Hemoglobin ß Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma.

BACKGROUND: The regulation of the redox balance in the tumor microenvironment is thought to be an adaptive response of tumor cells to hypoxic environments. In recent years, it has been reported that the hemoglobin ß-chain (HBB), which is involved in scavenging reactive oxygen species (ROS), is expressed in several carcinomas. However, the relationship between HBB expression and the prognosis of renal cell carcinoma (RCC) remains unclear. METHODS: HBB expression was immunohistochemically analyzed in 203 nonmetastatic clear cell RCC (ccRCC) cases. Cell proliferation, invasion, and ROS production were measured in ccRCC cell lines treated with HBB-specific siRNA. RESULTS: The prognosis of HBB-positive patients was worse than that of HBB-negative patients. Cell proliferation and invasion were inhibited, and ROS production was increased by treatment with HBB-specific siRNA. Oxidative stress increased HBB expression in cells exposed to H2O2. CONCLUSIONS: HBB expression in ccRCC contributes to cancer cell proliferation by suppressing ROS production under hypoxic conditions. Taken together with clinical results and in vitro experiments, HBB expression may serve as a new prognostic biomarker for RCC in the future.

Fibroblast growth factor receptor type 4 as a potential therapeutic target in clear cell renal cell carcinoma.

BACKGROUND: Several clear cell renal cell carcinoma (ccRCC) cases harbour fibroblast growth factor receptor 4 (FGFR4) gene copy number (CN) gains. In this study, we investigated the functional contribution of FGFR4 CN amplification in ccRCC. METHODS: The correlation between FGFR4 CN determined via real-time PCR and protein expression evaluated using western blotting and immunohistochemistry was assessed in ccRCC cell lines (A498, A704, and 769-P), a papillary RCC cell line (ACHN), and clinical ccRCC specimens. The effect of FGFR4 inhibition on ccRCC cell proliferation and survival was assessed via either RNA interference or using the selective FGFR4 inhibitor BLU9931, followed by MTS assays, western blotting, and flow cytometry. To investigate whether FGFR4 is a potential therapeutic target, a xenograft mouse model was administered BLU9931. RESULTS: 60% of ccRCC surgical specimens harboured an FGFR4 CN amplification. FGFR4 CN was positively correlated with its protein expression. All ccRCC cell lines harboured FGFR4 CN amplifications, whereas ACHN did not. FGFR4 silencing or inhibition attenuated intracellular signal transduction pathways, resulting in apoptosis and suppressed proliferation in ccRCC cell lines. BLU9931 suppressed tumours at a tolerable dose in the mouse model. CONCLUSION: FGFR4 contributes to ccRCC cell proliferation and survival following FGFR4 amplification, making it a potential therapeutic target for ccRCC.

Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma.

(1) Background: Extracellular signal-regulating kinase 5 (ERK5) has been implicated in many cellular functions, including survival, proliferation, and vascularization. Our objectives were to examine the expression and effect of ERK5 in clear cell renal cell carcinoma (ccRCC). (2) Methods: The expressions of ERK5 and its regulating micro-RNA miR-143 were investigated using immunohistochemistry and quantitative reverse transcriptase PCR in surgical specimens of ccRCC patients. With invitro and in vivo studies, we used pharmacologic ERK5 inhibitor XMD8-92, RNA interference, pre-miR-143 transduction, Western blotting, MTS assay, apoptosis assay, and subcutaneous xenograft model. (3) Results: A strong ERK5 expression in surgical specimen was associated with high-grade (p = 0.01), high-recurrence free rate (p = 0.02), and high cancer-specific survival (p = 0.03). Expression levels of ERK5 and miR-143 expression level were correlated (p = 0.049). Pre-miR-143 transduction into ccRCC cell A498 suppressed ERK5 expression. ERK5 inhibition enhanced cyclin-dependent kinase inhibitor p21 expression and decreased anti-apoptotic molecules BCL2, resulting in decreased cell proliferation and survival both in ccRCC and endothelial cells. In the xenograft model, ERK5 inhibitor XMD8-92 suppressed tumor growth. (4) Conclusions: ERK5 is regulated by miR-143, and ERK5 inhibition is a promising target for ccRCC treatment.

