Male Colorectal Cancer Patients Research Articles

Sex differences in health-related quality of life and psychological distress among colorectal cancer patients: a 2-year longitudinal study.

While sex differences in the incidence and mortality of colorectal cancer (CRC) are well documented, less is known about sex differences in patients' health-related quality of life (HRQoL) and psychological distress. To enhance patient-tailored care, we aimed to longitudinally examine sex differences in HRQoL and psychological distress among CRC patients from diagnosis up until 2-year follow-up. Newly diagnosed CRC patients from four Dutch hospitals were eligible for participation. Patients (N = 334) completed questions on HRQoL (EORTC QLQ-C30) and psychological distress (HADS) before initial treatment (baseline), 4 weeks after surgery, and at 1 and 2 years after diagnosis. Also, HRQoL and psychological distress were assessed in a sex- and age-matched reference population. When directly comparing female (N = 126, 38%) and male (N = 208, 62%) CRC patients, female patients reported significantly worse HRQoL, such as more insomnia at baseline, worse physical and role functioning 4 weeks after surgery, more diarrhea at 1 year, and more pain and constipation at 2-year follow-up. However, a comparison with the reference population revealed larger differences between patients and reference in males than in females. For example, at 1- and 2-year follow-up, male patients reported significantly worse cognitive and social functioning, more insomnia, and more anxiety compared with a reference population. Especially male CRC patients reported worse HRQoL and more psychological distress when compared with a reference population. Knowledge of sex-specific differences in HRQoL and psychological distress among CRC patients may help healthcare providers anticipate and appropriately address patients' unique healthcare needs.

Oxidative balance score: a potential tool for reducing the risk of colorectal cancer and its subsites incidences.

The Oxidative Balance Score (OBS) is commonly used to assess oxidative stress and provides a comprehensive evaluation of dietary and lifestyle-related exposures. However, there is limited research on the association between OBS and colorectal cancer (CRC), its subsites, and complications. The objective of this study was to assess the relationship between OBS and the risk of CRC, its subsites, and common complications in a large prospective cohort study. We included data from 175,808 participants in the UK Biobank data sample repository from 2006 to 2010. We evaluated OBS using a scoring system based on 22 dietary and lifestyle factors. Multiple adjustments, including multivariate Cox proportional hazard regression, gender stratification, subgroup analysis, and sensitivity analysis, were performed to fully explore the relationship between OBS and CRC, its subsites, and complications. The mediation analysis was conducted to investigate whether serum albumin, uric acid, and neutrophil levels mediate the relationship between OBS and CRC. After adjusting for potential confounding factors, a significant negative correlation was found between OBS and the risk of CRC and its subsites (proximal colon cancer, distal colon cancer, and rectal cancer). This correlation was particularly pronounced in male CRC patients. Serum albumin, uric acid, and neutrophil count, which are biomarkers, were found to have a significant mediating effect between OBS and CRC. Our study suggests that higher exposure to antioxidants assessed through OBS (diet and lifestyle rich in antioxidants) may decrease the occurrence of CRC and its subsites.

Colorectal cancer survival in Thailand

Background: Colorectal cancers are third among the world's most common cancers. Among the top five most common malignancies in Thailand, colorectal cancer primarily affects the elderly but affects persons of all ages as well. In addition, its incidence is rising yearly. Objectives: This retrospective cohort study aimed to describe the survival rate of Colorectal cancer patients in Thailand. Methods: The study used secondary data from the Ministry of Public Health between 2013 and 2020, a total of 57,321 cases were enrolled. Descriptive statistical analysis and inferential statistical analysis were performed by Cox regression analysis to observe survival rate estimate, Kaplan-Meier Survival estimate with 95% CI. Results: Among the total participants, 51.28% were male. Female survival rate was 9% higher than male Colorectal cancer patients (HR = 0.91, 95% CI: 0.86-0.94). The Colorectal cancer patients who were aged 61-70 years were more likely to pass away than patients aged £ 60 years (HR= 1.25, 95% CI:1.17- 1.34). Similarly, Colorectal cancer patients aged ≥70 years were more likely to have demise 1.58 times earlier than patients aged £ 60 years (HR= 1.58, 95% CI: 1.49-1.68). Conclusion: The survival rate of patients with colorectal cancer was significantly affected by gender. In addition, age was one of the variables which is also statistically significant that impacted on the colorectal cancer patient survival rate. Therefore, the formulation of screening policies for colorectal cancer in targeted populations, particularly in elderly should be established to support colorectal cancer prevention and reduce the risk to achieve a greater health impact among them.

