Location Of Colorectal Cancer Research Articles

Analysis of NLR, PLR, and Carcinoembryonic Antigen in Colorectal Cancer Patients

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. The development and prognosis of CRC are affected by the tumor's appearance and the host's inflammatory response. A combination of several parameters, including the Neutrophil-Lymphocyte Ratio (NLR) and Platelet-Lymphocyte Ratio (PLR), has been used as a cancer prognostic marker. Research needs to be performed to analyze its role in CRC. This study aimed to determine the differences in the NLR, PLR, and CEA values with the severity and site of CRC. Medical record data were collected from 246 CRC patients from January 2021 to June 2022 at Dr. Wahidin Sudirohusodo Hospital were used and grouped by severity (metastatic and non-metastatic) and site (left colon, right colon, rectum). This study collected the data on NLR, PLR, and CEA levels. The Mann-Whitney, Spearman Rho, and Kruskal-Wallis tests were used for statistical analysis by the research objectives (significant if p<0.05). There were differences in median PLR (194.47 vs. 201.18; p=0.045) and CEA (3.3 ng/mL vs. 11.95 ng/mL; p<0.001) between the metastatic and non-metastatic groups, whereas there was no significant difference of median NLR between the two groups (2.77 vs. 2.79; p=0.438). No correlation was found between the NLR, PLR, and CEA level values with the location of CRC (p-values 0.978, 0.511, 0.419, respectively). PLR and CEA values were higher in metastatic CRC than in non-metastatic CRC, while NLR value was not significantly different. There was no correlation between the NLR, PLR, and CEA level values with the CRC site.

Disease characteristics and prognostic factors of colorectal cancer patients with bone metastasis: A real-world data from Turkey.

Bone metastasis is rarely seen in colorectal cancer (CRC) patients, and there is insufficient data available regarding such cases. The study aimed to identify the prognostic factors and characteristics associated with overall survival in patients with bone metastatic CRC. Data from bone metastatic CRC patients referred to a high-volume tertiary cancer center in Turkey, between January 2018 and April 2021, were retrospectively collected. The records of 150 consecutive patients treated for bone metastases due to CRC were reviewed. Overall survival curves were generated by the Kaplan-Meier method and analyzed using the log-rank test. Median age was 55 years (19-86 years). Bone metastases were more common in men and those with metachronous metastases. The axial skeleton was the most commonly involved site, and patients were frequently presented with single bone metastasis. Peritoneal metastases were significantly correlated with extra-axial metastases (P = 0.002), and radiotherapy was applied to axial metastases significantly, more frequently (P = 0.02). Lung metastasis was also more prevalent in K-RAS mutated patients (P = 0.008). The median survival time from diagnosis of bone metastasis was 8.3 months (95% confidence interval (CI), 5.5-10.6), and the three-year survival rate was 76.9% (95% CI, 69.8-84.0). Multivariate analysis revealed that brain metastases, right-sided colon tumor, high serum ALP, and Ca 19-9 levels were independent poor prognostic factors (P = 0.01, 0.02, <0.001, and 0.04, respectively). The location of CRC correlates significantly with the site of bone metastasis; the prognosis of CRC patients with bone metastasis is very poor, and the significant poor prognostic factors are brain metastases, right-sidedness, high serum ALP, and Ca 19-9 levels. More attention should be paid to bone metastasis in CRC patients.

WITHDRAWN: Characterization of mutational landscape reveals influencing factors for therapeutic response and prognosis of colorectal cancer patients with synchronous liver metastases underwent simultaneous resection of primary and metastatic lesions

