Right-sided Colorectal Cancer Research Articles

Effectiveness of Colonoscopy in Reducing Incidence of Late-stage Colorectal Cancer Within an Opportunistic Screening Program.

The effectiveness of colonoscopy in preventing colorectal cancer (CRC) within opportunistic screening programs has not been clearly established. The aim of this study was to analyze the effectiveness of colonoscopy within an opportunistic screening program using nested case-control study. Subjects who received a diagnosis of CRC (CG) between the ages of 50 and 90 years were included and matched by age and gender in a 1:5 ratio with patients without CRC diagnosis (COG) during the period 2015 to 2023. Using conditional regression analyses, we tested the association between screening colonoscopy and CRC. Subgroup analyses were then performed for CRC location, endoscopist specialty, and colonoscopy quality. Of the 134 patients in CG, 19 (14.18%) had a colonoscopy in the preceding 5 years compared with 258 out of 670 (38.51%) in COG (AOR, 0.24; 95% CI: 0.14-0.41). Any colonoscopy was strongly associated with decreased odds for left-sided CRC (AOR, 0.09; 95% CI: 0.04-0.24) but not for right-sided CRC (AOR, 0.58; 95% CI: 0.29-1.17). Only complete colonoscopy (AOR, 0.41; 95% CI: 0.19-0.89) and colonoscopy with satisfactory bowel preparation (AOR, 0.38; 95% CI: 0.15-0.98) were associated with decreased odds for right-sided CRC. No significant differences in colonoscopy outcomes were found when stratifying by endoscopist specialty. In the setting of an opportunistic screening program, exposure to any colonoscopy significantly reduced left-sided CRC incidence; however, only high-quality colonoscopy was associated with a lower incidence of right-sided CRC. Therefore, every possible effort should be made to optimize the quality and cost-effectiveness of colonoscopy within an opportunistic screening program.

Faecal haemoglobin concentration and colorectal cancer site, stage and grade in a symptomatic cohort.

Minimal evidence exists regarding faecal immunochemical tests (FITs) for colorectal cancer (CRC) site, stage and grade in symptomatic patients. The primary aim is to determine any association between faecal haemoglobin concentration (f-Hb) (analysed with OC-Sensor™ Pledia) and these prognostic factors. The secondary aim is to determine the association between f-Hb and anaemia, microcytosis and iron deficiency (Hb, mean corpuscular volume [MCV] and ferritin). Symptomatic 2-week wait CRC patients with FIT were included (July 2019-October 2022). Median f-Hb and interquartile range according to sex, stage, grade and site (right-sided, caecum to transverse colon, R-CRC; left-sided, splenic flexure to rectum, L-CRC) were compared using the Mann-Whitney U test. Hb, MCV and ferritin were categorized into two groups and the median f-Hb was compared using the Mann-Whitney U test. In all, 114 patients (57 women, 57 men) were studied; 46 had R-CRC (f-Hb = 113 μg Hb/g) and 68 had L-CRC (f-Hb = 342 μg Hb/g) (P = 0.07). Sixty-nine were moderately differentiated CRC (f-Hb = 183 μg Hb/g) and 29 were poorly differentiated (f-Hb = 866 μg Hb/g) (P = 0.04). By T-stage, 35 were early (T1/2) (f-Hb = 170 μg Hb/g) and 79 were advanced (T3/4) (f-Hb = 200 μg Hb/g) (P = 0.06). The relationship between f-Hb and Hb, MCV and ferritin was not significant. Poorly differentiated (P = 0.04) and later stage (P = 0.02) R-CRC had significantly lower f-Hb compared to L-CRC. Right-sided CRC is associated with lower f-Hb than left. Poorly differentiated and later staged L-CRC had higher median f-Hb. These data add to existing evidence suggesting that FIT may be less sensitive for right-sided CRC. Strategies to mitigate the potential for missed or FIT-negative right-sided CRC are required.

