Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

Assessment of the accuracy of biparametric MRI/TRUS fusion-guided biopsy for index tumor evaluation using postoperative pathology specimens.

BACKGROUND: Multiparametric MRI (mpMRI) is widely used for the diagnosis, surveillance, and staging of prostate cancer. However, it has several limitations, including higher costs, longer examination times, and the use of gadolinium-based contrast agents. This study aimed to investigate the accuracy of preoperatively assessed index tumors (ITs) using biparametric MRI (bpMRI)/transrectal ultrasound (TRUS) fusion biopsy compared with radical prostatectomy (RP) specimens. METHODS: We included 113 patients diagnosed with prostate cancer through bpMRI/TRUS fusion-guided biopsies of lesions with a Prostate Imaging Reporting and Data System (PI-RADS) category ≥ 3. These patients underwent robot-assisted laparoscopic radical prostatectomy (RARP) at our institution between July 2017 and March 2023. We examined the localization of preoperative and postoperative ITs, the highest Gleason score (GS), and tumor diameter in these patients. RESULTS: The preoperative cT stage matched the postoperative pT stage in 53 cases (47%), while 31 cases (27%) were upstaged, and 29 cases (26%) were downstaged (Weighted Kappa = 0.21). The preoperative and postoperative IT localizations were consistent in 97 cases (86%). The concordance rate between Gleason groups in targeted biopsies and RP specimens was 51%, with an upgrade in 25 cases (23%) and a downgrade in 27 cases (25%) (Weighted Kappa = 0.42). The maximum diameter of the IT and the maximum cancer core length on biopsy were correlated with the RP tumor's maximum diameter (p < 0.001 for both). CONCLUSION: The diagnostic accuracy of bpMRI/TRUS fusion biopsy is comparable to mpMRI, suggesting that it can be a cost-effective and time-saving alternative.

Chronic kidney disease and Charlson comorbidity index predict complications after robot-assisted radical cystectomy: A single-center study in Japan.

OBJECTIVES: To investigate preoperative patient factors that may predict the occurrence of perioperative complications following robot-assisted radical cystectomy at a single center in Japan. METHODS: From 2013 to 2022, 103 patients underwent RARC at our institution. Complications within 90 days after surgery were assessed using the Clavien-Dindo classification. Preoperative characteristics and surgical outcomes were compared between cohorts with and without complications ≥grade 3. Logistic regression analysis was used to identify the risk factors associated with perioperative complications. RESULTS: Overall, 27% of patients (27/103) experienced grade 3 or higher complications. The cohort that developed complications ≥grade 3 exhibited significantly higher Charlson comorbidity index (p = 0.046) and significantly lower estimated glomerular filtration rate (p = 0.048). Charlson comorbidity index ≥2 (p = 0.037) and estimated glomerular filtration rate <53 (p = 0.008) were independent predictors for the occurrence of complications ≥grade 3. The incidence of complications ≥grade 3 was 61.5% in the group possessing both factors, which was significantly higher than those in the groups possessing neither factor nor only one of the two factors. CONCLUSIONS: Our results suggest that the Charlson comorbidity index and preoperative estimated glomerular filtration rate may be predictors of perioperative complications. It is important to evaluate the patient's preoperative characteristics and choose the surgical procedure accordingly.

Sarcopenia is associated with survival in patients with urothelial carcinoma treated with systemic chemotherapy.

