UBTD1 is a potential prognostic biomarker in colorectal cancer.

Colorectal cancer (CRC) is a complex malignancy with poorly understood molecular mechanisms, necessitating the identification of genetic markers. Although Ubiquitin domain-containing protein 1 (UBTD1) has received significant attention in the study of human cancers, its specific role in CRC is yet to be fully clarified. This study sought to examine how UBTD1 expression was associated with various clinical and pathological characteristics of CRC, and to determine its prognostic significance and biological function, utilizing data from clinical samples and large-scale databases. Notably, UBTD1 expression was found to be upregulated in CRC, resulting in decreased survival rates and unfavorable clinical characteristics such as advanced T, N, and pathological stages. The findings of the multivariate Cox regression analysis illustrated that UBTD1 expression upregulation is a significant independent marker of unfavorable outcomes in CRC patients. An examination of the functional enrichment of UBTD1 and the genes it co-expresses indicated that it could serve as an oncogene by modulating the expression of genes implicated in crucial tumorigenesis pathways and functions. Additionally, immune cell infiltration analysis suggested a link between UBTD1 levels and various immune cells, particularly macrophages. In conclusion, the use of UBTD1 as a biomarker for both the prognosis and diagnosis of CRC has promising prospects for further investigation and therapeutic approaches.

How to compensate for frailty? The real life impact of geriatric co-management on morbi-mortality after colorectal cancer surgery in patients aged 70 years or older.

In Europe, CRC is the second most common cause of cancer death, and surgery remains the mainstay curative treatment. Age and frailty are associated with an increased risk of postoperative morbidity and 1-year mortality. Chronological age is not sufficient to assess the risk of postoperative complications. The CGA has been developed to better identify frail patients. Geriatric co-management have been developed to optimize the post-operative outcomes. We analyzed the real-life of geriatric co-management within an ERAS program on surgical outcomes at 90 days and oncologic outcomes at 1 year in patients aged 70 years or older after surgery for CRC. This was a retrospective study based on a prospective cohort. Fifty-one patients with a G8 score ≤ 14 were referred to geriatricians for preoperative CGA (Frail Group). They were compared with 151 patients with a G8 score ≥ 15 (Robust Group). In the Frail Group, patients were significantly older with more comorbidities than the patients in the Robust Group. Oncologic characteristics, treatments and global post-operative outcomes were comparable between the two groups. One year after surgery mortality and recurrence rates were similar between the two groups. Our study suggests that geriatric co-management is feasible and contributes to the reduction of postoperative morbimortality. Moreover, performing the CGA after G8 score screening and completion of geriatric interventions resulted in similar 90-day postoperative outcomes, in frail patients than in robust patients. Our results confirmed the benefit of geriatric co-management, involving G8 screening, CGA, and ERAS, for frail older patients undergoing surgery for CRC.

Primary tumor resection for asymptomatic colorectal cancer patients with synchronous unresectable metastases: a meta-analysis of randomized controlled trials and case-matched studies.

PURPOSE: The value of upfront primary tumor resection (PTR) for asymptomatic unresectable metastatic colorectal cancer (mCRC) patients remains contentious. This meta-analysis aimed to assess the prognostic significance of upfront PTR for asymptomatic unresectable mCRC. METHODS: A systematic literature search was performed on June 21st, 2024. To minimize the bias and ensure robust evidence, only randomized controlled trials (RCTs) and case-matched studies (CMS) that compared PTR followed by chemotherapy to chemotherapy alone were included. The primary outcome was overall survival (OS), while cancer-specific survival (CSS) served as the secondary outcome. RESULTS: Eight studies (three RCTs and five CMS) involving 1221 patients were included. Compared to chemotherapy alone, upfront PTR followed by chemotherapy did not improve OS (hazard ratios [HR] 0.91, 95% confidence interval [CI] 0.79-1.04, P = 0.17), but was associated with slightly better CSS (HR 0.59, 95% CI 0.40-0.88, P = 0.009). CONCLUSIONS: The current limited evidence indicates that upfront PTR does not improve OS but may enhance CSS in asymptomatic unresectable mCRC patients. Ongoing trials are expected to provide more reliable evidence on this issue.

Ferroptosis: the balance between death and survival in colorectal cancer.

