Incidence and Risk Factors for Cerebrovascular-Specific Mortality in Patients with Colorectal Cancer: A Registry-Based Cohort Study Involving 563298 Patients

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from Surveillance Epidemiology and End Results database with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general US population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during study period. While age and surgery positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, more recent year (2001-2015) of diagnosis as well as multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM, which may be helpful for risk stratification and therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

Improving Prognosis of Surrogate Assay for Breast Cancer Patients by Absolute Quantitation of Ki67 Protein Levels Using Quantitative Dot Blot (QDB) Method

BackgroundImmunohistochemistry (IHC)-based surrogate assay is the prevailing method in daily clinical practice to determine the necessity of chemotherapy for Luminal-like breast cancer patients worldwide. It relies on Ki67 scores to separate Luminal A-like from Luminal B-like breast cancer subtypes. Yet, IHC-based Ki67 assessment is known to be plagued with subjectivity and inconsistency to undermine the performance of the surrogate assay. A novel method needs to be explored to improve the clinical utility of Ki67 in daily clinical practice.Materials and MethodsThe Ki67 protein levels in a cohort of 253 specimens were assessed with IHC and quantitative dot blot (QDB) methods, respectively, and used to assign these specimens into Luminal A-like and Luminal B-like subtypes accordingly. Their performances were compared with the Kaplan–Meier, univariate, and multivariate survival analyses of the overall survival (OS) of Luminal-like patients.ResultsThe surrogate assay based on absolutely quantitated Ki67 levels (cutoff at 2.31 nmol/g) subtyped the Luminal-like patients more effectively than that based on Ki67 scores (cutoff at 14%) (Log rank test, p = 0.00052 vs. p = 0.031). It is also correlated better with OS in multivariate survival analysis [hazard ratio (HR) at 6.89 (95% CI: 2.66–17.84, p = 0.0001) vs. 2.14 (95% CI: 0.89–5.11, p = 0.087)].ConclusionsOur study showed that the performance of the surrogate assay may be improved significantly by measuring Ki67 levels absolutely, quantitatively, and objectively using the QDB method.

Prognostic Significance of Signet-Ring Cell Components in Patients With Gastric Carcinoma of Different Stages

Background: Gastric carcinoma (GC), which contains signet ring cell (SRC) components are frequently observed in postoperative pathological assessment. This study aims to study the prognostic significance of SRC components in GC patients.Methods: From 2003 to 2017, surgically resected primary GC patients were retrospectively reviewed. All enrolled patients were divided into three groups according to the proportion of SRC. The overall survival (OS) and disease-free survival (DFS) of GC patients with different tumor stages were analyzed.Results: Patients with SRC or mixed-SRC were more associated with female, younger age, middle or lower third of the stomach, larger tumor, higher pN stage, and more lymphovascular invasion. For GC patients in stage I, multivariate survival analysis showed that age >60, SRC components >50%, and pT stage were independent prognostic factors for OS (all p < 0.05). The 5-year OS of patients with SRC were higher than that of patients with pure adenocarcinoma (p = 0.021). For GC patients in stage II/III, multivariate survival analysis showed that age >60, SRC proportion, surgical types, Borrmann's type, pT stage, pN stage, and lymphovascular invasion were independent prognostic factors for OS (all p < 0.05). The 5-year OS/DFS of patients with SRC were lower than that of patients with pure adenocarcinoma (p < 0.001).Conclusions: SRC seemed to be a favorable prognostic factor in GC patients in stage I. However, for GC patients in stage II/III, the SRC components were associated with poor prognosis, independent of other clinicopathological factors.