BackgroundPatients with stage IV colorectal cancer (CRC) with liver metastasis represent a specific group that can be treated with surgery. However, the influence of genomic alterations on the therapeutic response and prognosis was not clear in CRC patients underwent simultaneous surgery of primary and metastatic lesions. MethodsFifty-two patients underwent simultaneous surgery on primary and metastatic lesions were retrospectively recruited. The mutational landscape of primary lesion was established by whole-exome sequencing(WES). Non-parametric test, Fisher's exact test, multivariate analyses, Kaplan-Meier analyses were performed to identify risk factors for response and prognosis, and a Nomogram model was established. Analyses were performed and figures were plotted using the Graphpad PRISM 5.0 and the R software. ResultsSeveral top mutated genes were identified from the mutational landscape of primary lesions, including APC, TP53, KRAS and TTN, and many co-mutations, mutually exclusive mutations and aberrant functions or pathways were revealed. KRAS(P = 0.047) and TTN(P < 0.001) exhibited significant differences in tumor mutational burden(TMB) between mutant and wild-type groups. TP53(P = 0.045), MUC12(P = 0.012) and CEL(P = 0.032) mutational status significantly stratified the patient therapeutic response, in which MUT12 was an independent risk factor(P = 0.02). CRC location(P = 0.014), patient therapeutic response(P < 0.001), and the mutational status of ANKRD20A4(P = 0.006), EVC(P = 0.05), FHOD3(P = 0.05), MYO15A(P = 0.008) and POTEE(P < 0.001) showed significant stratification on patient prognosis, in which cancer location, response to therapy and ANKRD20A4 and EVC mutational status were independent risk factors. These factors were used to establish a Nomogram model to predict the individual patient prognosis. Internal and external validation verified the effectiveness of the model. ConclusionsIndependent risk factors including cancer location, response to therapy and ANKRD20A4 and EVC mutational status were identified and were used in the establishment of a Nomogram model for patient prognosis prediction.

Colorectal Cancer: 35 Cases in Asbestos-Exposed Workers

Background: Asbestos is considered one of the major global work-related carcinogens. Some studies suggest a potential causal relationship between asbestos exposure and colorectal cancer (CRC). However, the role of asbestos in CRC carcinogenesis is still controversial. Methods: 35 claims of occupational CRC among asbestos-exposed workers were reviewed. All claims were rejected by the Italian National Institute for Insurance against Accidents (INAIL) due to the “lack of scientific evidence in the causality” between asbestos exposure and CRC; causality was finally assessed in civil trials. All cases were categorized by age, gender, industry type, task, exposure and latency periods, anatomical location, and histopathological characteristics of CRC and concomitant respiratory diseases. Results: Most workers were males aged 60 years or more and employed in occupational activities with extensive use of asbestos for over 20 years. In 31 out of 35 cases, CRC was diagnosed over 39 years after employment. Right-sided colic adenocarcinoma was diagnosed in nine cases; rectum was involved in eight cases. Respiratory comorbidities were observed in 22 workers. Conclusions: Our study provides some interesting points in the assessment of the causal relationship between asbestos exposure and CRC.

Black-White disparities in colorectal cancer outcomes: a simulation study of screening benefit.

The US Black population has higher colorectal cancer (CRC) incidence rates and worse CRC survival than the US White population, as well as historically lower rates of CRC screening. The Surveillance, Epidemiology, and End Results incidence rate data in people diagnosed between the ages of 20 and 45 years, before routine CRC screening is recommended, were analyzed to estimate temporal changes in CRC risk in Black and White populations. There was a rapid rise in rectal and distal colon cancer incidence in the White population but not the Black population, and little change in proximal colon cancer incidence for both groups. In 2014-2018, CRC incidence per 100 000 was 17.5 (95% confidence interval [CI] = 15.3 to 19.9) among Black individuals aged 40-44 years and 16.6 (95% CI = 15.6 to 17.6) among White individuals aged 40-44 years; 42.3% of CRCs diagnosed in Black patients were proximal colon cancer, and 41.1% of CRCs diagnosed in White patients were rectal cancer. Analyses used a race-specific microsimulation model to project screening benefits, based on life-years gained and lifetime reduction in CRC incidence, assuming these Black-White differences in CRC risk and location. The projected benefits of screening (via either colonoscopy or fecal immunochemical testing) were greater in the Black population, suggesting that observed Black-White differences in CRC incidence are not driven by differences in risk. Projected screening benefits were sensitive to survival assumptions made for Black populations. Building racial disparities in survival into the model reduced projected screening benefits, which can bias policy decisions.

Effectiveness and Safety of Apatinib Plus Programmed Cell Death Protein 1 Blockades for Patients with Treatment-refractory Metastatic Colorectal Cancer: A Retrospective Exploratory Study.

