Effect of general self-efficacy on promoting health-related quality of life during recovery from radical prostatectomy: a 1-year prospective study.

BACKGROUND: The decline of health-related quality-of-life (QOL) during the year after radical prostatectomy is severe. General self-efficacy (GSE) is an effective psychological factor for long-term regulation of patient behavior and emotions. GSE is expected to facilitate enhanced health-related quality of life. We evaluated changes in GSE and analyzed the relationship between GSE and prostate cancer-specific and general health-related QOL. METHODS: We conducted a longitudinal survey with 104 patients who underwent radical prostatectomy and administered the General Self-efficacy Scale (GSES), Expanded Prostate Cancer Index Composite (EPIC), and SF8 Health Survey (SF-8). ANCOVA was performed to compare EPIC and SF-8 between GSES high and low-medium groups. RESULTS: GSES scores increased significantly after 6 months. Regarding EPIC urinary summary scores, high GSES group was significantly higher than low-medium group at 1 month (mean score difference [MSD], 7.3; 95% CI 1.1-13.2, P = 0.016), 3 months (MSD, 6.8; 95% CI 0.7-12.8, P = 0.028), and 6 months (MSD, 6.3; 95% CI 0.9-11.7, P = 0.022). High GSES group had significantly higher SF-8 physical component summary score at 6 months (MSD, 3.2; 95% CI 1.4-5.0, P = 0.001), and significantly higher SF-8 mental component summary score at 1 month (MSD, 2.6; 95% CI 0.4-4.9, P = 0.022), 3 months (MSD, 2.7; 95% CI 0.8-4.6, P = 0.007), and 6 months (MSD, 2.8; 95% CI 1.0-4.6, P = 0.003). CONCLUSION: This study suggests that high GSE was associated with better prostate cancer-specific and general health-related QOL after radical prostatectomy.

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.

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.

[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.

[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.

[CEREBRAL VENOUS SINUS THROMBOSIS IN PATIENTS WITH METASTATIC TESTICULAR CANCER DURING CHEMOTHERAPY: REPORTS OF TWO CASES].

Cerebral venous sinus thrombosis (CVT) is rare but sometimes develops in association with malignant neoplasm. We report two cases of CVT that occurred during cisplatin-based chemotherapy for testicular cancer. A 46-year-old man with stage IIA non-seminomatous germ cell tumour was treated with conventional doses of etoposide and cisplatin (EP). On day 11 of the third treatment course, he developed a systemic seizure. Brain computed tomography (CT) and magnetic resonance (MR) imaging could not detect the cause. Enhanced chest-pelvic CT revealed pelvic thrombosis. Administration of phenytoin for epilepsy of unknown cause and heparin for thrombosis was started. He had completed 4 courses of EP therapy without seizure recurrence. After re-evaluating the brain CT images retrospectively, we found high density of superior sagittal sinus (SSS) and strongly suspected CVT. Another patient was a 47-year-old man with stage IIIB seminomatous germ cell tumour treated with bleomycin, etoposide, and cisplatin (BEP) therapy. On day 11 of the second treatment course, he developed a systemic seizure. Brain CT revealed subarachnoid haemorrhage localised in the right parietal lobe. CT venography revealed a filling defect in the superior sagittal sinus (SSS). MR venography revealed a SSS stenosis. We diagnosed the cause of the seizure as CVT and started administration of anticoagulant therapy. After the thrombus had diminished, chemotherapy was restarted and another 2 courses of BEP therapy was completed.

[Asynchronous Bilateral Testicular Infarction with Suspected Polyarteritis Nodosa : A Case Report].

This report documents a case of asynchronous bilateral testicular infarction. The patient was a 42- year-old man who presented with left testicular pain and swelling. He had a past history of right idiopathic testicular infarction and underwent a right orchiectomy 6 years ago. He also had received treatment for 5 years for suspected polyarteritis nodosa (PAN). The left scrotal pain persisted for a week and left orchiectomy was performed. Pathological evaluations demonstrated a benign testis with testicular hemorrhage and chronic vasculopathy. There was no fibrinoid necrosis of medium-size vessel walls which characterizes PAN. In this report, we review the pathogenesis, risk of contralateral testicular infarction, and management of testicular infarction.

Sequential molecularly targeted drug therapy including axitinib for a patient with end-stage renal failure and metastatic renal cell carcinoma.

A 62-year-old male patient with end-stage renal disease and metastatic renal cell carcinoma (RCC) was referred to our hospital. Sequential targeted therapy consisting of sorafenib, sunitinib, and everolimus was administered, but the patient's disease gradually progressed. Axitinib was subsequently administered at a decreased dose of 6 mg/day for 2 weeks, after which the dose was escalated to 10 mg/day. Axitinib therapy was maintained for a total of 6 months without severe adverse effects. Sequential molecularly targeted drug therapy including axitinib, with careful monitoring, is one possible treatment option for patients with metastatic RCC with renal impairment.

[Extracorporeal partial nephrectomy and auto-transplantation after presurgical targeted therapy with tyrosine kinase inhibitors for renal cell cancer].

A 74-year-old woman who had previously undergone left nephrectomy because of calculi was referred to our department with a right renal mass that was detected by computed tomography (CT) during treatment for pyelonephritis. Repeated CT showed a contrast-enhanced 4.7 cm tumor close to the renal sinus, and no metastatic lesion was detected. Sunitinib was administered as a presurgical therapy ; however, the patient experienced grade 3 neutropenia and thrombocytopenia, and sunitinib was discontinued. Sorafenib was administered 7 days after discontinuation of sunitinib ; however, the patient experienced febrile neutropenia and rash, and sorafenib was discontinued. Extracorporeal partial nephrectomy and auto-transplantation were performed 24 days after discontinuation of sorafenib. Though peri-graft abscess was suspected to be present and resolved by antibacterial therapy, severe complications were not experienced, and the patient did not require dialysis therapy after surgery. There was no evidence of recurrence at 30 months after the surgery.

GSK-3 inhibition in vitro and in vivo enhances antitumor effect of sorafenib in renal cell carcinoma (RCC).

Sorafenib is a multikinase inhibitor approved for the systemic treatment of renal cell carcinoma (RCC). However, sorafenib treatment has a limited effect due to acquired chemoresistance of RCC. Previously, we identified glycogen synthase kinase-3 (GSK-3) as a new therapeutic target in RCC. Here, we observed that sorafenib inhibits proliferation and survival of RCC cells. Significantly, we revealed that sorafenib enhances GSK-3 activity in RCC cells, which could be a potential mechanism of acquired chemoresistance. We found that pharmacological inhibition of GSK-3 potentiates sorafenib antitumor effect in vitro and in vivo. Our results suggest that combining GSK-3 inhibitor and sorafenib might be a potential new therapeutic approach for RCC treatment.