5-year MIBC-RFS, CSS and OS rates in the 107 patients who completed the protocol were 97%, 93% and 91%, respectively. As for preserved bladder function, the median maximum voided volume, post-void residual urine volume, and nighttime frequency were 350 mL, 25 mL, and two voids, respectively. In the SF-36, patients had favourable scores, equivalent to the age-matched references in all the QoL scales. CONCLUSION: Selective tetramodal bladder-preservation therapy, incorporating consolidative PC with PLND, yielded favourable oncological and functional outcomes in patients with MIBC. Consolidative PC may have contributed to the low rate of MIBC recurrence in patients treated according to this protocol.

Incidence and predictive factors of hypoglycemia after pheochromocytoma resection.

OBJECTIVES: To determine the incidence and preoperative risk factors of post-excisional hypoglycemia in patients undergoing pheochromocytoma resection. METHODS: Patients who underwent surgical resection of pheochromocytoma at a single institution were retrospectively enrolled in the present study. The primary end-point was the development of post-excisional hypoglycemia; that is, a serum glucose level <70 mg/dL. The serum levels of immunoreactive insulin and glucose levels during the preoperative oral glucose-tolerance test and surgery were analyzed to elucidate the mechanism of hypoglycemia. RESULTS: A total of 49 patients underwent surgical resection of pheochromocytoma, of which 21 patients (43%) developed post-excisional hypoglycemia. The incidence of hypoglycemia was not statistically different between patients with adrenal tumors and those with extra-adrenal tumors (18/41 [44%] vs 3/8 [38%], respectively, P = 0.73). There was no difference in the immunoreactive insulin/glucose ratio during the preoperative oral glucose-tolerance test between patients with and those without post-excisional hypoglycemia. The intraoperative immunoreactive insulin/glucose ratio was significantly higher in patients with hypoglycemia than in those without hypoglycemia. A higher 24-h urinary epinephrine level, but not norepinephrine level, was a predictive factor for post-excisional hypoglycemia. CONCLUSIONS: Post-excisional hypoglycemia is a frequent complication of pheochromocytoma resection, irrespective of the tumor location, and might be common in patients with epinephrine-predominant tumors. All patients undergoing resection of adrenal and extra-adrenal pheochromocytoma require intensive monitoring of serum glucose levels during and after surgery.

Acute kidney injury and intermediate-term renal function after clampless partial nephrectomy.

OBJECTIVES: To evaluate the incidence and predictors of acute kidney injury after clampless partial nephrectomy, and its impact on intermediate-term renal function. METHODS: The incidence and severity of acute kidney injury were assessed for 262 patients undergoing clampless partial nephrectomy between 2010 and 2015. The association between perioperative covariates and acute kidney injury was evaluated using multivariate logistic regression analysis. An annual change in estimated glomerular filtration rate from 1 year after surgery was calculated according to the presence or absence of acute kidney injury. An impact of acute kidney injury on postoperative renal impairment, defined as a ≥25% estimated glomerular filtration rate decrease, was evaluated. RESULTS: Overall, 21 (8.0%) patients experienced grade 1 acute kidney injury after clampless partial nephrectomy, and grade ≥2 acute kidney injury was not observed. High tumor complexity was the only independent predictor of acute kidney injury. Estimated glomerular filtration rate in patients with acute kidney injury improved within 1 year, and annual estimated glomerular filtration rate changes were similar among patients with or without acute kidney injury. Ultimately, 13 (5.0%) patients showed postoperative renal impairment during the median follow-up period of 37 months. Advanced age and diabetes mellitus were independent risk factors for renal impairment, but acute kidney injury was not. CONCLUSIONS: The incidence and severity of acute kidney injury after clampless partial nephrectomy are low. Low-grade acute kidney injury after clampless partial nephrectomy does not seem to affect intermediate-term renal function.

Predictive ability of renal cortex enhancement in dynamic computed tomography for residual renal function after nephroureterectomy: Comparison with 99m Tc-diethylenetriaminopentacetic acid renography and validation study.