Clinical utility of head computed tomography scan during systemic therapy for metastatic renal cell carcinoma.

OBJECTIVES: The utility of brain metastasis screening in asymptomatic metastatic renal cell carcinoma is controversial. Our study evaluated the utility of routine head computed tomography during systemic therapy. METHODS: We retrospectively investigated 152 metastatic renal cell carcinoma patients who did not initially have brain metastasis at Yamagata University Hospital from January 2008 to July 2019. Patients who routinely received head computed tomography scan together with routine contrast-enhanced chest/abdominal/pelvic computed tomography scan every 2-4 months during systemic therapy ("Routine head computed tomography" group, n = 95) and patients without routine head computed tomography ("No routine head computed tomography" group, n = 57) were compared. RESULTS: Brain metastasis occurred in 16 patients in the "Routine head computed tomography" group and six patients in the "No routine head computed tomography" group. There was no statistical difference in overall survival after metastatic renal cell carcinoma diagnosis between groups (53.4 vs 37.3 months, respectively, P = 0.357) and neurological symptom-free survival after metastatic renal cell carcinoma diagnosis (53.4 vs 36.6 months, P = 0.336). Although there was no statistical difference on incidence of unrecovered neurological symptom (25.0% vs 50.0%, P = 0.334), fewer patients in the "Routine head computed tomography" group required craniotomy (0% vs 66.7%, P = 0.002). In the "No routine head computed tomography" group, the neurological symptom resolved for all patients without craniotomy. CONCLUSIONS: Routine head computed tomography during systemic therapy for metastatic renal cell carcinoma is not significantly associated with improved brain metastasis prognosis. However, routine head computed tomography enables brain metastasis diagnosis in the asymptomatic phase, which can avoid craniotomy.

Living kidney transplantation without perioperative anticoagulation therapy for a patient with heparin-induced thrombocytopenia.

INTRODUCTION: Heparin-induced thrombocytopenia is an antibody-mediated acquired prothrombotic state induced by heparin exposure. The risk of thromboembolic diseases in kidney transplantation with heparin-induced thrombocytopenia without perioperative anticoagulation has not been determined. CASE PRESENTATION: A 64-year-old male hemodialysis patient with heparin-induced thrombocytopenia was referred to our hospital for living kidney transplantation. Anti-heparin-induced thrombocytopenia antibody was positive at the time of referral; however, it turned negative 4 months after heparin cessation during hemodialysis sessions. Living kidney transplantation by donation from his wife was performed using the standard technical procedure. Both heparinization and application of medical equipment containing heparin were avoided; however, no anticoagulant was administered intra- and postoperatively. The graft kidney functioned immediately, and no thromboembolic event related to heparin-induced thrombocytopenia occurred. CONCLUSION: Kidney transplantation without perioperative anticoagulation therapy after disappearance of anti-heparin-induced thrombocytopenia antibody is a well-tolerated treatment option for patients with end-stage kidney disease.

Association between Hyposensitivity of C-fiber Afferents at The Proximal Urethra and Storage/voiding Dysfunction in Female Patients with Detrusor Overactivity.

PURPOSE: We examined the associations between urethral sensation and storage/voiding function in female patients with detrusor overactivity (DO) by measuring urethral current perception threshold (CPT). MATERIALS AND METHODS: We retrospectively investigated the medical records of 27 consecutive patients with lower urinary tract symptoms who underwent cystometry, uroflowmetry (UFM), and urethral CPT tests from 2000 to 2015. Patients were classified into 2 groups: with/without DO. Seven DO-negative cases were selected as normal controls on cystometrogram (CMG) matching the inclusion criteria: bladder compliance ?12.5 mL/cmH2O, volume <275 mL at first sensation, and no comorbidities possibly influencing micturition. Finally, 17 patients were included. Urethral CPT was evaluated with intraurethral square-wave impulses at 3 Hz to stimulate C-fibers. Urethral loss coefficient (LC), reflecting urethral resistance during voiding, was calculated by curve-fitting a mathematical model to a UFM waveform. RESULTS: Urge incontinence (UI) was observed in 7 DO-positive patients, but not in those with normal CMG. Urethral CPT and LC were significantly higher in patients with DO than in those with normal CMG. Median urethral CPT significantly increased in patients with both DO and UI than in those without these symptoms (p<0.005). CPT values were correlated with the volume at first sensation (?=0.53, p<0.05) and LC (?=0.59, p<0.05). LC was not calculated in 3 cases due to poor curve-fitting. CONCLUSIONS: In females, urethral C-fiber afferents may become hyposensitive as the detrusor becomes overactive with UI in the storage phase. During voiding, C-fiber hyposensitivity may relate to increased functional resistance of the urethra to urine outflow.

