Clinicopathological and prognostic features of Borrmann type IV gastric cancer versus other Borrmann types: A unique role of signet ring cell carcinoma.

Background: Evidence specifically comparing the clinicopathology of Borrmann type IV (B-IV) gastric cancer with that of other Borrmann types is insufficient. Methods: A total of 3130 patients with advanced gastric cancer who underwent gastrectomy from January 2001 to September 2017 were enrolled in the analysis. Logistic regression and survival analysis methodology were used to investigate factors associated with peritoneal metastasis and overall survival (OS). Results: Of the total cohort, 264 (8.43%) patients were B-IV type, 1752 (55.97%) were small-size other Borrmann types, and 1114 (35.59%) were large-size other Borrmann types. Signet ring cell carcinoma (SRC) was more common in B-IV types than in other Borrmann types (33.71% vs 11.42% vs 12.66%, P < 0.001). In B-IV gastric cancers, SRC was significantly associated with peritoneal metastasis (HR = 1.898, 95% CI = 1.112 ~ 3.241, P = 0.019) and poorer OS (HR = 1.492, 95% CI = 1.088 ~ 2.045, P = 0.013) in multivariable analysis. Furthermore, stratified analysis revealed that SRC had worse survival than adenocarcinoma in the B-IV subgroups, with locally advanced stages (stages II ~ III) or negative surgical margins (all P < 0.05). In contrast, SRC failed to be significantly associated with peritoneal metastasis and poor OS in other Borrmann types (all P > 0.05). Conclusion: SRC was more common in B-IV gastric cancer than in other Borrmann types. It was significantly associated with peritoneal metastasis and poorer OS in the B-IV type but not in other Borrmann types. As a unique prognostic factor for B-IV gastric cancer, SRC might help evaluate risk stratification and optimize treatment for this entity, especially for patients with locally advanced stages or R0 resection.

Transcriptomic study of gastrointestinal stromal tumors with liver metastasis.

Introduction: GIST (gastrointestinal stromal tumor) is the most prominent mesenchymal neoplasms of the gastrointestinal tract, and liver is the most common metastasis site for GIST. The molecular mechanism leading to liver metastasis of GIST is currently unclear. Methods: With the goal of revealing the underlying mechanism, we performed whole-genome gene expression profiling on 18 pairs of RNA samples comprised of GIST tissues (with liver metastasis) and corresponding non-tumor tissues. After identifying differentially expressed gene, functional annotation and signal pathway analyses were conducted. GSE13861, datasets that compare GIST (without liver metastasis) with adjacent tissues, served as a comparison. Results: A total of 492 up-regulated genes and 629 down-regulated genes were identified as differentially expressed genes between liver metastasis tissues and non-tumor tissues. We characterized expression patterns of DEGs identified from our cohort and GSE13861 that show signatures of enrichment for functionality. In subsequent gene set enrichment analysis, differentially expressed genes were mainly enriched in Epithelial Mesenchymal Transition in both datasets. 493 genes were overlapped among our whole-genome gene expression profiling results and GSE13861, consisting 188 up-regulated genes and 305 down-regulated genes. By using CytoHubba plugin of Cytoscape, CDH1, CD34, KIT, PROM1, SOX9, FGF2, CD24, ALDH1A1, JAG1 and NES were identified as top ten hub genes in tumorigenesis and liver metastasis of GIST. higher expression levels of FGF2, JAG1, CD34, ALDH1A1 and the lower expression level of CDH1 were respectively associated with unfavorable overall survival. Meanwhile higher expression levels of CD34, FGF2, KIT, JAG1, ALDH1A were correlated with worse disease-free survival. Discussion: The present study may help to provide candidate pathways and targets for treatment of GIST and prevention methods to liver metastasis.

The inflammatory-nutritional score and nomogram for R0 resected head and neck soft tissue sarcoma.

OBJECTIVES: To explore the predictive value of inflammatory-nutritional score (INS) and a nomogram for survivals in head and neck soft tissue sarcoma (HNSTS) patients with negative resection margins (R0). METHODS: Clinical characteristics and hematological features of 315 HNSTS patients underwent R0 surgery were analyzed. RESULTS: The 5-year overall survival (OS) rate, 3-year recurrence-free survival rate and disease-free survival (DFS) rate were 77.3%, 61.0% and 55.4%, respectively. High INS was associated with a deep tumor location (p < 0.001), high tumor grade (p < 0.001), and advanced AJCC stage (p < 0.001). The low-risk group (INS 0) exhibited a higher 5-year OS rate and 3-year DFS rate than others (87.6% vs. 81.3% vs. 53.3%, p < 0.001; 62.2% vs. 56.9% vs. 37.9%, p = 0.007). The INS (p = 0.023), tumor depth (p < 0.001), pT classification (p = 0.022), pN classification (p < 0.001) and tumor grade (p < 0.001) were independent survival predictors. Moreover, a novel nomogram for predicting OS was generated and assessed by the concordance index, exhibiting a better performance than the p7TNMG classification alone (p < 0.001). CONCLUSIONS: For R0 resected HNSTS patients, the oncological outcomes can be predicted using the INS system and a specific nomogram.