Robotic purse-string suture technique for intracorporeal anastomosis using double-stapling technique in robotic resection of rectal and sigmoid colon cancer: a propensity score-matched analysis

BackgroundRobotic three-dimensional magnified visual effects and field of view stabilization have enabled precise surgical operations. Intracorporeal anastomosis in right-sided colorectal cancer surgery is expected to shorten operation times, avoid paralytic ileus, and shorten wound lengths; however, there are few reports of intracorporeal anvil fixation for intestinal anastomosis in left-sided colorectal cancer surgery. Herein, we introduce a simple, novel procedure for using robotic purse-string suture (RPSS) in intracorporeal anastomosis with the double-stapling technique in rectal and sigmoid cancer surgery and report short-term outcomes.MethodsFrom September 2022 to April 2024, 105 consecutive patients underwent robotic surgery with double-stapling technique anastomosis for rectal or sigmoid colon cancer at our institution. Their data were retrospectively analyzed. Intracorporeal anastomosis with the double-stapling technique using RPSS was performed in 26 patients (the RPSS group), while the double-stapling technique anastomosis with extracorporeal anvil fixation was performed in 79 patients (the EC group). A 1:1 propensity score-matched analysis was performed (matching criteria: sex, age, body mass index (BMI), tumor location and tumor size) using a caliper 0.3.In the RPSS group, after tumor-specific or total mesorectal excision, specimens were extracted from the umbilical wound with simultaneous anvil placement in the body cavity. The oral colonic stump was robotically excised and robotically circumferentially stitched with 3–0 Prolene in all layers. After anvil insertion into the stump, the bowel wall of the colon was completely sewn onto the central rod of the anvil. Reconstructions were anastomosed using the double-stapling technique.ResultsThe matched cohort contained 23 patients in each group. The RPSS group had significantly less bleeding than the EC group (p = 0.038). Super-low anterior resection (SLAR) in the RPSS group had shorter total operative times than those in the EC group (p = 0.045). The RPSS group experienced no perioperative complications greater than Clavien–Dindo grade III or any anastomosis-related complications.ConclusionsThe RPSS technique can be performed safely without any anastomosis-related complications and reduces the total operative times in SLAR and blood loss through total robotic surgery. This may be a useful modality for robotic colorectal surgery.

Single-cell RNA sequencing reveals the heterogeneity of MYH11+ tumour-associated fibroblasts between left-sided and right-sided colorectal cancer.

Colorectal cancer (CRC) exhibits considerable heterogeneity on tumour location. However, there is still a lack of comprehensive annotation regarding the characteristics and differences between the left-sided (L-CRC) and right-sided (R-CRC) CRC. Here, we performed single-cell RNA sequencing (scRNA-seq) on immune and stromal cells from 12 L-CRC and 10 R-CRC patients. We found that L-CRC exhibited stronger tumour invasion and poor prognosis compared with R-CRC. In addition, functional enrichment analysis of a normal cohort showed that fibroblasts of left colon are associated with tumour-related pathways. This suggested that the heterogeneity observed in both L-CRC and R-CRC may be influenced by the specific location within the colon itself. Further, we identified a potentially novel MYH11+ cancer-associated fibroblast (CAF) subset predominantly enriched in L-CRC. Moreover, we found that MYH11+ CAFs may promote tumour migration via interacting with macrophages, and was associated with poor prognosis in CRC. In summary, our study revealed the crucial role of MYH11+ CAFs in predicting a poor prognosis, thereby contributing valuable insights to the exploration of heterogeneity in L-CRC and R-CRC.

Trends in colorectal cancer surgical resection rates during the screening era: a retrospective study in Italy

BackgroundFaecal immunochemical test (FIT)-based screening is effective in reducing colorectal cancer (CRC) incidence, but its sensitivity for proximal lesions remains low.ObjectivesWe compared age-adjusted CRC surgical resection rates across anatomic sites...

High Probability of Lynch Syndrome Among Colorectal Cancer Patients Is Associated With Higher Occurrence of KRAS and PIK3CA Mutations.

In Indonesia, early-onset colorectal cancer (EOCRC) rates are higher in patients < 50 years old compared to Western populations, possibly due to a higher frequency of Lynch syndrome (LS) in CRC patients. We aimed to examine the association of KRAS and PIK3CA mutations with LS. In this retrospective cross-sectional single-center study, the PCR-HRM-based test was used for screening of microsatellite instability (MSI) mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1), MLH1 promoter methylation, and oncogene mutations of BRAF (V600E), KRAS (exon 2 and 3), and PIK3CA (exon 9 and 20) in FFPE DNA samples. All the samples (n = 244) were from Dr. Sardjito General Hospital Yogyakarta, Indonesia. KRAS and PIK3CA mutations were found in 151/244 (61.88%) and 107/244 (43.85%) of samples, respectively. KRAS and PIK3CA mutations were significantly associated with MSI status in 32/42 (76.19%) and 25/42 (59.52%) of samples, respectively. KRAS mutation was significantly associated with LS status in 26/32 (81.25%) of samples. The PIK3CA mutation was present in a higher proportion in LS samples of 19/32 (59.38%), but not statistically significant. Clinicopathology showed that KRAS mutation was significantly associated with right-sided CRC and higher histology grade in 39/151 (25.83%) and 24/151 (16.44%) samples, respectively. PIK3CA mutation was significantly associated with female sex and lower levels of tumor-infiltrating lymphocytes in 62/107 (57.94%) and 26/107 (30.23%) samples, respectively. KRAS and PIK3CA mutations did not significantly affect overall survival (120 months) in LS and non-LS patients. The high probability of LS in Indonesian CRC patients is associated with KRAS and PIK3CA mutations.