OBJECTIVE: To estimate postoperative residual renal function after radical nephroureterectomy for upper tract urothelial carcinoma using the preoperative dynamic computed tomography renal cortex enhancement ratio in comparison with the split kidney glomerular filtration rate measured by 99m Tc-diethylenetriaminopentacetic acid renography. METHODS: A total of 47 patients who received radical nephroureterectomy and underwent both preoperative dynamic computed tomography and renography were the model-development cohort; and 109 patients who underwent dynamic computed tomography alone were the validation cohort. Postoperative renal function of the unremoved kidney was estimated using the following formulas: preoperative estimated glomerular filtration rate × the percentage of total renal cortex radiodensity for the intact kidney in Hounsfield units obtained from corticomedullary phase images in the computed tomography-based model, or the percentage of the total glomerular filtration rate measured by renography in the nuclear model. The correlation between observed and estimated postoperative renal function was determined. The computed tomography-based prediction model derived from linear regression analysis was validated externally. RESULTS: The correlation of computed tomography-based split renal function with the observed postoperative estimated glomerular filtration rate (r = 0.80) was equivalent to that of nuclear split renal function (r = 0.78). In the validation cohort, the computed tomography-based prediction model showed an equivalently strong correlation (r = 0.78). CONCLUSIONS: The present study showed that the percentage of total renal cortex radiodensity for the intact kidney is a useful tool for predicting unremoved kidney function in upper tract urothelial carcinoma patients, thereby allowing appropriate patient selection for perioperative cisplatin-based combination chemotherapy.

[Availability of Early Balloon Kyphoplasty for the Treatment of Osteoporotic Compression Fractures].

INTRODUCTION: Japan has many patients with osteoporosis; however, only about one-fifth of these patients receive treatment. Although some treatment guidelines exist for osteoporosis, the number of newly diagnosed patients with osteoporotic compression fractures is increasing and protocols for treatment of osteoporotic compression fractures vary from one hospital to another. This study aims to investigate the availability of early balloon kyphoplasty(BKP)in relation to our treatment strategy for osteoporotic compression fractures. METHODS: In our hospital, patients diagnosed with osteoporotic compression fractures were treated conservatively with a corset and rehabilitation. In cases where pain was prolonged and computed tomography(CT)imaging revealed formation of a cavity, we performed BKP. We divided the patients admitted between April 2016 and December 2016 with osteoporotic compression fractures into 2 groups, based on whether they received conservative treatment or BKP. We assessed the patients' age, fracture site, CT and MRI findings, bone density, Numerical Rating Scale(NRS), duration of hospital stay, and outcomes. RESULTS: In the BKP group, the number of Th12 and L1 compression fractures was higher than fractures to other vertebral bodies. No difference was observed in bone density, improvement of NRS, and outcomes between groups. CT cavity signs were more frequently observed in the BKP group than in the conservative group. CONCLUSIONS: This study establishes a correlation between the appearance of CT cavity sign and prolonged pain, which increases the likelihood of a patient undergoing BKP. The CT cavity sign and prolonged pain could be indicators of pre-stage pseudoarthrosis. BKP performed in the early stages of a fracture is safe and does not result in complications. However, BKP should be performed according to appropriate indications, including delayed neurological deficit, pain, and reduced bone adhesion.

Adherent Perinephric Fat in Asian Patients: Predictors and Impact on Perioperative Outcomes of Partial Nephrectomy.

INTRODUCTION: This study is aimed at evaluating the incidence and predictors of adherent perinephric fat (APF) in Asians during partial nephrectomy (PN), and determining the impact of APF on perioperative outcomes. MATERIALS AND METHODS: A total of 231 Asian patients with renal tumors underwent PN, and their Mayo adhesive probability (MAP) score was calculated. APF was intraoperatively determined, and the perioperative data were compared according to the presence of APF. The predictors of APF were examined using logistic regression analyses. RESULTS: APF was observed in 40 (17%) patients. In multivariate analysis, male gender and higher MAP score were the independent predictors of APF. The estimated blood loss was higher in patients with APF, however, the complication rates did not differ between the 2 groups. CONCLUSIONS: The MAP score can predict APF in an Asian population. The presence of APF was associated with greater blood loss; however it did not increase the postoperative complications in PN.

Higher Serum C-reactive Protein Level Represents the Immunosuppressive Tumor Microenvironment in Patients With Clear Cell Renal Cell Carcinoma.

