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      Prognostic value of preoperative combined with postoperative systemic immune-inflammation index for disease-free survival after radical rectal cancer surgery: a retrospective cohort study

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          Abstract

          Background

          Colorectal cancer (CRC) ranks highly in malignant tumor incidence and mortality rates, severely affecting human health. The predictive value of the systemic immune-inflammation index (SII) in CRC prognosis is gaining attention, but there is limited research on the combined preoperative and postoperative SII. This study aims to explore the prognostic value of combined SII on disease-free survival (DFS) in patients undergoing radical surgery for rectal cancer.

          Methods

          We enrolled 292 patients with rectal cancer who underwent radical resection at the Affiliated Hospital of Xuzhou Medical University from May 2018 to September 2020, along with regular follow-ups to document the DFS. Patients’ complete blood cell counts were assessed before surgery and between 21–56 days postoperatively. Calculating preoperative and postoperative SII, patients were categorized into four groups based on the optimal cutoff values: (I) low-low group (preoperative SII <449.325 and postoperative SII <568.13); (II) high-low group (preoperative SII ≥449.325 and postoperative SII <568.13); (III) low-high group (preoperative SII <449.325 and postoperative SII ≥568.13); and (IV) high-high group (preoperative SII ≥449.325 and postoperative SII ≥568.13). The receiver operating characteristic (ROC) curve analysis evaluated the prediction efficacy of preoperative, postoperative, and combined SII. Kaplan-Meier analysis generated DFS curves, and Cox regression analysis determined prognostic factors.

          Results

          With a median follow-up of 41 months, 65.4% (191/292) patients reached DFS. The clinical pathological features between the four groups are balanced and comparable (P>0.05). The area under the ROC curve for preoperative, postoperative, and combined SII was 0.668 [95% confidence interval (CI): 0.6–0.737], 0.696 (95%CI: 0.63–0.763), and 0.741 (95% CI: 0.681–0.802), respectively. After adjusting for confounding factors such as adjuvant therapy, differentiation, vascular invasion, neural invasion, tumor-node-metastasis (TNM) stage, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9), significant differences were observed between the high-low group [hazard ratio (HR) =2.403; 95% CI: 1.255–4.602; P=0.008], low-high group (HR =5.058; 95% CI: 2.389–10.71; P<0.001), and high-high group (HR =6.214; 95% CI: 3.474–11.115; P<0.001) compared to the low-low group, with higher risks of adverse outcomes.

          Conclusions

          Combined SII has better predictive efficacy than monitoring preoperative or postoperative SII alone in rectal cancer patients undergoing radical surgery.

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          Most cited references27

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          Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance

          Immune checkpoint inhibitors (ICIs) have made an indelible mark in the field of cancer immunotherapy. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, ICIs—which now also include antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1)—quickly gained US Food and Drug Administration approval for the treatment of a wide array of cancer types, demonstrating unprecedented extension of patient survival. However, despite the success of ICIs, resistance to these agents restricts the number of patients able to achieve durable responses, and immune-related adverse events complicate treatment. Thus, a better understanding of the requirements for an effective and safe antitumor immune response following ICI therapy is needed. Studies of both tumoral and systemic changes in the immune system following ICI therapy have yielded insight into the basis for both efficacy and resistance. Ultimately, by building on these insights, researchers should be able to combine ICIs with other agents, or design new immunotherapies, to achieve broader and more durable efficacy as well as greater safety. Here, we review the history and clinical utility of ICIs, the mechanisms of resistance to therapy, and local and systemic immune cell changes associated with outcome.
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            Colorectal cancer statistics, 2023

            Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC statistics based on incidence from population-based cancer registries and mortality from the National Center for Health Statistics. In 2023, approximately 153,020 individuals will be diagnosed with CRC and 52,550 will die from the disease, including 19,550 cases and 3750 deaths in individuals younger than 50 years. The decline in CRC incidence slowed from 3%-4% annually during the 2000s to 1% annually during 2011-2019, driven partly by an increase in individuals younger than 55 years of 1%-2% annually since the mid-1990s. Consequently, the proportion of cases among those younger than 55 years increased from 11% in 1995 to 20% in 2019. Incidence since circa 2010 increased in those younger than 65 years for regional-stage disease by about 2%-3% annually and for distant-stage disease by 0.5%-3% annually, reversing the overall shift to earlier stage diagnosis that occurred during 1995 through 2005. For example, 60% of all new cases were advanced in 2019 versus 52% in the mid-2000s and 57% in 1995, before widespread screening. There is also a shift to left-sided tumors, with the proportion of rectal cancer increasing from 27% in 1995 to 31% in 2019. CRC mortality declined by 2% annually from 2011-2020 overall but increased by 0.5%-3% annually in individuals younger than 50 years and in Native Americans younger than 65 years. In summary, despite continued overall declines, CRC is rapidly shifting to diagnosis at a younger age, at a more advanced stage, and in the left colon/rectum. Progress against CRC could be accelerated by uncovering the etiology of rising incidence in generations born since 1950 and increasing access to high-quality screening and treatment among all populations, especially Native Americans.
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              Neutrophil phenotypes and functions in cancer: A consensus statement

              There is a growing appreciation for the vastness of neutrophil functional states in cancer. Quail et al. provide a consensus statement on mechanisms governing neutrophil heterogeneity in the context of malignancy and discuss controversies and solutions in neutrophil research. Neutrophils are the first responders to infection and inflammation and are thus a critical component of innate immune defense. Understanding the behavior of neutrophils as they act within various inflammatory contexts has provided insights into their role in sterile and infectious diseases; however, the field of neutrophils in cancer is comparatively young. Here, we summarize key concepts and current knowledge gaps related to the diverse roles of neutrophils throughout cancer progression. We discuss sources of neutrophil heterogeneity in cancer and provide recommendations on nomenclature for neutrophil states that are distinct in maturation and activation. We address discrepancies in the literature that highlight a need for technical standards that ought to be considered between laboratories. Finally, we review emerging questions in neutrophil biology and innate immunity in cancer. Overall, we emphasize that neutrophils are a more diverse population than previously appreciated and that their role in cancer may present novel unexplored opportunities to treat cancer.
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                Author and article information

                Journal
                Transl Cancer Res
                Transl Cancer Res
                TCR
                Translational Cancer Research
                AME Publishing Company
                2218-676X
                2219-6803
                08 January 2024
                31 January 2024
                : 13
                : 1
                : 371-380
                Affiliations
                [1 ]deptDepartment of General Practice , Affiliated Hospital of Xuzhou Medical University , Xuzhou, China;
                [2 ]deptDepartment of Interventional Radiology , Affiliated Hospital of Xuzhou Medical University , Xuzhou, China
                Author notes

                Contributions: (I) Conception and design: J Sun; (II) Administrative support: R Yang; (III) Provision of study materials or patients: H Wu; (IV) Collection and assembly of data: L Li; (V) Data analysis and interpretation: Y Gu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Yuming Gu, MMed. Department of Interventional Radiology, Affiliated Hospital of Xuzhou Medical University, No. 99, West Huaihai Road, Quanshan District, Xuzhou 221000, China. Email: m13361831892_1@ 123456163.com ; Ruiling Yang, MMed. Department of General Practice, Affiliated Hospital of Xuzhou Medical University, No. 99, West Huaihai Road, Quanshan District, Xuzhou 221000, China. Email: lingeryang@ 123456126.com .
                Article
                tcr-13-01-371
                10.21037/tcr-23-1289
                10894347
                38410202
                3538dc36-3a30-4e6c-b2b9-30664138bbc8
                2024 Translational Cancer Research. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 21 July 2023
                : 17 November 2023
                Funding
                Funded by: the Demonstration of the Application of a Friendly Smart City Environment for the Elderly and Disabled
                Award ID: No. 2021YFC2009406
                Categories
                Original Article

                preoperative,postoperative,systemic immune-inflammation index (sii),rectal cancer,disease-free survival (dfs)

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