Association of genetic polymorphism of glutathione S-transferases with colorectal cancer susceptibility in snuff (Naswar) addicts.

The current study aimed to investigate the relationship between polymorphisms in detoxifying (GSTM1, GSTT1, and GSTP1) genes and their association with colorectal cancer (CRC) in tobacco addicts of Pashtun ethnicity. Polymorphisms in the selected genes were genotyped in a case-control study consisting of 100 histologically confirmed male CRC patients and 100 birth-year and gender-matched healthy controls using the PCR-RFLP method. The GSTM1 null, and GSTT1 null genotypes were significantly contributed to the risk of CRC in the cases (OR= 3.131, 95% CI: 1.451-6.758, P = 0.004, and OR= 3.541, 95% CI: 1.716-7.306, P = 0.001, respectively), whereas the association observed for GSTP1 Val/Val (1.139, 95% CI: 0.356-3.644, P = 0.826) did not show statistical significance. The combined GSTM1 null and GSTT1 null showed a 41-fold increased risk (95% CI: 4.945-351.950, P = 0.001), while, the combined GSTM1 null and GSTP1 Ile/Val or Val/Val variant genotypes exhibited about 3-fold (95% CI: 1.196-7.414, P = 0.019) increased risk to CRC. Similarly, the combined GSTT1 null and GSTP1 Ile/Val or Val/Val variant genotypes showed about a 3-fold (95% CI: 1.285-8.101, P = 0.013) increased risk of CRC. In the combination of three GST genotypes, the GSTM1 null, GSTT1 null, and GSTP1 Ile/Val or Val/Val variant genotypes demonstrated a more than a 22-fold (95% CI: 2.441-212.106, P = 0.006) increased risk of CRC. Our findings suggest that GSTM1 and GSTT1 polymorphism and its combination with GSTP1 may be associated with CRC susceptibility in the Naswar addicted Pashtun population of Khyber Pakhtunkhwa, Pakistan.

XRCC1 R194W and R399Q Polymorphisms and Colorectal Cancer Risk in a Northeastern Mexican Population.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Its etiopathogenesis is complex, mainly influenced by genetic instability caused by the accumulation of mutations. The XRCC1 gene, which is involved in DNA repair, has been associated with CRC through the R194W (C194T) and R399Q (G399A) polymorphisms, but the results are inconsistent. Here, we analyzed the association of these polymorphisms with sporadic CRC in a northeastern Mexican population, including 155 male CRC patients and 155 male controls. Genotyping was performed using the RFLP method. An association with CRC was found for the 399A allele (G vs A; OR = 1.48 (1.03-2.13), P=0.034) and for the 399AA genotype in a codominant model (AA vs GG; OR = 3.11 (1.06-9.10), P=0.031). In contrast, there were no significant differences between CRC patients and controls for the C194T polymorphism (C vs T; OR = 0.82 (0.52-1.31), P=0.41). These results are consistent with many similar studies, but further research is needed to verify whether the XRCC1 R194W and R399Q polymorphisms play a role in CRC etiology. The functional significance of these polymorphisms is unclear, but some studies suggest that they influence DNA repair capacity and, thus, cancer risk.

Pre- and post-diagnosis body mass index in association with colorectal cancer death in a prospective cohort study