INTRODUCTION: C-reactive protein (CRP), a representative inflammatory marker, could serve as a biomarker in renal cell carcinoma because CRP is an important prognostic factor. However, its detailed mechanism remains unknown. This study showed that higher CRP levels correlated with the tumor immune microenvironment, which leads to a worse prognosis. These findings can help to clarify the underlying mechanisms between the presence of systemic inflammatory reaction and prognosis. The aim of this study is to investigate the association between tumor immune microenvironment and CRP in patients with renal cell carcinoma (RCC) to explore the underlying mechanisms between CRP level and prognosis. PATIENTS AND METHODS: Immunohistochemical measurement of CD4, CD8, CD163 (M2 macrophages), and Foxp3 (Regulatory T [Treg] cells) was performed in patients with clear-cell RCC (n = 111) treated with radical or partial nephrectomy at our institution. The association between immunohistochemical status and preoperative serum CRP level and cancer-specific survival (CSS) was analyzed. RESULTS: Thirty-three patients (30%) had a high CRP level (≥ 5.0 mg/L), and the CSS rate was significantly worse among these patients than among the remaining patients (P < .001). In patients with strong infiltration of CD8+, Foxp3+, or CD163+ cells, CRP levels were significantly higher (P = .041, P = .001, and P = .035, respectively), and CSS was significantly worse compared with patients with weak infiltration (P = .040, P = .026, and P < .001, respectively). In multivariate analysis, strong CD163+ cells infiltration (P = .001) as well as pathologic T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P < .001), and Fuhrman nuclear grade 4 (P = .003) were independent prognostic factors for CSS. CONCLUSIONS: Infiltration of the immunosuppressive cells known as Tregs and M2 macrophages in the tumor microenvironment is associated with higher CRP and poor prognosis in patients with clear-cell RCC. CRP could reflect an immunosuppressive microenvironment.

Impact of Immunohistochemistry-Based Subtypes in Muscle-Invasive Bladder Cancer on Response to Chemoradiation Therapy.

PURPOSE: A bladder-sparing strategy is a useful option for patients with muscle-invasive bladder cancer (MIBC), in which the response to chemoradiation therapy (CRT) is primarily important in achieving favorable oncologic outcomes. Our objective is to evaluate the impact of immunohistochemistry (IHC)-based subtyping in MIBC on prediction of CRT response. METHODS AND MATERIALS: Treatment protocol consisted of induction CRT followed by partial or radical cystectomy as consolidative surgery; 118 eligible patients with nonmetastatic MIBC were retrospectively analyzed. Of these patients, 92 eventually underwent partial or radical cystectomy after CRT. We applied the IHC-based subtyping model developed by Lund University, which classifies patients into urobasal (Uro), genomically unstable (GU), and squamous cell cancer-like (SCCL) subtypes. GU and SCCL cancers are supposed to be highly aggressive and to have worse prognoses than Uro. Correlations of subtypes with CRT response were analyzed clinically in all patients and pathologically in 92 cystectomized patients. The impact of each subtype on cancer-specific mortality (CSM) was also analyzed. RESULTS: Of all patients, 26 (22%), 61 (52%), and 31 (26%) were classified into Uro, GU, and SCCL subtypes, respectively. Clinical complete response (CR) was achieved in 42% of patients overall after CRT, with a significantly higher proportion in GU patients (52%) and SCCL patients (45%) than in Uro patients (15%; P < .001 and P = .01, respectively). On multivariate analysis, the GU/SCCL subtype was a significant predictor of clinical CR, as was absence of hydronephrosis or concomitant carcinoma in situ. Analyses for pathologic CR in the cystectomized patients revealed analogous findings. Five-year CSM of Uro, GU, and SCCL patients was 16%, 23%, and 28% overall, respectively, and 19%, 22%, and 23% in cystectomized patients, respectively, with no significant difference among the subtypes. CR status after CRT was significantly and independently correlated with low CSM in both clinical and pathologic evaluations. CONCLUSIONS: GU and SCCL cancers showed significantly more favorable CRT response than did Uro cancers. IHC-based subtyping may improve clinical decisions about the indication of CRT for MIBC patients.

Effect of Eplerenone on the Glomerular Filtration Rate (GFR) in Primary Aldosteronism: Sequential Changes in the GFR During Preoperative Eplerenone Treatment to Subsequent Adrenalectomy.

Objective Eplerenone (EPL) is a mineralo-corticoid receptor antagonist that is highly selective and has few side effects. This study was conducted to examine whether or not EPL treatment was able to reverse glomerular hyperfiltration, as an indicator of aldosterone renal action, in primary aldosteronism (PA) patients. Methods Changes in the estimated glomerular filtration rate (ΔGFR) were examined in 102 PA patients with EPL treatment. Furthermore, the sequential ΔGFR in 40 patients initially treated with EPL followed by adrenalectomy was examined in order to evaluate the extent of the remaining glomerular hyperfiltration in the patients treated with EPL. Results EPL decreased the GFR at 1 month after treatment. The GFR at baseline was the sole significant predictor for the ΔGFR. Patients initially treated by EPL followed by adrenalectomy showed three different ΔGFR patterns during the treatment, despite having comparable doses of EPL and comparable control of blood pressure and serum potassium levels. The urinary aldosterone excretion was significantly different among these three groups, and the group with no decrease in the GFR after EPL treatment showed greater urinary aldosterone excretion. Glomerular hyperfiltration was completely restored only in 17.5% of our unilateral PA patients after EPL treatment. Conclusion The present study revealed that blockade of aldosterone action by EPL could, at least partially, reverse glomerular hyperfiltration in PA. Whether or not these differential effects on the GFR affect the long-term outcome needs to be investigated, especially in patients with unilateral PA who do not want adrenalectomy and choose the EPL treatment option.

