Irinotecan plus raltitrexed as second­line chemotherapy for metastatic colorectal cancer: A retrospective study.

The present study evaluated the efficiency, prognostic factors for and the safety of irinotecan combined with raltitrexed (TOMIRI) in patients with metastatic colorectal cancer (CRC). Outcome data of patients who received TOMIRI as first-, second- and third- or later-line treatment regimens were assessed to compare the efficacy of this regimen. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were evaluated for each group. Kaplan-Meier curves and univariate and multivariate analyses were performed to evaluate efficacy. From January 2017 to December 2019, TOMIRI was administered as a first-line treatment in 23 patients, second-line treatment in 164 patients and third- or later-line treatment in 18 patients. Irinotecan and 5-fluorouracil (FOLFIRI) was administered to another 50 patients, who served as the control group. The median PFS was 9, 7 and 6 months and the median OS was 37, 21 and 17 months for first-, second- and third- or later-line treatments, respectively. The ORRs of the included patients were 21.7, 13.4 and 11.1%, respectively, and the DCRs were 91.3, 81.7 and 66.7%, respectively. Compared with FOLFIRI, TOMIRI as a second-line chemotherapy treatment was associated with longer survival of the patients with CRC. Further analysis demonstrated that pathologic tumor-node-metastasis category, carcinoembryonic antigen, carbohydrate antigen 19-9, treatment cycles, targeted therapy, treatment of local metastases and first-line PFS were prognostic factors for second-line treatment. Among these, the number of treatment cycles was of vital importance. Hepatic dysfunction was the most commonly reported grade 1-2 (55.1%) and grade 3-4 (7.3%) adverse event. Neutropenia (12.2%), thrombocytopenia (10.2%), anemia (27.3%), proteinuria (38.1%) and hematuria (21.0%) were also common grade 1-2 adverse events. In conclusion, TOMIRI may be recommended as an effective and safe second-line treatment for metastatic CRC in the clinic.

Critical review and recent advances of emerging real-time and non-destructive strategies for meat spoilage monitoring.

Monitoring and evaluating food quality, especially meat quality, has received a growing interest to ensure human health and decrease waste of raw materials. Standard analytical approaches used for meat spoilage assessment suffer from time consumption, being labor-intensive, operation complexity, and destructiveness. To overcome shortfalls of these traditional methods and monitor spoilage microorganisms or related metabolites of meat products across the supply chain, emerging analysis devices/systems with higher sensitivity, better portability, on-line/in-line, non-destructive and cost-effective property are urgently needed. Herein, we first overview the basic concepts, causes, and critical monitoring indicators associated with meat spoilage. Then, the conventional detection methods for meat spoilage are outlined objectively in their strengths and weaknesses. In addition, we place the focus on the recent research advances of emerging non-destructive devices and systems for assessing meat spoilage. These novel strategies demonstrate their powerful potential in the real-time evaluation of meat spoilage.

Identification of colon cancer subtypes based on multi-omics data-construction of methylation markers for immunotherapy.

Background: Being the most widely used biomarker for immunotherapy, the microsatellite status has limitations in identifying all patients who benefit in clinical practice. It is essential to identify additional biomarkers to guide immunotherapy. Aberrant DNA methylation is consistently associated with changes in the anti-tumor immune response, which can promote tumor progression. This study aims to explore immunotherapy biomarkers for colon cancers from the perspective of DNA methylation. Methods: The related data (RNA sequencing data and DNA methylation data) were obtained from The Cancer Genome Atlas (TCGA) and UCSC XENA database. Methylation-driven genes (MDGs) were identified through the Pearson correlation analysis. Unsupervised consensus clustering was conducted using these MDGs to identify distinct clusters of colon cancers. Subsequently, we evaluated the immune status and predicted the efficacy of immunotherapy by tumor immune dysfunction and exclusion (Tide) score. Finally, The Quantitative Differentially Methylated Regions (QDMR) software was used to identify the specific DNA methylation markers within particular clusters. Results: A total of 282 MDGs were identified by integrating the DNA methylation and RNA-seq data. Consensus clustering using the K-means algorithm revealed that the optimal number of clusters was 4. It was revealed that the composition of the tumor immune microenvironment (TIME) in Cluster 1 was significantly different from others, and it exhibited a higher level of tumor mutation burdens (TMB) and stronger anti-tumor immune activity. Furthermore, we identified three specific hypermethylation genes that defined Cluster 1 (PCDH20, APCDD1, COCH). Receiver operating characteristic (ROC) curves demonstrated that these specific markers could effectively distinguish Cluster 1 from other clusters, with an AUC of 0.947 (95% CI 0.903-0.990). Finally, we selected clinical samples for immunohistochemical validation. Conclusion: In conclusion, through the analysis of DNA methylation, consensus clustering of colon cancer could effectively identify the cluster that benefit from immunotherapy along with specific methylation biomarkers.

