Colon Rectal Cancer Research Articles

Social Vulnerability and Receipt of Guideline-Concordant Care among Patients with Colorectal Cancer.

Cancer outcome disparities have been reported in highly vulnerable communities. The objective of this study was to evaluate the association of social vulnerability with receipt of guideline-concordant care (GCC) and mortality risk for patients with colorectal cancer. This retrospective observational study identified patients with stage I-III colon or stage II-III rectal cancer between 2018 and 2020 from the National Program of Cancer Registries Database. Data were merged with the Centers for Disease Control and Prevention Social Vulnerability Index (SVI) at the county level. GCC was defined as stage-appropriate lymphadenectomy, radiation therapy, or systemic therapy. Multivariable logistic regression and Cox proportional hazards regression investigated associations of SVI, as a continuous and categorical variable stratified into quartiles, with GCC and 3-year cancer-specific mortality risk, respectively. Among 124,950 patients (colon, n=102,399; rectal, n=22,551), median SVI was 60.9 (IQR 35.0 to 79.5). Patients in the highest SVI quartile had 21% decreased odds of receiving GCC (95% CI 0.76 - 0.83). Treatment at Commission on Cancer (CoC) accredited hospitals was associated with increased GCC (OR 1.79; 95% CI 1.72 - 1.85). Although there was an inverse, decreasing association between SVI and probability of GCC, probability at non-CoC-accredited hospitals declined faster than at CoC-accredited hospitals (p<0.05). After adjusting for receipt of GCC, highly vulnerable patients treated at CoC-accredited hospitals had decreased mortality risk (HR 0.91; 95% CI 0.83 - 0.98). For highly vulnerable patients, treatment at CoC-accredited hospitals was associated with increased receipt of GCC and decreased mortality risk, which may reflect CoC-accreditation requirements for treatment guideline adherence, community engagement, and addressing barriers to care.

Prophylactic para-aortic lymph node dissection in Colo-rectal cancer; pilot study

BackgroundColorectal cancer is the 3rd most common cancer worldwide, representing 10% of all cancer types, and is considered the 2nd leading cause of cancer-related deaths. It usually metastasizes to the liver or lung. Para-aortic lymph node metastasis is considered a metastatic disease (stage 4) according to the AJCC and is considered a regional disease (stage 3) according to the JSCCR. Para-aortic lymph node metastases occur in about 1% of cases. Neoadjuvant CTH, followed by PALN, is the best option for metastatic para-aortic LNs in colorectal cancer patients. This study addresses the value of prophylactic para-aortic LN dissection among colon-rectal cancer patients (overtreatment protocol).MethodologyThis is a prospective study that included patients attending NCI, Cairo University, from December 2020 to December 2023 who were complaining of left colonic cancer or recto-sigmoid cancer and underwent left hemicolectomy, sigmoid colectomy, or LAR. All patients underwent formal mesenteric LN dissection and prophylactic para-aortic LN dissection.ResultsAmong 60 patients who underwent colorectal surgery with prophylactic para-aortic LN dissection, 21 cases (35%) were in the descending colon, 22 cases (36.7%) were in the sigmoid colon, 11 cases (18.3%) were in the recto-sigmoid, and 6 cases (10%) were in the upper rectum. 55 cases (91.7%) were in grade 2, and 5 cases (8.3%) were in grade 3. Neoadjuvant CTH was given in 3 cases (5%) while neoadjuvant RTH was given in 6 cases (10%). Regarding reported postoperative complications, lymphorrhea was reported in 2 patients (3.3%) and wound infection occurred in 6 patients (10%). A recurrence was reported among 8 cases (13.4%).ConclusionsWe aimed in this study to highlight the value of prophylactic para-aortic lymph node dissection among colorectal cancer patients (over-treatment protocol) and report its reflection on predicting the behavior of the disease and subsequently selecting the patients who will be suitable to do this procedure.

