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BackgroundThree immune-nutritional parameters exist for malignant tumors using serum C-reactive protein (CRP) and albumin: the Glasgow prognostic score (GPS), the modified GPS (mGPS), and the CRP-albumin ratio (CAR). However, it remains unclear which of the three parameters is the most predictive of prognosis. Therefore, this study compared the clinical and prognostic significance of these parameters for non-small cell carcinoma (NSCLC).MethodsThe study retrospectively enrolled 596 NSCLC patients who underwent surgical resection at the authors’ institution from January 2010 to December 2015 and investigated the clinicopathologic significance of GPS, mGPS, and CAR. The optimal cutoff value for CAR was determined by a receiver operating curve (ROC).ResultsThe median age of the patients was 69 years. Lymph node metastases were identified in 99 patients, and 455 patients had a diagnosis of stage 1 disease. The positivity for GPS was 7.6%, and that of mGPS (score, 1 or 2) was 12.2%. Of the 596 patients, 480 patients (80.5%) were classified in the high CAR group. In univariate survival analyses, all three parameters were associated significantly with postoperative survival. The multivariate analyses showed CAR to be an independent prognostic factor. Additionally, survival analyses of the stage 1 subgroup were performed because CAR was higher for patients with an advanced stage of disease or lymph node metastases. In these subgroup analyses, CAR also was an independent prognostic factor.ConclusionAs the most prognostic index, CAR may be useful among the immunonutritional parameters using CRP and albumin for resected NSCLC.

BackgroundInterleukin (IL)-38 was discovered in 2001 and is a member of the IL-1 family of cytokines. IL-38 shows anti-inflammatory activity in several inflammatory diseases. In lung adenocarcinoma, we previously demonstrated that high IL-38 expression in tumor cells was associated with poor prognosis. However, the role of IL-38 in the tumor microenvironment has not been clarified.MethodsIL-38-plasmid-transfected Lewis lung carcinoma cells (LLC-IL38) and empty vector-transfected LLC cells (LLC-vector) were established. Cell proliferation in vitro and tumor growth in vivo were examined, and immunohistochemical staining was used to assess tumor-infiltrating lymphocytes (TILs). A CD8+ lymphocyte depletion model was established to show the association between IL-38 and CD8+ lymphocytes. Moreover, we examined the association between IL-38 expression and CD8+ TILs in human samples, analyzing immunohistochemical staining in 226 patients with radically resected lung adenocarcinoma.ResultsTumor growth of LLC-IL38 in vivo was significantly increased compared with that of LLC-vector, although cell proliferation of LLC-IL38 in vitro was lower than that of LLC-vector. CD8+ TILs were significantly decreased in LLC-IL38 tumor compared with LLC-vector tumor. The difference in tumor growth between LLC-IL38 and LLC-vector became insignificant after depletion of CD8+ lymphocytes. In immunohistochemical staining in tissues from patients with lung adenocarcinoma, multivariate analysis showed high IL-38 expression was an independent negative predicter of high density of CD8+ TILs.ConclusionWe demonstrated that high IL-38 expression in tumor cells was significantly associated with reduction of CD8+ TILs and tumor progression. These results suggest that IL-38 could be a therapeutic target for lung cancer.