Clinical Implications of Naples Prognostic Score for Patients with Resected Cholangiocarcinoma: A Real-World Experience.

Purpose: The Nutritional Prognostic Score (NPS) is a composite indicator that effectively reflects the preoperative nutritional and inflammation status of patients. Its prognostic value has been extensively confirmed in various types of tumors. Our study aims to investigate the clinical implications of the NPS in the postoperative patients with cholangiocarcinoma (CCA). Patients and Methods: Data on clinicopathological characteristics were collected from CCA patients who underwent radical surgery between 2014 and 2019 at Harbin Medical University Cancer Hospital. NPS was calculated using relevant indicators to categorize the patients, and association of NPS with clinicopathological characteristics and survival outcomes were analyzed. To assess differences in survival rates between different groups, we utilized the Kaplan-Meier method. Independent prognostic risk factors were identified by Cox regression analysis. A CONomogram was created, and its accuracy in survival prediction was evaluated using receiver operating characteristic (ROC) curves. Independent verification was conducted in the validation group. Results: For this study, a cohort of 232 patients was enlisted and subsequently divided into training group (N=162) and validation group (N=70). An evident correlation was detected between NPS and preoperative malnutrition. Patients with higher NPS exhibited a worse overall survival (OS), with 5-year OS rates of 79.1%, 33.1%, and 10.6%. Multivariate analysis revealed that NPS was an independent risk factor for OS in resected CCA patients (P<0.001). The NPS-based Nomogram was developed to accurately assess the risk of patients. Conclusion: The NPS was identified as a significant risk factor that impacts the prognosis of patients with resected CCA. In order to improve prognosis management, the NPS-based Nomogram has been demonstrated to be a precise and efficient tool.

Dynamic monitoring of serum CEA and CA19-9 predicts the prognosis of postoperative stage II colon cancer.

BACKGROUND: We sought to investigate the prognostic significance of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) dynamics for stage II colon cancer patients undergoing radical resection. METHODS: This study retrospectively analyzed 1517 stage II colon cancer patients admitted to the Harbin Medical University Cancer Hospital from January 2011 to December 2016. To observe the relationship between tumor markers dynamic monitoring and survival, we calculated cut-off values for ΔCEA and ΔCA19-9. Group according to the cut-off values and compare the differences in survival between subgroups. RESULTS: Preoperative CA199 (HR = 3.122), postoperative CEA (HR = 2.941) and histological type (HR = 2.855) were independent prognostic factors in multivariate Cox proportional hazards models. The 5-year overall survival (OS) in the patients with normal preoperative CEA and CA19-9 was significantly better than the patients with elevated preoperative CEA or CA19-9 and the patients with elevated preoperative CEA and CA19-9 (92.6 % vs. 87.6 % vs. 81.0 %, P < 0.05). 469 patients with normal pre- and post-operative CEA had the highest 5-year OS (93.5 %, P < 0.05). Among the 177 patients with elevated pre- and post-operative CEA, the 5-year OS rate was only 81.8 % (P < 0.05). The cut-off values for Δ CEA and Δ CA19-9 in stage II colon cancer patients with elevated preoperative tumor markers were 2.625 ng/ml and 7.835 U/ml, respectively. The Kaplan-Meier curves showed that Δ CEA≥2.625 ng/ml and Δ CA19-9≥7.835 U/mL were associated with better outcome (87.8 % vs. 79.6 %, P < 0.05; 85.8 % vs. 79.1 %, P > 0.05). At the same time, we found that adjuvant chemotherapy significantly improved 5-year OS in patients with elevated preoperative CEA or CA19-9 (91.0 % vs. 80.9 % and 89.6 % vs. 80.2 %, P < 0.05). CONCLUSIONS: Persistent postoperative elevation of CEA/CA19-9 is associated with a poor prognosis. CEA and CA19-9 may be high-risk factors for postoperative adjuvant therapy in stage II colon cancer patients. For stage II colon cancer patients with elevated preoperative CEA, patients with Δ CEA<2.625 ng/ml have poor survival and can improve prognosis by receiving adjuvant therapy.