Free-fatty acid receptor-4 gene polymorphism (rs61866610) and colorectal cancer risk

This study aimed to investigate the impact of Free-fatty acid receptor-4 (FFAR4) rs61866610 polymorphism on colorectal cancer (CRC) risk. Herein, ninety-two histopathologically confirmed CRC patients and 95 healthy individuals were evaluated for FFAR4 polymorphism by RFLP-PCR. Gender, age, body mass index (BMI), underlying disease, and smoking status were recorded for all subjects. Clinical and histopathologic findings including tumor grade and TNM stage were also prepared in the patient group. Except for type 2 diabetes which was more prevalent in the control group, there were no differences between the two groups regarding underlying diseases (p > 0.05). The frequency of genotypes was as follows: in the CRC group 75% wild type, 23.9% heterozygous, and 1.1% homozygous mutant. In the control group 85.3% wild type, 12.6% heterozygous, and 2.1% homozygous mutant. Mutant allele carriers were more frequent in CRC subjects (25%) than in the normal group (14.7%) but it did not reach a significant level. The frequency of mutant genotypes in colon cancer and rectal cancer was 27.5% and 8.3% respectively (p = 0.282). The mutant genotypes were found more in patients with high-grade tumors (p = 0.154). Subjects with stage III/IV had a higher frequency of mutant genotypes than low-stage cases (p = 0.011). No association was found regarding rs61866610 and obesity or type 2 diabetes (p > 0.05). In conclusion, FFAR4 (rs61866610) has no significant association with the risk of CRC, but the higher frequency of mutant genotypes in subjects with advanced cancer stages (III/IV) suggests further studies to determine the role of FFAR4 in colorectal tumorigenesis.

Differences in characteristics and outcomes between early-onset colorectal cancer and late-onset colorectal cancers

IntroductionColorectal cancer (CRC) represents a significant health burden worldwide, with a notable increase in early-onset colorectal cancer (EOCRC) cases, defined as those diagnosed before the age of 50 years. Materials and methodsUsing data from Taiwan's national cancer registry and a retrospective cohort from Chang Gung Memorial Hospital, this study analyzed CRC cases diagnosed between 2008 and 2019. The analysis compared the EOCRC and late-onset CRC (LOCRC) groups in terms of clinicopathological characteristics, pre-diagnostic symptoms, and survival outcomes. ResultsThe analysis revealed a continuous increase in the annual incidence of EOCRC, with colon cancer and rectal cancer rising by 3.2 % and 3.3 %, respectively. Patients with EOCRC presented with more aggressive disease characteristics, such as signet-ring cell adenocarcinoma, mucinous adenocarcinoma, and poorly differentiated grade. Advanced stages at diagnosis, stages III and IV, were more common with EOCRC (62.4 %) than with LOCRC (50.3 %). Patients with EOCRC reported rectal bleeding, changes in bowel habits, and abdominal pain more frequently than those in the LOCRC group. There is a strong association between stool-related symptoms and left-sided CRC. Despite similar surgical outcomes, the 5-year cancer-specific survival rate of patients with stage IV EOCRC was significantly lower than that of patients with LOCRC (32.8 % vs. 51.9 %, p = 0.012). ConclusionThis study highlights a persistent rise in the incidence of EOCRC, with patients presenting with more aggressive disease and experiencing inferior survival. These findings underscore the importance of heightened awareness and early detection strategies for CRC, especially in younger populations, to improve the prognosis.

The Controlling Nutritional Status (CONUT) Score Predicts Post-operatory Risks and Prognosis in Patients With Surgically Treated Colon Cancer: A Retrospective Study.