BACKGROUND: Sarcopenia impacts perioperative outcomes and prognosis in various carcinomas. We aimed to investigate whether sarcopenia at the time of chemotherapy induction in patients with urothelial carcinoma is associated with prognosis. METHODS: We evaluated patients treated with chemotherapy for urothelial carcinoma between April 2013 and February 2018 at our institution and affiliated centers. Skeletal muscle mass (total psoas muscle, paraspinal muscle, and total skeletal muscle areas) were used to calculate the total psoas muscle index, paraspinal muscle index, and skeletal muscle index. All participants were grouped as per cutoff points set at the median value for each sex. Overall survival was evaluated using Cox regression analysis. RESULTS: Of the 240 patients, 171 were men and 69 were women; mean age during chemotherapy was 71 years (range: 43-88); and 36, 56, and 148 patients were at stages II, III, and IV, respectively. Paraspinal muscle index was most associated with the prognosis; groups with lower paraspinal muscle index were defined as sarcopenic (men: ≤ 20.9 cm2/m2, women: ≤ 16.8 cm2/m2). The overall survival was significantly longer in the non-sarcopenia group including all stages (p = 0.001), and in stage III (p = 0.048) and IV (p = 0.005) patients. There was no significant difference among stage II patients (p = 0.648). After propensity score matching, survival was still significantly longer in the non-sarcopenia group (p = 0.004). CONCLUSIONS: Paraspinal muscle index measurements obtained during chemotherapy induction for urothelial carcinoma were independent prognostic factors. The absence of sarcopenia may lead to long-term survival in patients undergoing chemotherapy for urothelial carcinoma.

Extent of pelvic lymph node dissection improves early oncological outcomes for patients with high-risk prostate cancer without lymph node involvement after robot-assisted radical prostatectomy.

BACKGROUND: We investigated the effect of the extent of pelvic lymph node dissection (LND) on biochemical recurrence (BCR) in patients with prostate cancer (PCa) without lymph node involvement (LNI) treated with robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively analyzed data from 378 patients who underwent RARP with LND at our hospital between October 2010 and June 2019. The BCR-free survival rate was determined using Kaplan-Meier analysis, and Cox regression analysis was used to investigate BCR prognostic factors. The total score calculated from the D'Amico risk classification and the percentage of positive biopsy cores were used for analysis. Patients were classified into 3 BCR risk groups (low risk: 0-3 points, intermediate risk: 4-5 points, and high risk: 6-8 points). RESULTS: Limited LND was performed in 161 patients (42.6%), extended LND in 217 patients (57.4%), and BCR was confirmed in 66 patients (17.5%) after RARP. Both univariate and multivariate analyses showed no significant difference in the association between the extent of LND and BCR. The Kaplan-Meier curve for BCR generated using our risk classification for patients with PCa without LNI showed no significant association between the extent of LND and BCR in the low-risk group (p = 0.790). A significantly improved BCR-free survival was observed in the extended LND group among patients with PCa at intermediate risk or higher (p < 0.05). CONCLUSION: According to our risk classification, BCR may be less likely to occur when extended LND is performed during RARP for patients with localized PCa at intermediate risk or higher.

Incidence and predictive factors of orgasmic dysfunction after robot-assisted radical prostatectomy: A cross-sectional, questionnaire-based study.

OBJECTIVE: We sought to evaluate the incidence and extent of orgasmic dysfunction in patients after robot-assisted radical prostatectomy and to identify factors that could predict patients at risk. METHODS: A single-center, questionnaire-based, cross-sectional study was conducted on patients who underwent robot-assisted radical prostatectomy (n = 523) between October 2010 and November 2019. In addition to six questions about sexual activity, orgasmic function, altered perception of orgasms, dysorgasmia, and climacturia, the International Consultation on Incontinence Questionnaire Short Form was administered. In February 2020, a letter was mailed inviting patients to participate in the survey. The primary outcome measure was the rate of orgasmic dysfunction. Logistic regression analyses were used to identify predictors of orgasmic dysfunction. RESULTS: Overall, 259 questionnaires were used for analysis. Among sexually active patients (n = 145), 33 (22.8%) reported anorgasmia, and 83 (57.2%) reported decreased orgasm intensity. Twenty-two (15.1%) patients reported dysorgasmia; among these patients, the pain was experienced almost always or always in 13.6%, sometimes in 13.6%, and a few times in 72.8% of cases. Climacturia was reported by 44 patients (30.3%). Nerve-sparing procedures decreased the risk of anorgasmia (odds ratio 0.37, 95% confidence interval 0.15-0.88) and urinary incontinence increased the risk of climacturia (odds ratio 3.13, 95% confidence interval 1.20-8.15). CONCLUSIONS: These results indicate that orgasmic dysfunction after robot-assisted radical prostatectomy is relatively common.

