A prospective follow-up study of the relationship between high-sensitivity C-reactive protein and primary liver cancer.

BACKGROUND: Competing risk method has not been used in a large-scale prospective study to investigate whether increased levels of high-sensitivity C-reactive protein (hs-CRP) elevate the risk of primary liver cancer (PLC). Our study aims to prospectively investigate the relationship between hs-CRP and new-onset PLC. METHODS AND RESULTS: Ninety-five thousand seven hundred fifty-nine participants without the diagnosis of PLC, and who had their demographic characteristics and biochemical parameters recorded, were analyzed from the Kailuan Cohort study. Cox proportional hazards regression models and competing risk regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of PLC. During a median follow-up of 11.07 years, 357 incidental PLC cases were identified over a total of 1,035,039 person-years. The multivariable HRs (95%CI) for the association of hs-CRP of 1-3 mg/L group and hs-CRP>3 mg/L with PLC were 1.07(0.82 ~ 1.38), 1.51(1.15 ~ 1.98) in a Cox proportional hazard regression analysis adjusted for other potential confounders. In the cause-specific hazard model, the multivariable HRs (95%CI) for the association of hs-CRP of 1-3 mg/L group and hs-CRP>3 mg/L with PLC were 1.06(0.81 ~ 1.40), 1.50(1.14 ~ 1.99). Similar results were also observed in the sub-distribution hazard function model with corresponding multivariate HRs (95%CI) of 1.05(0.80 ~ 1.40), 1.49(1.13 ~ 1.98) in hs-CRP of 1-3 mg/L group and hs-CRP>3 mg/L group, respectively. CONCLUSIONS: This prospective study found a significant association of higher levels of hs-CRP with new-onset PLC. The main clinical implications would be an increased awareness of hs-CRP and its correlation to the risk of PLC. This study should be a steppingstone to further research on chronic inflammation and PLC. TRIAL REGISTRATION: Registration number: ChiCTR-TNRC-11001489 .

Exploring the landscape of drug resistance in gastrointestinal cancer immunotherapy: A review.

Gastrointestinal (GI) cancers pose a significant challenge due to high prevalence and mortality. While advancements in detection and conventional treatments have been made, prognosis often remains poor, particularly for advanced-stage cancers. Immunotherapy has emerged as a transformative approach, leveraging the body immune system against cancer, including immune checkpoint inhibitors (ICIs), cancer vaccines, and adoptive cell transfer. These modalities have shown promise, achieving sustained responses and improved survival in some patients. However, their efficacy in GI cancers is less pronounced, hindered by drug resistance mechanisms that are either intrinsic or acquired over time. This review examines the latest understanding of immunotherapy in GI cancers, focusing on ICIs, cancer vaccines, and adoptive cell transfer, along with their associated outcomes and limitations. It delves into the mechanisms behind drug resistance, including alterations in immune checkpoints, the immunosuppressive tumor microenvironment, and genetic/epigenetic changes. The role of the gut microbiome is also considered as an emerging factor in resistance. To combat drug resistance, strategies such as enhancing immune response, targeting the tumor microenvironment, and modulating resistance mechanisms are explored. The review underscores the potential of ferroptosis induction as a novel approach. Looking forward, it highlights the need for personalized immunotherapies, understanding the influence of the gut microbiome, and further exploration of ferroptosis in overcoming resistance. While challenges persist, the continuous evolution in GI cancer immunotherapy research promises innovative treatments that could significantly improve patient outcomes.

The histologic features, molecular features, detection and management of serrated polyps: a review.

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance.

Choline metabolism and its implications in cancer.

Choline, a quintessential quaternary ammonium compound, plays a cardinal role in several pivotal biological mechanisms, chiefly in safeguarding cell membrane integrity, orchestrating methylation reactions, and synthesizing vital neurotransmitters. This systematic review meticulously dissects the complex interplay between choline metabolism and its profound implications in oncology. The exposition is stratified into three salient dimensions: Initially, we delve into the intricacies of choline metabolism, accentuating its indispensability in cellular physiology, the enzymatic labyrinth governing its flux, and the pivotal cellular import mechanisms. Subsequently, we elucidate the contemporary comprehension of choline metabolism in the cancer paradigm, traversing its influence from inception to the intricate metamorphosis during oncogenic progression, further compounded by dysregulated enzyme activities and aberrant signaling cascades. Conclusively, we illuminate the burgeoning potential of choline-centric metabolic imaging modalities, notably magnetic resonance spectroscopy (MRS) and positron emission tomography (PET), as avant-garde tools for cancer diagnostics and therapeutic trajectory monitoring. Synoptically, the nuanced perturbations in choline metabolism in neoplastic entities unfurl critical insights, potentially heralding paradigm shifts in diagnostic and therapeutic oncological stratagems. A deeper foray into this realm is anticipated to fortify our molecular understanding and refine intervention modalities in cancer theranostics.