Colorectal cancer (CRC) is a common malignant tumor associated with high morbidity and mortality. Despite an increase in early screening and treatment options, people with CRC still have a poor prognosis and a low 5-year survival rate. Therefore, mining more therapeutic targets and developing means of early diagnosis and determining prognosis are now imperative in the clinical treatment of CRC. Ferroptosis is a recently identified type of regulated cell death (RCD) characterized, which is identified by the accumulation of iron-dependent lipid peroxidation, thereby causing membrane damage and cell death. Recent studies have shown that ferroptosis is associated with tumors, including CRC, and can be involved in CRC progression; however, the underlying mechanisms are complex and heterogeneous and have not been thoroughly summarized. Therefore, this study reviewed the roles of ferroptosis in CRC progression to target ferroptosis-related factors for CRC treatment. The significance of ferroptosis-related biomarkers and genes in the early diagnosis and prognosis of CRC was also investigated. Furthermore, the limitations of ferroptosis studies in the current treatment of CRC, as well as future research perspectives, are discussed.

Optimization of colorectal cancer screening strategies: New insights.

In this editorial, we discuss the article by Agatsuma et al. We concentrate specifically on the current routinely used screening tests recommended by society guidelines and delve into the significance of early diagnosis of colorectal cancer (CRC) and its substantial impact on both incidence and mortality rates. Screening is highly recommended, and an early diagnosis stands out as the most crucial predictor of survival for CRC patients. Therefore, it is essential to identify and address the barriers hindering adherence to screening measures, as these barriers can vary among different populations. Furthermore, we focus on screening strategy optimization by selecting high-risk groups. Patients with comorbidities who regularly visit hospitals have been diagnosed at an early stage, showing no significant difference compared to patients undergoing regular screening. This finding highlights the importance of extending screening measures to include patients with comorbidities who do not routinely visit the hospital.

Efficacy and safety of PD-1/L1 inhibitors as first-line therapy for metastatic colorectal cancer: a meta-analysis.

Objective: To evaluate the efficacy and safety of PD-1/L1 inhibitors as first-line therapy in metastatic colorectal cancer(mCRC). Method: Articles evaluating first-line PD-1/L1 inhibitors for mCRC were sought in four databases (Pubmed, Embase, Web of Science, and the Cochrane Library) from the inception of the databases until 11 November 2023. Meta-analyses were conducted to assess the rates of progression-free survival (PFS), overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), disease control rate (DCR), and grade ≥ 3 treatment-related adverse events (trAEs). Results: Totally nine studies were included for meta-analysis. A subgroup analysis was performed based on mismatch repair(MMR) status and regimens. In patients diagnosed with mismatch repair-deficient(dMMR) mCRC who received PD-1/L1 inhibitors as their first-line treatment, the ORR was 0.54 (95% CI, 0.39 to 0.68), the median PFS was 53.2 months, the Grade≥ 3 TRAEs rate was 0.33(95% CI, 0.12 to 0.60) and the median OS was not determined. For patients with proficient mismatch repair (pMMR) mCRC who underwent a combined treatment of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody and chemotherapy as their first-line therapy, the ORR was 0.62 (95% CI, 0.56 to 0.68), the median PFS was 10.1 months, the median OS was 26.7 months, and the Grade≥ 3 TRAEs rate was 0.59(95% CI, 0.39 to 0.77). Conclusion: Our results revealed that the utilization of PD-1/L1 inhibitors as first-line therapy for dMMR mCRC yielded highly favorable outcomes, while maintaining an acceptable level of safety. Administering a combination of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody, and chemotherapy as first-line treatment in patients with pMMR mCRC led to an improved ORR. However, there was no significant improvement in the long-term prognosis of the tumor. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506196, identifier CRD42024506196.

Comparative analysis of short- and long-term outcomes in laparoscopic versus open surgery for colorectal cancer patients undergoing hemodialysis.

PURPOSE: Although minimally invasive colorectal surgery has been proven to have a shorter hospital stay and fewer short-term complications than open surgery, the advantages of laparoscopic surgery for colorectal cancer patients undergoing hemodialysis have not been validated. This study compared the outcomes of open and laparoscopic approaches in these patients. MATERIALS AND METHODS: Between January 2007 and December 2020, we retrospectively analyzed the clinical data of 78 hemodialysis patients who underwent curative-intent, elective colorectal surgery. Patients were divided into two groups according to the surgical method: open and laparoscopic. RESULTS: Postoperative morbidity (p = 0.480) and mortality (p = 0.598) rates and length of hospital stay (28.8 vs. 27.5 days, p = 0.830) were similar between the groups. However, laparoscopic surgery patients had a shorter return to clear liquid, full liquid, or soft food time than open surgery patients (p < 0.001, p = 0.007, and p = 0.002, respectively). Disease-free survival and long-term cancer-specific survival rates were also similar between the two groups (p = 0.353 and p = 0.201, respectively). Multivariate analysis revealed that intraoperative blood transfusion was a risk factor for severe complications and mortality (OR 6.055; p = 0.046), and the odds ratio (OR) of laparoscopic surgery was not significantly greater than that of open surgery (OR = 0.537, p = 0.337). CONCLUSION: Although laparoscopic surgery did not result in hemodialysis patients having a shorter postoperative hospital stay, our results suggest that the laparoscopic approach is as safe as open surgery for hemodialysis patients and may be beneficial for shortening the return time to food intake.

