Prognostic significance of pre-treatment albumin-bilirubin grade in metastatic urothelial carcinoma receiving pembrolizumab.

BACKGROUND: Pre-treatment albumin-bilirubin grade is a useful biomarker for predicting prognosis in patients receiving immune checkpoint inhibitors for advanced malignancies. We evaluated the prognostic impact of pre-treatment albumin-bilirubin grade in patients receiving pembrolizumab for metastatic urothelial carcinoma. METHODS: In this multicenter retrospective study, we calculated pre-treatment albumin-bilirubin scores of 96 patients who received pembrolizumab for metastatic urothelial carcinoma between January 2018 and March 2022. Patients were classified according to albumin-bilirubin grade. Progression-free survival and cancer-specific survival were compared between the groups. To evaluate the prognostic impact of pre-treatment albumin-bilirubin grade, we also performed Cox proportional regression analyses for progression-free survival and cancer-specific survival. RESULTS: The median pre-treatment albumin bilirubin score was -2.52 (quartile: -2.76 to -2.10), and albumin-bilirubin grade was grade 1 in 37 patients (39%), grade 2a in 30 patients (31%), 2b in 22 patients (23%) and grade 3 in 7 patients (7%). The median progression-free survival and cancer-specific survival were 2 and 7 months, respectively. Progression-free survival and cancer-specific survival were significantly different between the albumin-bilirubin grade groups (P < 0.01 and P < 0.01, respectively) and prognosis became poorer as albumin-bilirubin grade increased. High albumin-bilirubin grade was shown in multivariable Cox proportional analyses to be independently associated with both poor progression-free survival and poor cancer-specific survival. CONCLUSIONS: High pre-treatment albumin-bilirubin grade could be a significant independent predictor of poor prognosis in patients receiving pembrolizumab for advanced urothelial carcinoma.

Usefulness of Preoperative High Systemic Immune-Inflammation Index as a Prognostic Biomarker in Patients Who Undergo Radical Cystectomy for Bladder Cancer: Multicenter Analysis.

Evidence of the prognostic value of pretreatment systemic immune-inflammation index (SII) after radical cystectomy (RC) for bladder cancer is limited. This study aims to assess the association between preoperative SII and prognosis after RC for bladder cancer. In this multicenter retrospective study, we calculated preoperative SII as well as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in 237 patients who underwent RC for bladder cancer between March 2009 and March 2018. Patients were classified into high SII and low SII groups by using the optimal cutoff value (438 × 109/L) based on receiver operating characteristic curve analysis for cancer-specific death. We compared cancer-specific survival (CSS) and overall survival (OS) between the two groups. To evaluate the prognostic impact of preoperative SII, we also performed Cox proportional regression analyses for CSS and OS. Of 237 patients, 127 patients were classified into the high SII group and 110 patients into the low SII group. During the follow-up period, 70 patients died of bladder cancer (30%) and 21 patients died from other causes (9%). Patients with high SII had significantly lower rates of CSS and OS than those with low SII (p < 0.01 and p < 0.01, respectively). Multivariable Cox proportional hazard analysis showed that high SII was independently associated with poor CSS (p = 0.01) and poor OS (p < 0.01). In conclusion, high SII could be an independent significant predictor of poor prognosis after RC in patients with bladder cancer.

Myosteatosis as a novel prognostic biomarker after radical cystectomy for bladder cancer.

This study aims to evaluate the influence of myosteatosis on survival of patients after radical cystectomy (RC) for bladder cancer. We retrospectively identified 230 patients who underwent RC for bladder cancer at our three institutions between 2009 and 2018. Digitized free-hand outlines of the left and right psoas muscles were made on axial non-contrast computed tomography images at level L3. To assess myosteatosis, average total psoas density (ATPD) in Hounsfield Units (HU) was also calculated as an average of bilateral psoas muscle density. We compared cancer-specific survival (CSS) between high ATPD and low ATPD groups and performed cox regression hazard analyses to identify the predictors of CSS. Median ATPD was 44 HU (quartile: 39-47 Hounsfield Units). Two-year CSS rate in overall patients was 76.6%. Patients with low ATPD (< 44 HU) had significantly lower CSS rate (P = 0.01) than patients with high ATPD (≥ 44 HU). According to multivariate analysis, significant independent predictors of poor CSS were: Eastern Cooperative Oncology Group performance status ≥ 1 (P = 0.03), decreasing ATPD (P = 0.03), non-urothelial carcinoma (P = 0.01), pT ≥ 3 (P < 0.01), and pN positive (P < 0.01). In conclusion, myosteatosis (low ATPD) could be a novel predictor of prognosis after RC for bladder cancer.

Placental extract ameliorates liver fibrosis in a methionine- and choline-deficient diet-induced mouse model of non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, which ultimately leads to cirrhosis and hepatocellular carcinoma. We previously showed that human placental extract (hPE) was intramuscularly injected to ameliorates liver injury in a methionine- and choline-deficient (MCD) diet-induced NASH model. In the present study, we investigated the effects of hPE using dB/dB mice which exhibit obesity and insulin resistance and are thought to reproduce the pathological background of NASH. The MCD-diet induced liver atrophy accompanied by fibrosis around the liver sinusoids. hPE dose-dependently reduced the perivascular fibrosis. Moreover, αSMA-positive activated hepatic stellate cells increased in number in mice on the MCD diet, with this effect reversed by hPE treatment. hPE significantly decreased expression of Acta2, Col1a1, and Tgfb1 genes in hepatic stellate cells, and inhibited Smad phosphorylation. Moreover, hPE treatment increased the expression of the anti-oxidative genes Hmox1, Nqo1, Cat, and Sod1, and significantly enhanced nuclear factor erythroid 2-related factor 2 activity. Furthermore, hPE decreased the expression of Nox4 and attenuated the levels of intracellular reactive oxygen species. These results, along with our previous study, suggest that hPE effectively ameliorates liver fibrosis in NASH. This beneficial effect may, in part, be due to suppression of hepatic stellate cell activation.