The Controlling Nutritional status (CONUT) score, a valuable tool evaluating the preoperative conditions of patients from a nutritional point of view, has been successfully adopted for a plethora of malignancies including colorectal cancer (CRC). However, since rectal cancer has characteristics that differ from colon cancer (CC) and because, as of 2024, investigations targeted to surgical CC patients are lacking in the pertinent literature, we decided to assess the predictive role of this scoring system in relation to postoperative course and survival of surgical patients affected only by this malignancy. However, as of 2024, the existing literature on CONUT has typically treated colorectal cancer (CRC) as a single homogeneous entity, often combining results for both colon cancer (CC) and rectal cancer (RC). Since CC differs from RC in pathobiology, prognosis and treatment, we preferred to investigate CONUT in patients affected with CC in order to corroborate or refute the current knowledge on this score system when applied to CRC. With this stated aim, we proceeded to assess the predictive role of CONUT in relation to postoperative course and prognosis of patients who underwent CC surgery only. We retrospectively analyzed data from 341 CC patients who underwent surgery at our Hospital between 2013 and 2018. Starting from serum measurements of lymphocytes, total cholesterol and albumin we used a simplified two-tier CONUT classification in order of increasing severity: high (score ≥3) and low score (scoring <3). On equal staging class and other clinicopathological terms, compared to their high score counterpart, low CONUT subjects went through postoperative complications (both nonsurgical and surgical ones) less frequently, shorter mean hospital stay (11.2 versus 15 days) and more favorable survival (both overall and disease-free survival) with statistical significance. In the light of our results, we encourage to systematically resort to the CONUT score classification in all CC patients scheduled for a curative surgery. Preoperative correction of CONUT parameters through artificial nutrition or other measures appears mandatory as it can drastically improve the postoperative course as well as the long-term prognosis of these subjects.

Importance of diet and intestinal microbiota in the prevention of colorectal cancer - colonoscopy early screening diagnosis.

Colorectal cancer is a term used to describe colon and rectal cancer, which is the third most common type of cancer. A MEDLINE and PubMed search resulted in the inclusion of manuscripts written in the last 10 years, using keywords relevant to the topic of the manuscript. By analyzing the aim of the searched studies and manuscripts, adequate articles were included that described the stated problem. The frequency of colorectal cancer varies with climate, nutrition, and many other factors, primarily endogenous, hereditary, intestinal microbiome, as well as external factors, such as exposure of the individual to stress, and bad eating habits. Colon cancer and rectal cancer or colorectal cancer in general in the early stages of the disease, may not show symptoms or are barely noticeable. Colorectal cancer symptoms will most often not develop until the disease has progressed to stage 2 or beyond. Regular screening tests for colon or rectal cancer, especially colonoscopy, are recommended as part of a regular checkup for people aged 50 years or younger who are at high risk due to a family history of the disease or other cancers. Diet and colonoscopy as an early screening method play an important role in the prevention of colorectal cancer.

Comparing the effectiveness of panitumumab combined with FOLFOX4 treatment in patients with colon cancer vs. rectal cancer

Comparing the effectiveness of panitumumab combined with FOLFOX4 treatment in patients with colon cancer vs. rectal cancer

Epidemiology of Colorectal Cancer in Saudi Arabia: A Review.

Colorectal cancer (CRC) is the second leading cause of cancer death in the world, originating from the glandular epithelial cells of the large intestine and the rectum. This article aims to review the epidemiology of CRC in Saudi Arabia, focusing on prevalence, incidence, risk factors, preventive measures, and outcomes. This narrative review utilized the PubMed database for data extraction, including freely accessible studies published in the last 15 years. Sixteen articles from different study designs were included, while awareness and non-English language studies were excluded. In 2020, the incidence and mortality rate of CRC in Saudi Arabia were 14.6% and 1.48% among all cancers, respectively. From 2006 to 2016, the number of colon cancer and rectal cancer cases increased by 8% and 7%, respectively. Risk factors for CRC in Saudi Arabia include low education level, unemployment, physical inactivity, excess weight, poor knowledge of foods rich in fiber, cigarette smoking, reduced serum vitamin D and calcium levels, and certain gene mutations. National guidelines in Saudi Arabia recommend CRC screening for all individuals above 45 years using colonoscopy, flexible sigmoidoscopy, or fecal occult blood test. The 10-year survival rate for CRC in Saudi Arabia is 44.6%. The overall 5-year survival rate for the Ministry of National Guard-Health Affairs is 52.0%. To lower the incidence and mortality of CRC, primary, secondary, and tertiary prevention are all very important. The most crucial aspect is to concentrate on primary prevention, which may involve raising public awareness of CRC risk factors and strategies for reducing or eliminating them.