Background Many cancer patients suffer from the common side effect of chemotherapy-induced nausea and vomiting (CINV). Guidelines recommend a combination of two prophylactic antiemetics for moderately emetogenic chemotherapy (MEC) and three for highly emetogenic chemotherapy (HEC) and certain MEC regimens. Methods This multicenter, prospective, observational study analyzed data for 1,910 patients in Japan scheduled for MEC or HEC. Use of antiemetic prophylaxis in relation to type of chemotherapy, incidences of and risk factors for nausea, vomiting, and acute versus delayed CINV, and estimated incidence of CINV by staff were analyzed using Fisher’s exact test and multivariate logistic regression. The patients recorded the incidence of CINV and severity of nausea by visual analogue scales daily for 7 days after receiving chemotherapy. Results A total of 240 (20.1 %) HEC and 476 MEC patients (66.6 %) received 2 antiemetics, compared with 883 (73.9 %) and 200 (28.0 %), respectively, who received 3 antiemetics. Approximately 74 % of HEC and 95 % of MEC patients received antiemetic therapy in compliance with guidelines. Acute nausea and vomiting were well controlled, but high incidences of delayed nausea occurred in both HEC and MEC patients. Delayed vomiting ( p  < 0.0001) was significantly less frequent in patients receiving three compared with 2 antiemetics. Female sex was a major risk factor for CINV. Medical staff tended to overestimate the incidence of CINV. Among HEC regimens, the incidence of CINV and the degree of nausea on day 1 of anthracycline–cyclophosphamide combination therapy were higher than with a cisplatin-based regimen. Conclusions Adherence to antiemetic guidelines effectively controls vomiting but is less effective against delayed nausea in HEC and MEC patients. Identification of individual risk factors, such as female sex, will assist in the development of personalized treatments for CINV. More intensive antiemetic therapy or a different modality of prophylaxis should be considered for the control of acute CINV in an anthracycline–cyclophosphamide regimen.

Age- and sex-specific reference values for muscle mass and body composition are essential for evaluating childhood cancer survivors at risk of muscle loss and abnormal body composition. To establish standard values for Japanese children, we conducted a cross-sectional study of healthy children aged 6 to 17 years. From April to June 2023, height, weight, and body composition were measured via bioelectrical impedance analysis (Tanita MC 780 A-N) in 9,202 students at 16 schools in Fukuoka City and nearby areas in Japan. Boys had significantly higher lean mass index (LMI) than girls at all ages ( p  < 0.001). In boys, LMI and skeletal muscle mass index (SMI) showed strong positive correlations with age (γ = 0.748, γ = 0.806), whereas girls exhibited moderate correlations (γ = 0.482, γ = 0.622). Although no sex difference in SMI was observed at age 6, boys surpassed girls thereafter. Trunk LMI increased linearly with age in boys (γ = 0.904), while in girls it plateaued around age 13 (γ = 0.819). Upper limb LMI peaked in girls around 14 years (γ = 0.771), with strong growth seen in boys (γ = 0.824). Lower limb LMI correlated strongly with age in both sexes (boys γ = 0.909, girls γ = 0.868). Girls had consistently higher fat mass index (FMI) and body fat percentage (BFP) across all ages ( p  < 0.001). Boys showed little correlation between FMI/BFP and age (γ = 0.117, γ = 0.004), whereas girls exhibited weak positive correlations (γ = 0.544, γ = 0.595). In healthy Japanese children aged 6 to 17 years, boys show a progressive increase in lean body mass and muscle mass, whereas girls demonstrate an age-related increase in fat mass. These normative data would offer a useful reference for monitoring body composition in children, particularly in targeted interventions for childhood cancer survivors.

Delayed chemotherapy‐induced nausea and vomiting (CINV) is not well controlled in colorectal cancer (CRC) patients undergoing oxaliplatin (L‐OHP)‐based chemotherapy. Whether neurokinin‐1 receptor antagonist addition to a first‐generation 5HT3 antagonist (1st 5‐HT3RA) and dexamethasone (DEX) is beneficial to these patients remains controversial. Furthermore, whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV is unclear. We, therefore, investigated whether PALO+DEX or 1st 5‐HT3RA+DEX+APR was more effective in controlling delayed CINV, and the risk factors for delayed CINV, in CRC patients undergoing L‐OHP–based chemotherapy. Data were pooled from two prospective observational Japanese studies and a phase III trial to compare CINV incidence between the PALO + DEX (PALO) and 5‐HT3RA+DEX+APR (APR) groups by propensity score–matched analysis. CINV risk factors were identified using logistic regression models. The CINV incidence was higher in the PALO group than in the APR group. Logistic regression analysis revealed alcohol consumption, motion sickness, and the PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and the PALO+DEX regimen as those for delayed vomiting. Compared with prophylactic PALO + DEX, 1st 5‐HT3RA+DEX+APR was more effective in controlling delayed CINV. Thus, CRC patients receiving L‐OHP–based chemotherapy should be treated with three antiemetics, including APR. This study demonstrates that the triplet antiemetic prophylaxis with first‐generation 5HT3 receptor antagonist plus dexamethasone plus aprepitant was more effective in controlling delayed chemotherapy‐induced nausea and vomiting (CINV) compared with prophylaxis with palonosetron plus dexamethasone in colorectal cancer patients receiving oxaliplatin‐based chemotherapy.