This study aimed to investigate the efficacy and safety of apatinib plus programmed cell death protein 1 (PD-1) blockades for patients with metastatic colorectal cancer (CRC) who were refractory to the standard regimens. In this retrospective study, patients with metastatic CRC who received apatinib plus PD-1 blockades in clinical practice were included. The initial dosage of apatinib was 250 mg or 500 mg, and PD-1 blockades were comprised of camrelizumab, sintilimab and pembrolizumab. Efficacy and safety data were collected through the hospital's electronic medical record system. From October 2018 to March 2022, a total of 43 patients with metastatic CRC were evaluated for efficacy and safety. The results showed an objective response rate of 25.6% (95% CI, 13.5%-41.2%) and a disease control rate of 72.1% (95% CI, 56.3%-84.7%). The median progression-free survival (PFS) of the cohort was 5.8 months (95% CI, 3.81-7.79), and the median overall survival (OS) was 10.3 months (95% CI, 5.75-14.85). The most common adverse reactions were fatigue (76.7%), hypertension (72.1%), diarrhea (62.8%), and hand-foot syndrome (51.2%). Multivariate Cox regression analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance status and location of CRC (left or right-side) were independent factors to predict PFS of patients with metastatic CRC treated with the combination regimen. Consequently, the combination of apatinib and PD-1 blockades demonstrated potential efficacy and acceptable safety for patients with treatment-refractory metastatic CRC. This conclusion should be confirmed in prospective clinical trials subsequently.

Trends in Colorectal Cancer Mortality in the United States, 1999 - 2020.

The United States faces a significant public health issue with colorectal cancer (CRC), which remains the third leading cause of cancer-related fatalities despite early diagnosis and treatment progress. This investigation utilized death certificate data from the Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database to investigate trends in CRC mortality and location of death from 1999 to 2020. Additionally, the study utilized the annual percent change (APC) to estimate the average annual rate of change over the specific time period for the given health outcome. Incorporating the location of death in this study served the purpose of identifying patterns related to CRC and offering valuable insights into the specific locations where deaths occurred. Between 1999 and 2020, there were 1,166,158 CRC-related deaths. The age-adjusted mortality rates (AAMRs) for CRC consistently declined from 20.7 in 1999 to 12.5 in 2020. Men had higher AAMR (18.8) than women (13.4) throughout the study. Black or African American patients had the highest AAMR (21.1), followed by White (15.4), Hispanic/Latino (11.8), American Indian or Alaska native (11.4), and Asian or Pacific Islanders (10.2). The location of death varied, with 41.99% at home, 28.16% in medical facilities, 16.6% in nursing homes/long-term care facilities, 7.43% in hospices, and 5.80% at other/unknown places. There has been an overall improvement in AAMR among most ethnic groups, but an increase in AAMR has been observed among white individuals below the age of 55. Notably, over one-quarter of CRC-related deaths occur in medical facilities.

Exploring the Influence of Age, Gender and Body Mass Index on Colorectal Cancer Location.

Background and objectives: The global burden of non-communicable diseases like obesity and cancer, particularly colorectal cancer (CRC), is increasing. The present study aimed to investigate the association between CRC location (proximal vs. distal) and patient demographic factors including age, sex, and BMI, as well as cancer stage at diagnosis. Materials and Methods: In this cross-sectional study, data from 830 patients diagnosed with CRC were analyzed. The variables included age, sex, weight, height, BMI, cancer location, and cancer stage at diagnosis. Patients were stratified into three age groups and three BMI categories, and we analyzed the association between cancer location and these variables using Chi-squared tests and multivariate logistic regression. Results: The rectum and ascending colon were the most common locations of malignant neoplasms. No statistically significant differences in cancer location across age groups were observed. Significant differences were found in the BMI across age groups, particularly in the normal weight and overweight categories. Normal weight and obese patients had a higher proportion of Stage 3 and Stage 4 cancers. Obesity emerged as a significant predictor for rectal cancer in a multivariate logistic regression analysis, with an odds ratio of 1.56. However, no significant associations were found between cancer location and other factors like age, gender, or cancer stage. Conclusions: Our study revealed that normal weight and obese patients had a higher proportion of Stage 3 and Stage 4 cancers, with obesity emerging as a significant predictor for rectal cancer. It is important to note that while obesity was found to be a significant predictor for rectal cancer, the development and location of colorectal cancer is likely influenced by various factors beyond those studied here. Therefore, further research is needed to investigate the roles of other potential risk factors, like loss of SIRT6 and adipose tissue homeostasis. Additionally, inflammation associated with microbiota in the colorectal mucosa, systemic gene expression, and visceral obesity may also play important roles in the development and progression of colorectal cancer. Understanding these intricate relationships is crucial for better screening, disease prognosis, and management strategies.