Influence of multinerve-sparing, robot-assisted radical prostatectomy on the recovery of erection in Japanese patients.

Purpose: To evaluate in Japanese patients their sexual function after robot-assisted radical prostatectomy (RARP) and to investigate the influence of the multinerve-sparing (NS) grade on their sexual function. Methods: In total, 225 patients were reviewed with localized prostate cancer who underwent RARP at the authors' institution. They underwent RARP >3 months ago, without pre- and posthormone therapy and salvage radiation. Self-administered International Index of Erectile Function (IIEF) questionnaires were used for assessment preoperatively and 1-48 months postoperatively. In all, 129 patients were evaluated with the preoperative IIEF-Question 1 and who achieved a score of ≥2 by being divided into five NS groups. The recovery rates of erection (postoperative IIEF-Question 1 score of ≥2) were calculated by using the Kaplan-Meier analysis. Results: Seventy-four percent of all the patients had not attempted sexual intercourse, but 60% had felt sexual desire at 24 months postoperatively. In those patients with a preoperative erection, the recovery rate of erection was 58% at 24 months after the RARP. Across the five NS groups, as the procedure was more nerve-sparing, the recovery rate of erection became significantly higher. The postoperative effects on erection in the bilateral and unilateral NS groups were significantly superior to those in the other NS groups. Conclusion: In Japanese patients, erection after a RARP is improved with multiNS grade procedures.

Characterization of mild and severe post-radical nephrectomy renal functional deterioration utilizing histopathological evaluation of non-neoplastic nephrectomized renal parenchyma.

BACKGROUND: We investigated factors affecting mild (MRFD) and severe renal functional deterioration (SRFD) after radical nephrectomy with a special focus on the histopathology of nephrectomized non-neoplastic renal parenchyma. METHODS: MRFD was defined as a postoperative decline of percent estimated glomerular filtration rate (eGFR) lower than the value of the mean minus standard deviation (SD). SRFD was defined as a rate greater than the value of the mean plus SD. The histopathological factors of global glomerulosclerosis (GS) and arteriosclerosis in non-neoplastic renal parenchyma and multiple clinical factors were analyzed to determine whether they affected postoperative renal functional deterioration in 100 renal cell carcinoma cases. The prognoses, including non-cancer mortality, were collected from long-term follow-up data. RESULTS: A higher preoperative eGFR and a higher global GS extent in non-neoplastic renal parenchyma were independently associated with MRFD and SRFD, respectively. The cardiovascular disease-specific survival rates of the SRFD group and the group with global GS extent >14 % were significantly worse than those of their counterparts. CONCLUSIONS: This is the first report to identify global GS extent in nephrectomized non-neoplastic renal parenchyma as a factor affecting the development of life-threatening post-nephrectomy renal functional deterioration. Moreover, we are the first to advocate the importance of the characterization of favorable post-nephrectomy renal functional deterioration. The identification of MRFD and SRFD by histopathological evaluation of nephrectomized non-neoplastic renal parenchyma will contribute to personalized postoperative follow-up. It may improve follow-up of individual patients with SRFD by permitting collaboration with other clinical departments such as cardiology.

Robot-assisted radical cystectomy is a promising alternative to open surgery in the Japanese population with a high rate of octogenarians.