PD-1 blockade enhances the effect of targeted chemotherapy on locally advanced pMMR/MSS colorectal cancer.

Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. In this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10-8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively). Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.

Deep neural network for the prediction of KRAS, NRAS, and BRAF genotypes in left-sided colorectal cancer based on histopathologic images

BackgroundThe KRAS, NRAS, and BRAF genotypes are critical for selecting targeted therapies for patients with metastatic colorectal cancer (mCRC). Here, we aimed to develop a deep learning model that utilizes pathologic whole-slide images (WSIs) to accurately predict the status of KRAS, NRAS, and BRAFV600E. Methods129 patients with left-sided colon cancer and rectal cancer from the Third Affiliated Hospital of Sun Yat-sen University were assigned to the training and testing cohorts. Utilizing three convolutional neural networks (ResNet18, ResNet50, and Inception v3), we extracted 206 pathological features from H&E-stained WSIs, serving as the foundation for constructing specific pathological models. A clinical feature model was then developed, with carcinoembryonic antigen (CEA) identified through comprehensive multiple regression analysis as the key biomarker. Subsequently, these two models were combined to create a clinical-pathological integrated model, resulting in a total of three genetic prediction models. Result103 patients were evaluated in the training cohort (1782,302 image tiles), while the remaining 26 patients were enrolled in the testing cohort (489,481 image tiles). Compared with the clinical model and the pathology model, the combined model which incorporated CEA levels and pathological signatures, showed increased predictive ability, with an area under the curve (AUC) of 0.96 in the training and an AUC of 0.83 in the testing cohort, accompanied by a high positive predictive value (PPV 0.92). ConclusionThe combined model demonstrated a considerable ability to accurately predict the status of KRAS, NRAS, and BRAFV600E in patients with left-sided colorectal cancer, with potential application to assist doctors in developing targeted treatment strategies for mCRC patients, and effectively identifying mutations and eliminating the need for confirmatory genetic testing.

THE EFFECT OF PRIMARY LOCALIZATION OF COLORECTAL CANCER&#x0D; ON KRAS STATUS AND ITS PROGNOSTIC VALUE

Relevance: Colorectal cancer (CRC), arising from the right-sided or left-sided colon, is a separate clinical and pathological unit. The status&#x0D; of KRAS and its predictive value in CRC remain controversial.&#x0D; The study aimed to explore the effect of primary tumor localization on KRAS gene status in CRC.&#x0D; Methods: The study included 60 patients with colon and rectal cancer. The KRAS mutation test was performed on paraffin-coated tumor samples&#x0D; using PCR methods. Colon cancer was divided into right-sided colon cancer (RSCC) and left-sided colon cancer (LSCC).&#x0D; Results: KRAS mutation was found much more often in rectal cancer (RC) and sigmoid colon (SC) (p=0.413) than in tumors in other parts&#x0D; of the colon. A combined analysis of our data and previously published data showed that KRAS mutation was more common in PSTC, especially&#x0D; in the area of the hepatic bend of the colon than in LSTC (p=0.120). The association of the KRAS mutation with the patient’s age (p&lt;0.012) and&#x0D; the duration of hospitalization (p&lt;0.001) was established.&#x0D; Conclusion: Our study revealed no significant difference in the KRAS status between colon cancer and rectal cancer. However, KRAS&#x0D; mutation was much more common in RSCC compared to LSCC. Patients with RSCC with mutated KRAS also had a worse prognosis and&#x0D; required longer hospitalization compared to wild-type KRAS. However, patients with LSCC did not demonstrate a similar effect.

Prognostic impact of primary tumour location after curative resection in Stage I-III colorectal cancer: a single-centre retrospective study.