New prognostic model for synchronous metastatic renal cell carcinoma.

OBJECTIVES: To create a new model for the prediction of overall survival in synchronous metastatic renal cell carcinoma. METHODS: Medical records of 158 patients with metastatic renal cell carcinoma diagnosed at the Yamagata University Hospital from August 2007 to February 2018 were reviewed. Among them, 77 with synchronous metastatic renal cell carcinoma were retrospectively analyzed using the univariate and multivariate analyses. A new prognostic model was constructed, followed by a bootstrap validation to estimate the model fitting. In addition, these prognostic factors were estimated in 67 metachronous metastatic renal cell carcinoma patients. RESULTS: Five independent prognostic factors were identified in synchronous metastatic renal cell carcinoma: cT3/4, cN1, high corrected calcium, >3.6 neutrophil-to-lymphocyte ratio and central nerve system metastasis. The number (%) and overall survival (95% confidence interval) in the favorable- (0 or 1 risk factor), intermediate- (2 risk factors) and poor-risk (≥3 risk factors) groups were 29 (45.3%) and 67.4 (31.8-NA), 21 (32.8%) and 16.8 (10.0-27.6), and 14 (21.9%) and 9.1 (7.3-13.7) months, respectively. The C-index was 0.72. Patients in the favorable-risk group had better overall survival with nephrectomy than without nephrectomy (hazard ratio 0.29, 95% confidence interval 0.09-0.91 with nephrectomy). In metachronous metastatic renal cell carcinoma, these prognostic factors showed no statistical differences in the overall survival. CONCLUSIONS: Prognostic factors are completely different between synchronous and metachronous metastatic renal cell carcinoma. The new model for synchronous metastatic renal cell carcinoma can predict a good candidate for cytoreductive nephrectomy.

Primary mesenchymal chondrosarcoma of the kidney without HEY1-NCOA2 and IRF2BP2-CDX1 fusion: A case report and review.

Mesenchymal chondrosarcoma (MC) of the kidney is rare. To the best of our knowledge, the current report is the first case of a giant extraskeletal MC that arose primarily from the right kidney and mimicked renal cell carcinoma at the locally advanced stage (cT3bN0) with vena cava thrombus and multiple pulmonary arterial tumor emboli. Additionally, the literature on renal EMC is reviewed and the possibilities of oncogenic heterogeneity are discussed. A 64-year-old woman was admitted to Yamagata University Hospital for sudden onset of asymptomatic gross hematuria. CT revealed a 90 mm renal mass without calcification in the right kidney and tumor thrombus extending to the inferior vena cava. Radical nephrectomy with thrombectomy was performed. Lung metastasis was detected 2 months later. The patient received systemic chemotherapy, which was only marginally effective. She died of the malignancy 8 months after surgery. Microscopic examination of the tumor revealed typical histology of MC and a lack of HEY1-NCOA2 and IRF2BP2-CDX1 gene fusions in the tumor tissues. Not all MC patients may exhibit chromosomal alterations in the tumor, suggesting the presence of genetically heterogeneous pathways of MC oncogenesis. Further studies are required to confirm the present findings and reinforce the molecular diagnosis of MC.

Effect of third- and fourth-line systemic therapies for metastatic renal cell carcinoma.