Early Symptom Patterns by Tumor Laterality, Age at Onset, Stage, and Symptom-to-Treatment Initiation in Patients with Colorectal Cancer.

In Indonesia incidence of colorectal cancer (CRC) remains high. Information about early symptoms that can offer clinicians insights for timely diagnosis, prompt referral and quick treatment decisions is very limited. This study aims to examine the pattern of CRC early symptoms and its association with tumor laterality, age at onset, metastatic status, and symptom-to-treatment initiation (STI) duration and delay. This cross-sectional study recruits 258 patients diagnosed with CRC between November 2022 and October 2023 from two distinct study databases. Patient baseline characteristics were also obtained from medical records and through interviews at baseline. Symptom-to-treatment initiation (STI) duration was defined as the number of days between the date of the symptom's onset and the date of the first treatment's initiation. Relative risk estimation for metastatic disease and the STI delay, based on tumor laterality and the age at onset group, were estimated using a log-binomial regression for each early symptom. Experiencing abdominal mass as an early symptom is significantly associated with metastatic disease, specifically in right-sided CRC cases (relative risk/RR=2.08, 95% confidence interval/CI 1.29-3.37, p=0.003). In all study subjects, the median STI duration was 182 days (2-5,082 days), with more than half of the subjects experiencing an STI delay of >180 days. Experiencing rectal mass as an early symptom is significantly associated with a higher risk of STI delay >180 days in early onset CRC (RR=1.97, 95% CI 1.27-3.06, p=0.003) and left sided-CRC cases (RR=1.54, 95% CI 1.13-2.08, p=0.005). The non-specific early symptom of weight loss is associated with a higher risk of STI delay >180 days in right-sided CRC cases (RR=1.73, 95% CI 1.06-2.84, p=0.029). The findings underlined the importance of maintaining a high clinical suspicion, particularly in patients with rectal masses and unexplained weight loss, as they might experience STI delay.

Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients.

RAS, BRAF, and mismatch repair (MMR)/microsatellite instability (MSI) are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer (CRC). However, their characteristics and influencing factors in Chinese patients have not been thoroughly described. To analyze the clinicopathological features of KRAS, NRAS, BRAF, and PIK3CA mutations and the DNA MMR status in CRC. We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression. The KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ, stage I, or stage II tumors. This study analyzed the molecular profiles of KRAS, NRAS, BRAF, PIK3CA, and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC.

RWD135 Right-Sided vs Left-Sided Colorectal Cancer Hospitalization Outcomes in the US

RWD135 Right-Sided vs Left-Sided Colorectal Cancer Hospitalization Outcomes in the US

Comprehensive Proteogenomic Profiling Reveals the Molecular Characteristics of Colorectal Cancer at Distinct Stages of Progression.