The relationship of tumour site with post-recurrence course and outcome after primary surgery in resectable colorectal cancer is unclear. This study investigated the prognostic impact of primary tumour location following radical resection without preoperative treatment in Stage I-III colorectal cancer. We analyzed 3770 patients with Stage I-III colorectal cancer who underwent curative resection at our hospital during 2000-15. We defined the right-sided colon as the cecum, ascending colon and transverse colon, and the left-sided colon as the descending colon, sigmoid and rectosigmoid junction. Patients were divided into three groups according to tumour site: right-sided colon, left-sided colon and rectum. Endpoints were overall survival, recurrence-free survival by stage and survival after recurrence, respectively. The 5-year overall survival rates of patients with stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 98.2, 97.3 and 97.2%, respectively (P=0.488). The 5-year overall survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 96.2, 88.7 and 83.0, respectively (P=0.070). The 5-year overall survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 88.7, 83.0 and 80.2, respectively (P=0.001). The 5-year recurrence-free survival rates of patients with Stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 95.1, 94.5 and 90.6% (P=0.027). The 5-year recurrence-free survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 85.2, 90.2 and 76.1%, respectively (P<0.001). The 5-year recurrence-free survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 75.3, 75.3 and 59.8%, respectively (P<0.001). Right-sided colon cancer was significantly associated with better recurrence-free survival compared with left-sided colon cancer (HR 1.29, 95% CI 1.03-1.63; P=0.025) and rectal cancer (HR 1.89, 95% CI 1.51-2.38; P<0.001) after adjusting for clinical factors. Amongst patients with recurrence, right-sided colon cancer was significantly associated with poorer survival after recurrence compared with left-sided colon cancer (HR 0.68, 95% CI 0.48-0.97; P=0.036), and showed a tendency towards poorer survival after recurrence compared with rectal cancer (HR 0.79, 95% CI 0.57-1.10; P=0.164). In Stage I-III colorectal cancer without preoperative treatment, our results suggest that the three tumour sites (right-sided colon, left-sided colon or rectum) may have prognostic significance for recurrence-free survival and survival after recurrence, rather than sidedness alone.

Abstract 3431: Genetically determined circulating lactase/phlorizin hydrolase concentrations and risk of colorectal cancer: A two-sample mendelian randomization study

Abstract Background: Colorectal cancer (CRC) ranks as the third most common cancer worldwide. Despite its established connection with genetic, dietary, and lifestyle factors, gaps remain in the understanding of its etiology. Lactase-phlorizin hydrolase (LPH) plays a critical role in milk digestion and influences crucial nutrient absorption and gut microbiota composition. A direct relationship of CRC risk with LPH level remains unexplored. Our study aims to elucidate the potential causal link between genetically determined LPH levels and CRC risk. Methods: We applied a two-sample Mendelian Randomization (MR) strategy to investigate the causal link between elevated LPH levels and CRC risks. Genetic instruments for LPH (one cis-variant and three trans-variants) were derived from the Fenland Study, and CRC-associated summary statistics for these instruments were extracted from the FinnGen Study, PLCO Atlas Project, and Pan-UK Biobank. Primary MR analyses focused on a cis-variant (rs4988235) for LPH levels, with results integrated via meta-analysis. MR analyses using all variants were also undertaken. This analytical approach was further extended to assess CRC subtypes, specifically colon and rectal cancer. Results: Meta-analysis across the three datasets illustrated an inverse association between genetically predicted LPH level and CRC risk (OR: 0.92 [95% CI, 0.89-0.95]). Subtype analyses revealed associations of genetically predicted elevated LPH levels with reduced risks for both colon cancer (OR: 0.92 [95% CI, 0.89-0.96]) and rectal cancer (OR: 0.92 [95% CI, 0.87, 0.98]). Consistency was observed across varied analytical methods and different datasets. Conclusions: Our study suggests an inverse relationship between genetically determined LPH level and CRC risk. Further exploration is warranted to unveil the underlying mechanisms and validate LPH’s potential role in CRC prevention. Citation Format: Sihao Han, Jiemin Yao, Hajime Yamazaki, Samantha Streicher, Jianyu Rao, Roch Nianogo, Zuo-Feng Zhang, Brian Huang. Genetically determined circulating lactase/phlorizin hydrolase concentrations and risk of colorectal cancer: A two-sample mendelian randomization study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3431.