Cisplatin (cis-diamminedichloroplatinum [CDDP]) is a widely used anticancer drug with a significant risk of nephrotoxicity. This study aimed to compare the nephroprotective effects of mannitol and furosemide as forced diuretics in patients receiving CDDP-based chemotherapy. This multicenter retrospective study analyzed 472 patients with cancer receiving CDDP (≥ 60 mg/m 2 ) with either mannitol or furosemide as forced diuretics. Patient characteristics were balanced using inverse probability treatment weighting. Nephrotoxicity was assessed using the Common Terminology Criteria for Adverse Events (ver. 5.0) criteria. The results showed that the incidence of nephrotoxicity was significantly lower in the furosemide group than in the mannitol group (6.2% vs. 23.2%, p < 0.007). The mean serum creatinine increase was significantly lower with furosemide (21.7% ± 19.3%) than with mannitol (29.5% ± 40.7%, p = 0.007). Hypertension, cisplatin dose ≥ 75 mg/m 2 , absence of magnesium supplementation, and mannitol use were associated with a higher risk of nephrotoxicity. Stratified analysis demonstrated furosemide’s superior nephroprotective effects regardless of nonsteroidal anti-inflammatory drug use. Thus, furosemide was associated with superior renoprotective effects compared with mannitol in CDDP-based chemotherapy regimens, thereby making it a viable therapeutic alternative to mannitol. Large randomized controlled trials are warranted to further validate our findings.

BackgroundImmunotherapy has become a standard treatment option for non-small cell lung cancer (NSCLC), with the tumor microenvironment attracting significant attention. CD8 + and forkhead box protein P3 + (FoxP3 +) tumor-infiltrating lymphocytes (TILs) influence the tumor microenvironment, but the clinical significance of CD8 + and FoxP3 + TILs in stage IA lung adenocarcinoma (LAD) is poorly understood.MethodsWe analyzed 203 patients with stage IA primary LAD who had undergone surgery at Kyushu University from January 2003 to December 2012. We evaluated CD8 + and FoxP3 + TILs by immunohistochemistry. We set the cutoff values at 50 cells/0.04 mm2 for CD8 + TILs and 20 cells/0.04 mm2 for FoxP3 + TILs, respectively. We divided the patients into four groups: CD8-Low/FoxP3-Low; CD8-High/FoxP3-Low; CD8-Low/FoxP3-High; and CD8-High/FoxP3-High. We compared clinical outcomes among them. Programmed cell death ligand-1 (PD-L1) expression by tumor cells was also evaluated as previously reported.ResultsRespectively, 104 (51.2%), 46 (22.7%), 22 (10.8%), and 31 (15.3%) patients were classified as CD8-Low/FoxP3-Low, CD8-High/FoxP3-Low, CD8-Low/FoxP3-High, and CD8-High/FoxP3-High. Both disease-free survival (DFS) and overall survival (OS) were significantly worse in the CD8-Low/FoxP3-High group than the other groups (5-year DFS: 66.3% vs. 90.5%; P = 0.0007, 5-year OS: 90.9% vs. 97.0%; P = 0.0077). In the multivariate analysis, CD8-Low/FoxP3-High and PD-L1 expression were independent prognostic factors of DFS, and lymphatic invasion, surgical procedure, and PD-L1 expression were independent prognostic factors of OS.ConclusionsCD8-Low/FoxP3-High was an independent prognostic factor of DFS (hazard ratio: 3.22; 95% confidence interval: 1.321–7.179; P = 0.0121) in stage IA LAD. Immunosuppressive conditions were associated with poor prognosis in stage IA LAD.