Objective: To evaluate the association between pre-and post-diagnosis body mass index (BMI) and risk of colorectal cancer (CRC) death. Methods: The cohort consisted of 3, 057 CRC patients from Shanghai who were diagnosed from Jan. 1, 2009 to Dec. 31, 2011 and aged from 20 to 74 years. The pre- and post-diagnosis BMI and clinical and lifestyle factors were collected at baseline. Death information was collected using record linkage with the Shanghai Cancer Registry and telephone confirmation during follow-up by the end of 2019. The Cox proportional regression model was used to estimate HR with 95% CI. Results: Analysis by multivariable Cox model showed no association between pre-diagnosis BMI and death risk in both male and female patients. Male patients with a post-diagnosis underweight BMI had an elevated risk of death compared to those in normal weight (HR=1.69, 95% CI: 1.21-2.37), especially in early stage cases. Overweight patients (HR=0.74, 95% CI: 0.61-0.89) and patients with obesity class Ⅰ (HR=0.63, 95% CI: 0.45-0.89)had better survival with decreased risks of death, especially in advanced stage cases. The decreased death risk in patients with obesity class Ⅱ was not significant (HR=0.57, 95% CI: 0.24-1.39). The P(trend) value for decreased risk of death with increased BMI in female patients was statistically significant (P<0.001), and the overweight and obesity class Ⅰ categories had better survival in advanced stage(HR(overweight)=0.62, 95% CI: 0.42-0.93; HR(obesity class Ⅰ)=0.39, 95% CI: 0.16-0.98). Both male and female patients with post-diagnosis BMI loss >2.0 kg/m(2) had an increased death risk when compared with those with stable BMI (change≤1.0 kg/m(2)) between pre- and post-diagnosis. BMI gain after diagnosis did not change death risk. Conclusions: Post-diagnosis BMI in the overweight or obesity class Ⅰ groups might be conducive to prolonging male CRC patients' survival, while underweight might result in poor prognosis. Keeping weight and avoiding excessive weight loss should be suggested for all CRC patients after diagnosis.

Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations

Aberrant tumor metabolism is a hallmark of cancer in which metabolic rewiring can support tumor growth under nutrient deficient conditions. KRAS mutations occur in 35–45% of all colorectal cancer (CRC) cases and are difficult to treat. The relationship between mutant KRAS and aberrant metabolism in CRCs has not been fully explored and could be a target for intervention. We previously acquired non-targeted metabolomics data from 161 tumor tissues and 39 normal colon tissues from stage I-III chemotherapy naïve CRC patients. In this study, we revealed that only in male patients, tumors with KRAS mutations had several altered pathways that suppress ferroptosis, including glutathione biosynthesis, transsulfuration activity, and methionine metabolism. To validate this phenotype, MC38 CRC cells (KRASG13R) were treated with a ferroptosis inducer; RAS-selected lethal (RSL3). RSL3 altered metabolic pathways in the opposite direction to that seen in KRAS mutant tumors from male patients confirming a suppressed ferroptosis metabolic phenotype in these patients. We further validated gene expression data from an additional CRC patient cohort (Gene Expression Omnibus (GEO)), and similarly observed differences in ferroptosis-related genes by sex and KRAS status. Further examination of the relationship between these genes and overall survival (OS) in the GEO cohort showed that KRAS mutant tumors are associated with poorer 5-year OS compared to KRAS wild type tumors, and only in male patients. Additionally, high compared to low expression of GPX4, FTH1, FTL, which suppress ferroptosis, were associated with poorer 5-year OS only in KRAS mutant tumors from male CRC patients. Additionally, low compared to high expression of ACSL4 was associated with poorer OS for this group. Our results show that KRAS mutant tumors from male CRC patients have suppressed ferroptosis, and gene expression changes that suppress ferroptosis associate with adverse outcomes for these patients, revealing a novel potential avenue for therapeutic approaches.

The Impact of Matrix Metalloproteinase-11 Polymorphisms on Colorectal Cancer Progression and Clinicopathological Characteristics

Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide and the most prevalent cancer in Taiwan. The matrix metalloproteinase (MMP)-11 is a proteolytic enzyme of the MMP family which is involved in extracellular matrix degradation and tissue remodeling. In this study, we focused on the associations of MMP-11 single-nucleotide polymorphisms (SNPs) with CRC susceptibility and clinicopathological characteristics. The MMP-11 SNPs rs131451, rs738791, rs2267029, rs738792, and rs28382575 in 479 controls and 479 patients with CRC were analyzed with real-time polymerase chain reaction. We found that the MMP-11 SNP rs738792 “TC + CC” genotype was significantly associated with perineural invasion in colon cancer patients after controlling for clinical parameters [OR (95% CI) = 1.783 (1.074–2.960); p = 0.025]. The MMP-11 rs131451 “TC + CC” genotypic variants were correlated with greater tumor T status [OR (95% CI):1.254 (1.025–1.534); p = 0.028] and perineural invasion [OR (95% CI):1.773 (1.027–3.062); p = 0.040) in male CRC patients. Furthermore, analyses of The Cancer Genome Atlas (TCGA) revealed that MMP-11 levels were upregulated in colorectal carcinoma tissue compared with normal tissues and were correlated with advanced stage, larger tumor sizes, and lymph node metastasis. Moreover, the data from the Genotype-Tissue Expression (GTEx) database exhibited that the MMP-11 rs738792 “CC” and “CT” genotypic variants have higher MMP-11 expression than the “TT” genotype. In conclusion, our results have demonstrated that the MMP-11 SNPs rs738792 and rs131451 may have potential to provide biomarkers to evaluate CRC disease progression, and the MMP-11 rs131451 polymorphism may shed light on sex discrepancy in CRC development and prognosis.