BACKGROUND: Japanese patients who undergo radical cystectomy have a unique feature, i.e., the ratio of octogenarians is higher than in Western patients because of the aging Japanese population. The purpose of this study was to compare perioperative outcomes, complications, and oncologic outcomes between robot-assisted radical cystectomy and open radical cystectomy. METHODS: From 2010-2015, 20 (of which 8 were octogenarians) and 40 (of which 11 were octogenarians) patients underwent robot-assisted radical cystectomy and open radical cystectomy, respectively. RESULTS: There was no significant difference in terms of patient demographics between the two surgical cohorts, regardless of patient age. In the octogenarian patient cohort, the rates of previous abdominal surgery and the median age-adjusted Charlson comorbidity index were higher. The median estimated blood loss, transfusion rate and the days to resumption of a regular diet were significantly lower in the robot-assisted radical cystectomy cohort, regardless of patient age. Robot-assisted radical cystectomy significantly decreased grade II or higher complications, but there were no significant differences in terms of decreasing grade III or higher complications, regardless of patient age. Positive surgical margin and the mean number of lymph nodes removed were similar between the two surgical cohorts, regardless of patient age. CONCLUSION: Although robot-assisted radical cystectomy has a short history in Japan, the outcomes were generally comparable to those of previous studies. In a country that is aging rapidly like Japan, robot-assisted radical cystectomy could be a valid option for the management of muscle-invasive and high-risk superficial bladder cancer.

Effects of perirenal fat thickness on postoperative renal dysfunction in patients who underwent robot-assisted partial nephrectomy for renal tumours.

BACKGROUND: Despite partial nephrectomy (PN) renal function preservation benefits, postoperative renal dysfunction may occur. Perirenal fat thickness (PFT) is associated with renal dysfunction such as diabetes; however, its role in renal tumour surgery is unclear. This study investigates the role of PFT in renal function after robot-assisted partial nephrectomy (RAPN). METHODS: Pre-operative factors for postoperative renal dysfunction were analysed in 156 patients undergoing RAPN with ≥1-year follow-up. PFT measured using computed tomography categorised patients with PFT >21.0 mm (median) as high-PFT. RESULTS: Tumour size, total R.E.N.A.L. nephrometry score and its N component, renal calyx opening, achievement of trifecta, and PFT were risk factors for renal dysfunction 1 year postoperatively. Age ≥75 years (p = 0.024), total RNS ≥7 (p = 0.036), and PFT >21.0 mm (p = 0.002) significantly correlated with postoperative renal dysfunction. CONCLUSIONS: CT-measured PFT is a valuable predictor of postoperative renal dysfunction.

Initial Experience and Surgical Setup of Robot-Assisted Nephroureterectomy Using the Hugo Robot-Assisted Surgery System.

Introduction and Hypothesis: Robot-assisted radical nephroureterectomy (RANU) has emerged as a valid alternative to open or laparoscopic nephroureterectomy in recent years. However, different types of robotic platforms can limit surgical maneuvers in various ways. This study aimed to describe the surgical procedure and demonstrate RANU's technical feasibility and safety using the Hugo robot-assisted surgery (RAS) system. Materials and Methods: Using the Hugo RAS system, we reported data from the first five consecutive patients who underwent RANU at Tottori University Hospital. We adjusted the docking angles of the four independent arm carts in each case and performed a complete RANU via a transperitoneal approach. We collected patients' sociodemographic and perioperative data, including complications, and compared them retrospectively with data obtained using the da Vinci surgical system. Results: Arms positions were modified after the first patient to be placed all at the back of the patient. Median overall operative time was 283 minutes (203-377) and the median time using the robotic system was 187 minutes (121-277). The median estimated blood loss was 20 mL (5-155). None of the patients required a blood transfusion and none suffered postoperative complications of Clavien-Dindo grade ≥3. These outcomes were similar to those obtained with the da Vinci Xi system. Conclusion: This series represents the first report of RANU executed using the novel Hugo RAS system. Our proposed arm-setup will assist other surgeons and help ensure safe implementation of RANU on the Hugo platform.

Advanced Reconstruction of Vesicourethral Support May Improve Urinary Continence and Quality of Life After Non-nerve-sparing Robot-assisted Radical Prostatectomy.