CT-guided percutaneous microwave ablation for pulmonary metastases from colorectal cancer: Prognosis analyses based on the origin of the primary tumor.

Microwave ablation (MWA) is becoming an effective therapy for inoperable pulmonary metastases from colorectal cancer (CRC). However, it is unclear whether the primary tumor location affects survival after MWA. This study aims to investigate the survival outcomes and prognostic factors of MWA based on different primary origins between colon and rectal cancer. Patients who underwent MWA for pulmonary metastases from 2014 to 2021 are reviewed. Differences in survival outcomes between colon and rectal cancer are analyzed with the Kaplan-Meier method and log-rank tests. The prognostic factors between groups are then evaluated by univariable and multivariable Cox regression analyses. A total of 118 patients with 154 pulmonary metastases from CRC are treated in 140 MWA sessions. Rectal cancer has a higher proportion with seventy (59.32%) than colon cancer with forty-eight (40.68%). The average maximum diameter of pulmonary metastases from rectal cancer (1.09 cm) is greater than that of colon cancer (0.89 cm; p = 0.026). The median follow-up is 18.53 months (range 1.10-60.63 months). The disease-free survival (DFS) and overall survival (OS) in colon and rectal cancer groups are 25.97 vs 11.90 months (p = 0.405), and 60.63 vs 53.87 months (p = 0.149), respectively. Multivariate analyses show that only age is an independent prognostic factor in patients with rectal cancer (HR = 3.70, 95% CI: 1.28-10.72, p = 0.023), while none in colon cancer. Primary CRC location has no impact on survival for patients diagnosed with pulmonary metastases after MWA, while a disparate prognostic factor exists between colon and rectal cancer.

Analysis of the gut microbiome using extracellular vesicles in the urine of patients with colorectal cancer.

We evaluated the gut microbiome using extracellular vesicles (EVs) in the urine of patients with colorectal cancer (CRC) to determine whether gut-microbe-derived EVs could be a potential biomarker for the diagnosis of CRC. EVs were isolated from the urine of patients with CRC and healthy controls. DNA was extracted from the EVs, and the bacterial composition was analyzed using next-generation sequencing of the 16S rRNA. A total of 91 patients with CRC and 116 healthy controls were enrolled. We found some specific microbiomes that were more or less abundant in the CRC group than in the control group. The alpha-diversity of the gut microbiome was significantly lower in the CRC group than in the control group. A significant difference was observed in the beta-diversity between the groups. The alpha-diversity indices between patients with early- and late-stage CRC showed conflicting results; however, there was no significant difference in the beta-diversity according to the stage of CRC. There was no difference in the alpha- and beta-diversity of the gut microbiome corresponding to the location of CRC (proximal vs. distal). A distinct gut microbiome is reflected in the urine EVs of patients with CRC compared with that in the healthy controls. Microbial signatures from EVs in urine could serve as potential biomarkers for the diagnosis of CRC.

Lymph Node Ratio Is Associated with Time to Pulmonary Metastasis in Patients with Resected Colorectal Cancer

