Prognostic impact of radiological tumor burden in patients with metastatic urothelial carcinoma treated with pembrolizumab.

PURPOSE: Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC. METHODS: We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab. Radiological tumor burden was represented by baseline tumor size (BTS) and baseline tumor number (BTN). Optimal cut-off value of BTS was determined as 50 mm using the Youden index (small BTS: n = 194, large BTS: n = 114). Overall (OS), cancer-specific (CSS), progression-free survival (PFS), and objective response rate (ORR) were compared. Non-linear associations between BTS and OS and CSS were evaluated using restricted cubic splines. RESULTS: Patients with large BTS were less likely to have undergone the surgical resection of the primary tumor (P = 0.01), and more likely to have liver metastasis (P < 0.001) and more metastatic lesions (P < 0.001). On multivariable analyses controlling for the effects of confounders (resection of primary tumor, metastatic site, number of metastases and lactate dehydrogenase level), large BTS and high BTN were independently associated with worse OS (HR 1.52; P = 0.015, and HR 1.69; P = 0.018, respectively) and CSS (HR 1.59; P = 0.01, and HR 1.66; P = 0.031, respectively), but not PFS. Restricted cubic splines revealed BTS was correlated with OS and CSS in linear relationships. Additionally, large BTS was significantly predictive of lower ORR and complete response rate on univariable analyses (P = 0.041 and P = 0.032, respectively), but its association disappeared on multivariable analyses. CONCLUSION: Radiological tumor burden has independent prognostic value with a linear relationship in pembrolizumab-treated patients with mUC and might help drive the earlier introduction of second-line pembrolizumab and/or switching to subsequent therapies.

The Genotypic and Phenotypic Characteristics Contributing to Flomoxef Sensitivity in Clinical Isolates of ESBL-Producing E. coli Strains from Urinary Tract Infections.

We carried out a molecular biological analysis of extended-spectrum ß-lactamase (ESBL)-producing E. coli strains and their sensitivity to flomoxef (FMOX). Sequence type (ST) analysis by multilocus sequence typing (MLST) and classification of ESBL genotypes by multiplex PCR were performed on ESBL-producing E. coli strains isolated from urine samples collected from patients treated at our institution between 2008 and 2018. These sequences were compared with results for antimicrobial drug susceptibility determined using a micro-liquid dilution method. We also analyzed cases treated with FMOX at our institution to examine its clinical efficacy. Of the 911 E. coli strains identified, 158 (17.3%) were ESBL-producing. Of these, 67.7% (107/158) were strain ST-131 in ST analysis. Nearly all (154/158; 97.5%) were CTX-M genotypes, with M-14 and M-27 predominating. The isolated strains were sensitive to FMOX in drug susceptibility tests. Among the patient samples, 33 cases received FMOX, and of these, 5 had ESBL-producing E. coli. Among these five cases, three received FMOX for surgical prophylaxis as urinary carriers of ESBL-producing E. coli, and postoperative infections were prevented in all three patients. The other two patients received FMOX treatment for urinary tract infections. FMOX treatment was successful for one, and the other was switched to carbapenem. Our results suggest that FMOX has efficacy for perioperative prophylactic administration in urologic surgery involving carriers of ESBL-producing bacteria and for therapeutic administration for urinary tract infections. Use of FMOX avoids over-reliance on carbapenems or ß-lactamase inhibitors and thus is an effective antimicrobial countermeasure.

HUGE RENAL ANGIOMYOLIPOMA (AML) IN TUBEROUS SCLEROSIS COMPLEX (TSC) WHICH IS CONTROLED BY EVEROLIMUS: A CASE REPORT.

We report a 43-year-old TSC man with repeated hemorrhage of bilateral renal AML. He was diagnosed with TSC based on the findings of facial angiofibroma, mental retardation and epilepsy in childhood. In 2011, he experienced three times in AML-associated hemorrhage from the left kidney and received selective transarterial embolotherapy (TAE). In 2013, he also experienced AML-associated hemorrhage from the right kidney and received selective TAE. To control his AML, treatments with Everolimus was started and well tolerated. So far, his renal AML remarkably shrunk without retroperitoneal hemorrhage for 24 months, while he had some episode of side effect.