Prognostic significance of hemoglobin, albumin, lymphocyte, platelet in gastrointestinal stromal tumors: A propensity matched retrospective cohort study

Background: It is inconclusive whether R1 margin determined by postoperative pathological examination indicates worse long-term survival in gastric cancer (GC) patients after curative intent resection (CIR). Hence, we aimed to systematically pool the conflicting evidence to fill this gap. Methods: The present study was performed according to the published protocol and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Published studies examining the impact of microscopic margin status on overall survival (OS) and 5-year OS rate in GC were systematically searched in PubMed, Embase, and Cochrane Library databases. RevMan 5.3 was used to conduct statistical analysis, and the Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the certainty of evidence for each outcome. Results: Twenty-three retrospective cohort studies including 19 992 patients were analyzed. The pooled hazard ratio for OS of 14 studies was 2.06 (95% confidence interval [CI]: 1.61–2.65, low certainty), indicating that R1 margin predicted inferior OS. Subgroup and sensitivity analyses upheld the statistical stability of this finding. The pooled odds ratio (OR) of 14 studies was .21 (95% CI: .17–.26, moderate certainty), demonstrating that the presence of R1 margins was associated with a poorer 5-year OS rate. Sensitivity analyses and most of the subgroup analyses confirmed this finding, except the “esophagogastric junction (EGJ) cancers” subgroup, which included two studies with a pooled OR of .41 (95% CI: .10–1.61). Conclusion: R1 margin detected by pathological examination might exhibit a high correlation with poorer OS and 5-year OS rate in GC (except EGJ cancers) patients who underwent CIR. To figure out the effect of R1 margin on survival of different stages and histological types need prospective studies with large sample sizes and standardized methods. What is the best treatment for R1 margin patients also need more in-depth and special research.

Abciximab (c7E3 Fab, ReoPro^®) blocks GPIIb/IIIa and αvβ3 and inhibits thrombotic and proliferative events only in humans and non-human primates. The bivalent F(ab’)₂ fragment is an effective anti-thrombotic agent in canine models. In the present study, 7E3 F(ab’)₂ was also found to bind to rat GPIIb/IIIa (K_D = 27 ± 4 g/mL) and αvβ3 (K_D = 9 ± 8 μg/mL), to block in vitro rat platelet aggregation (IC₅₀ = 16 ± 6 μg/mL), and to inhibit αvβ3-mediated microvessel sprout formation in a rat aortic ring assay. Following administration of 7E3 F(ab’)₂ (4 mg/kg) to rats, platelet aggregation was completely blocked for up to 6 h and thrombus formation in response to a rat abdominal aorta double crush injury was prevented. Effective chronic dosing was achieved with 6 mg/kg daily I.P. injections. In vitro mixing experiments indicated that 7E3 F(ab’)₂ redistributed to unlabeled platelets in 2 h. Ex vivo, 7E3 F(ab’)₂ was detected on platelets for up to 4 days after a single 4-mg/kg injection. These data suggest that 7E3 F(ab’)₂ may be a useful agent to study the effects of GPIIb/IIIa and αvβ3 blockade in rat models of thrombosis and vascular disease.

Gastrointestinal stromal tumors (GISTs) are considered insensitive to radiotherapy. However, a growing number of case reports and case series have shown that some lesions treated by radiotherapy achieved an objective response. The aim of the study was to perform a systematic review of all reported cases, case series, and clinical studies of GISTs treated with radiotherapy to reevaluate the role of radiotherapy in GISTs. A systematic search of the English-written literature was conducted using PubMed, Web of Science, and Embase databases. Overall, 41 articles describing 112 patients were retrieved. The included articles were of low to moderate quality. Bone was the most common site treated by radiotherapy, followed by the abdomen. In order to exclude the influence of effective tyrosine kinase inhibitors (TKIs), a subgroup analysis was conducted on whether and which TKIs were concurrently applied with radiotherapy. Results showed that radiotherapy alone or combined with resistant TKIs could help achieve objective response in selected patients with advanced or metastatic GISTs; however, survival benefits were not observed in the included studies. Pain was the most common symptom in symptomatic GISTs, followed by neurological dysfunction and bleeding. The symptom palliation rate was 78.6% after excluding the influence of effective TKIs. The adverse reactions were mainly graded 1–2. Radiotherapy was generally well-tolerated. Overall, radiotherapy may relieve symptoms for GIST patients with advanced or metastatic lesions and even help achieve objective response in selected patients without significantly reducing the quality of life. In addition to bone metastases, fixed abdominal lesions may be treated by radiotherapy. Publication bias and insufficient quality of included studies were the main limitations in this review. Further clinical studies are needed and justified.

Background: The global burden of digestive cancer is expected to increase. Therefore, crucial for the prognosis of patients with these tumors is to identify early diagnostic markers or novel therapeutic targets. There is accumulating evidence connecting histone chaperones to the pathogenesis of digestive cancer. Histone chaperones are now broadly defined as a class of proteins that bind histones and regulate nucleosome assembly. Recent studies have demonstrated that multiple histone chaperones are aberrantly expressed and have distinct roles in digestive cancers. Objective: The purpose of this review is to present the current evidence regarding the role of histone chaperones in digestive cancer, particularly their mechanism in the development and progression of esophageal, gastric, liver, pancreatic, and colorectal cancers. In addition, the prognostic significance of particular histone chaperones in patients with digestive cancer is discussed. Methods: According to PRISMA guidelines, we searched the PubMed, Embase, and MEDLINE databases to identify studies on histone chaperones and digestive cancer from inception until June 2022. Results: A total of 104 studies involving 21 histone chaperones were retrieved. Conclusions: This review confirms the roles and mechanisms of selected histone chaperones in digestive cancer and suggests their significance as potential prognostic biomarkers and therapeutic targets. However, due to their non-specificity, more research on histone chaperones should be conducted in the future to elucidate novel strategies of histone chaperones for prognosis and treatment of digestive cancer.