A New Genetic Signature of Lactate Metabolism-Associated Genes Predicting Clinically Distinctive Features and Tumor Microenvironment in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is characterized by its high malignancy and challenging prognosis. A significant aspect of cancer is metabolic reprogramming, where lactate serves as a crucial metabolite that contributes to the development of cancer and the tumor microenvironment (TME). Current studies have indicated that lactate plays a significant role in the progression of CRC. However, the relationship between lactate and the tumor microenvironment remains understudied, underscoring the potential of lactate as a novel biomarker. METHODS: We sourced transcriptomic data for colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO) portals, along with the corresponding clinical information. Utilizing univariate Cox regression in conjunction with LASSO regression analysis, we identified genes involved in lactate metabolism that are associated with CRC prognosis. Subsequently, we developed models based on multi-factor Cox regression. To evaluate the correlation between tumor mutational burden (TMB), tumor microenvironment (TME), and lactate scores with patient survival, we conducted gene set enrichment analysis (GSEA) and immunogenic signature analyses. RESULTS: 3 lactate metabolism-related genes (LMRGs) (SLC16A8, GATA1, and PYGL) were used to construct models that categorized patients into 2 subgroups based on their lactate scores. The function of the differential genes between the 2 subgroups was mainly enriched in cell cycle and mRNA division, and the prognosis of patients in the high score subgroup was poor. Furthermore, a significant positive correlation was observed between TMB and LMRGs scores in the high-scoring group (P = 0.003, r2 = 0.12). Lastly, LMRGs also reflected the characteristics of TME, with differences in immune cells and immune checkpoints between the 2 subgroups. CONCLUSIONS: LMRGs may serve as a promising biomarker for predicting prognostic survival in CRC patients and to assess the TME.

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Inflammation and Colorectal Cancer: A Meta-Analysis of the Prognostic Significance of the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI).

The overall prognosis for colorectal cancer (CRC) remains challenging as the survival time varies widely, even in patients with the same stage of disease. Recent studies suggest prognostic relevance of the novel markers of systemic inflammation, the systemic immune-inflammation index (SII), and the systemic inflammation response index (SIRI). We conducted a comprehensive meta-analysis to assess the prognostic significance of the SII and the SIRI in CRC. We searched the relevant literature for observational studies, and random effects models were employed to conduct a statistical analysis using the metaanalysisonline.com platform. Pooled effect sizes were reported with hazard ratios (HRs) and corresponding 95% confidence intervals (CI). Data from 29 studies published between 2016 and 2024, comprising 10,091 participants, were included in our meta-analysis on SII. CRC patients with high SII levels had worse disease outcomes, which were associated with poor OS (HR: 1.75; 95% CI: 1.4-2.19) and poor PFS/DFS/RFS (HR: 1.25; 95% CI: 1.18-1.33). This increased risk of worse OS was present irrespective of the treatment strategy, sample size (<220 and ≥220), and cutoff used to define high and low SII (<550 and ≥550) groups. Based on data from five studies comprising 2362 participants, we found a strong association between the high SIRI and worse OS (HR: 2.65; 95% CI: 1.6-4.38) and DFS/RFS (HR: 2.04; 95% CI: 1.42-2.93). According to our results, both the SII and SIRI hold great promise as prognostic markers in CRC. Further validations are needed for their age- and stage-specific utility in the clinical routine.

LncRNA FAM30A Predicts Adverse Prognosis and Regulates Cellular Processes in Colorectal Cancer via Modulating miR-21-3p.