Role of endogenous and exogenous antioxidants in risk of six cancers: evidence from the Mendelian randomization study.

Background: Although oxidative stress is known to contribute to cancer, and endogenous and exogenous antioxidants are thought to prevent tumorigenesis by suppressing oxidative stress-induced DNA damage, antioxidants have also been reported to show negative effects on tumor formation, necessitating characterization of the causal associations between antioxidants and cancer risk. Methods: In this study, Mendelian randomization (MR) analysis, primarily inverse-variance weighted MR, was used to assess the causal effect of six endogenous and five exogenous diet-derived antioxidants on the risk of six cancers. MR-Egger intercept test and Cochran's Q statistic were utilized to assess pleiotropy and heterogeneity, respectively. Results: For endogenous antioxidants, a bidirectional two-sample MR analysis was conducted. Our findings suggested that serum albumin has a negative causal association with the risk of prostate cancer [odds ratio (OR) = 0.78, 95% confidence interval (CI): 0.68-0.91, p = 0.001]. The risks of the six cancers showed no significant associations with endogenous antioxidants in the converse MR analysis. For exogenous antioxidants, the unidirectional two-sample MR analysis exhibited a nominal relationship between the serum retinol level and non-small-cell lung cancer risk (OR = 0.29, 95% CI: 0.11-0.76, p = 0.011). Conclusions: Thus, our study revealed the protective effects of genetic susceptibility to high circulating albumin levels on prostate cancer, providing potential targeted interventions for prostate cancer prevention.

Survival rate of colorectal cancer in China: A systematic review and meta-analysis.

Background: This study aims to comprehensively summarize the colorectal survival rate in China. Method: In PubMed and Web of Science, keywords such as "colorectal cancer", "survival" and "China" were used to search literatures in the past 10 years. Random effect models were selected to summarize 1-year, 3-year, and 5-year survival rates, and meta-regression and subgroup analyses were performed on the included studies. Results: A total of 16 retrospective and prospective studies providing survival rates for colorectal cancer in China were included. The 1-year, 3-year, and 5-year survival rates of colorectal cancer in China were 0.79, 0.72 and 0.62, respectively. In the included studies, the 5-year survival rates of stage I (5474 cases), stage II (9215 cases), stage III (8048 cases), and stage IV (4199 cases) colorectal cancer patients were 0.85, 0.81, 0.57 and 0.30, respectively. Among them, the 5-year survival rates of colorectal cancer were 0.82, 0.76, 0.71, 0.67, 0.66, 0.65 and 0.63 in Tianjin, Beijing, Guangdong, Shandong, Liaoning, Zhejiang and Shanghai, respectively. Conclusion: The 5-year survival rate in China is close to that of most European countries, but still lower than Japan and South Korea, and the gap is gradually narrowing. Region, stage, differentiation, pathological type, and surgical approach can affect 5-year survival in colorectal cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/ identifier, CRD42022357789.

Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions?

Neoadjuvant chemoradiotherapy (NACRT) or chemotherapy (NACT) followed by radical resection and then adjuvant therapy is considered the optimal treatment model for locally advanced colorectal cancer (LACRC). A recent total neoadjuvant therapy (TNT) strategy further improved the tumour regression rate preoperatively and reduced local-regional recurrence in locally advanced rectal cancer (LARC). However, distant metastasis was still high, and little overall survival benefit was obtained from these preoperative treatment models. According to mismatch repair protein expression, MSI-H/dMMR and non-MSI-H/pMMR statuses were defined in colorectal cancer (CRC) patients. Due to the special features of biologics in MSI-H/dMMR CRC patients, this subgroup of patients achieved little treatment efficacy from chemoradiotherapy but benefited from immune checkpoint inhibitors (ICIs). The KEYNOTE-177 trial observed favourable survival outcomes in metastatic CRC patients treated with one-line pembrolizumab with tolerable toxicity. Given the better systemic immune function, increased antigenic exposure, and improved long-term memory induction before surgery, neoadjuvant ICI (NAICI) treatment was proposed. The NICHE trial pioneered the use of NAICI treatment in LACRC, and recent reports from several phase II studies demonstrated satisfactory tumour downsizing in CRC. Preclinical rationales and preliminary early-phase human trials reveal the feasibility of NAICI therapy and the therapeutic efficacy provided by this treatment model. Better tumour regression before surgery also increases the possibility of organ preservation for low LARC. However, the optimal treatment strategy and effective biomarker identification for beneficiary selection remain unknown, and potential pitfalls exist, including tumour progression during neoadjuvant treatment due to drug resistance and surgery delay. Given these foundations and questions, further phase II or III trials with large samples need to be conducted to explore the right regimens for the right patients.

