Nomograms to predict tumor regression grade (TRG) and ypTNM staging in patients with locally advanced esophageal cancer receiving neoadjuvant therapy.

BACKGROUND: Neoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult. METHODS: A retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors. RESULTS: A total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility. CONCLUSION: The nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC.

Prognostic and clinicopathological significance of tertiary lymphoid structure in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary reason for cancer-related deaths globally. Tertiary lymphoid structure (TLS) is an organized collection of immune cells acquired in non-physiological, non-lymphoid tissues. High expression of TLS in tumor tissues is generally associated with better prognosis. This research aimed to investigate the prognostic and clinicopathological significance of TLS in patients with NSCLC. METHODS: A comprehensive literature search was conducted based on Pubmed, EMBASE, and Cochrane Library databases to identify eligible studies published up to December 8, 2023. The prognostic significance and clinicopathological value of TLS in NSCLC were evaluated by calculating the combined hazard ratios (HRs) and odds ratios (ORs) and their 95% confidence intervals (CIs). Following that, additional analyses, including subgroup analysis and sensitivity analysis, were conducted. RESULTS: This meta-analysis evaluated the prognostic and clinicopathological significance of TLS in 10 studies involving 1,451 patients with NSCLC. The results revealed that the high levels of TLS were strongly associated with better overall survival (OS) (HR = 0.48, 95% CI: 0.35-0.66, p < 0.001), disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 0.37, 95% CI: 0.24-0.54, p < 0.001), and disease-specific survival (DSS) (HR = 0.45, 95% CI: 0.30-0.68, p < 0.001) in NSCLC patients. In addition, the increased expression of TLS was closely related to the Tumor Node Metastasis (TNM) stage of tumors (OR = 0.71, 95% CI: 0.51-1.00, p < 0.05) and neutrophil-lymphocyte ratio (NLR) (OR = 0.33, 95% CI: 0.17-0.62, p < 0.001). CONCLUSIONS: The results revealed that highly expressed TLS is closely associated with a better prognosis in NSCLC patients. TLS may serve as a novel biomarker to predict the prognosis of NSCLC patients and guide the clinical treatment decisions.

Prognostic significance and survival benefits of postoperative adjuvant chemotherapy in patients with stage IA lung adenocarcinoma with non-predominant micropapillary components.

BACKGROUND: The prognostic significance of adjuvant chemotherapy (ACT) for patients with stage IA micropapillary non-predominant (MPNP) lung adenocarcinoma (LUAD) remains unknown. This study aimed to investigate the effects of postoperative ACT in patients with stage IA MPNP-LUAD. METHODS: A total of 149 patients with pathological stage IA MPNP-LUAD who underwent surgery at our center were retrospectively analyzed. Propensity score matching (PSM) analysis was conducted to reduce potential selection bias. Kaplan-Meier analyses were used to assess the impact of ACT on recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS). Subgroup analyses were performed for the survival outcomes based on the percentage of micropapillary components. Cox proportional hazards regression analyses were applied to identify risk factors associated with survival. RESULTS: The receipt or non-receipt of postoperative ACT had no significant effect on RFS, OS, and DSS among all enrolled patients with stage IA MPNP-LUAD (P > 0.05). For patients with a micropapillary component > 5%, the 5-year rates of RFS, OS, and DSS were significantly higher in the ACT group compared to the observation group, both before and after PSM (P < 0.05). However, the differences between the two groups were not significant for patients with a micropapillary component ≤ 5% (P > 0.05). The resection range (HR = 0.071; 95% CI: 0.020-0.251; P < 0.001), tumor size (HR = 2.929; 95% CI: 1.171-7.330; P = 0.022), and ACT (HR = 0.122; 95% CI: 0.037-0.403; P = 0.001) were identified as independent prognostic factors for RFS through Cox regression analysis. CONCLUSION: Patients with stage IA MPNP-LUAD who have a micropapillary component greater than 5% might benefit from postoperative ACT, while those with a micropapillary component ≤ 5% did not appear to derive the same benefit from postoperative ACT.

Prognostic significance of Lymphocyte-activation gene 3 (LAG3) in patients with solid tumors: a systematic review, meta-analysis and pan-cancer analysis.