Sex-specific associations of empirically derived dietary patterns with colorectal cancer risk in a Korean population: a case‒control study

Dietary patterns may be a crucial modifiable factor in colorectal cancer (CRC) risk. This study aimed to examine the associations of dietary patterns derived from two methods with CRC risk in Korea. In a study of 1420 CRC patients and 2840 control participants, we obtained dietary patterns by principal component analysis (PCA) and reduced rank regression (RRR) using 33 predefined food groups. The associations between dietary patterns and CRC risk were assessed using unconditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We identified two similar dietary patterns, derived from PCA 1 (prudent) and RRR (healthy), characterized by higher consumption of green/yellow vegetables, light-colored vegetables, fruits, eggs, and milk in both men and women. In women, higher prudent and healthy pattern scores were significantly associated with a lower risk of CRC (prudent, ORQ4 vs. Q1 = 0.59, 95% CI 0.40–0.86, P for trend = 0.005; healthy, ORQ4 vs. Q1 = 0.62, 95% CI 0.43–0.89, P for trend = 0.007). In men, a significant inverse association between dietary pattern and risk of rectal cancer was found only for the healthy dietary pattern (ORQ4 vs. Q1 = 0.66, 95% CI 0.45–0.97, P for trend = 0.036). Compared with the dietary pattern derived by PCA, the RRR dietary pattern had a slightly stronger association with a lower risk of distal colon cancer (ORQ4 vs. Q1 = 0.58, 95% CI 0.35–0.97, P for trend = 0.025) and rectal cancer (ORQ4 vs. Q1 = 0.29, 95% CI 0.15–0.57, P for trend < 0.001) in women. Our findings suggest cancer prevention strategies focusing on a diet rich in vegetables, fruits, eggs, and milk. Moreover, the use of both PCA and RRR methods may be advantageous to explore the associations between dietary patterns and risk of CRC.

SLC4A4 moulds the inflammatory tumor microenvironment and predicts therapeutic expectations in colorectal cancer.

In this report, we performed a comprehensive analysis of data in colorectal cancer (CRC), to elucidate the association among Solute Carrier Family 4 Member 4 (SLC4A4) and the abundance of immunological features and immune cell infiltration in CRC, and to explore the impact of SLC4A4 on the CRC tumor microenvironment. Colorectal cancer (CRC) cases with advanced or distal metastases experience a survival rate of less than 20%, with the lack of spectral therapeutic targets and prognostic markers posing a significant challenge for CRC treatment. SLC4A4 may be a CRC-targeted therapy for which there is currently inadequate evidence Objective: To deeply and systematically reveal the characteristics of the tumor microenvironment created by SLC4A4. We downloaded RNA sequencing files (TCGA-COADREAD), clinical data for Colon Cancer (COAD) and Rectal Cancer (READ) from the Cancer Genome Atlas. We evaluated the spearman correlation of SLC4A4 with immune features, Tracking Tumor Immunophenotype (TIP) score, and immune checkpoint gene expression. SLC4A4/immunity-related differentially expressed genes (DEGs) were identified in SLC4A4 expression groups and immune groups, and an assessment system for predicting CRC prognosis was constructed based on univariate COX and multivariate COX analyses. Based on the prognostic factors in CRC, we also constructed a nomogram to assess the survival risk status of CRC. Besides, we evaluated the potential association of SLC4A4 to immunotherapy. We found that SLC4A4 expression trended positively with immune checkpoint expression (PD-L1, CTLA4) and promoted infiltration of 27 immune cells. SLC4A4 promoted the infiltration of CD8 T cells, Dendritic cells, Macrophage, NK cells, and Th1 cells in CRC, shaping the inflammatory tumor microenvironment. Up-regulation of SLC4A4 expression might promote drug response to Anti-FGFR3_therapy, Anti-PPARG_therapy, Nivolumab, Ipilimumab in CRC patients, and down-regulation of SLC4A4 expression might promote drug response to Anti-EGFR_therapy, Aflibercept drug response. Based on the SLC4A4/immunization-related DEGs, we constructed RiskScore to assess the prognosis of CRC, which showed excellent predictive effect and robustness. RiskScore showed a trend of negative correlation with SLC4A4, which was consistent with the trend of the effect of SLC4A4 on CRC survival. Besides, RiskScore could also be useful for predicting patient prognosis. Finally, we constructed a nomogram for predicting CRC survival based on metrics with independent prognostic value (Age, M stage, Stage, RiskScore), which showed potential clinical value. Overall, upregulation of SLC4A4 expression promoted an inflammatory tumor microenvironment in CRC, and RiskScore predicted therapeutic expectancy. SLC4A4 could be a potentially clinically valuable target for CRC therapy.