Clinicopathologic characteristics and prognosis for male breast cancer compared to female breast cancer.

Male breast cancer (MBC) is rare. Due to limited information, MBC has always been understudied. We conducted a retrospective population-based cohort study using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. The clinical and biological features of female breast cancer (FBC) patients were compared with MBC patients. Cox regression models and competing risks analyses were used to identify risk factors associated with cancer-related survival in MBC and FBC groups. Results showed that MBC patients suffered from higher TNM stages, tumor grades, and a higher percentage of hormone receptor-positive tumors, compared with FBC patients (all p < 0.05). In addition, the breast tumor locations varied a lot between males and females (p < 0.05). FBC patients were associated with superior overall survival than MBC patients. Results from multivariate cox regression and competing risks analyses showed age, race, T, N, M-stages, tumor grades, estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) overexpression were independent prognosis factors in FBC patients (all p < 0.05). MBC patients had similar risk factors to FBC patients, but PR and HER-2 status did not independently influence survival (all p > 0.05). Tumor location was an independent prognostic factor for both gender groups.

Risk of primary liver cancer associated with gallstones and cholecystectomy: A competing risks analysis.

Previous research has revealed a positive relationship between GSD, cholecystectomy and primary liver cancer (PLC). However, previous studies had several limitations including the retrospective design, narrow assessment of potential confounders and lack of competing risk models in time-to-event analyses. We conducted a large prospective cohort study to explore the relationship between GSD, cholecystectomy and PLC. A total of 95,021 participants who had not been diagnosed with PLC previously were enrolled from the Kailuan Cohort study. Demographic characteristics and biochemical parameters were recorded at baseline for all participants. We used Cox regression models and competing risk regression models to evaluate the association of GSD and cholecystectomy with the risk PLC. A total of 306 incidental PLC cases were identified during a median follow-up of 9.05 (8.75-9.22) years per participant. Compared with the normal group, the multivariable HRs (95%CI) for the association of GSD and cholecystectomy with PLC were 1.77 (1.05-2.94), 5.25 (1.95-14.17). In the CS model, the multivariable HRs (95%CI) was 1.76 (1.05-2.94) for the association of GSD and cholecystectomy with PLC and 5.25 (1.95-14.17) for GSD and cholecystectomy. Similar results were also obtained in the SD model with corresponding multivariate HRs (95%CI) of 1.75 (1.01-3.00), 5.22 (1.90-14.07) in the GSD group and cholecystectomy group, respectively. GSD and cholecystectomy were associated with an elevated risk of PLC.Registration number: ChiCTR-TNRC-11001489.

Relationship between high-sensitivity C reactive protein and the risk of gallstone disease: results from the Kailuan cohort study.

OBJECTIVES: Gallstone disease (GSD) can be caused by various health and clinical factors such as obesity, dyslipidaemia and an unhealthy diet, all of which are associated with higher high-sensitivity C reactive protein (hs-CRP) concentrations. Whether hs-CRP represents an independent risk factor for GSD is still unclear. We prospectively investigated hs-CRP in relation to the occurrence of GSD based on the Kailuan study. STUDY DESIGN: Prospective cohort study. SETTING: The Kailuan cohort study was conducted in Tangshan City in northern China. PARTICIPANTS: 95 319 participants who were free from GSD were recruited in this study. Epidemiological data, anthropometric parameters and biochemical data of participants were collected. PRIMARY AND SECONDARY OUTCOME MEASURES: Cox proportional hazards regression models were used to evaluate the association between hs-CRP concentrations and the risk of GSD after adjustments for potential confounders. RESULTS: During the mean 7.58 years of follow-up among 95 319 participants, 4205 participants were identified as newly diagnosed with GSD or having undergone cholecystectomy for cholelithiasis. Compared with the hs-CRP<1 mg/L group, elevated hs-CRP concentrations were significantly associated with higher risk of GSD with the corresponding HR of 1.11 (95% CI 1.03 to 1.19), 1.12 (95% CI 1.04 to 1.22) in the 1≤hs-CRP≤3 mg/L and hs-CRP>3 mg/L group, respectively. The multivariate model which included hs-CRP not only had a better line of fitness but also had better predictive values to help identify new cases of GSD during follow-up. CONCLUSION: Elevated hs-CRP concentration is an independent risk factor for new-onset GSD among the Chinese population. TRIAL REGISTRATION NUMBER: ChiCTR-TNC-11001489.