BACKGROUND: Lymphocyte-activation gene 3 (LAG3) is a recently discovered immune checkpoint molecule that has been linked to immunosuppression and the advancement of cancer in different types of solid tumors. This study aimed to evaluate the prognostic importance of LAG3 and its role in the immune system within solid tumors. METHODS: Extensive literature searches were conducted using the Pubmed, EMBASE, and Cochrane Library databases to identify relevant studies exploring the effect of LAG3 on survival outcomes. Pooled hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to evaluate the prognostic values of LAG3. Afterwards, subgroup analysis and sensitivity analysis were conducted. Pan-cancer analysis investigated the possible relationships between LAG3 expression and genetic alterations, RNA methylation modification-related genes, genomic instability, immune checkpoint genes, and infiltration of immune cells. RESULTS: A total of 43 studies with 7,118 patients were included in this analysis. Higher expression of LAG3 was associated with worse overall survival (HR = 1.10, 95% CI 1.01-1.19, P = 0.023), but not disease-free survival (HR = 1.41, 95% CI 0.96-2.07, P = 0.078), progression-free survival (HR = 1.12, 95% CI 0.90-1.39, P = 0.317) or recurrence-free survival (HR = 0.98, 95% CI 0.81-1.19, P = 0.871). Subgroup analysis showed that LAG3 might play different prognostic roles in different solid tumors. LAG3 expression was positively associated with immune cell infiltration and immune checkpoint genes in all of the cancers included. LAG3 expression was also found to be associated with microsatellite instability (MSI), copy number variation (CNV), simple nucleoside variation (SNV), tumor mutation burden (TMB), and neoantigen in various types of cancers. CONCLUSIONS: Elevated expression of LAG3 is linked to poorer prognosis among patients diagnosed with solid cancers. LAG3 might play varying prognostic roles in different types of solid tumors. Given its substantial involvement in cancer immunity and tumorigenesis, LAG3 has garnered attention as a promising prognostic biomarker and a potential target for immunotherapy.

Nomogram based on TNM stage to predict the prognosis of thymic epithelial tumors (TETs) patients undergoing extended thymectomy.

Background: Thymomas and thymic carcinoma are thymic epithelial tumors (TETs) of the anterior mediastinum. On the basis of The AJCC 8th Edition of TNM classification, no prognostic prediction model has been established for TETs patients undergoing surgical resection. In this study, based on data from Qilu Hospital of Shandong University, we identified prognostic factors and developed a nomogram to predict the prognosis for TETs patients undergoing extended thymectomy. Methods: Patients with TETs who underwent thymectomy between 2010 and 2020 were consecutively enrolled. An analysis of multivariate Cox regression and stepwise regression using the Akaike information criterion (AIC) was conducted to identify prognostic factors, and a nomogram for TETs was derived from the results of these analyses. The model was validated internally with the Kaplan-Meier curves, ROC curves and calibration curves. Results: There were 350 patients with TETs enrolled in the study, and they were divided into a training group (245,0.7) and a validation group (105,0.3). Age, histological type, tumor size, myasthenia gravis, and TNM stage were independent prognostic factors for CSS. The Kaplan-Meier curves showed a significant difference between high nomorisk group and low nomorisk group. A nomogram for CSS was formulated based on the independent prognostic factors and exhibited good discriminative ability as a means of predicting cause-specific mortality, as evidenced by the area under the ROC curves (AUCs) of 3-year, 5-year, and 10-year being 0.946, 0.949, and 0.937, respectively. The calibration curves further revealed excellent consistency between the predicted and actual mortality when using this nomogram. Conclusion: There are several prognostic factors for TETs. Based on TNM stage and other prognostic factors, the nomogram accurately predicted the 3-, 5-, and 10-year mortality rates of patients with TETs in this study. The nomogram could be used to stratify risk and optimize therapy for individual patients.

Feasibility research of enhanced recovery after surgery implemented in esophageal cancer patients who underwent neoadjuvant chemotherapy.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a perioperative management protocol to accelerate patient recovery. This study aimed to evaluate the feasibility of ERAS protocols implemented in patients who underwent neoadjuvant chemotherapy (NACT) before minimally invasive McKeown esophagectomy. METHODS: This retrospective study compared the short-term clinical outcomes in esophagectomy patients from June 2018 to June 2021. Subjects were divided into two categories: those who underwent NACT (NACT group) and the non-NACT group. RESULTS: There was no significant difference in total postoperative complication morbidity between the NACT and non-NACT groups (21.2% vs. 20.7%, P=0.936). In addition, the hospital length of stay post-surgery (7.90 vs. 7.71 days, P=0.424) was not significantly longer when compared to the non-NACT group. The time to chest tube removal (5.37 vs. 5.13 days, P=0.238) and first bowel movement (2.92 vs. 3.01 days, P=0.560) was also similar between the two groups. CONCLUSIONS: There was no significant difference in postoperative complications rate, postoperative hospital length of stay, and readmission rate between the two group. This study proved that ERAS protocols seemed to be safe and feasible for patients who received NACT before esophagectomy.