Adult Height and Risk of Colorectal Cancer: A Pooled Analysis of 10 Population-based Cohort Studies in Japan.

While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians. We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models. We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07-1.40), 1.22 (95% CI, 1.09-1.36), and 1.27 (95% CI, 1.08-1.49), respectively, in men and 1.21 (95% CI, 1.09-1.35), 1.23 (95% CI, 1.08-1.40), and 1.35 (95% CI, 1.003-1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes. This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC.

Incidence patterns of colorectal cancer in Norway 1993-2022 by age, site, and morphology.

44 Background: The incidence of colorectal cancer (CRC) has decreased or stabilized in most high-income countries, but an alarming increase is observed in younger adults. Norway has high CRC incidence, which increased until the past two decades, then stabilized. A national screening program started in 2022; hence, this study is on a screening-naïve population. We aim to describe up-to-date incidence patterns of CRC, with emphasis on age-specific differences in tumor site and morphology. Methods: We extracted data on all CRC cases diagnosed 1993 to 2022 from the Cancer Registry of Norway, with completeness estimated to be &gt;99%. Data was stratified by age groups (20-49, 50-74, and ≥75), sex, primary tumor location and morphology. Age-adjusted incidence rates were calculated using Stata 17 and analyzed using Joinpoint regression to provide annual percentage change (APC) and average annual percentage change (AAPC) of incidence rates. Results: There were 107 524 cases eligible for analysis. In the age group ≥75, overall incidence increased (AAPC 0.8), mainly caused by right-sided colon cancer (RCC), which increased until 2016 (APC 2.5), followed by a slight decrease (APC -0.9). The age group 50-74 had stable incidence (AAPC -0.2). Incidence in the age group 20-49 increased (AAPC 1.3), caused by left-sided colon cancer (LCC) and rectal cancer (RC). When stratifying on morphology, incidence of mucinous carcinomas was stable (AAPC -0.6), approx. 10% of all CRC cases. Neuroendocrine neoplasms (NEN) increased in all age groups (AAPC 4.2), accounting for only 1.4% of all CRC cases; but contributed somewhat to the overall incidence in age group 20-49, in particular RC where 8.8% of cases were NEN. In the age group 20-49, adenocarcinomas had an AAPC of 1.4, mucinous carcinomas -0.8, and NEN 4.1. Conclusions: We found an increasing incidence of CRC in the youngest (&lt;50) and elderly (≥75). LCC and RC incidence increased in the youngest age group, still increasing up until 2022. In contrast, the increase in the elderly was mostly due to RCC. Different incidence patterns of primary tumor locations in younger and older age groups may imply differences in etiology and prognosis, different biological features and possibly therapeutic implications. [Table: see text]

Patient-reported outcomes in patients with gastrointestinal cancer on oral chemotherapy.

