Impact of an enhanced recovery protocol in frail patients after intracorporeal urinary diversion.

OBJECTIVE: To determine whether an enhanced recovery after surgery (ERAS) protocol enhances bowel recovery and reduces postoperative ileus (POI) in both non-frail and frail patients after robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS: This retrospective cohort study included 186 patients (104 with and 82 without ERAS) who underwent iRARC between 2012 and 2023. 'Frail' patients was defined as those with a low Geriatric-8 questionnaire score (≤13). The primary outcomes were postoperative bowel recovery and the incidence of POI. Secondary outcomes included length of stay (LOS), 30- and 90-day complications, 90-day readmission rate, and POI predictors. RESULTS: The ERAS group exhibited a significantly shorter LOS, early bowel recovery, a lower POI rate, fewer 90-day high-grade complications, and fewer 90-day readmissions than the non-ERAS group in the entire cohort. Non-frail patients in the ERAS group had a lower rate of POI (7.1% vs. 22.1%; P = 0.008), whereas ERAS did not reduce POI in frail patients (44.1% vs. 36.6%; P = 0.50). In the multivariate analysis, ERAS was associated with a reduced risk of POI in both the entire cohort (odds ratio [OR] 0.39, P = 0.01) and in non-frail patients (OR 0.24, P = 0.01), whereas ERAS was not likely to reduce POI (OR 1.14, P = 0.70) in frail patients. Prehabilitation was identified as a favourable predictor of POI. CONCLUSIONS: The ERAS protocol did not reduce POI in frail patients after iRARC, although it enhanced bowel recovery and reduced POI in non-frail patients. Prehabilitation for frail patients might reduce POI.

Genotype-phenotype correlation of renal lesions in the tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by loss-of-function mutations in either of two tumor suppressor genes, TSC1 and TSC2. These mutations lead to the growth of benign tumors and hamartomas in many organs, including those of the central nervous system, the skin, and the kidneys. To investigate the genotype-phenotype correlation, we performed sequence analysis of the TSC1/2 genes using next-generation sequencing. We classified 30 patients with TSC whose pathogenic variants were identified into two groups: those with mutations producing premature termination codons (PTCs) and those with missense mutations. Then, we compared the phenotypes between the two groups. Patients with a PTC were significantly more likely to manifest the major symptoms of the diagnostic criteria than those without a PTC (P = 0.035). The frequencies of subependymal nodules (P = 0.026), cortical tubers (P = 0.026), and renal cysts (P = 0.026) were significantly higher in PTC-containing variants than in cases without a PTC. When the analyses were limited to renal angiomyolipoma (AML) cases with TSC2 mutations, there was no difference in tumor size between cases with and without a PTC. However, the cases with a PTC showed a trend toward disease onset at a younger age and multiple tumors, and bilateral disease was observed in their AML lesions. TSC patients with PTC-producing mutations might potentially manifest more severe TSC phenotypes than those with missense mutations. A larger-scale study with appropriate samples deserves further investigation.

Tryptophan 2,3-dioxygenase in tumor cells is associated with resistance to immunotherapy in renal cell carcinoma.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme associated with immunomodulation through its regulation of the tryptophan-kynurenine (Kyn) pathway in advanced cancers, including metastatic renal cell carcinoma (mRCC). However, the failure of IDO1 inhibitors when used in combination with immune checkpoint inhibitors (ICIs), as observed in clinical trials, raises a number of questions. This study aimed to investigate the association of tryptophan 2,3-dioxygenase (TDO) and IDO1 with cancer development and resistance to immunotherapy in patients with RCC. In our analysis of RCC tissue samples, tissue Kyn levels were elevated in advanced-stage RCC and correlated well with TDO expression levels in RCC tumor cells. In patients with mRCC, TDO rather than IDO1 was expressed in RCC tumor cells, showing a strong association with Kyn expression. Furthermore, immunohistochemical staining of TDO was strongly associated with the staining intensity of forkhead box P3, as well as ICI therapy response and survival in patients with mRCC. Our study is the first to show that TDO expression in tumor tissues is associated with progression and survival, confirming its potential as a predictive biomarker of primary resistance to immunotherapy in patients with mRCC. Our findings suggest that strategies aimed at inhibiting TDO, rather than IDO1, in combination with ICI therapy may aid in the control of mRCC progression.