Relationship between Sarcopenia in Abdomen CT Scan Results with C-Reactive Protein Level in Colorectal Cancer Patients at Dr. Soetomo General Academic Hospital Surabaya

Introduction: Colorectal cancer is the third most malignant and the fourth-largest cause of death in the world, one of which is caused by cachexia cancer. Sarcopenia is the main diagnostic criterion for cachexia. The inflammatory response, one of the markers of which is C-Reactive Protein (CRP), is also involved in the occurrence of sarcopenia associated with cachexia cancer. This study aimed to determine the occurrence of sarcopenia and its relationship with CRP preoperative colorectal cancer patients. Methods: This type of observational retrospective analytic study assessed sarcopenia based on the Psoas muscle index (IOP) on preoperative CT scan images and CRP levels measured by an integrated automatic tool Dimension RxL Max with Flex liquid reagent preoperative CRP range (RCRP). Results: Sarcopenia occurs in male colorectal cancer patients with a p-value of 0.001&lt;0.05 (5%) with an IOP mean value of 26.75 m2, while in female patients the IOP mean value was 21.33 m2, it does not occur sarcopenia with p-value 0.583&gt;0.05 (5%). There was an increase in CRP in 62.5% of colorectal cancer patients, but the relationship between IOP values and CRP values of colorectal cancer patients was still categorized as weak with p value of -0.387 in men and -0.046 in women with α=0.05. Conclusion: There was a nonsignificant relationship between sarcopenia and CRP levels in colorectal cancer patients. Further prospective studies are required to consider the indicators of sarcopenia besides the decrease in IOP and identification of confounding factors known to be associated with CRP, muscle strength, and muscle mass.

Association between family history and prognosis of patients with colorectal cancer: a systematic review and meta-analysis.

BackgroundA family history of colorectal cancer (CRC) increases the risk of developing CRC, and numerous studies have assessed the influence of family history on survival among CRC patients. However, the prognostic effect of a family history of CRC remains uncertain. The aim of this meta-analysis was to systematically assess the association between family history and CRC prognosis.MethodsA comprehensive literature search was performed in the PubMed, Embase, Medline, Web of Science and Scopus databases up to October 2021, based on the Population, Intervention, Comparator, Outcomes and Study designs framework. Two reviewers independently extracted data on baseline characteristics and outcomes from the included studies. The Newcastle-Ottawa Scale was used for quality assessment of each study. Either a fixed- or a random-effects model was used to calculate the pooled hazard ratio (HR).ResultsEighteen studies comprising 80,093 CRC patients were finally included in this meta-analysis. The Newcastle-Ottawa Scale scores of the included studies ranged from 4 to 8, and 12 studies were of high quality. A significant association between family history and improved overall survival was determined in the CRC patients (HR =0.89, 95% CI: 0.81–0.99) with significant heterogeneity (I2=65.7%, P<0.001). This effect was found in male CRC patients (HR 0.70, 95% CI: 0.56–0.88) but not females (HR =0.77, 95% CI: 0.54–1.09). The association between family history and disease-free survival was not significant (HR =0.94, 95% CI: 0.88–1.01) (I2=21.0%, P=0.263). However, a subgroup analysis supported the prognostic value of disease-free survival in patients with stage III CRC (pooled HR =0.78, 95% CI: 0.67–0.92).DiscussionIn conclusion, a positive family history was associated with improved overall survival in CRC patients. It was also a favorable predictor of disease-free survival in patients with stage III CRC. These findings should be interpreted with caution because of limitations related to study quality and differences in the adjusted factors across studies.