BACKGROUND/AIMS:  Colorectal cancer (CRC) is a prevalent gastrointestinal cancer with high incidence and mortality rate. lncRNAs could regulate the expression of miRNAs and further affect cancer development. Previous research has suggested that FAM30A is involved in various cancer. We aimed to investigate the function of FAM30A in the prognosis of CRC and its underlying molecular mechanisms. MATERIALS AND METHODS:  Matched tissues were collected from 107 CRC patients. FAM30A was measured by quantitative real-time transcription polymerase chain reaction and its clinical significance was evaluated by its correlation with patients' prognosis and clinicopathological features. Furthermore, the dual luciferase reporter assays were employed to assess the interactions between FAM30A and miR-21-3p and to evaluate the role of miR-21-3p in regulating the tumor suppressor effects of FAM30A. Cell proliferation and metastasis were evaluated by the Transwell assay and cell counting kit-8 assay. RESULTS:  FAM30A level was markedly decreased in CRC tissues (P <.001). A prominent association was observed in FAM30A with tumor- node-metastasis stage (P = .022), carcinoembryonic antigen (P = .027), and differentiation (P = .043) of CRC patients. The lower the FAM30A level was associated with the lower the survival rate of the CRC patients (log rank P = .034). FAM30A could negatively modulate miR-21-3p (P <.001), and the overexpression of FAM30A significantly suppressed CRC cell proliferation and metastasis (P <.001). The suppressive function of FAM30A overexpression was mediated by miR-21-3p. CONCLUSION:  FAM30A can be considered a poor prognostic indicator in CRC. Decreased FAM30A can promote the proliferation and metastasis of CRC cells by negatively regulating miR-21-3p.

Estimating cure and risk of death from other causes of cancer patients: EUROCARE-6 data on head & neck, colorectal, and breast cancers.

BACKGROUND: To estimate net survival and cancer cure fraction (CF), i.e. the proportion of patients no longer at risk of dying from cancer progression/relapse, a clear distinction needs to be made between mortality from cancer and from other causes. Conventionally, CF is estimated assuming no excess mortality compared to the general population. METHODS: A new modelling approach, that corrects for patients' extra risk of dying (RR) from causes other than the diagnosed cancer, was considered to estimate both indicators. We analysed EUROCARE-6 data on head and neck (H&N), colorectal, and breast cancer patients aged 40-79, diagnosed from 1998 to 2002 and followed-up to 31/12/2014, provided by 65 European cancer registries. FINDINGS: Young male H&N cancer patients have 4 times the risk of dying from other causes than their peers, this risk decreases with age to 1.6. Similar results were observed for female. We observed an absolute increase in CF of 30 % using the new model instead of the conventional one. For colorectal cancer, CF with the new model increased by a maximum of 3 % for older patients and the RR ranged from 1 to 1.2 for both sexes. CF of female breast cancer ranged from 73 % to 79 % using the new cure model, with RR between 1.2 and 1.4. INTERPRETATION: Not considering a RR> 1 leads to underestimate the proportion of patients not bound to die of their diagnosed cancer. Estimates of cancer mortality risk have an important impact on patients' quality of life.

Long-term effects of once-only flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: 21-year follow-up of the UK Flexible Sigmoidoscopy Screening randomised controlled trial.

BACKGROUND: Flexible sigmoidoscopy screening reduces colorectal cancer incidence and mortality; however, uncertainty exists about the duration of protection and differences by sex and age. We assessed effects of once-only flexible sigmoidoscopy screening after 21 years' follow-up. METHODS: The UK Flexible Sigmoidoscopy Screening Trial is a multicentre randomised controlled trial that recruited men and women aged 55-64 years from general practices serving 14 hospitals. Among participants indicating that they would attend flexible sigmoidoscopy screening if invited, randomisation (2:1) to the control (no further contact) or intervention (invited to once-only flexible sigmoidoscopy screening) group was performed centrally in blocks of 12, stratified by centre, general practice, and household type. Masking of intervention was infeasible. Primary outcomes were colorectal cancer incidence and mortality. The Kaplan-Meier method estimated cumulative incidence. Primary analyses estimated intention-to-treat hazard ratios (HRs) and risk differences, overall and stratified by subsite, sex, and age. The trial is registered with ISRCTN, number 28352761. FINDINGS: Among participants recruited between Nov 14, 1994, and March 30, 1999, 170 432 were eligible and 113 195 were randomly assigned to the control group and 57 237 were randomly assigned to the intervention group. 406 participants were excluded from analyses (268 in the control group and 138 in the intervention group), leaving 112 927 participants in the control group (55 336 [49%] men and 57 591 [51%] women) and 57 099 in the intervention group (27 966 [49%] men and 29 103 [51%] women). Of participants who were invited to be screened, 40 624 (71%) attended screening. Median follow-up was 21·3 years (IQR 18·0-22·2). In the invited-to-screening group, colorectal cancer incidence was reduced compared with the control group (1631 vs 4201 cases; cumulative incidence at 21 years was 3·18% [95% CI 3·03 to 3·34] vs 4·16% [4·04 to 4·29]; HR 0·76 [95% CI 0·72 to 0·81]) with 47 fewer cases per 100 000 person-years (95% CI -56 to -37). Colorectal cancer mortality was also reduced in the invited-to-screening group compared with the control group (502 vs 1329 deaths; cumulative incidence at 21 years was 0·97% [0·88 to 1·06] vs 1·33% [1·26 to 1·40]; HR 0·75 [0·67 to 0·83]) with 16 fewer deaths per 100 000 person-years (-21 to -11). Effects were particularly evident in the distal colorectum (726 incident cancer cases in the invited-to-screening group vs 2434 cases in the control group; HR 0·59 [0·54 to 0·64]; 47 fewer cases per 100 000 person-years [-54 to -41]; 196 cancer deaths in the invited-to-screening group vs 708 deaths in the control group; HR 0·55 [0·47 to 0·64]; 15 fewer deaths per 100 000 person-years [-19 to -12]) and not the proximal colon (871 incident cancer cases in the invited-to-screening group vs 1749 cases in the control group; HR 0·98 [0·91 to 1·07]; one fewer case per 100 000 person-years [-8 to 5]; 277 cancer deaths in the invited-to-screening group vs 547 deaths in the control group; HR 1·00 [0·86 to 1·15]; zero fewer deaths per 100 000 person-years [-4 to 4]). The HR for colorectal cancer incidence was lower in men (0·70 [0·65-0·76]) than women (0·86 [0·79 to 0·93]; pinteraction=0·0007) but there was no difference by age. INTERPRETATION: We show that once-only flexible sigmoidoscopy screening reduces colorectal cancer incidence and mortality for two decades and provide important data to inform colorectal cancer screening guidelines. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme and the Medical Research Council.

