High T-cell infiltration in tumor tissue and younger age predict the response to pembrolizumab in recurrent urothelial cancer.

Targeting the programmed cell death-1 signaling pathway has been approved for the anti-cancer therapy in several cancers including urothelial cancer. To determine predictive factors of the responsiveness to pembrolizumab in urothelial cancer patients, a retrospective study that used clinical information and paraffin-embedded samples obtained from patients diagnosed with urothelial cancer between 2015 and 2020 were performed. Seventeen patients who underwent total cystectomy or nephroureterectomy of the primary lesion and were treated with pembrolizumab for chemo-resistant disease were enrolled, and immunohistochemical analysis was performed. A key difference in the characteristics between the non-responder group and the responder group was the age of the patients (74 vs. 63 years, p = 0.0194). Although there was no statistically significant difference, the histological subtype with sarcomatoid and micropapillary components was only seen in the non-responder group, and squamous differentiation and lymph node metastasis were only seen in cases with a complete response. In the results of immunohistochemistry, the density of CD8-positive T-cells and Tregs was significantly increased in the responder group than in the non-responder group. In conclusion, younger age and a high number of tumor-infiltrating lymphocytes were predictive factors of a good response to immune checkpoint inhibitors, although further studies with more enrolled patients are necessary.

Lower urinary tract dysfunction in type 1 familial amyloidotic polyneuropathy in Kumamoto, Japan.

OBJECTIVE: To evaluate lower urinary tract dysfunction of type 1 familial amyloidotic polyneuropathy (FAP) patients in Kumamoto, Japan. METHODS: Lower urinary tract symptoms were evaluated in FAP patients. Urodynamic studies were evaluated in FAP patients as compared to those in control subjects. The location and distribution of amyloid deposits were evaluated in the urinary bladder in an autopsy case. RESULTS: In lower urinary symptoms, 86%, 19% and 38% patients showed difficulty in urination, urinary frequency and urinary incontinence. In detrusor function during filling cystometry, 14% patients showed detrusor overactivity. Moreover, 43% patients showed low compliance bladder, 62% and 38% patients showed normal and reduced bladder sensation, respectively. First desire to void (FDV), strong desire to void (SDV) and post-voided residual urine (PVR) were increased in FAP patients as compared to those in control subjects. In the urethral pressure profilometry, 71%, 10% and 19% patients showed incompetent, normal functional and overactive urethral closure mechanism, respectively. Maximum urethral pressure (MUP), maximum urethral closure pressure (MUCP) and functional profile length (FPL) were decreased in FAP patients compared to those in control subjects. CONCLUSION: Autonomic, somatic nerve systems and bladder detrusor musculature might be impaired in lower urinary tract of type 1 FAP patients in Kumamoto, Japan.

Neurologic toxicity associated with interferon alpha therapy for renal cell carcinoma.

A 67-year-old man received interferon alpha (IFN alpha) therapy for lung metastases of renal cell carcinoma (RCC). Multiple pulmonary metastases disappeared completely. However, neurological toxicity was detected by magnetic resonance imaging (MRI) as abnormal brain lesions. After discontinuation of IFN alpha therapy, his neurological symptoms and abnormal lesions on MRI disappeared completely. Complete remission of RCC has continued, and results of neurological study have remained normal for 5 years after discontinuation of IFN alpha therapy.