Time to Local Recurrence as a Predictor of Survival in Adult Head and Neck Soft Tissue Sarcoma.

OBJECTIVES: We sought to evaluate the impact of the time interval from surgical resection to local recurrence (TTLR) on clinical outcomes in head and neck soft tissue sarcoma (HNSTS). METHODS: A total of 401 patients who underwent R0 resection for primary HNSTS were included in this study. Patients with local recurrence as the first event after their initial resection were divided into early local recurrence (ELR) or late local recurrence (LLR) groups according to TTLR. Multiple survival analyses were performed to identify the independent prognostic predictors of overall survival (OS) and survival after local recurrence (SAR). RESULTS: Two hundred and nine of the 401 patients (52.1%) developed local recurrence during a median follow-up period of 134.6 months. Patients in the ELR group had a shorter median OS time (35.0 vs. 120.6, p < 0.001) and lower 5-year OS rate (47.7% vs. 80.9%, p < 0.001) than those in the LLR group. Moreover, the ELR group exhibited worse SAR (p = 0.001) than the LLR group, and multivariate analyses demonstrated TTLR as an independent prognostic factor for SAR (p = 0.048) and OS (p = 0.004). Additionally, re-resection significantly prolonged SAR than other salvage interventions or no treatment (p < 0.001). CONCLUSION: In patients with HNSTS, ELR after R0 resection presents adverse effects on OS and SAR than those with LLR, and TTLR could serve as a promising predictor for survival. Salvage therapies, especially the re-resection could improve SAR and should be recommended when there are surgical indications after recurrence. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2174-2182, 2023.

Impact of time to first relapse on long-term outcome in adult retroperitoneal sarcoma patients after radical resection.

BACKGROUND: Local recurrence of primary retroperitoneal sarcoma (RPS) is one of the major causes of treatment failure and death. We attempted to assess the effects of time to local recurrence (TLR) on the survival after recurrence (SAR) and overall survival (OS) of RPS. METHODS: Included in this study were 224 patients who underwent R0 resection for primary RPS at our institution between January 2000 and December 2020, 118 of whom had local recurrence. Based on the median TLR (19.8 months), patients were divided into two groups: early local recurrence (ELR < 20 months) and late local recurrence (LLR > 20 months). The Kaplan-Meier method was employed to calculate the local recurrence-free survival (LRFS), SAR and OS. Univariate and multivariate analyses were conducted to explore the prognostic value of TLR. RESULTS: The median follow-up time was 60.5 months for the entire cohort and 58.5 months for the recurrence cohort. There were 60 (50.8%) patients in the ELR group and 58 (49.2%) in the LLR group. The ELR group exhibited a worse SAR (29.2 months vs. 73.4 months, P < 0.001), OS (41.8 months vs. 120.9 months, P < 0.001), and a lower 5-year OS rate (35.9% vs. 73.2%, P = 0.004) than the LLR group. Furthermore, multivariate analysis indicated that TLR was an independent prognostic indicator for SAR (P = 0.014) and OS (P < 0.001). CONCLUSIONS: In patients with RPS, ELR after R0 resection presents adverse effects on OS and SAR than those with LLR, and TLR could serve as a promising predictor for OS and SAR.

Comparison of a Tumor-Ratio-Metastasis Staging System and the 8th AJCC TNM Staging System for Gastric Cancer.

BACKGROUND: Despite the implementation of the 8th American Joint Committee on Cancer (AJCC) TNM staging system for gastric cancer (GC) in 2017, it still holds a significant level of stage migration which affects patients' proper classification and accurate prognosis. Here, to reduce this effect, we evaluated the prognostic value of a lymph node ratio (LNR) and established a novel tumor-ratio-metastasis (TRM) staging system. METHOD: The data of 15,206 GC patients from the Sun Yat-sen University Cancer Center (Training set; n=2,032) and the US Surveillance, Epidemiology, and End Results (SEER) database (Validation set; n=13,174) were analyzed. The training set was classified into 5 LNR categories, based on which the novel TRM staging system was constructed. The overall survival (OS) between the TRM and AJCC TNM systems was compared in the training set and validated in the validation set. The likelihood ratio x 2, liner trend x 2, C-index, and Akaike information criterion (AIC) values were used to measure the discriminatory ability between the two different staging systems. Decision curve analyses (DCAs) were conducted to test the clinical value of the two staging systems. RESULT: The patients were classified into the following categories: LNR0: 0%, LNR1: 0%60%. Univariate analyses demonstrated that the log-rank x 2 of the LNR stage (Training/Validation set: x 2 = 463.1/2880.8) was larger than the AJCC pN stage (Training/Validation set: x 2 = 281.5/2240.8). For both the training set and validation set, stratified analyses using the Kaplan-Meier method identified significantly heterogeneous OS in every pN category but only one using the LNR. The TRM staging system had higher likelihood ratio x 2, liner trend x 2, C-index and smaller AIC values than the TNM system. CONCLUSION: The TRM staging system demonstrated improved homogeneity and discriminatory ability in predicting the prognosis of GC patients compared with the AJCC TNM staging system.