Colorectal cancer is the second most common malignant tumor worldwide. Analysis of the changes that occur during colorectal cancer progression could provide insights into the molecular mechanisms driving colorectal cancer development and identify improved treatment strategies. In this study, we performed an integrated multiomic analysis of 435 trace tumor samples from 148 patients with colorectal cancer, covering nontumor, intraepithelial neoplasia (IEN), infiltration, and advanced stage colorectal cancer phases. Proteogenomic analyses demonstrated that KRAS and BRAF mutations were mutually exclusive and elevated oxidative phosphorylation in the IEN phase. Chr17q loss and chr20q gain were also mutually exclusive, which occurred predominantly in the IEN and infiltration phases, respectively, and impacted the cell cycle. Mutations in TP53 were frequent in the advanced stage colorectal cancer phase and associated with the tumor microenvironment, including increased extracellular matrix rigidity and stromal infiltration. Analysis of the profiles of colorectal cancer based on consensus molecular subtype and colorectal cancer intrinsic subtype classifications revealed the progression paths of each subtype and indicated that microsatellite instability was associated with specific subtype classifications. Additional comparison of molecular characteristics of colorectal cancer based on location showed that ANKRD22 amplification by chr10q23.31 gain enhanced glycolysis in the right-sided colorectal cancer. The AOM/DSS-induced colorectal cancer carcinogenesis mouse model indicated that DDX5 deletion due to chr17q loss promoted colorectal cancer development, consistent with the findings from the patient samples. Collectively, this study provides an informative resource for understanding the driving events of different stages of colorectal cancer and identifying the potential therapeutic targets. Significance: Characterization of the proteogenomic landscape of colorectal cancer during progression provides a multiomic map detailing the alterations in each stage of carcinogenesis and suggesting potential diagnostic and therapeutic approaches for patients.

The Innate Immune System Surveillance Biomarker p87 in African Americans and Caucasians with Small High-Grade Dysplastic Adenoma [SHiGDA] and Right-Sided JAK3 Colon Mutations May Explain the Presence of Multiple Cancers Revealing an Important Minority of Patients with JAK3 Mutations and Colorectal Neoplasia.

Our team therefore examined colonic segments seeking to test the hypothesis that the immune response and somatic genetic profiles of the colonic anatomic segments may vary and thus account for variations in neoplasia risk among the various colonic segments revealing an antigenic relationship with precancerous lesions. The p87 antigenic field effect is recognized via Adnab-9 antibody immunohistochemistry to be significantly less in the right colon in African Americans, particularly in the cecum. Since small high-grade dysplastic adenomas (SHiGDA) likely missed by CRC screening may progress to cancer, we used Ion Torrent™ sequencing of DNA extracted from four normal colonic segments (two left-sided and two right) of patients with SHiGDAs. We also contrasted unique mutational fields in one patient with a large HiGDA (APC with unique mutations) and one patient who prospectively developed a SHiGDA (JAK3). The SHiGDA (small high-grade dysplastic polyp) patient was p87 negative for any extracted stool, saliva, or colonic effluent via ELISA (enzyme linked immunoadsorbant assay). Furthermore, mean values of expression in segments from the right colon were reduced with respect to the means obtained from the left segments in 233 patients evaluated for a p87 field effect. This has recently been shown to be the case in a large cohort of AA and Caucasian 2294 patients, possibly explaining the right-sided CRC disparity in African Americans and the subsequent increase in mortality. This field effect disparity is also true for two cancers contracted by the SHiGDa patient (lung and prostate). Thus, this pilot study suggests that the reduction in p87 in the right colon is possibly correlated with JAK3 mutations. If confirmed, JAK3 mutations, known to be associated with immune aberrations, may provide a mechanistic explanation for the lack of a p87 (protein 87 kilodaltons) field in some patients with HGD polyps who might benefit from possible intervention such as more intensive screening. Limited microbiome studies were also performed on two patients with familial cancer syndromes and these compared favorably with controls available from the literature.

Right-sided versus left-sided colorectal cancer in elderly patients: a sub-analysis of a large multicenter case–control study in Japan

PurposeThis study investigated the impact of sidedness of colorectal cancer (CRC) in elderly patients on the prognosis.MethodsIn a sub-analysis of a multicenter case–control study of CRC patients who underwent surgery at ≥ 80 years old conducted in Japan between 2003 and 2007, both short- and long-term outcomes were compared between right-sided colon cancers (RCCs) and left-sided colorectal cancers (LCCs). RCCs were defined as those located from the cecum to the transverse colon.ResultsAmong the 1680 patients who underwent curative surgery, 812 and 868 had RCCs and LCCs, respectively. RCCs were more frequent than LCCs in those who were female, had renal comorbidities, and had a history of abdominal surgery. Regarding tumor characteristics, RCCs were larger, invaded more deeply, and were diagnosed as either mucinous or signet ring-cell carcinoma more frequently than LCCs. Regarding the prognosis, patients with RCCs had a significantly longer cancer-specific survival (CS-S) and cancer-specific relapse-free survival (CS-RFS) than those with LCCs. Furthermore, sidedness was determined to be an independent prognostic factor for CS-S and CS-RFS.ConclusionRCCs, which accounted for half of the cases in patients ≥ 80 years old, showed better long-term outcomes than LCCs.