BACKGROUND/AIM: Postoperative urinary incontinence (UI) after robot-assisted radical prostatectomy (RARP) has a significant impact on patients' quality of life (QOL). Several surgical techniques have been reported to improve postoperative UI. The aim of the study was to investigate the impact of advanced reconstruction of vesicourethral support (ARVUS) on urinary symptoms and QOL after non-nerve-sparing robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Patients who underwent non-nerve-sparing RARP from October 2010 to October 2020 at the Division of Urology, Department of Surgery, Tottori University Faculty of Medicine were reviewed. Patients were divided into the ARVUS and non-ARVUS groups, and propensity score matching was performed. Patients were evaluated by the International Prostate Symptom Score (IPSS), Incontinence Modular Questionnaire Short Form (ICIQ-SF), QOL index, and number of pads used before and 1, 3, 6, and 12 months after RARP. RESULTS: The number of patients in the ARVUS and non-ARVUS group were 41 and 41, respectively. On cystography, the distance of the symphysis pubis to the bladder neck was significantly shorter (p<0.001) and the posterior urethrovesical angle was significantly smaller in the AUVUS group (p<0.001). In the ICIQ-SF, the ARVUS group was significantly better at 6 and 12 months postoperatively. In the IPSS, the ARVUS group was significantly better than the non-ARVUS group at 3 months postoperatively. In a multivariable analysis, membranous urethral length [odds ratio (OR)=3.44, p=0.015] and ARVUS (OR=2.72, p=0.046) were significant factors in achieving 0 pads and total ICIQ-SF Question 1 and 2 scores of ≤2 at 12 months postoperatively. CONCLUSION: ARVUS improved urinary symptoms and QOL. ARVUS seems to be a useful surgical procedure for non- nerve-sparing RARP.

Effect of Adjuvant Systemic Chemotherapy on Intravesical Recurrence After Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma.

BACKGROUND/AIM: There are few reports confirming the relationship between the therapeutic effects of adjuvant systemic chemotherapy and intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma. We aimed to evaluate the benefits of adjuvant systemic chemotherapy on intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 133 patients with pathological T stage ≥3 upper urinary tract urothelial carcinoma or lymph node metastasis who underwent radical nephroureterectomy between January 2010 and September 2020 at our hospital and other satellite hospitals. In total, 60 patients received adjuvant systemic chemotherapy, and 73 did not. The Student's t-test and chi-square (χ2) test were used to compare between-group differences. The log-rank test was utilized to compare differences in intravesical recurrence between patients with or without adjuvant systemic chemotherapy. Cox proportional hazards regression analysis was performed to identify the predictive factors of intravesical recurrence. RESULTS: The median follow-up period was 25 months. Forty (30.1%) patients presented with intravesical recurrence. The 1-year intravesical recurrence-free survival rates of patients with and without adjuvant systemic chemotherapy were 86.0% and 70.2%, respectively (p=0.046). Multivariate analysis showed that adjuvant systemic chemotherapy was significantly associated with a lower risk of intravesical recurrence (p=0.032). CONCLUSION: Patients with pathological T stage ≥3 upper urinary tract urothelial carcinoma or lymph node metastasis can have a satisfactory intravesical recurrence-free survival rate with adjuvant systemic chemotherapy.

Initial Experience of Robot-Assisted Adrenalectomy in Japan: What is the Optimal Selection of Robotic Forceps for Adrenalectomy?

Minimally invasive adrenalectomy is the preferred technique for managing adrenal tumors. Laparoscopic adrenalectomy is widely performed and covered by insurance in Japan, but robot-assisted adrenalectomy is not. To investigate the best forceps combinations for performing robot-assisted adrenalectomy safely, we performed robot-assisted adrenalectomy for two left and two right adrenal adenomas using different robotic forceps combinations (bipolar forceps, monopolar curved scissors, Vessel Sealer Extend, and SynchroSeal) for each case. Although we evaluated a small number of RAs, lower blood loss was observed in patients where the vessel sealing devices were used. The extent of dissection is small for adrenalectomy, and robotic bipolar vessel sealing tools may not be necessary, especially for the small adrenal tumors. However, considering the risk benefits, the combination of forceps with Vessel Sealer Extend (by the left arm) and monopolar curved scissors (by the right arm) will become one of the best forceps combinations for performing robot-assisted adrenalectomy safely.

Utility of the HYBRID Method Incorporating the Advantages of Both Extracorporeal and Intracorporeal Urinary Diversion in Robotic-Assisted Radical Cystectomy.