Data on the outcomes of third- or fourth-line therapy for metastatic renal cell carcinoma (mRCC) are limited. The aim of our study was to evaluate the efficacy of therapy beyond the second line. We retrospectively analysed data of mRCC patients who underwent systemic therapy at Yamagata University Hospital. The best objective response (BOR), response rate (RR), and progression-free survival (PFS) were assessed for each line of treatment. To investigate the correlation between overall survival (OS) and the number of treatment lines during a patient's lifetime, the median OS was assessed using univariate and multivariate analyses. In the first-, second-, and third-line therapies, approximately 20% of patients had long PFS of >15 months. In targeted treatments beyond the third line, only one treatment suppressed disease progression for >10 months. Among patients who died during the follow-up period, those treated with triple and quadruple lines had similar OS (42.5 months vs. 48.4 months, respectively). Multivariate analysis showed that patients with triple or more lines of therapy had better OS; however, quadruple or more lines of therapy was not an independent prognostic factor. We concluded that third-line systemic therapy could improve OS; however, fourth-line therapy could not.

Risk of SOFA Deterioration in Conservative Treatment for Emphysematous Pyelonephritis: Pitfalls of Current Trends in Therapeutics from Multicenter Clinical Experience.

INTRODUCTION: We investigated relationships between therapeutic outcomes of patients with emphysematous pyelonephritis (EPN) and changes in the Sequential Organ Failure Assessment (SOFA) score. MATERIALS AND METHODS: We retrospectively evaluated EPN patients treated in our hospitals using the SOFA score incorporated in the Sepsis-3 updated in 2016. RESULTS: Seventeen typical EPN patients were included in this study, and were treated with medical management with no drainage (n = 3), retrograde stenting (n = 10), or percutaneous drainage (n = 3). One patient without drainage died of sepsis, yielding an overall mortality rate of 5.9%. Twelve patients recovered without increase in the SOFA score during hospitalization. However, the SOFA score deteriorated in the other patients from admission, with the initial scores not significantly different from those of the 12 cases. The changes in the SOFA score were significantly affected by the selected approaches of drainage (100% patients for no drainage, 22% for stenting, and 0% for percutaneous drainage, p = 0.029), but not by other clinical data. CONCLUSION: Most EPN patients can currently be conservatively managed successfully. However, it should be noted that less-invasive management could cause deterioration in SOFA after admission, yielding a risk of septic mortality.

Impact of eIF4E phosphorylation at Ser209 via MNK2a on tumour recurrence after curative surgery in localized clear cell renal cell carcinoma.

Background: We investigated the roles of eIF4E phosphorylation (Ser209) in tumour recurrence after curative nephrectomy for localized clear cell renal cell carcinoma (ccRCC). Methods: Expression of eIF4E, p eIF4E and MNKs (MAPK interacting kinases), was evaluated in surgical specimens obtained from consecutive non metastatic ccRCC patients (n = 290) by immunohistochemistry (IHC), immunoblotting, and qRT PCR at the protein and mRNA levels. In human RCC cell lines, the effects of eIF4E phosphorylation were examined using immunoblotting, proliferation, migration and invasion assays with pharmacological inhibitors (CGP57380 or ETP45835) and specific small interfering (si) RNAs against MNK1/2(a/b). Results: In postoperative follow-up (median, 7.9 y), 40 patients experienced metastatic recurrence. In multivariate Cox analyses, higher IHC expression of p eIF4E in ccRCC significantly predicted a longer recurrence-free interval. eIF4E is phosphorylated mainly by MNK2a in tumour specimens and cell lines. In 786-O and A-498 cell lines, pharmacological inhibition of MNKs decreased p-eIF4E and increased vimentin and N cadherin but did not influence proliferation. Similarly, MNK2 or MNK2a inhibition with siRNA reduced p-eIF4E and enhanced vimentin translation, cell migration and invasion in the cell lines. Conclusions: MNK2a-induced eIF4E phosphorylation may suppress metastatic recurrence of ccRCC, partially due to vimentin downregulation at the translational level, consequently leading to inhibition of epithelial-mesenchymal transition.

Expression of total and phospho 4EBP1 in metastatic and non-metastatic renal cell carcinoma.

Eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) is phosphorylated and activated by mammalian target of rapamycin complex 1, which serves as a regulator of cell growth, cell survival, metastasis and angiogenesis in many types of cancer. The aim of this study was to evaluate the role of phosphorylated 4EBP1 (p4EBP1) in primary renal cell carcinoma (RCC) as a biomarker in metastatic RCC (mRCC) and non-mRCC cohorts. Primary tumor tissue from 254 non-mRCC and 60 mRCC patients were immunohistochemically stained for t4EBP1 and p4EBP1. The disease-free interval (DFI) categorized by the expressions and clinical parameters were assessed by univariate and multivariate analysis in the non-mRCC cohort. Then, the cause-specific survival (CSS) was assessed in the mRCC cohort by the same methods as used in the non-mRCC cohort. In the non-mRCC cohort, patients with t4EBP1 expression had no RCC recurrence. Patients with p4EBP1 expression had the shorter DFI in univariate analysis (P=0.037). p4EBP1 and pT1b-4 expression levels were independent predictors for de novo metastasis. In the mRCC cohort, intermediate/poor MSKCC risk, non-clear cell RCC, and no p4EBP1 expression were correlated with poor CSS on multivariate analysis. Expression of p4EBP1 could be a predictive biomarker for de novo metastasis in non-mRCC patient cohort. By contrast, mRCC patients showing no p4EBP1 expression had shorter CSS than patients with p4EBP1 expression.

Reinforcement of the Triple D score with simple addition of the intrarenal location for the prediction of the stone-free rate after shockwave lithotripsy for renal stones 10-20 mm in diameter.

PURPOSE: We investigated the clinical efficacy of the Triple D score (TrD-S) on stone-free rate (SFR) prediction following shockwave lithotripsy (SWL) for renal stones 10-20 mm in diameter and modified the scoring system to improve outcome prediction. METHODS: We retrospectively examined clinical data from the medical records of 226 consecutive patients who underwent SWL for 10-20 mm kidney stones. The TrD-S was calculated according to the cutoffs of < 150 mm3 for stone volume, < 600 Hounsfield unit for stone density, and < 12 cm for skin-to-stone distance on computed tomography. The Quadruple D score was defined as the sum of the TrD-S and stone location (0/1 point for intrarenal stone distribution at lower/non-lower poles, respectively). Complete clearance 3 months after the final SWL was considered the stone-free status. RESULTS: The residual group (n = 102) had significantly older age, larger stones, higher stone density, higher lower-pole stone incidence, and lower TrD-S than the stone-free group (n = 124). In the multivariate analysis, age, TrD-S, and non-lower-pole stones independently predicted the SFR. The TrD-Ss of 0, 1, 2, and 3 points showed SFRs of 40.0%, 51.9%, 73.0%, and 100.0%, respectively. The Quadruple D scores of 0, 1, 2, 3, and 4 points showed SFRs of 0.0%, 37.9%, 54.5%, 84.4%, and 100.0%, respectively, with better prediction accuracy than the TrD-S (p = 0.01). CONCLUSIONS: The TrD-S is successfully validated for use in Japanese patients with 10-20-mm renal stones. Simple addition of the stone location to the TrD-S could reinforce SFR prediction after SWL.

Possible role of hyposensitivity of C-fiber afferents at the proximal urethra in the development of urge urinary incontinence in patients with detrusor overactivity.

OBJECTIVE: The aim of the present study was to investigate associations between urethral sensation and urge urinary incontinence (UUI) in patients with and without detrusor overactivity (DO). METHODS: The medical records of 80 consecutive patients who underwent filling cystometry and urethral current perception threshold (CPT) tests were examined retrospectively. Following the exclusion of 4 patients not eligible for analysis, patients were classified into neurogenic DO, idiopathic DO, or DO-negative groups based on neurological and cystometric findings (n = 30, 12, and 34, respectively). Eleven DO-negative patients were defined as normal controls on cystometrograms (CMG) using the following exclusion criteria: bladder compliance <12.5 mL/cmH2 O, volume >275 mL at first filling sensation, and comorbidities possibly affecting lower urinary tract function. Thus, 53 patients were finally included in the study. Proximal urethral CPT was evaluated with intraurethral square-wave stimulation at 3 Hz to activate C-fiber afferents. RESULTS: Median CPT was higher in neurogenic and idiopathic DO than in the normal CMG group (11.3 and 9.0 vs. 2.8 mA, respectively; P < .05), as well as in patients with UUI (n = 19) compared with non-UUI patients (n = 34; 12.5 vs. 5.4 mA, respectively; P < .05). The proportion of UUI patients was significantly greater in the DO-positive groups than in the normal CMG group (P < .05). CPTs were not associated with bladder capacity at the first filling sensation (r = 0.11). CONCLUSION: Hyposensitive C-fibers of the proximal urethra may contribute to the development of urodynamic DO as well as UUI in patients complaining of lower urinary tract symptoms.