Incidence and Mortality due to Colorectal Cancer in Mongolia, 2018-2022.

OBJECTIVE: We aimed to update data on the morbidity and mortality rate of colorectal cancer (CRC) among the population of Mongolia by province between 2018 and 2022. METHODS: This study was designed using a descriptive method. The data were collected from 21 general hospitals of provinces, 9 general hospitals of districts, and the National Cancer Center in 2018-2022. The incidence and mortality were calculated as mean annual numbers per 100,000 populations. The age-standardized rate (ASR) was utilized by the direct method, and it was rated by weighted average of age-specific incidence rates against the world population. RESULT: In the country, a total of 1316 new cases were diagnosed and 782 deaths were caused by CRC in the last 5 years (2018-2022). The incidence of CRC in the last 5 years (2018-2022) was 7.9 per 100,000 populations, and the mortality rate was 4.7 per 100,000. The provinces of Orkhon (12), Khentii (11), and Central (10) reported the highest incidences of CRC, whereas the provinces of Sukhbaatar (6.9), Selenge (6.6), Dornod (6), and Darkhan-Uul (6) had the highest death rates (per 100,000 populations). The incidence of CRC didn't differ statistically significantly between men and women. Additionally, the estimated incidence has grown dramatically with patients' ages. CONCLUSION: Our study presents evidence of a steadily increasing CRC incidence in Mongolia over the past five years. Therefore, it is necessary to determine the distribution of risk factors, learn from.

The prognostic significance of CD117-positive mast cells and microvessel density in colorectal cancer.

The prognostic significance of angiogenesis has been demonstrated in various types of cancer. However, in colorectal cancer (CRC), there are conflicting results regarding the relationship between angiogenesis and clinical-histopathological prognostic factors. Mast cells are immune system cells found in the inflammatory microenvironment; their role in carcinogenesis and prognosis remains unclear although they are considered to cause cancer development and progression. The present study aims to evaluate the prognostic significance of mast cell accumulation and angiogenesis assessed by microvessel density (MVD) in patients with CRC. Patients who underwent curative resection and who were not treated with neoadjuvant chemotherapy were included. The anti-CD34 antibody and anti-CD117 antibody were utilized for the immunohistochemical assessment of MVD and the mast cell count (MCC) in the tissue samples, respectively. The relationship between MCC, MVD, survival and clinical-histopathological prognostic factors were evaluated. A total of 94 patients were enrolled to the study. In a median 49-month follow-up, 65 patients (69.1%) died. The 5-year disease-free survival was 61.1% and 31.3% for the group with CD34 < 18.3% and CD34 > 18.3%, respectively (P = .001). The same groups presented 5-year overall survival rates of 77, 1% and 51, 4%, respectively (P, .012). The MVD was found to be associated with the pathological T stage, lymph node metastasis and distant metastasis (P < .05). Although the MCC was positively correlated with MVD, there was no association between the MCC and clinical-histopathological prognostic factors. MVD-assessed angiogenesis was significantly related to survival and the clinical-histopathological prognostic factors in patients diagnosed with CRC.