Background: Robotic-assisted radical cystectomy (RARC) is a well-known standard procedure for muscle-invasive bladder cancer. However, it remains controversial whether extracorporeal urinary diversion (ECUD) or intracorporeal urinary diversion (ICUD) is superior in this technique. We have developed a HYBRID method that combines ECUD and ICUD to retain the advantages of each. The purpose of this study was to compare perioperative outcomes between HYBRID and ECUD in RARC and to evaluate the usefulness of the HYBRID method. Methods: We retrospectively analyzed the perioperative outcomes of 36 consecutive bladder cancer patients who underwent RARC with ileal conduit at our institution between March 2013 and December 2021. Propensity-score matching was used to align patient backgrounds between the HYBRID and ECUD groups. Results: After matching, 12 cases were selected for each group. There was no significant difference in patient demographics between the groups except for the rate of neoadjuvant chemotherapy. Mean console time was significantly longer in the HYBRID group due to intracorporeal manipulation; however, a relatively favorable trend of mean blood loss was observed in this group. There was no significant difference between the groups in terms of positive surgical margin, mean number of lymph node removed, or positive lymph node. The incidences of complications associated and non-associated with the urinary tract and grade ≥III complications at postoperative day (POD) 0-30 and 31-90 were similar between the groups. In the HYBRID group, no complications non-associated with the urinary tract or grade ≥III complications were observed at POD 31-90. Conclusion: The HYBRID method takes advantage of the benefits of both ICUD and ECUD and is a highly applicable technique that can be used in a variety of patient backgrounds.

Activation of PPARγ in bladder cancer via introduction of the long arm of human chromosome 9.

Bladder cancer is divided into two molecular subtypes, luminal and basal, which form papillary and nodular tumors, respectively, and are identifiable by gene expression profiling. Although loss of heterozygosity (LOH) of the long arm of human chromosome 9 (9q) has been observed in the early development of both types of bladder cancer, the functional significance of LOH remains to be clarified. The present study introduced human chromosome 9q into basal bladder cancer cell line, SCaBER, using microcell-mediated chromosome transfer to investigate the effect of LOH of 9q on molecular bladder cancer subtypes. These cells demonstrated decreased proliferation and migration capacity compared with parental and control cells. Conversely, transfer of human chromosome 4 did not change the cell phenotype. Expression level of peroxisome proliferator-activated receptor (PPAR)γ, a marker of luminal type, increased 3.0-4.4 fold in SCaBER cells altered with 9q compared with parental SCaBER cells. Furthermore, the expression levels of tumor suppressor PTEN, which regulates PPARγ, also increased in 9q-altered cells. These results suggested that human chromosome 9q may carry regulatory genes for PPARγ that are involved in the progression of neoplastic transformation of bladder cancer.

[Hemichorea in a patient with acute cerebral infarction of the somatosensory cortex].

A 86-year-old woman with left hemiparesis was admitted to our hospital. When visiting to our hospital, hemichorea appeared on her left extremities in an ambulance. She also had mild disturbance of consciousness, spatial disorientation, and sensory disturbance. Blood biochemical studies revealed mild renal failure. DWI MRI showed hyperintensities in the postcentral gyrus and a posterior part of the insula in the right hemisphere, but no signal changes in FLAIR. No lesions were detected in the basal ganglia. The DWI-FLAIR mismatch suggested acute cerebral infarction, and we performed intravenous thrombolysis therapy. Her neurological symptoms including hemichorea gradually improved, and she was finally discharged on foot. Two conspicuous points of the present patient are the sensory cortical infarction and an association with renal failure. In this patient, the sensory cortical infarction must produce chorea even though sensory cortical lesions rarely caused chorea. The associated renal dysfunction may play some role in the production of chorea. The double-crash of cerebral infarction and metabolic abnormality (renal dysfunction) may cause hemichorea which is rarely seen in patients with cerebral infarction of the sensory cortex and insula with no metabolic abnormalities.

Response to Platinum-based Chemotherapy Rechallenge for Patients With Pembrolizumab-refractory Urothelial Carcinoma.