KDM5D inhibits the transcriptional activation of FKBP4 by suppressing the expression of E2F1 in colorectal cancer in males

Colorectal cancer (CRC) remains the most frequently diagnosed malignancy and also a major contributor to cancer-related death throughout the world. Here, we first revealed the role of histone lysine-specific demethylase 5D (KDM5D) in CRC in males. KDM5D expression in tumor and adjacent tissues of male CRC patients was investigated using immunohistochemistry and RT-qPCR, and the correlation between its expression and patients’ prognosis was analyzed. Downregulation of KDM5D in CRC patients was associated with poor prognoses. Overexpression of KDM5D significantly inhibited the growth and metastasis of CRC in vitro and in vivo. The downstream mechanism of KDM5D in CRC was investigated using bioinformatics analysis, and the regulatory relationship was confirmed by ChIP-qPCR and luciferase reporter assays. KDM5D suppressed E2F1 expression by mediating H3K4me3 demethylation. E2F1, highly expressed in CRC, promoted the expression of FKBP4 at the transcriptional level by binding to the FKBP4 promoter. Finally, rescue experiments revealed that overexpression of FKBP4 significantly reversed the inhibitory effect of KDM5D on CRC growth and metastasis. Collectively, KDM5D exerted an anti-tumor and anti-metastatic in CRC through demethylation in E2F1 and suppression of FKBP4 transcription, which might represent a novel target in CRC treatment in male.

Expression and Polymorphism of TSLP/TSLP Receptors as Potential Diagnostic Markers of Colorectal Cancer Progression.

Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer-related mortality worldwide. Inflammation is considered as a critical driver for CRC development and growth. We investigated the association between polymorphisms/expression levels of thymic stromal lymphopoietin (TSLP) /TSLP receptors and CRC risk in Saudi population. DNA samples were isolated from blood samples from 220 participants. Case subjects were 112 patients diagnosed with CRC, while control subjects were 108 healthy individuals, who were not diagnosed with any type of malignancy. We selected two single nucleotide polymorphisms (SNPs) located in the thymic stromal lymphopoietin gene (rs10043985 and rs2289276), three SNPs in TSLP receptor gene (TSLPR; rs36139698, rs36177645, and rs36133495), and two other SNPs in interleukin-7 receptor gene (IL-7R; rs12516866 and rs1053496), and designated these SNPs for a case-control genotyping study. The gene expression was analyzed using quantitative RT-PCR and immunohistochemistry assays array on 20 matching colorectal cancer/normal tissues. mRNA expressions and protein levels of TSLP, TSLPR-α subunit, and IL-7R-α subunit showed a 4-fold increase in colon cancer tissues when compared to normal colon tissues. Furthermore, two SNPs (rs10043985 of TSLP and rs1053496 of IL-7R) showed statistically significant correlations with CRC susceptibility. Interestingly, only rs10043985 showed a statistically significant association (p < 0.0001) in the genotypic and phenotypic levels with CRC for all clinical parameters (age, gender, and tumor location) tested. However, IL-7R rs1053496 genotyping results presented a significant correlation (p < 0.05) in male CRC patients and in individuals under 57 years of age. TSLP rs2289276, IL-7R rs12516866, and all TSLPR variants did not display any significant genotypic or phenotypic correlations in all tested clinical parameters. This study identified that TSLP rs10043985 and IL-7R rs1053496 SNPs, and the expression levels of TSLP and TSLPR-α subunit, can be used as markers for CRC development and treatment. However, additional investigations are required on larger group of patients from diverse ethnicities to confirm the genetic association of these variants to CRC.

