Although immune checkpoint inhibitors have shown benefit for advanced urothelial carcinoma (aUC) patients, prognostication of treatment efficacy and response duration remains a clinical challenge. We evaluated the expression of immune markers in the tumor microenvironment and assessed their associations with response to and survival after pembrolizumab treatment in 26 aUC patients. High levels of CD8⁺ tumor-infiltrating lymphocytes (TILs) were associated with favorable objective responses (23.0% vs. 15.3%, p = 0.0425), progression-free survival (median, 8.8 vs 2.1 months; hazard ratio (HR), 0.24; 95% confidence interval (CI), 0.07–0.66, p = 0.0060), and overall survival (median, >24.0 vs. 5.3 months; HR, 0.17; 95% CI, 0.04–0.56, p = 0.0034) compared with low levels. High interferon-gamma (IFNγ) expression levels were associated with longer post-progression survival (median, 4.9 vs. 1.0 months; HR, 0.18; 95% CI, 0.04–0.59, p = 0.0027) compared with low expression. Multivariate analysis incorporating clinical prognosticators demonstrated that the coincidence of low CD8⁺ T cells/IFNγ was an independent factor for unfavorable overall survival after pembrolizumab treatment (HR, 4.07; 95% CI, 1.36–12.73; p = 0.0125). The combination of low CD8⁺ TILs and IFNγ expression was an independent prognostic factor with predictive ability equivalent to previously reported clinical prognosticators.

In robot-assisted surgery, in which haptics should be absent, surgeons experience haptics-like sensations as “pseudo-haptic feedback”. As surgeons who routinely perform robot-assisted laparoscopic surgery, we wondered if we could make these “pseudo-haptics” explicit to surgeons. Therefore, we created a simulation model that estimates manipulation forces using only visual images in surgery. This study aimed to achieve vision-based estimations of the magnitude of forces during forceps manipulation of organs. We also attempted to detect over-force, exceeding the threshold of safe manipulation. We created a sensor forceps that can detect precise pressure at the tips with three vectors. Using an endoscopic system that is used in actual surgery, images of the manipulation of excised pig kidneys were recorded with synchronized force data. A force estimation model was then created using deep learning. Effective detection of over-force was achieved if the region of the visual images was restricted by the region of interest around the tips of the forceps. In this paper, we emphasize the importance of limiting the region of interest in vision-based force estimation tasks.

PURPOSE: Circulating tumor DNA (ctDNA) analysis is an alternative to tissue biopsy for genotyping in various cancers. We aimed to establish a plasma ctDNA sequencing assay, then evaluate its clinical utility in advanced urothelial cancer (UC). MATERIALS AND METHODS: This study included 82 patients with muscle-invasive or metastatic UC. A total of 158 blood samples and 73 tumor tissue samples were sequenced using our designed panel covering 53 UC-relevant genes and TERT promoter. We investigated the association between the proportion of ctDNA in total cell-free DNA (ctDNA fraction) and response to pembrolizumab treatment. ctDNA dynamics were explored during systemic therapy. RESULTS: In paired tissue-ctDNA samples with estimated tumor fraction, half (50.2%) of the somatic mutations were shared between both sources, while some (17.6%) mutations were found only in ctDNA. In the metastatic setting, on-treatment increase in ctDNA fraction during pembrolizumab treatment was significantly associated with a poor response rate (18.7% v 76.1%; P = .001) and progression-free survival (median 2.8 v 9.8 months; P < .001). A comparison of cancer cell fraction, the fraction of tumor cells carrying somatic mutations, between pembrolizumab initiation and on-treatment showed a strong correlation among patients where ctDNA fraction increased during treatment ( r = 0.73). By contrast, no correlation was observed in patients without ctDNA fraction increase ( r = 0.09). Most mutations newly detected at pembrolizumab resistance have already been identified in tumor tissues at earlier stages. CONCLUSION: Our newly established assay is suitable for assessing the genomic profile of ctDNA in patients with advanced UC. Our data may support future analyses of prognostic or predictive biomarkers for UC.

The anatomic features of a horseshoe kidney are unique—the kidney is fixed and poorly mobile, with many arterial and venous blood supplies, thereby complicating minimally invasive surgery for renal cancer in this setting. Several reports have described robot-assisted partial nephrectomy (RAPN) to treat renal cancer in a horseshoe kidney, but no reports of RAPN for renal cancer in the isthmus of a horseshoe kidney have been published to date. This case report describes the technique and usefulness of RAPN for treatment of renal cancer located in the isthmus of a horseshoe kidney.