Enhanced Recovery After Surgery Improves Short-term Outcomes in Patients Undergoing Esophagectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a perioperative management protocol used to accelerate patient recovery. This study evaluated its benefits in patients with resectable esophageal cancer. METHODS: This retrospective study compared patients before (January 2013 to December 2016) and after (June 2018 to December 2020) ERAS protocol implementation in our hospital. A propensity score-matched analysis was used to compare short-term surgical outcomes between ERAS and non-ERAS groups. After propensity score matching each group included 243 patients. RESULTS: There were significant differences in hospital length of stay after surgery (7.40 vs 11.17 days, P < .001) and hospitalization cost (¥69380 vs ¥78075, P < .001) between the ERAS and non-ERAS groups. The time to chest tube removal (4.91 vs 7.16 days, P < .001) and first bowel movement (2.87 vs 3.97 days, P < .001) was significantly shorter in the ERAS group. However there was no significant difference in total postoperative complication morbidity (20.2% vs 25.1%, P = .193). The complication of postoperative atelectasis or pneumonia was significantly lower in the ERAS group (P = .003), but there was no significant difference in occurrence of at least grade III complications between the 2 groups (12.3% vs 11.5%, P = .889). CONCLUSIONS: We demonstrated that ERAS could reduce hospital stay, numerical pain scores, and hospitalization costs without increasing postoperative complication and readmission. Furthermore subgroup analyses revealed that ERAS was safe for older people (>70 years old).

Platelet Count is Associated with the Rate of Lymph Node Metastasis in Lung Adenocarcinoma.

PURPOSE: Emerging studies have revealed that platelets are involved in tumor metastasis in lung adenocarcinoma (ADC). The solid pathological subtype of lung ADC is associated with metastasis, recurrence, and poor prognosis. However, there is no study exploring the relationship between platelets and different lung pathological subtypes. PATIENTS AND METHODS: The association between platelet counts and lymph node metastasis was analyzed in 852 patients with lung ADC who underwent surgery and lymph node dissection. Multivariate logistic analysis was conducted to identify the risk factors of lymph node metastasis. Then, lymph node metastasis and other factors were analyzed to determine their correlation with platelet count and histological subtype. RESULTS: We found that the platelet count was associated with lymph node metastasis (P = 0.01) in multivariable analysis, independent of tumor size, predominant subtype, visceral pleural invasion, and microvessel invasion. In patients with a platelet count ≥300 × 109/L, the rate of lymph node metastasis was 38.5%, almost twice as high as that in patients with a platelet count <300 × 109/L (23.2%). Additionally, elevated platelet counts, even those within the normal range, were significantly associated with a higher rate of lymph node metastasis. The mean platelet count in patients with solid-predominant histology (269.70 ± 69.38 × 109/L) was significantly higher than that in patients with other histologies (P < 0.001). CONCLUSION: Elevated platelet counts are significantly associated with a higher rate of lymph node metastasis, even if the platelet counts are within the reference range. Platelet counts were significantly higher in patients with solid-predominant histology than in patients with other histologies. In addition, VEGF-C may play an important role in lymphatic metastasis in patients with lung ADC. We hypothesize that antiplatelet therapy may reduce lymph node metastasis in lung ADC patients.

Karrikin Signaling Acts Parallel to and Additively with Strigolactone Signaling to Regulate Rice Mesocotyl Elongation in Darkness.

Seedling emergence in monocots depends mainly on mesocotyl elongation, requiring coordination between developmental signals and environmental stimuli. Strigolactones (SLs) and karrikins are butenolide compounds that regulate various developmental processes; both are able to negatively regulate rice (Oryza sativa) mesocotyl elongation in the dark. Here, we report that a karrikin signaling complex, DWARF14-LIKE (D14L)-DWARF3 (D3)-O. sativa SUPPRESSOR OF MAX2 1 (OsSMAX1) mediates the regulation of rice mesocotyl elongation in the dark. We demonstrate that D14L recognizes the karrikin signal and recruits the SCFD3 ubiquitin ligase for the ubiquitination and degradation of OsSMAX1, mirroring the SL-induced and D14- and D3-dependent ubiquitination and degradation of D53. Overexpression of OsSMAX1 promoted mesocotyl elongation in the dark, whereas knockout of OsSMAX1 suppressed the elongated-mesocotyl phenotypes of d14l and d3 OsSMAX1 localizes to the nucleus and interacts with TOPLESS-RELATED PROTEINs, regulating downstream gene expression. Moreover, we showed that the GR24 enantiomers GR245DS and GR24 ent-5DS specifically inhibit mesocotyl elongation and regulate downstream gene expression in a D14- and D14L-dependent manner, respectively. Our work revealed that karrikin and SL signaling play parallel and additive roles in modulating downstream gene expression and negatively regulating mesocotyl elongation in the dark.