INTRODUCTION: Despite curative resection for colorectal cancer (CRC), pulmonary metastasis (PM) may occur in up to 18% of cases. Among biomarkers that have been previously explored to inform CRC prognosis, Lymph Node Ratio (LNR) has been associated with shorter overall and disease-free survival in patients with resectable disease. We sought to investigate LNR from primary CRC pathology as a risk factor for overall development as well as time to development of PM. METHODS: A retrospective analysis of patients from prospectively maintained institutional thoracic and colorectal surgical databases (2000-2017) was performed. Patients were categorized based on whether they developed PM. LNR was defined as ratio of malignant nodes to total nodes harvested during primary colorectal resection. Multivariable Cox regression analysis (MVA) was performed to investigate the effect of LNR on time to PM diagnosis. RESULTS: 1600 patients were included in the analysis, among whom 233 (14.6%) were diagnosed with PM during follow-up. Patients without PM had median LNR of 0.00 (interquartile range [IQR]: 0.00 to 0.07), while patients who were diagnosed with PM had median LNR of 0.06 (IQR: 0.00 to 0.18). MVA controlling for clinicopathologic variables (Table) revealed LNR to predict time to PM diagnosis in CRC patients (hazard ratio: 14.93, 95% confidence interval: 6.13 to 36.37, p < 0.001). CONCLUSION: Elevated LNR is associated with both diagnosis and time to development of PM in patients with resectable CRC. As such, LNR should be considered during discussions of prognosis and recommendations for surveillance after primary CRC resection. Table. - Multivariable Cox Regression Analysis Investigating the Effect of Lymph Node Ratio on Pulmonary Metastasis development Clinicopathologic characteristics Hazard ratio (95% CI) p Value Lymph Node Ratio (Increasing) 14.93 (6.13-36.37) <0.001 Neoadjuvant Chemotherapy 1.44 (1.06-1.95) 0.020 Pathologic T Status >2 1.59 (1.05-2.38) 0.027 CRC Location Right Reference Left 1.74 (1.18-2.56) 0.005 Rectum 0.91 (0.58-1.43) 0.683 KRAS Mutated 5.62 (4.12-7.65) <0.001 Adjuvant Chemotherapy 5.68 (3.87-8.34) <0.001

The Contradictory Phenomena: Development of a New Life and a Life-Threatening Illness: Colorectal Cancer in Pregnancy

Colorectal cancer (CRC) is a common and lethal disease. Genetic and environmental factors contribute to the development of CRC, with different incidence and mortality rates around the world. Geographic differences appear to be attributable to exposures that are superimposed on a background of genetically determined susceptibility. Globally, CRC is the third most commonly diagnosed cancer in males and the third in females, with 1.8 million new cases and approximately 861,000 deaths in 2018, according to the World Health Organization (WHO). Epidemiologically, it is a disease of the middle-aged and elderly. However, it may occur in young patients, presenting with an aggressive biological behaviour and poor prognosis. Among this young age group are childbearing women, with CRC in pregnancy being rarely diagnosed and reported. Its diagnosis is a challenge to the unaware and, once diagnosed, management options are limited. This study aims to elucidate the presentation, diagnosis, anatomical location, pathogenesis, and treatment options of CRC in pregnancy.

Clinicopathological Characteristics and Overall 5-Year Survival of Colorectal Cancer: A Retrospective Study.

Colorectal cancer (CRC) is the third leading cause of cancer-related death. We aimed to investigate the clinicopathological characteristics and 5-year survival in CRC. This retrospective study reviewed King Abdulaziz University Hospital records from 2009 to 2019. Tumor staging was performed using Dukes’ pathological classification. Additionally, we measured the frequency of qualitative data and performed the chi-square and Mann–Whitney U-tests. Kaplan–Meier analysis was performed to calculate overall survival. Of the 574 included patients (age (mean ± standard deviation), 55.51 ± 14.28 years), 43.2% were Saudis, and most were male (58.7%). The rectum was the most common location of CRC (30.8%); 33.1% of patients presented with abdominal pain. The dominant histological variant was mucinous adenocarcinoma (95.5%). Age at diagnosis was significantly associated with Dukes’ staging; 36.3% of individuals aged <50 years had Dukes’ D stage. The 5-year survival rate was 47.9%. Better survival was noted for those of Saudi nationality, those with Dukes’ A stage, and those who were overweight (51.6%, 56.3%, and 46.8%, respectively). Significantly better survival was seen in Saudi patients due to accessible healthcare and in overweight patients due to better treatment tolerance. The outcome of CRC was not related to sex or metformin use in patients with diabetes mellitus.

Application of Imaging Indicators Based on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Colorectal Peritoneal Carcinomatosis.