Mortality rate and predictors of colorectal cancer patients in Ethiopia: a systematic review and meta-analysis.

INTRODUCTION: The incidence of colorectal cancer (CRC) has been increasing in Sub-Saharan countries, including Ethiopia. However, the real mortality rate for CRC patients in Ethiopia has not been established. Therefore, this systematic review and meta-analysis aimed to determine the overall mortality rate and identify predictors among CRC patients in Ethiopia. METHODS: PubMed, EMBASE, Web of Science, Scopus, Science Direct, and Google Scholar were searched to identify relevant articles. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed. The quality of the included studies was assessed using the Newcastle-Ottawa Scale Critical Appraisal checklist. A random effect model was used to estimate the pooled mortality rate and adjusted hazard ratio (AHR). Publication bias was assessed using funnel plots and Egger's regression test, while heterogeneity was evaluated through the Cochran Q test and I2 statistics. RESULTS: After reviewing 74 articles, only 7 studies met the criteria and were included in the analysis. The analysis revealed that the overall mortality rate among CRC patients in Ethiopia was 40.5% (95% confidence interval [CI]: 32.05, 48.87) while the survival rates at 1 year, 3 years, and 5 years were 82.3% (95% CI: 73.33, 91.31), 48.8% (95% CI: 43.35, 54.32), and 26.6% (95% CI: 21.26, 31.91) respectively. Subgroup analysis indicated that studies conducted after 2017 had higher mortality rates compared to those studied earlier (43.0% vs. 38.2%). Older age (AHR: 1.89, 95% CI: 1.27, 2.82); being married (AHR: 2.53, 95% CI: 1.79, 3.57); having comorbidities (AHR: 1.84, 95% CI: 1.45, 2.35); having high CEA levels (AHR: 2.06, CI: 1.35, 3.13); being in stage II (AHR: 4.13, 95% CI: 1.85, 9.22), III (AHR: 8.62, 95% CI: 3.88, 19.15), and IV (AHR: 8.06, CI: 2.89, 22.49) were the most important predictors. CONCLUSION: In Ethiopia, the mortality rate among individuals diagnosed with CRC is high, with two out of five patients dying from this disease. Age, marital status, CEA level, comorbidities, and cancer stage were identified as predictors of mortality in CRC patients. Therefore, early detection and screening should be prioritized, particularly for older patients, those who are married, have comorbidities, elevated CEA levels, and advanced cancer stages.

Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death.

Importance: The fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening, but evidence of its effectiveness is limited. Objective: To evaluate whether FIT screening is associated with a lower risk of dying from CRC overall, according to cancer location, and within demographic groups. Design, Setting, and Participants: This nested case-control study in a cohort of screening-eligible people was conducted in 2 large, integrated health systems of racially, ethnically, and socioeconomically diverse members with long-term programs of mailed FIT screening outreach. Eligible participants included people aged 52 to 85 years who died from colorectal adenocarcinoma between 2011 and 2017 (cases); cases were matched in a 1:8 ratio based on age, sex, health-plan membership duration, and geographic area to randomly selected persons who were alive and CRC-free on case's diagnosis date (controls). Data analysis was conducted from January 2002 to December 2017. Exposures: Completing 1 or more FIT screenings in the 5-year period prior to the CRC diagnosis date among cases or the corresponding date among controls; in secondary analyses, 2- to 10-year intervals were evaluated. Main Outcomes and Measures: The primary study outcome was CRC death overall and by tumor location. Secondary analyses were performed to assess CRC death by race and ethnicity. Results: From a cohort of 2 127 128 people, a total of 10 711 participants (3529 aged 60-69 years [32.9%]; 5587 male [52.1%] and 5124 female [47.8%]; 1254 non-Hispanic Asian [11.7%]; 973 non-Hispanic Black [9.1%]; 1929 Hispanic or Latino [18.0%]; 6345 non-Hispanic White [59.2%]) was identified, including 1103 cases and 9608 controls. Among controls during the 10-year period prior to the reference date, 6101 (63.5%) completed 1 or more FITs with a cumulative 12.6% positivity rate (768 controls), of whom 610 (79.4%) had a colonoscopy within 1 year. During the 5-year period, 494 cases (44.8%) and 5345 controls (55.6%) completed 1 or more FITs. In regression analysis, completing 1 or more FIT screening was associated with a 33% lower risk of death from CRC (adjusted odds ratio [aOR], 0.67; 95% CI, 0.59-0.76) and 42% lower risk in the left colon and rectum (aOR, 0.58; 95% CI, 0.48-0.71). There was no association with right colon cancers (aOR, 0.83; 95% CI, 0.69-1.01) but the difference in the estimates between the right colon and left colon or rectum was statistically significant (P = .01). FIT screening was associated with lower CRC mortality risk among non-Hispanic Asian (aOR, 0.37; 95% CI, 0.23-0.59), non-Hispanic Black (aOR, 0.58; 95% CI, 0.39-0.85) and non-Hispanic White individuals (aOR, 0.70; 95% CI, 0.57-0.86) (P for homogeneity = .04 for homogeneity). Conclusions and Relevance: In this nested case-control study, completing FIT was associated with a lower risk of overall death from CRC, particularly in the left colon, and the associations were observed across racial and ethnic groups. These findings support the use of FIT in population-based screening strategies.