Computer-aided diagnosis of prostate cancer on magnetic resonance imaging using a convolutional neural network algorithm.

OBJECTIVE: To develop a computer-aided diagnosis (CAD) algorithm with a deep learning architecture for detecting prostate cancer on magnetic resonance imaging (MRI) to promote global standardisation and diminish variation in the interpretation of prostate MRI. PATIENTS AND METHODS: We retrospectively reviewed data from 335 patients with a prostate-specific antigen level of <20 ng/mL who underwent MRI and extended systematic prostate biopsy with or without MRI-targeted biopsy. The data were divided into a training data set (n = 301), which was used to develop the CAD algorithm, and two evaluation data sets (n = 34). A deep convolutional neural network (CNN) was trained using MR images labelled as 'cancer' or 'no cancer' confirmed by the above-mentioned biopsy. Using the CAD algorithm that showed the best diagnostic accuracy with the two evaluation data sets, the data set not used for evaluation was analysed, and receiver operating curve analysis was performed. RESULTS: Graphics processing unit computing required 5.5 h to learn to analyse 2 million images. The time required for the CAD algorithm to evaluate a new image was 30 ms/image. The two algorithms showed area under the curve values of 0.645 and 0.636, respectively, in the validation data sets. The number of patients mistakenly diagnosed as having cancer was 16/17 patients and seven of 17 patients in the two validation data sets, respectively. Zero and two oversights were found in the two validation data sets, respectively. CONCLUSION: We developed a CAD system using a CNN algorithm for the fully automated detection of prostate cancer using MRI, which has the potential to provide reproducible interpretation and a greater level of standardisation and consistency.

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.

Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas.

The pathophysiology of aldosterone-producing adenomas (APAs) has been investigated via genetic approaches and the pathogenic significance of a series of somatic mutations, including KCNJ5, has been uncovered. However, how the mutational status of an APA is associated with its molecular characteristics, including its transcriptome and methylome, has not been fully understood. This study was undertaken to explore the molecular characteristics of APAs, specifically focusing on APAs with KCNJ5 mutations as opposed to those without KCNJ5 mutations, by comparing their transcriptome and methylome status. Cortisol-producing adenomas (CPAs) were used as reference. We conducted transcriptome and methylome analyses of 29 APAs with KCNJ5 mutations, 8 APAs without KCNJ5 mutations and 5 CPAs. Genome-wide gene expression and CpG methylation profiles were obtained from RNA and DNA samples extracted from these 42 adrenal tumors. Cluster analysis of the transcriptome and methylome revealed molecular heterogeneity in APAs depending on their mutational status. DNA hypomethylation and gene expression changes in Wnt signaling and inflammatory response pathways were characteristic of APAs with KCNJ5 mutations. Comparisons between transcriptome data from our APAs and that from normal adrenal cortex obtained from the Gene Expression Omnibus suggested similarities between APAs with KCNJ5 mutations and zona glomerulosa. The present study, which is based on transcriptome and methylome analyses, indicates the molecular heterogeneity of APAs depends on their mutational status. Here, we report the unique characteristics of APAs with KCNJ5 mutations.

Early response of C-reactive protein as a predictor of survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

BACKGROUND: Pretreatment C-reactive protein (CRP) has been shown to be an independent prognostic factor for metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). We further evaluated the early response of CRP after the initiation of TKIs. METHODS: A total of 103 patients (80 men and 23 women) were treated with TKIs for mRCC from 2008-2013. Patients were divided into three groups according to their early CRP kinetics-patients whose baseline CRP levels were <10 mg/L (non-elevated), patients whose baseline CRP levels were ≥10 mg/L and had decreased by >20% at 4 weeks after the initiation of TKIs (early CRP responder), and the remaining patients (non-early CRP responder). The endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: The median follow-up period was 21 (interquartile range 10-34) months. The numbers of patients classified as non-elevated, early CRP responder, and non-early CRP responder were 62, 19, and 22, respectively. The 1-year PFS rates of patients in the non-elevated, early CRP responder, and non-early CRP responder groups were 50, 23, and 9.7%, respectively (p < 0.001). The 1-year OS rates of patients in these three groups were 79, 62, and 36%, respectively (p < 0.001). In multivariate analysis, the early CRP kinetics assessment was a significant independent factor for PFS and OS. CONCLUSIONS: Early CRP response at 4 weeks is predictive of survival for patients with mRCC treated with TKI.