Intrinsic resistance and efficacy of immunotherapy in microsatellite instability-high colorectal cancer: A systematic review and meta-analysis.

Some patients with microsatellite instability-high colorectal cancer (MSI-H CRC) have shown a poor response to immunotherapy in clinical trials. We investigated the intrinsic resistance to and efficacy of immunotherapy in patients with MSI-H CRC. The PubMed and Web of Science databases were searched using keywords such as "colorectal cancer," "immunotherapy," and "clinical experiment." Random-effects models were used to generate the combined complete response, partial response, stable disease, progressive disease, objective response rate (ORR), disease control rate (DCR), and incidence of adverse events. We then performed a subgroup analysis based on the ORR and incidence of intrinsic resistance. The meta-analysis included seven clinical trials. The incidences of complete response, partial response, stable disease, and progressive disease summarized by the random-effects model were 8%, 37%, 26%, and 25%, respectively. The ORR and DCR were 45% and 71%, respectively. The ORRs of programmed cell death protein 1 inhibitor (anti-PD-1), programmed death ligand 1 inhibitor (anti-PD-L1), and anti-PD-1 combined with cytotoxic T lymphocyte-associated antigen 4 inhibitor (anti-CTLA-4) immunotherapy were 38%, 54%, and 57%, respectively. The ORR of immune checkpoint inhibitors for first- and third-line therapy was 56% and 32%, respectively. Dual-drug immunotherapy significantly reduced the incidence of intrinsic resistance to immunotherapy (12% vs 31%). The incidences of intrinsic resistance to first-line therapy and second-line and later therapy were 29% and 26%, respectively. Approximately 25% of patients with MSI-H CRC had intrinsic resistance to immunotherapy. Anti-PD-1 combined with anti-CTLA-4 significantly increased the ORR, thereby reducing the incidence of intrinsic resistance. Moving immunotherapy into earlier lines of therapy, although not reducing the incidence of intrinsic resistance, can improve the ORR in patients with MSI-H CRC.

Real-world survival of colon cancer after radical surgery: A single-institutional retrospective analysis.

The survival rate for colon cancer after radical surgery has been the focus of extensive debate. To assess the postoperative survival and prognostic factors for overall survival (OS), we collected clinicopathological information for 2,655 patients. The survival time and potential risk factors for OS were analyzed by using Kaplan-Meier curves, Cox proportional hazards models, best subset regression (BSR), and least absolute shrinkage and selection operator (LASSO). The 5-year survival rates of stage I-IV colon cancer were 96.6%, 88.7%, 69.9%, and 34.3%, respectively. Adjuvant chemotherapy improved the survival rate (90.4% vs. 82.4%, with versus without adjuvant chemotherapy, respectively) in stage II patients with high-risk factors. Elevated preoperative carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were significantly associated with worse OS compared with patients without these elevations. Less than 12 versus more than 12 harvested lymph nodes (LNs) affected prognosis (84.6% vs. 89.7%, respectively). Regarding the lymph node ratio (LNR), the 5-year OS rate was 89.2%, 71.5%, 55.8%, and 34.5% in patients with LNR values of 0, 0.3, 0.3-0.7, and >0.7, respectively. We constructed a nomogram comprising the independent factors associated with survival to better predict prognosis. On the basis of these findings, we propose that stage II colon cancer patients without high-risk factors and with both elevated preoperative CEA and CA199 should receive adjuvant therapy. Furthermore, the LNR could complement TNM staging in patients with <12 harvested LNs. Our nomogram might be useful as a new prognosis prediction system for colon cancer patients.