BACKGROUND: This study aimed to investigate the response to platinum-based chemotherapy rechallenge in patients with pembrolizumab-refractory urothelial carcinoma. PATIENTS AND METHODS: We retrospectively reviewed 14 patients with pembrolizumab-refractory urothelial carcinoma. Each patient received a regimen that they had not previously received (paclitaxel plus carboplatin in 10, gemcitabine plus docetaxel and carboplatin in four). Tumor response and adverse events were assessed. We evaluated overall survival from the chemotherapy rechallenge start date until death. RESULTS: The median overall survival was 11.2 months. The disease-control rate was 85.7%. Partial responses occurred in the metastases in lymph nodes in three (37.5%) patients, lung in one (25%), peritoneal in three (75%), and liver in three (100%). Neutropenia of grade ≥3 occurred in 13 (92.9%) patients. CONCLUSION: The activity of platinum-based chemotherapy rechallenge after pembrolizumab was maintained. Neutropenia was observed in most patients.

Splice variants of lysosome­associated membrane proteins 2A and 2B are involved in sunitinib resistance in human renal cell carcinoma cells.

Sunitinib, a tyrosine kinase inhibitor, is among the first­line treatments for metastatic or advanced stage renal cell carcinoma (RCC). However, patients with RCC develop resistance to sunitinib. We have previously demonstrated that lysosome­associated membrane protein 2 (LAMP­2), which has three splice variants with different functions (LAMP­2A, LAMP­2B, and LAMP­2C), is involved in RCC. In the present study, we examined which splice variants of LAMP­2 contributed to sunitinib resistance in RCC cells. In vitro analysis using ACHN, human RCC cell line, revealed that the IC50 of sunitinib was significantly increased by overexpression of LAMP­2A and LAMP­2B, but not LAMP­2C (P<0.01). Kaplan­Meier survival analysis using clinical samples revealed an association between shorter survival and high expression of LAMP­2A and LAMP­2B, but not LAMP­2C, in patients with RCC treated with sunitinib (P=0.01). Furthermore, high expression of LAMP­2A and LAMP­2B in RCC revealed a weak to moderate inverse correlation with the tumor shrinkage rate and progression­free survival, respectively. Thus, high expression of LAMP­2A and LAMP­2B contributed to the acquisition of sunitinib resistance, indicating that the expression of these two variants can predict the efficacy of sunitinib treatment in patients with RCC.

Cross-Sectional Investigations of Pre- and Post-Operative Renal Global Function and Renal Parenchymal Volumetry in Both Partial and Radical Nephrectomy Utilizing Film-Based Technology.

OBJECTIVES: To investigate pre- and post-operative renal global function and renal parenchymal volume (RPV) in both partial nephrectomy (PN) and radical nephrectomy (RN) utilizing film-based technology. PATIENTS AND METHODS: The patient cohort consisted of 81 and 82 cases with T1 tumors (≤ 7 cm) treated by PN and RN, respectively. Renal global function was assessed using the estimated glomerular filtration rate (eGFR), and RPV was measured using a Synapse Vincent volumetric analyzer which creates a reconstructed image from a computed tomography scan. Renal global function and RPV were evaluated pre-operatively and 6 months post-operatively. RESULTS: The percent eGFR decline of PN cases was significantly reduced compared with RN cases (p < 0.0001). Post-operative RPV of the contralateral side was significantly increased compared with pre-operative RPV (p < 0.0001) in RN cases. The percent change of the contralat-eral side RPV was slightly increased in RN compared with PN cases (p = 0.1881). A strong positive correlation was noted between post-operative eGFR and post-operative total RPV (r = 0.69, p < 0.0001), and a strong negative correlation was noted between percent eGFR decline and post-operative total RPV (r = -0.63, p < 0.0001). CONCLUSIONS: Prominent compensatory renal hypertrophy occurred within 6 months after RN. Post-operative renal functional outcome was closely correlated with the post-operative total RPV. In addition to RPV, further studies to unravel post-operative renal function from multifactorial aspects including surgical factors and intrinsic medical disease should be performed in the future.