[AN EXPERIENCE OF PARTIAL NEPHRECTOMY IN A PATIENT WITH VON WILLEBRAND DISEASE].

A 28-year-old male visited a nearby hospital with chief complaint of bilateral back pain and fever. He was diagnosed with a right complex renal cyst (Bosniak classification, IIF) with a kidney stone and was referred to our hospital. We first suspected an incarcerated kidney stone and performed flexible transurethral lithotomy; however, his symptoms did not improve. Blood examination revealed prolonged APTT; subsequently, he was diagnosed with von Willebrand disease (VWD). Because he experienced pain due to the hemorrhagic renal cyst, we performed partial nephrectomy. Preoperatively, we supplemented the von Willebrand factor (VWF) based on the VWF activity in the patient. Although intraoperative bleeding was well controlled, he developed bleeding from pseudoaneurysms on the postoperative day (POD) 6. We immediately performed transarterial embolization along with VWF replenishment. VWF supplementation was discontinued on POD 14, and the patient was discharged on POD 23. Since then, he has not experienced a bleeding recurrence or pain. In patients with VWD, the perioperative administration of desmopressin or VWF is recommended. Although several reports showed that surgeries involving these treatments are safe, only three cases with VWD, including the present case where the patient underwent partial nephrectomy, have been reported. In the present case, postoperative bleeding occurred despite exhibiting adequate perioperative VWF activity. Thus, bleeding complications in patients with VWD undergoing partial nephrectomy must be considered and should be carefully followed up.

Levels of 4EBP1/eIF4E Activation in Renal Cell Carcinoma Could Differentially Predict Its Early and Late Recurrence.

BACKGROUND: The objective was to explore the predictive markers of late recurrence (LR) > 5 years after curative nephrectomy for renal cell carcinoma (RCC). PATIENTS AND METHODS: We retrospectively examined the data from 303 patients with localized clear cell RCC treated surgically at our institution from 1993 to 2011. Activation of the eukaryotic initiation factor (eIF)4E-binding protein 1 (4EBP1)/eIF4E axis at the mammalian target of rapamycin complex 1 (mTORC1) was evaluated in the tumor specimens. Weak, intermediate, and strong immunohistochemistry staining grades were defined for 4EBP1, phosphorylated 4EBP1, and eIF4E. The effects of clinicopathologic factors and activation level grades on tumor recurrence were analyzed using multivariate Cox regression models. To validate the present findings, we investigated clinical data from The Cancer Genome Atlas and protein/phosphoprotein data from corresponding patients from The Cancer Proteome Atlas. RESULTS: Of the 303 patients, 31 and 16 patients developed early recurrence (ER, ≤ 5 years) and LR, respectively. The activation levels were comparable among the subcategories of pathologic TN stage, Fuhrman grade, and microvascular and capsular invasion. Pathologic stage ≥ T1b, Fuhrman grade 3/4, and an intermediate or strong activation level correlated significantly with overall recurrence and ER. Strong activation of the axis and pathologic stage ≥ T1b were identified as independent predictors of LR. Only 2 patients with weak activation experienced recurrence (1 each with ER and LR). Similar results were confirmed by the analyses of The Cancer Genome Atlas and The Cancer Proteome Atlas data. CONCLUSION: The activation level of the axis in RCC tissues could independently predict for recurrence and differentially affect the timing of recurrence.

Pazopanib-induced crystal deposition in intestinal mucosa in a patient with retroperitoneal liposarcoma.