Cigarette smoking associated with colorectal cancer survival: a nationwide, population-based cohort study

BACKGROUND AND AIM: The association between cigarette smoking and survival in patients with colorectal cancer (CRC) is inconsistent. Thus, we aim to investigate whether cigarette smoking is associated with the overall survival rates of CRC patients using a nationwide population-based cohort study in Taiwan. METHODS: Taiwan Cancer Registry and Taiwan’s national health insurance research database were used to identify CRC patients from 2011 to 2017. All patients were censored to date of death or the end of 2017. Tobacco use was evaluated by smoking status, duration, and amount of cigarette smoking before cancer diagnosis. Survival was estimated using Kaplan-Meier analysis and Cox regression was used to investigate the effect of smoking on overall survival (OS). RESULTS:A total of 49,837 CRC patients were included for analysis. The Kaplan–Meier survival analysis illustrated smoking to be significant association with OS in CRC patients (log-rank p=0.0123). The multivariable Cox model showed that CRC patients with ever smoking habit had 1.11-fold mortality risk (HR=1.11, 95% CI=1.05-1.16; p.0001) compared with CRC patients whom never smoking. This increased risk was also present in CRC patients who smoking cigarettes 20 per day (HR=1.13; 95% CI=1.02-1.25; p=0.0149) or smoking year of 11-30 years (HR=1.15; 95% CI=1.06-1.24; p=0.0004). Furthermore, stratified analysis of sex and tumour location showed the impact of smoking was higher in male CRC patients or cancer developed in rectum. CONCLUSIONS:Our results indicate that cigarette smoking significantly associates with worse survival in CRC patients. An integrated smoking cessation campaign is warranted to prevent the CRC mortality. KEYWORDS: Colorectal cancer, Cigarette smoking, Survival

NLRP3-inflammasome activation is associated with epithelial-mesenchymal transition and progression of colorectal cancer.

Objective(s):Since activation of NLRP3 inflammasome results in the production of interleukin-1β (IL 1β) and initiation of inflammation as the key players in development of cancer, this study investigated possible activation of NLRP3 inflammasome during the progression of colorectal cancer (CRC) and evaluated the role of NLRP3 inflammasome in epithelial-mesenchymal transition (EMT) process. Materials and Methods:Tissue samples were collected from cancerous (test) and adjacent normal tissues (control) of forty-three male CRC patients (18 grade I and 25 grade III). The gene expression and protein levels were determined by qRT PCR and Western blotting, respectively, and tissue morphological was examined by histopathology. Results:The gene and protein expression levels of transforming growth factor-β (TGF β), IL 1β, nuclear factor κB (NF κB), NLRP3, and caspase-1, as well as the enzyme activity of caspase-1, were significantly increased in CRC. mRNA and protein levels of TGF-β, mature IL 1β, NF κB, and NLRP3 were higher in patients with grade III. EMT markers N cadherin, vimentin, and MMP 9 markedly increased in CRC, and were higher in grade III than grade I, whereas expression of E-cadherin declined by the progression of CRC. NLRP3 protein level was inversely correlated with E-cadherin whereas it positively was correlated with IL 1β, active NF κB, N cadherin, vimentin, and MMP 9. Conclusion:This study for the first time showed that activation of NLRP3 inflammasome contributed to the progression of CRC and is correlated with the EMT process. Although the present study showed that EMT markers are positively correlated with tumor grade, further investigations are required to strongly link the EMT markers to the progression of CRC.

Smoking status before and after colorectal cancer diagnosis and mortality in Korean men: A population-based cohort study.

BackgroundSmoking is a well‐known risk factor for colorectal cancer incidence; however, the effect of smoking before and after cancer diagnosis on mortality has not been addressed well. Thus, we aimed to evaluate the association of prediagnosis and postdiagnosis smoking status and mortality among colorectal cancer patients.MethodsA retrospective cohort consisted of 37,079 male colorectal cancer patients. Smoking status was defined from information within 2 years of colorectal cancer diagnosis for prediagnosis and at least 1 year later for postdiagnosis. The prediagnostic and postdiagnostic smoking status were categorized into four groups (nonsmoker/nonsmoker, nonsmoker/smoker, smoker/nonsmoker, and smoker/smoker). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard model.ResultsDuring a median of 6.3 years of follow‐up, a total of 3980 deaths and 2137 deaths from colorectal cancer occurred. The number of prediagnosis smokers were 11,100 and 62.4% of them quitted smoking after the diagnosis. Significantly elevated mortality rate in prediagnosis smokers was observed regardless of postdiagnosis smoking status (smoker/nonsmoker [HR, 1.30; 95% CI, 1.20–1.41] and smoker/smoker [HR, 1.21; 95% CI, 1.09–1.34]). Among patients treated with surgical operation only, those who quit smoking after diagnosis showed lower mortality rates compared to continual smokers (HR, 0.80; 95% CI, 0.67–0.96).ConclusionsSmoking before cancer diagnosis rather than postdiagnosis has stronger impact on prognosis colorectal cancer patients, and quitting smoking may improve survival, especially among early stage colorectal cancer patients.