The impact of metformin on clinical outcomes of metastatic colorectal cancer with known molecular profile treated with cytotoxic chemotherapy or immune checkpoint inhibitor.

e15580 Background: Colorectal cancer (CRC) is the third most common cancer in the US, with a dismal 5-year OS of 13% in mCRC. Concomitant metformin with chemotherapy or immune checkpoint inhibitors (ICIs) revealed improved outcomes in various cancers. Metformin's anti-cancer effects stem its effects on cancer metabolism, cell cycle modulation, cancer stem cells, gut microbiota, immunomodulatory properties. The aim of this retrospective study was to study the impact of concomitant metformin use with the type of systemic therapy (chemotherapy or ICIs) in CRC. Methods: CRC tumors were analyzed by NGS of DNA (592-gene) and RNA (whole transcriptome) at Caris Life Sciences. MSS was assessed by NGS, with MSI-H and MSS patients subcategorized by concomitant metformin use with ICI or with chemotherapy, respectively. Real-world OS, derived from insurance claims data, was calculated from the time of CRC sample collection to the last contact. Hazard ratio (HR) was calculated using the Cox proportional hazards model, with p values calculated using the log-rank test. Results: The study cohort included 31,083 CRC cases (male: female = 1.2, age: 80% &gt; = 50 years). Common molecular alterations included TP53 (73.6%), APC (77.6%), KRAS (47.4%), CTNNB1 (2.0%), and HER2 amplification (1.7%). 1,503 patients were MSI-H (4.83%), 21,330 as MSS (68.6%), and 8,250 indeterminate. MSI-H patients receiving concurrent ICI/metformin had similar OS (52.7 vs. 55.4 months, HR = 0.78, 95% CI: 0.41 – 1.51, p = 0.462). Conversely, OS was increased in MSS patients on concomitant chemotherapy and metformin (38.1 vs 31.1 months, HR = 0.77, 95% CI: 0.69 – 0.86, p &lt; 0.00001). In comparing real-world OS between left-sided and right-sided colorectal cancer (CRC), regardless of metformin use, multivariate analysis incorporating molecular alterations revealed longer OS for left-sided MSS CRC compared to right-sided (HR = 0.80, 95% CI: 0.76 – 0.84, p &lt; 0.00001). However, further improvement in OS was associated with concurrent metformin use in both right-sided and left-sided tumors. Conclusions: In this retrospective analysis of real-world clinical outcomes, patients receiving concomitant metformin and cytotoxic chemotherapy had improved clinical outcomes in MSS CRC compared to those not on concurrent metformin. However, the concurrent use of metformin with ICIs in MSI-H CRC did not show an impact on clinical outcomes given low sample size. These results add to the existing body of literature on the potential benefits of metformin in the context of MSS CRC and underscore the importance of a prospective controlled study of concurrent metformin use with systemic chemotherapy in metastatic CRC. Limitations of this study involves the potential inclusion of cases with prior metformin use, small sample size, retrospective analyses, and the lack of control for the patients with type II DM.

38P Modified (m)-FOLFOXIRI plus cetuximab versus bevacizumab for right-sided or BRAF mutant metastatic colorectal cancer (mCRC): Subgroup analysis of the DEEPER trial (JACCRO CC-13)

38P Modified (m)-FOLFOXIRI plus cetuximab versus bevacizumab for right-sided or BRAF mutant metastatic colorectal cancer (mCRC): Subgroup analysis of the DEEPER trial (JACCRO CC-13)

Screening value of methylated Septin9 and lymphocyte-to-monocyte ratio in colorectal cancer.

The lymphocyte-to-monocyte ratio (LMR) is an indicator of inflammation in blood routine tests; however, little is known about its screening value in patients with colorectal cancer (CRC). The aim of this study was to explore the screening value of LMR and methylated Septin9 (mSEPT9) in CRC patients. The clinical data of 420 patients with CRC, 61 with adenomatous polyps, and 175 healthy individuals from 2018 to 2022 were retrospectively analyzed, and corresponding predictive nomograms were established. The results showed that the levels of LMR and mSEPT9 in the CRC group were significantly lower than those in the control group (P < .05). Meanwhile, the levels of LMR and mSEPT9 in right-sided CRC were significantly lower than those in left-sided CRC (P < .05). With the progression of CRC from stage I to IV, the levels of LMR and mSEPT9 also decreased gradually, and the levels of mSEPT9 in stages III and IV were significantly lower than those in stages I and II (P < .05). Receiver operating curve (ROC) results showed that mSEPT9 had the highest single diagnostic value for CRC, with an area under curve (AUC) of 0.810. The LMR with mSEPT9 combination showed the best combined diagnostic value for CRC, with AUC of 0.885. When the cutoff values of mSEPT9 and LMR were taken as 43.835 and 3.365, the sensitivity and specificity of this combination reached 82.3% and 84.6%, respectively. Our findings suggest that LMR and mSEPT9 differ in non-tumor group and CRC groups with different subtypes and stages, LMR with mSEPT9 combination can further improve sensitivity, and the novel predictive nomogram for CRC based on LMR and mSEPT9 can be further promoted.

