Predictive factors of nivolumab plus ipilimumab treatment efficacy in metastatic renal cell carcinoma patients.

OBJECTIVE: Nivolumab plus ipilimumab is a recommended first-line therapy regimen for metastatic renal cell carcinoma. However, it is not clear which patient characteristics are associated with its effectiveness. METHODS: We retrospectively examined 67 metastatic renal cell carcinoma patients treated with nivolumab plus ipilimumab as a first-line therapy in multiple institutions from September 2018 to August 2022. We analyzed the relationships between survival outcomes and patient-related variables, including paraneoplastic symptoms. We also analyzed the relationships between changes in symptoms and parameters and outcomes. RESULTS: Of the 67 patients, 32 patients had paraneoplastic symptoms. The median progression-free survival was 14.9 months and median overall survival was 43.3 months. The objective response rate was 49.25% (33 patients), including two patients with complete response. Patients with cytoreductive nephrectomy, bone metastasis, high C-reactive protein levels and paraneoplastic symptoms were significantly correlated with short progression-free survival in the univariate analysis. Multivariate analysis of these factors showed that the presence of paraneoplastic symptoms at treatment initiation remained an independent predictor of progression-free survival. Of the 32 patients with paraneoplastic symptoms at treatment initiation, 12 patients had symptomatic improvement and 20 did not. The 1-year progression-free survival rates were significantly longer in improved patients compared with those with no improvement. CONCLUSIONS: Patients without cytoreductive nephrectomy and with bone metastasis, liver metastasis, high C-reactive protein levels and paraneoplastic symptoms were significantly correlated with shorter progression-free survival. The presence of paraneoplastic symptoms was an independent predictor of progression-free survival. Improvement in paraneoplastic symptoms may reflect the treatment efficacy of nivolumab plus ipilimumab.

The Relationship between the Presence of an Earlobe Crease and Overactive Bladder: A Cross-Sectional Case-Controlled Study.

Background and Objectives: To examine the relationship between the presence of earlobe crease (EC) and overactive bladder (OAB). Materials and Methods: The earlobes of the participants were examined macroscopically. ECs were further divided into four groups (grades 0-3) according to severity. Subjective symptoms were assessed using the OAB symptom score (OABSS), and objective findings were assessed using uroflowmetry. The relationship between these findings and the presence or absence and severity of EC was also examined. A score of ≥2 points on OABSS question 3 (urinary urgency), with a total score of ≥3 points, indicated OAB. Results: We analyzed 246 participants, including 120 (48.8%) in the EC group and 126 (51.2%) in the non-EC (N-EC) group. On the OABSS, the EC group scored higher than the N-EC group for all questions and for the total score. The total OABSS of EC grade 3 was the highest of all groups. A total of 115 (95.8%) patients in the EC group (100% in grade 3) and 69 (54.8%) in the N-EC group met the OAB criteria (p < 0.001). The voided volume and maximum flow rate of the EC group were significantly lower than those of the N-EC group (both p < 0.001). The post-void residual urine volume in the EC group was significantly higher than that in the N-EC group (p = 0.029). Multivariate analysis revealed that EC was an independent risk factor for OAB (odds ratio, 8.15; 95% confidence interval, 2.84-24.75; p < 0.001). Conclusions: The presence of an earlobe crease may be a predictive marker for OAB.

[A CASE OF CONGENITAL UNILATERAL ABSENCE OF THE VAS DEFERENS WITH SUSPECTED IPSILATERAL RENAL AGENESIS].

A 5-month-old boy was referred to our department to examine poor development of external genitalia. The patient was diagnosed with micropenis and bilateral impalpable testes, and testosterone replacement therapy was recommended. The testes remained impalpable at 14 months of age; therefore, laparoscopy was performed to explore intra-abdominal testes. The patient was incidentally diagnosed with congenital unilateral absence of the right vas deferens. A renal sonography performed after the operation revealed a high possibility of right renal agenesis. Congenital absence of the vas deferens is associated with a high probability of renal anomalies. It is, therefore, essential to pay careful attention to renal dysfunction.

[A Case of Moyamoya Disease Associated with SAPHO Syndrome].

Moyamoya disease is a unique occlusive disease of the internal carotid artery(ICA)with moyamoya vessels that can lead to transient ischemic attacks and hemorrhagic stroke. When other inherited or acquired disorders and conditions occur in conjunction with moyamoya disease, the syndrome is known as quasi-moyamoya disease. We report the case of a 34-year-old woman with a past history of SAPHO(Synovitis-Acne-Pustulosis-Hyperostosis-Osteomyelitis)syndrome, who presented with arm weakness and headache. Magnetic resonance angiography revealed severe terminal stenosis of the left ICA with moyamoya vessels, and she was diagnosed as moyamoya disease associated with SAPHO syndrome. She underwent superficial temporal artery-middle cerebral artery anastomosis and her arm weakness improved postoperatively. Postoperative course was uneventful, although she showed transient right paresthesia, which improved with conservative therapy. Autoimmune response could contribute to the development of this moyamoya disease, and we discuss its mechanism with a literature review.

Excretion patterns of fecal progestagens, androgen and estrogens during pregnancy, parturition and postpartum in okapi (Okapia johnstoni).

The aim of the present study was to establish a simple method to monitor ovarian activity and non-invasively diagnose pregnancy in okapi (Okapia johnstoni). The feces of a female okapi were collected daily or every 3 days for 28 months. Steroids in lyophilized feces were extracted with 80% methanol, and the fecal levels of immunoreactive progestagens (progesterone and pregnanediol-glucuronide), androgen (testosterone), and estrogens (estradiol-17beta and estrone) were determined by enzyme immunoassays with commercially available antisera. Using the progesterone profiles, the durations of the luteal phase, follicular phase, and estrous cycle were determined to be 11.1 +/- 0.4, 5.3 +/- 0.6, and 16.5 +/- 0.7 days (n=22), respectively. Fecal levels of immunoreactive progesterone, pregnanediol glucuronide, and testosterone gradually increased from early pregnancy and peaked several months before parturition. More pregnanediol glucuronide was excreted in feces than progesterone during late pregnancy, but not during the estrous cycle. Although the fecal concentrations of immunoreactive estradiol-17beta and estrone change a little throughout pregnancy and non-pregnancy, they rose sharply and temporarily on the day following parturition. The present study indicates that fecal assays with commercial antisera for progesterone and pregnanediol glucuronide are useful for evaluating luteal activity and diagnosing pregnancy and indicates that estrogens might have some role as a trigger of parturition.