BACKGROUND:Limited data are available on the midterm outcomes of combination therapy with immune checkpoint inhibitors and VEGFR-TKIs (IO-TKI) for advanced renal cell carcinoma (RCC) in real-world settings. METHODS:We retrospectively evaluated data from 68 patients who received lenvatinib plus pembrolizumab (n = 14), cabozantinib plus nivolumab (n = 20), pembrolizumab plus axitinib (n = 23), or avelumab plus axitinib (n = 11) as first-line therapy for advanced RCC. All patients initiated IO-TKI at least 3 years before the data-cutoff, ensuring a potentially minimum follow-up of 3 years. Effectiveness and safety profiles were assessed. RESULTS:During a median follow-up of 32.7 months, the median progression-free survival (PFS) and overall survival (OS) were 19.9 and 46.7 months, respectively. The objective response rate was 57%. In subgroup analysis, histology was associated with survival outcomes; median PFS (23.0 vs. 13.8 months, p = 0.0503) and OS (not reached vs. 37.4 months, p = 0.0016) were longer in patients with clear-cell RCC than in those with non-clear-cell RCC. Regarding safety, Grade 3 adverse events occurred in 44 patients (65%). Treatment discontinuation of both drugs was required in 14 patients (21%), and discontinuation of one drug in 21 patients (31%). High-dose glucocorticoids (≥ 40 mg prednisone/day) were required in 10 patients (15%). CONCLUSION:With a minimum of 3 years of follow-up, IO-TKI demonstrated feasible effectiveness and manageable safety in patients with advanced RCC in the real world. More effective treatment strategies and novel therapeutic targets are needed for patients with non-clear-cell RCC.
Abstract Background Sarcoidosis-associated hypercalcemia can cause acute kidney injury (AKI); however, reports of severe cases superimposed on advanced chronic kidney disease (CKD) stage G4 requiring hemodialysis (HD) are rare. We report a case that offers important clinical insights into diagnostic pitfalls in patients with CKD and the clinical approach to identify reversible “treatable AKI.” Case presentation A man in his seventies with baseline CKD stage G4 (serum creatinine [Cr] 2.3–2.6 mg/dL, estimated glomerular filtration rate [eGFR] 19.0–23.0 mL/min/1.73m2) due to nephrosclerosis was emergently admitted for moderate hypercalcemia (corrected serum calcium 13.3 mg/dL) and AKI (Cr 5.15 mg/dL, eGFR 9.3 mL/min/1.73m2). Endocrinological examination revealed suppressed intact parathyroid hormone (PTH) and elevated 1,25-dihydroxyvitamin D (1,25(OH)2D), leading to a diagnosis of PTH-independent, vitamin D-dependent hypercalcemia. Although serum angiotensin-converting enzyme (ACE) levels were within the normal range, this was considered to be masked by the chronic use of an ACE inhibitor (imidapril). A clinical diagnosis of sarcoidosis was made on the basis of markedly elevated soluble IL-2 receptor and lysozyme levels and mediastinal lymphadenopathy. Owing to his poor general condition, tissue biopsy could not be performed. Emergency HD was promptly initiated, followed by corticosteroid therapy with prednisolone (30 mg/day) once the clinical diagnosis was strongly suspected. Following treatment, hypercalcemia normalized rapidly, and kidney function gradually improved, allowing liberation from dialysis after five HD sessions. Conclusions When encountering unexplained AKI with hypercalcemia in patients with CKD, clinicians should consider sarcoidosis as a potential underlying cause. Additionally, clinicians will perform a multifaceted evaluation including 1,25(OH)2D measurement. Even in severe cases requiring dialysis, early diagnosis and appropriate treatment can render the condition a “treatable AKI.”
Development of cholesterol crystal embolism (CCE) following an aortic dissection in the absence of endovascular procedures or anticoagulation therapy is rare. We report a case of a 68-year-old man who developed an aortic dissection and acute kidney injury (AKI) associated with the delayed-onset CCE. The patient developed an acute type B aortic dissection and was managed conservatively without any endovascular interventions or anticoagulation. Four weeks after the aortic dissection, the livedo reticularis on his lower extremities and purple toes appeared. One week later (five weeks after onset), he presented with AKI (serum creatinine level was 6.11 mg/dL) and peripheral eosinophilia. A skin biopsy from the lower leg revealed arterioles occluded by cholesterol clefts with surrounding mononuclear cell infiltration, confirming the diagnosis of CCE. Given the progressive deterioration of kidney function, oral prednisolone (PSL) was initiated. Following treatment, his kidney function improved, allowing him to avoid hemodialysis, with his serum creatinine level eventually recovering to 1.9 mg/dL. This case suggests that considering the diagnosis of delayed-onset CCE is important in patients with a recent history of aortic dissection presenting with AKI, even in the absence of typical iatrogenic triggers. Furthermore, corticosteroid therapy may be considered as a treatment option for CCE-associated AKI.
Introduction:The 2011 Fukushima nuclear disaster following the Great East Japan Earthquake did not cause significant physical health effects, but long-term mental distress persists, partly driven by radiation risk perception. Women, particularly those undergoing breast cancer screening in affected areas, may experience heightened breast cancer anxiety and mental distress. The interrelationships among radiation risk perception, breast cancer anxiety, and mental distress remain unclear. This study aimed to elucidate these associations among women in Minamisoma, one of the municipalities most severely affected by the disaster. Methods:A self-administered questionnaire survey was conducted among 479 women who attended breast cancer screening at two core breast cancer care centers located more than 20 km north of the Fukushima Daiichi Nuclear Power Plant. This cross-sectional study assessed breast cancer anxiety, risk perception of breast cancer and radiation exposure, and mental distress. Mental distress was evaluated using the Kessler Psychological Distress Scale (K6) scale, with scores ≥5 considered significant. Descriptive analyses and regression models were constructed to explore the relationships among these three outcomes. Results:Among participants, 47.4% (227/479) reported moderate mental distress. Higher odds of general breast cancer anxiety were observed among those who perceived a high likelihood of radiation-induced breast cancer (odds ratio [OR], 2.99; 95% confidence interval [CI]: 1.76-5.08; p < 0.001). Higher odds of mental distress were also associated with belief in radiation-induced breast cancer (OR, 1.76; 95% CI: 1.19-2.59; p = 0.004). However, breast cancer anxiety itself was not significantly associated with mental distress (OR, 1.29; 95% CI: 0.83-2.01). Conclusions:Approximately half of the women experienced moderate mental distress five years after the disaster. The results suggest that mental distress is heightened by radiation risk perception and underlying general health concerns, rather than specific factors such as breast cancer anxiety.