Background Patients with lung cancer who are treated with carboplatin-based chemotherapy regimens often experience chemotherapy-induced nausea and vomiting (CINV). However, knowledge on the effect of regimen and cofactors on the risk of CINV is limited. This study aimed to analyze and compare the incidence of CINV between lung cancer patients undergoing carboplatin plus pemetrexed (CBDCA+PEM) and those undergoing carboplatin plus paclitaxel (CBDCA+PTX) chemotherapy. Methods Pooled data of 240 patients from two prospective observational studies were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify risk factors for nausea and vomiting following chemotherapy. Results Delayed nausea was significantly more common in patients treated with CBDCA+PEM than in those treated with CBDCA+PTX (51.1% vs. 36.2%, P  = 0.04), but the incidence of vomiting did not significantly differ between the two groups (23.4% vs. 14.9%, P  = 0.14). The occurrence of CINV peaked on day 4 in the CBDCA+PTX group and on day 5 in the CBDCA+PEM group. Multivariate analysis showed that female sex, younger age, and CBDCA+PEM regimen were independent risk factors for delayed nausea, while female sex was an independent risk factor for delayed vomiting. Conclusions The CBDCA + PEM regimen has a higher risk of causing delayed nausea than the CBDCA + PTX regimen, and aggressive antiemetic prophylaxis should be offered to patients treated with CBDCA + PEM.

BackgroundSeveral inflammation-based prognostic scores have a prognostic value in patients with various cancers. This study investigated the prognostic value of various inflammation-based prognostic scores in patients who underwent a surgery for adenocarcinoma of the esophagogastric junction (AEG) and upper gastric cancer (UGC).MethodsWe reviewed data of 206 patients who underwent surgery for AEG and UGC. We calculated neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), modified GPS (mGPS), C-reactive protein (CRP)/albumin (Alb) ratio, prognostic index (PI), and prognostic nutritional index (PNI) and analyzed the relationship between these biomarkers and postoperative prognosis.ResultsIn multivariate analyses for overall survival, mGPS (P = 0.0337, hazard ratio [HR] = 5.211), PI (P = 0.0002, HR = 21.20), and PNI (P < 0.0001, HR = 6.907) were identified as independent predictive factors. A multivariate analysis for recurrence-free survival showed that only PI (P = 0.0006, HR = 11.89) and PNI (P = 0.0002, HR = 4.972) were independent predictive factors among the above-mentioned inflammation-based prognostic scores.ConclusionsIn various inflammation-based prognostic scores, PI and PNI were more strongly associated with poor prognosis in patients who underwent surgery for AEG and UGC.

Microsatellite instability (MSI) is now widely used as an indispensable biomarker. However, the relationship between MSI-H (high) and defective DNA mismatch repair (MMR) is not as straightforward as has been expected. Genome-edited cells carrying Lynch syndrome mutations do not exhibit drastic MSI typical in MSI-H ( i.e. Type B) but more subtle MSI ( i.e. Type A). In this study, we explored a connection between Type A MSI and 5-fluorouracil (5-FU) resistance in colorectal cancer patients. Using our precision and high-resolution MSI assay technique, tumour microsatellites were analysed in 30 colorectal cancer patients treated with FOLFOX or CAPOX. Among 30 tumours, eleven (37%) were judged as Type A MSI-positive. In Type A MSI + tumours, the patient response to fluoropyrimidine and oxaliplatin was significantly poor (Fisher’s exact test, p  = 0.021). Accordingly, median PFS and OS were significantly poor in Type A + patients (log-rank test, p  < 0.001/ p  = 0.009). Type A MSI was an independent predictor of patient prognosis in this pilot cohort (Cox regression analysis, p  = 0.003). Thus, more subtle Type A MSI better predicts fluoropyrimidine insensitivity in colorectal cancer patients, which may shed light on a hitherto overlooked connection between the MSI phenotypes and drug resistance in human cancer.