Pazopanib was administered to a 44-year-old man with local recurrence of retroperitoneal liposarcoma. Computed tomography showed an intestinal edema, which gradually progressed 15 months after pazopanib administration although he had no clinical symptoms. Upper gastrointestinal endoscopy implicated marked edematous hypertrophy of the Kerkling's fold. Pathological findings showed crystal deposition and fat accumulation, without a malignant component. All these abnormal findings resolved after pazopanib discontinuation.

[Spontaneous Remission of Everolimus-Induced Interstitial Lung Disease in Metastatic Renal Cell Carcinoma : An Autopsy Case Report].

Interstitial lung disease (ILD) is a common side effect of the mechanistic target of rapamycin inhibitor everolimus. Most cases of everolimus-induced ILD are mild and reversible. As per guidelines, even if Common Terminology Criteria for Adverse Events grade 1 or 2 everolimus-induced ILD occurs, either continuation of everolimus without dose reduction or readministration at a low dose is possible. However, the pathophysiology of everolimus-induced ILD is unknown. We present a case of everolimus-induced ILD with spontaneous remission during treatment in a patient with metastatic renal cell carcinoma. At autopsy, there was no evidence of remodeling or chronic inflammation in the lungs. Cryptogenic interstitual pneumonia and broncholitis obliterans with organizing pneumonia can be suspected as a pattern of mild everolimus-induced ILD. This case report provides evidence that everolimus-induced ILD is reversible fromthe pathological perspective.

Renoprotective Procedures with a Cold Ischemia Time of <60 min Minimize the Deterioration of Kidney Function in Open Nephron-Sparing Surgery for Renal Cell Carcinoma.

INTRODUCTION: We evaluated whether nephron sparing surgery (NSS) combined with meticulous suturing of the cut stump under clamping with cooling is beneficial for oncological outcomes and also assessed the relationship between cold ischemia time and deterioration of renal function. METHODS: One hundred and six patients with renal cell carcinoma (RCC) were subjected to this procedure. Oncological outcomes and renal function according to the estimated glomerular filtration rate (eGFR) and the tubular excretion rate on renoscintigraphy before and at 12 months after surgery were evaluated. RESULTS: Cancer recurrences were observed in 2 patients with past history of RCC; however, no patient died of cancer. Renal function was evaluated depending on 4 different ischemia times. All groups did not show a remarkable decrease of renal function in terms of eGFR. Renoscintigraphy revealed the deterioration of the affected kidney in patients with >60 min ischemia. CONCLUSION: The renoprotective procedure of NSS provided maximum preservation of renal function until 60 min of cold ischemia time.

Internal validation of a scoring system to evaluate the probability of ureteral stones: The CHOKAI score.

OBJECTIVE: The CHOKAI and STONE scores are prediction models for ureteral stones. The aims of the present study were to evaluate the diagnostic performance, to examine the optimal cut-off value, and to compare the diagnostic performance of each model. METHODS: Patients who presented to our emergency department with renal colic were considered for this prospective study. We analyzed the predictive performance of both STONE and CHOKAI scores at their optimal cut-off values, using receiver operating characteristic (ROC) curve and area under the curve (AUC), as well as sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) at the optimal cut-off value. RESULTS: Of the 96 patients who met the inclusion criteria, 79 were definitively diagnosed with ureteral stones. All patients were of Japanese descent. The AUC of the CHOKAI score was 0.971 at an optimal cut-off value of 6, showing a sensitivity of 0.911, specificity of 0.941, LR+ of 15.49, and LR- of 0.094. The AUC of the STONE score was 0.873 at an optimal cut-off value of 8, showing a sensitivity of 0.823, specificity of 0.824, LR+ of 4.662, and LR- of 0.215. The AUC of the CHOKAI score was significantly higher than that of the STONE score (p=0.010). Of the 73 patients with a CHOKAI score of ≥6, 98.6% had ureteral stones, and of the 68 patients with a STONE score of ≥8, 95.6% had ureteral stones. CONCLUSIONS: The simplified CHOKAI score is a useful tool to screen for ureteral stones in patients with renal colic.