Microsatellite Instability Testing and Prognostic Implications in Colorectal Cancer.

Given the crucial predictive implications of microsatellite instability (MSI) in colorectal cancer (CRC), MSI screening is commonly performed in those with and at risk for CRC. Here, we compared results from immunohistochemistry (IHC) and the droplet digital PCR (ddPCR) MSI assay on formalin-fixed paraffin-embedded tumor samples from 48 patients who underwent surgery for colon and rectal cancer by calculating Cohen's kappa measurement (k), revealing high agreement between the methods (k = 0.915). We performed Kaplan-Meier survival analyses and univariate and multivariate Cox regression to assess the prognostic significance of ddPCR-based MSI and to identify clinicopathological features associated with CRC outcome. Patients with MSI-high had better overall survival (OS; p = 0.038) and disease-free survival (DFS; p = 0.049) than those with microsatellite stability (MSS). When stratified by primary tumor location, right-sided CRC patients with MSI-high showed improved DFS, relative to those with MSS (p < 0.001), but left-sided CRC patients did not. In multivariate analyses, MSI-high was associated with improved OS (hazard ratio (HR) = 0.221, 95% confidence interval (CI): 0.026-0.870, p = 0.042), whereas the loss of DNA mismatch repair protein MutL homolog 1 (MLH1) expression was associated with worse OS (HR = 0.133, 95% CI: 0.001-1.152, p = 0.049). Our results suggest ddPCR is a promising tool for MSI detection. Given the opposing effects of MSI-high and MLH1 loss on OS, both ddPCR and IHC may be complementary for the prognostic assessment of CRC.

Clinicopathological Differences between Right and Left Colorectal Cancer by Sex.

Background: Until now, studies on colorectal cancer (CRC) have focused on clinicopathological characteristics based on location without considering sex differences. However, as men and women have fundamentally different physiological characteristics, research results in the clinical field are limited. We aimed to elucidate the differences in the clinicopathological characteristics between right-sided CRC (RCC) and left-sided CRC (LCC) according to sex. Methods: We classified 1492 South Korean patients with no history of colon surgery between July 2005 and June 2015 based on tumor location and sex. For these patients, differences in the clinical characteristics according to sex were compared using univariate and multivariate analyses. Results: Of the 1269 patients, 951 (74.9%) had LCC, and 318 (25.1%) had RCC, making LCC approximately three times more common than RCC. When sex was not taken into account, patients with RCC had significantly higher rates of anemia and undifferentiated cancers than the rates in those with LCC. Even considering sex, anemia and undifferentiated cancer were more prevalent in RCC than in LCC in both men and women. In contrast, age over 65 years and abnormal white blood cell count differed between RCC and LCC only in women. Conclusions: The clinicopathologic characteristics of CRC vary according to the location and sex. Therefore, sex must be considered as a fundamental characteristic of personalized treatment.

Right-side shift of colorectal cancer in Trinidad and Tobago: A change in distribution

Background and Objectives: Previously published epidemiologic data from Trinidad and Tobago suggested that left-sided colorectal cancer (CRC) was more common, but accepted, standardized definitions for CRC laterality were not used. This study aims to collect data from patients with CRC in Trinidad &amp; Tobago in order to determine anatomic site using standardized definitions. Methods: A retrospective audit of hospital records was carried out for all patients with CRC over a 10-year period from January 1, 2011 to January 30, 2021. Standardized definitions were used to classify CRC laterality: Right-sided CRC was defined as those that arose in the cecum, ascending colon, hepatic flexure and/or transverse colon. Left-sided primaries were defined as those that originated from the splenic flexure, descending colon and/or sigmoid colon. The following data were extracted: laterality, gender, age and ethnicity. Descriptive statistical analyses were generated with SPSS version 21. Results: The records of 326 patients with CRC were examined in this study. There was a predominance of right-sided (43%) over left sided primaries. There was a statistically significant relationship between right sided CRC and female (58.2% vs. 41.8%; P = 0.00168), black ethnicity (60.2% vs. 38.6%; P = 0.0076) and younger age (60.9 vs. 65.9 years; P = 0.00028). Conclusion: There is a predominance of right-sided CRC in this eastern Caribbean nation, significantly associated with younger, female and black population.