Effect of metformin on the mortality of colorectal cancer patients with T2DM: meta-analysis of sex differences.

To evaluate the effect of metformin as a treatment for the mortality of colorectal cancer (CRC) patients with type 2 diabetes mellitus (T2DM). We searched Medline, PubMed, EMBASE, Clinical Trials.gov (http://www.clinicaltrials.gov), and the Cochrane Collaboration Library from inception to November 2019. To analyze the relationship between metformin and the overall mortality, specific mortality, and sex differences in CRC patients with T2DM, hazard ratios (HRs) with 95% confidence intervals (CIs) were used. Egger's test and Begg's test were used to assess publication bias. We included 8 cohort studies in our meta-analysis. CRC patients with T2DM treated with metformin had a lower overall mortality than CRC patients with T2DM who did not receive metformin (HR = 0.80, 95% CI 0.67-0.95). There was no significant difference in CRC-specific mortality between CRC patients with T2DM who used metformin and those who did not (HR = 0.84, 95% CI 0.65-1.08). However, females had a lower CRC-specific mortality among CRC patients with T2DM than males (HR = 0.63, 95% CI 0.41-0.97). Metformin reduced the overall mortality of CRC patients with T2DM. Moreover, female CRC patients with T2DM using metformin had lower CRC-specific mortality than male CRC patients with T2DM.

New Concept Air Conditioning System for the Operating Room to Minimize Patient Cooling and Surgeon Heating: A Historical Control Cohort Study

BackgroundIntraoperative hypothermia is a common adverse event. For avoiding the complication due to hypothermia, many warming devices and methods have been used in perioperative period. It has been reported that more patients undergoing laparoscopic surgery tend to have hypothermia than with open surgery. To avoid intraoperative hypothermia, many kinds of warming tools have been used. But, it was also reported that some warming methods increased perceptions of distraction and physical demand.MethodsTo achieve both patients’ normothermia and surgeons’ comfort, new air conditioning (AC) system was designed with considering the characteristics of laparoscopic surgery. The temperature of the airflows to the patient and to the surgeons can be adjusted independently in this new system. The new system has two parts. One controls the temperature of the central area over the operation table. The air from this part falls on the patients. The other part is the lateral area beside the operating table; the air from this part falls on the surgeons. The subjects of this study were 160 gastric cancer patients and 316 colorectal cancer patients undergoing laparoscopic surgery. The temperature of the central flow was set 23.5 °C, and the temperature of the lateral flow was set 22 °C just after the anesthesia. The number of timepoints the patient spent in hypothermic state, defined as a temperature cooler by 0.5 °C or more than that at the starting point of surgery, was determined in each patient.ResultsIn the results, the rate of hypothermic state in old operation rooms was 23.8% and that in new operation rooms was 2.7% in male gastric cancer patients (p < 0.01). And those were 37.1% in old operation rooms and 0.9% in new operation rooms in female gastric cancer patients (p < 0.01). The rate of hypothermic state in old operation rooms was 30.0% and that in new operation rooms was 9.5% in male colorectal cancer patients (p < 0.01). And those were 41.6% in old operation rooms and 8.9% in new operation rooms in female colorectal cancer patients (p < 0.01). The similar results were showed in the study, which subjects were limited the patients undergoing surgery in 2015 and 2016; which were the last year the old operation rooms were used and the first year the new operation rooms were used.ConclusionsThus, the usefulness of the new air conditioning system for achieving both patients’ normothermia and comfort of surgeons could be verified in this study.

Over-Expression of Cyclooxygenase-2 in Colorectal Cancer Patients.