Biomarker Testing Disparities in Metastatic Colorectal Cancer.

Importance: Among patients with metastatic colorectal cancer (mCRC), data are limited on disparate biomarker testing and its association with clinical outcomes on a national scale. Objective: To evaluate the socioeconomic and demographic inequities in microsatellite instability (MSI) and KRAS biomarker testing among patients with mCRC and to explore the association of testing with overall survival (OS). Design, Setting, and Participants: This cohort study, conducted between November 2022 and March 2024, included patients who were diagnosed with mCRC between January 1, 2010, and December 31, 2017. The study obtained data from the National Cancer Database, a hospital-based cancer registry in the US. Patients with mCRC and available information on biomarker testing were included. Patients were classified based on whether they completed or did not complete MSI or KRAS tests. Exposure: Demographic and socioeconomic factors, such as age, race, ethnicity, educational level in area of residence, median household income, insurance type, area of residence, facility type, and facility location were evaluated. Main Outcomes and Measures: The main outcomes were MSI and KRAS testing between the date of diagnosis and the date of first-course therapy. Univariable and multivariable logistic regressions were used to identify the relevant factors in MSI and KRAS testing. The OS outcomes were also evaluated. Results: Among the 41 061 patients included (22 362 males [54.5%]; mean [SD] age, 62.3 [10.1] years; 17.3% identified as Black individuals, 78.0% as White individuals, 4.7% as individuals of other race, with 6.5% Hispanic or 93.5% non-Hispanic ethnicity), 28.8% underwent KRAS testing and 43.7% received MSI testing. A significant proportion of patients had Medicare insurance (43.6%), received treatment at a comprehensive community cancer program (40.5%), and lived in an area with lower educational level (51.3%). Factors associated with a lower likelihood of MSI testing included age of 70 to 79 years (relative risk [RR], 0.70; 95% CI, 0.66-0.74; P < .001), treatment at a community cancer program (RR, 0.74; 95% CI, 0.70-0.79; P < .001), rural residency (RR, 0.80; 95% CI, 0.69-0.92; P < .001), lower educational level in area of residence (RR, 0.84; 95% CI, 0.79-0.89; P < .001), and treatment at East South Central facilities (RR, 0.67; 95% CI, 0.61-0.73; P < .001). Similar patterns were observed for KRAS testing. Survival analysis showed modest OS improvement in patients with MSI testing (hazard ratio, 0.93; 95% CI, 0.91-0.96; P < .001). The median (IQR) follow-up time for the survival analysis was 13.96 (3.71-29.34) months. Conclusions and Relevance: This cohort study of patients with mCRC found that older age, community-setting treatment, lower educational level in area of residence, and treatment at East South Central facilities were associated with a reduced likelihood of MSI and KRAS testing. Highlighting the sociodemographic-based disparities in biomarker testing can inform the development of strategies that promote equity in cancer care and improve outcomes for underserved populations.

The effect of lymph node ratio on the surgical outcomes in patients with colorectal cancer.