Single-cell transcriptomics and Mendelian randomization reveal LUCAT1's role in right-sided colorectal cancer risk.

Background: Colorectal cancer (CRC) is a malignancy with high incidence and mortality rates globally, categorized into left-sided and right-sided CRC, each exhibiting significant differences in molecular characteristics, clinical manifestations, and prognosis. Methods: This study employed single-cell transcriptomic data and various bioinformatics approaches, such as two-sample Mendelian randomization, reverse Mendelian randomization, colocalization analysis, directed filtering, pseudotime analysis, and intercellular communication analysis. It analyzed cellular-level disparities between left-sided and right-sided CRC, identifying distinct subpopulations with characteristic variations. For these cells, two-sample Mendelian randomization was utilized to explore gene-to-one-sided CRC causality. Results: LUCAT1 was enriched in high-abundance monocyte subpopulations in right-sided CRC and demonstrated potential risk factor status through Mendelian randomization analysis. The specific single-nucleotide polymorphism (SNP) rs10774624 was associated with an increased risk of CRC. Moreover, metabolic pathway analysis revealed that LUCAT1+ monocytes exhibit lower communication activity in the tumor microenvironment and heightened activity in metabolic functions like glycosaminoglycan degradation. Its biological functions are related to the positive regulation of interleukin-6 production and NF-kappa B signaling, among others. Conclusion: This study confirmed a potential causal relationship between LUCAT1 and right-sided CRC risk through Mendelian randomization analysis. These findings provide novel insights into the pathogenesis of right-sided CRC and may aid in developing early detection and treatment strategies for right-sided CRC.

Relationship Between Farnesoid X Receptor and Macrophage Polarization Status in Colorectal Cancer

Objective: Most colorectal cancer patients are insensitive to immunotherapy, which is associated with the polarization state of macrophages in the immune microenvironment. Research indicates that the farnesoid X receptor can modulate the immune microenvironment of colorectal cancer, but its relationship with the polarization status of macrophages requires further investigation. This study aims to investigate the expression of farnesoid X receptor in colorectal cancer, and analyze its correlation with the clinical pathological features of colorectal cancer and the polarization status of macrophages. Methods: Pathological specimens from 31 cases diagnosed with colorectal adenocarcinoma and undergoing surgery at Wuhan Central Hospital between January 2022 and December 2022 were collected. Immunohistochemistry was employed to assess the expression of farnesoid X receptor in tumor cells and tumor stroma. The quantity of CD86-positive and CD206-positive cells in the samples was also measured to reflect the infiltration of M1 and M2 macrophages in the tumor immune microenvironment. Describe the expression of farnesoid X receptor in colorectal cancer tumor cells and tumor stroma, and analyze the relationship between farnesoid X receptor expression and clinical pathological features and macrophage polarization status. Results: The positive rates of farnesoid X receptor expression in tumor cells and tumor stroma were 29.03% and 45.16%, respectively. The expression of farnesoid X receptor in tumor cells was associated with tumor location (P=0.015), with a higher incidence of farnesoid X receptor expression loss in left-sided colon cancer compared to right-sided colon cancer. The expression of farnesoid X receptor in tumor stroma was correlated with macrophage polarization status. The positive expression of farnesoid X receptor in stroma was associated with a higher infiltration of M1-type macrophages (P=0.008) and a higher M1/M2 ratio compared to the farnesoid X receptor expression loss group (P=0.003), suggesting a better response to immunotherapy and a favorable prognosis. Conclusion: Farnesoid X receptor is expressed in both colorectal cancer tumor cells and tumor stroma, showing a close association with the primary site of colorectal cancer and the polarization status of macrophages. The positive expression of farnesoid X receptor in tumor cells is predominantly observed in right-sided colorectal cancer, while the positive expression of farnesoid X receptor in tumor stroma is associated with macrophage polarization towards the M1 phenotype.