Background:Colorectal carcinoma (CRC) is the most common neoplasm of the gastrointestinal tract. COX-2 plays an important role in CRC development and is a key target for the regression of colorectal tumorigenesis by non-steroidal anti-inflammatory drugs. The present study was conducted to examine the relationship of the levels of COX-2 in CRC patients with the clinico-pathological parameters and also to assess its usefulness as a potential biomarker for diagnosis of CRC. Methods:Prior to surgery, 30 CRC patients were enrolled and the samples from colon tumors and surrounding tissues were taken after they underwent surgical intervention at PGIMER, Chandigarh. mRNA expression levels of COX-2 were examined in 30 CRC and adjacent normal colonic mucosa by quantitative polymerase chain reaction (qPCR). The expression of COX-2 was assessed by immunohistochemical method using rabbit polyclonal antibodies against human COX-2 protein. Results:The quantitative relative expression of COX-2 mRNA was observed to be significantly higher (p<0.05) in colorectal cancer tissues as compared to adjacent normal colon tissues. Also, female CRC patients showed significantly higher (p<0.009) expression of COX-2 mRNA vis-a-vis male colorectal cancer patients. This is the first study which has reported a direct relationship between COX-2 mRNA expressions in male colorectal cancer patients versus females. Further, immunohistochemistry of COX-2 confirmed the quantitative real time-PCR findings. Conclusion:Our study shows that COX-2 over expression in colorectal carcinoma patients is closely associated with clinico-pathological parameters and is more pronounced in males versus females. Further, COX-2 mRNA expression can serve as a potential biomarker for the diagnosis of CRC.

Gender-related prognostic value and genomic pattern of intra-tumor heterogeneity in colorectal cancer.

Intra-tumor heterogeneity (ITH) is crucial in tumorigenesis and resistance to target therapy. Here, we used mutant-allele tumor heterogeneity (MATH) to measure ITH based on next-generation sequencing data and high MATH was proven as an independent risk prognostic factor in male CRC patients in both a training set of 284 colorectal cancer (CRC) patients with from The Cancer Genome Atlas (TCGA) and a validating set of 187 CRC patients from International Cancer Genome Consortium (ICGC). Further, the genomic pattern according to MATH demonstrated that mutation rates of TP53, IRF5 and KRAS were independently associated with MATH, and the latter two were only significant in male patients. As MATH increased, the fraction of somatic copy number alteration (SCNA) elevated. Moreover, more SCNA events was independently associated with MATH in male than in female. WNT pathway, TGF-β pathway and DNA repair deficiency was enriched in high MATH group and the latter two showed up only in male patients. In summary, we reveal the gender-related prognostic value of MATH and relevant genomic pattern in CRC. Potential mechanisms are provided and it remains to be proven whether they are drivers of subclone formation and ITH. Taking MATH into consideration in clinical trial might contribute to better therapeutic strategies in CRC with researches added on in the future.

Abstract B27: Serum uric acid levels as a prognostic factor in male patients with non-metastatic colorectal cancer

Abstract Objective: Uric acid may be a marker of oxidative stress, and can be act as an antioxidant or a prooxidant. The role of serum uric acid (SUA) in the prognostic impact of cancer is controversial. This study aimed to evaluate whether the preoperative SUA level is associated with long-term outcomes in patients with colorectal cancer (CRC). Methods: Between 2002 and 2010, 2,183 patients, who underwent curative surgical resection for non-metastatic CRC and had available SUA value, were included for this study. We analyzed the association between the overall survival (OS) and SUA level as quartile according to sex, using log-rank test and Cox proportional hazard regression to identify prognostic factors. Results: Mean SUA level was different between male and female (male [n=1,328]: 5.320 ± 1.363, female [n=855]: 4.065 ± 1.180, p&amp;lt;0.001). In female patients, there was no difference in OS according to SUA level. In male patients, SUA levels in the lowest quartile (&amp;lt; 3.5 mg/dL) was associated with poor overall survival (5-year OS of SUA level &amp;lt; 3.5 mg/dL vs ≥ 3.5 mg/dL: 72.0 % vs 97.1 %, p &amp;lt; 0.001). SUA level was an independently significant prognostic factor (HR 1.714, 95% CI 1.306-2.250, p&amp;lt;0.001). Conclusion: Our results do not support the protective role of SUA in CRC cancer, and rather lower SUA concentrations to be associated with poor long-term outcomes in male CRC patients. Citation Format: Shin Rumi, Park Ji Won, Lee Dong Woon, Ryoo Seung-Bum, Jeong Seung-Yong. Serum uric acid levels as a prognostic factor in male patients with non-metastatic colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B27.