The current study aimed to evaluate the effect of lymph node ratio (LNR) on the short-term and long-term outcomes of colorectal cancer (CRC) patients who underwent radical CRC surgery. We retrospectively collected CRC patients who underwent radical surgery from Jan 2011 to Jan 2020 in a single-center hospital. The patients were divided into the high LNR group and the low group according to the median. The baseline information and the short-term outcomes were compared between the high group and the low group. Univariate and multivariate logistic regression was performed to analyze the independent predictors for overall survival (OS) and disease-free survival (DFS). A 1:1 proportional propensity score matching (PSM) was used to reduce the selection bias between the two groups. Kaplan-Meier method was used to estimate the OS and DFS between the two groups in different T stages. A total of 1434 CRC patients undergoing radical surgery were enrolled in this study, and there were 730 (50.9%) patients in the low LNR group and 704 (49.1%) patients in the high LNR group. After the PSM, there were 618 patients in both groups, the baseline characteristics between the two groups had no significant difference (p > 0.05). After comparing the Surgery-related information and The Short-term outcomes, the high LNR group had a longer hospital stay (after PSM, p < 0.01). In univariate and multivariate logistic regression analyses, age (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), tumor location (univariate analysis, p = 0.020; multivariate analysis, p = 0.024), lymph-vascular space invasion (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), cancer nodules (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), tumor size (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), LNR (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), and overall complications (univariate analysis, p < 0.01; multivariate analysis, p < 0.01) were independent risk factors for OS, and age (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), tumor location (univariate analysis, p = 0.032; multivariate analysis, p = 0.031), T stage (univariate analysis, p < 0.01; multivariate analysis, p = 0.014), lymph-vascular space invasion (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), cancer nodules (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), LNR (univariate analysis, p < 0.01; multivariate analysis, p < 0.01), and overall complications (univariate analysis, p < 0.01; multivariate analysis, p < 0.01) were identified as independent risk factors for DFS. The high LNR group had a worse OS in T3 (p < 0.01) and T4 (p < 0.01) as well as a worse DFS in T3 (p < 0.01) and T4 (p < 0.01). No association was found between LNR and postoperative complications, but the high LNR group had a longer hospital stay. LNR was identified as an independent predictor for OS and DFS. Furthermore, high LNR had a worse OS and DFS under T3 and T4 stages. Therefore, LNR was more prognostically significant for CRC patients under T3 and T4 stages.

Conditional survival and the prognostic value of serum carcinoembryonic antigen level in oldest old with colorectal cancer.

BACKGROUND: To evaluate the clinical value of serum CEA levels and their implications on the diagnostic value of the conventional TNM staging system in the oldest-old patients with colorectal cancer (CRC). METHODS: The recruited subjects were colorectal cancer patients aged 85 and older. The cutoff value for normal CEA level is 5 ng/mL. Patients with elevated CEA levels were categorized as stage C1, and those with normal CEA levels as stage C0. A number of Cox proportional hazard regression models were established to evaluate the prognosis of different prognostic factors with hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan-Meier method was utilized to display the disparate prognostic impact of multiple clinicopathological factors with the log-rank test. RESULTS: A total of 17,359 oldest-old patients diagnosed with CRC were recruited from the SEER database. The conditional survival of oldest-old patients with CRC was dismal with a 1-year conditional survival of only 11%, 18%, and 30% for patients surviving 1, 3, and 5 years, respectively. Patients with stage C1 exhibited a 48.5% increased risk of CRC-specific mortality compared with stage C0 (HR = 1.485, 95%CI = 1.393-1.583, using stage C0 patients as the reference, P < 0.001). All the stage C0 patients indicated lower HRs relative to the corresponding stage C1 patients. CONCLUSIONS: Dismal conditional survival of oldest-old patients with CRC should be given additional consideration. C stage influences the prognosis of oldest-old patients with CRC.

Impact of Dementia in Colorectal Cancer Patients: United States Population-Based Cohort Study.

Background/Aims: Various socioeconomic and racial disparities are well-documented for colon cancer. However, the association of dementia, which is a growing cause of mortality in the elderly, remains unexplored. We aim to understand the association between these two conditions, in the elderly population group. Methods: We utilized the 2020 National Inpatient Sample to investigate records admitted for colorectal cancer identified through ICD-10 CM codes. We divided records by the presence of dementia. Adjusted odds ratios (aORs) for predefined outcomes were determined using multivariable logistic and linear regression models, adjusting for comorbidities. The primary outcome assessed was inpatient mortality, while secondary outcomes include other inpatient complications. Results: We identified 33,335 hospitalizations with ages more than 60. The mean age was 75.2 and males constituted 50.4%. In a survey multivariable logistic and linear regression model adjusting for patient and hospital factors, utilizing propensity score matching, the presence of dementia is associated with lower inpatient mortality (aOR 0.49, 95% confidence interval [CI] [0.26, 0.92], p=0.03), lower hospitalization costs (beta coefficient -2,823, 95% CI [-5,266, -440], p=0.02), lower odds of acute respiratory failure (aOR 0.54, p=0.01), lower mechanical ventilation usage (aOR 0.26, p<0.01) but higher odds of mental status change (aOR 1.97, 95% CI [1.37, 2.84], p<0.01). Conclusions: The presence of dementia is associated with a lower risk of inpatient mortality, and other clinical outcomes, in colorectal cancer cases admitted for hospitalization. Etiologies behind this relationship should be explored to understand this inverse relationship.