732 Background: Over the last several years, patient reported outcomes (PROs) have been demonstrated to address patient symptoms, improve outcomes, and reduce health care utilization. We aim to provide an electronic PRO (ePRO) tool for gastrointestinal (GI) oncology patients with the goals of improving adherence, reducing toxicity, and enhancing patient access to the clinical team. Methods: Patients are provided an ePRO tool consisting of a cellphone app integrated into the electronic health record with questions on adherence and 10 questions on symptoms adapted from the NCI PRO-CTCAE for local use. Emails are sent to the clinical team for nonadherence, new or worsening symptoms, or patient requested callback. Outcomes including time to first symptom assessment, emergency department (ED) visit and/or hospitalization at 30 and 90 days from enrollment will be compared with historical controls. Other outcomes including adherence and patient-reported access to the clinic will be assessed. Results: Six patients have been enrolled between May 1, 2023 and September 4, 2023. Five patients were newly starting oral chemotherapy agents and one patient had already been on therapy. Types of cancers included colon cancers (2), rectal cancer (1), pancreatic cancer (1), GIST (1), and cholangiocarcinoma (1). Types of oral chemotherapy included capecitabine (4), olaparib (1), and imatinib (1). Five patients have submitted a total of ten responses. Of the five who completed the ePROs, patients responded a median of one time (range 1-5). Reported symptoms were fatigue (4), pain (2), nausea (1), diarrhea (1), other symptoms (2) and a request callback (1). Seven (70%) responses have prompted emails alerts for clinical symptoms and one (10%) for adherence concerns. All alerts were resolved; average time to alert response 1.6 calendar days (range 1-3). Among historical controls, time to first symptom assessment after a new oral chemotherapy prescription was seven days, 30-day rate for ED and/or hospitalizations was 12%, and 90-day rate of ED visits and/or hospitalizations was 28%. Conclusions: Early data suggests a new process to manage ePROs can provide timely responses to email alerts. Of the responses thus far, 70% prompted email alerts due to clinical symptoms and 10% reported nonadherence, suggesting a high need for ongoing ePRO tools. Results are forthcoming on outcomes including time to symptom assessment/clinical action, ED visit/hospitalization and access.

Colorectal cancer genetic referral: Are we doing enough?

Purpose Guidelines are published for referral to genetic counseling and multigene panel genetic testing for colorectal cancer. We hypothesize that these guidelines are not recognized in practice, resulting in the underreferral of patients to genetic counseling. We aimed to investigate the clinical impact of these guidelines. Methods This was a retrospective cohort study conducted using a single academic-institution colorectal cancer patient registry. The registry included all patients ≥18 years old with a pathologic diagnosis of colon cancer, rectal cancer, or polyposis from January 2018 to January 2020 with complete chart data to determine inclusion into the genetic referral cohort. Results Out of 225 colon cancer patients, 92 met criteria for referral to genetic testing, but only 56 patients obtained referral and 39 completed testing. For rectal cancer, 29 out of 127 patients met criteria for referral, but only 11 obtained referral and 8 completed testing. Actionable variants, defined as pathogenic or likely pathogenic, were identified in 18 colon cancer and 5 rectal cancer patients. Age made a significant difference in the referral rate for colon cancer (P = 0.02) but not rectal cancer (P > 0.05). Conclusion Our study demonstrates poor adherence to guideline-based genetic testing. These data emphasize the need for more consistent referral to genetic testing for diagnosis of underlying inherited cancer syndromes.

Energy Alterations in Patients with Colon-Rectal Cancer

Introduction: Cancer in colon and rectum are the third most common malignancies diagnosed and second most deadly in both sexes. According to traditional Chinese medicine, patients with cancer has energy deficiency and Heat retention. Purpose: to demonstrate that patients with colorectal cancer has in the back ground energy deficiency and formation of internal Heat in the five internal massive organs (Liver, heart, Spleen, Lungs and Kidney) that is predisposing them to have cancer. Methods: through two cases reports of couple who had diagnosis of rectum cancer (in man) and malignancy tumor in the large intestine in the women. Both underwent to surgery, to take out the tumor. They went to my clinic after a year, for another reason and I measured the energy of the internal five massive organs, according to traditional Chinese medicine’s reasoning, by measuring the chakras’ energy centers using a crystal-pendulum through the radiesthesia procedure. Results: what I found was that all the internal massive organs, that corresponds to the chakras’ energy centers were in the lowest level of energy, rated one out of eight with exception of the seventh chakra, that was normal, rated in eight. Conclusion: the conclusion of this study is that patients with colorectum cancer has energy deficiency in the internal five massive organs. This result is important to us to understand how is formed colorectal cancer, in the energy point of view, because treating this condition of energy deficiency state could be one reason to establish preventive measurement for the formation of all types of cancer, in this case, colorectal cancer