ObjectiveThe imaging features of peritoneal carcinomatosis (PC) with different locations and pathological types of colorectal cancer (CRC) on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were analyzed and discussed.MethodsThe PET/CT data of 132 patients with colorectal peritoneal carcinomatosis (CRPC) who met the inclusion and exclusion criteria between May 30, 2016, and December 31, 2019, were collected and analyzed. Observations included the location and pathological type of CRC, the peritoneal cancer index (PCI), standardized uptake maximum value (SUVmax), and retention index (RI) of the CRPC. Statistical analysis was performed using SPSS 20.0 software, and P < 0.05 was considered statistically significant.Results(1) The range of the PCI in the 132 patients studied was 2–30, with a mean value of 7.40 ± 8.14. The maximum long diameter of the CRPC lesions ranged from 0.6 to 12.1 cm, with an average of 3.23 ± 1.94 cm. The SUVmax ranged from 1.2 to 31.0, with a mean value of 9.65 ± 6.01. The SUVmax and size correlation coefficient for maximal CRPC lesions was r = 0.47 (P < 0.001). The RI range of the 72 patients who underwent time-lapse scanning was -10.0–112.2%, with RI quartiles of 13.5–48.9%; RI was ≥5% in 65 cases and <5% in seven cases. (2) The patients were grouped by the location of their CRC: the right-sided colon cancer (RCC, n = 37), left-sided colon cancer (LCC, n = 44), and rectal cancer groups (RC, n = 51). There were significant differences in the CRC pathological types (P = 0.009) and PCI scores (P = 0.02) between the RCC and RC groups and the RI between the RCC group and the other two groups (P < 0.001). (3) There were 88 patients organized into three groups by the pathology of their CRC: the moderately well-differentiated adenocarcinoma (group A, n = 57), poorly differentiated adenocarcinoma (group B, n = 16), and mucinous adenocarcinoma groups (group C, n = 15 cases, including one case of signet-ring cell carcinoma). There were significant differences in the CRC position (P = 0.003) and SUVmax (P = 0.03) between groups A and C.ConclusionThe PCI, SUVmax, and RI of peritoneal metastatic carcinoma caused by CRC in different locations and pathological types vary. Mucinous adenocarcinoma and poorly differentiated adenocarcinoma are relatively common in the right colon, and the PCI of peritoneal metastatic carcinoma is fairly high, but the SUVmax and RI are somewhat low.

Demora en el diagnóstico y tratamiento de 5 tipos de cáncer en 2 centros de salud urbanos

ObjectivesTo assess the diagnostic (ID) and treatment (IT) intervals of the most prevalent cancers in patients attached to two health centres and to analyse the influence of sociodemographic, clinical and health system (HS) organisational factors. DesignObservational, retrospective, analytical cohort study. SitePrimary care. Two urban health centres. ParticipantsThree hundred sixty-five patients diagnosed with colorectal cancer (CRC), breast, lung, prostate or bladder cancer between 1/1/2012 and 31/12/2017. Main measuresThe medians of ID and IT and the risk (OR) of ID and IT above those medians according to the above factors are compared. The contribution of each process step to ID is analysed. ResultsMedian ID was 92 days, maximum in prostate cancer (395 days) and minimum in lung (54 days). Factors associated with prolonged ID (OR>92 days) were female sex, CRC or prostate location, localised stage, index primary care (AP) consultation and outpatient diagnostic pathway. Prolonged IT (OR>56 days) was related to CRC or prostate location and outpatient diagnostic route. ID components with the greatest influence on delay were: Primary Care Interval (IAP), Secondary Care Delay (DAS) and Secondary Care Adjunctive Test Delay (DPAS). The contribution of IAP was highest in patients with CRC, lung and bladder. ConclusionsID and IT were 92 and 56 days respectively. The ID components with the highest contribution to delay were IAP, DAS and DPAS. Increasing diagnostic capacity in PC and organising specific diagnostic and treatment pathways would shorten these intervals and allow earlier detection.

Prognostic Factors for Survival of Colorectal Adenocarcinoma Patients in Uganda.

BackgroundIn Uganda, similar to other countries in East Africa, the incidence of colorectal cancer (CRC) has been steadily increasing. This increase in incidence is accompanied by a poor prognosis. There is limited knowledge on factors responsible for the poor outcome of patients with CRC in Uganda. Cancer survival analysis is one way of determining some of these prognostic factors. The aim of this study was to determine prognostic factors associated with CRC survival in Ugandan patients.MethodsThis was a retroprospective cohort study involving patients with linked data in the Kampala cancer registry and medical records from hospitals in Uganda. Participants with a diagnosis of colorectal adenocarcinoma between 1st January 2008 and 31st December 2018 were included. Variables included patients’ demographic data, grade, stage and location of CRC, data on whether a patient was operated on, type of operation, treatment modalities and date of diagnosis. Our outcome variable was time to death after diagnosis. We computed and compared survival using the Log rank test and used Cox proportional hazards regression to determine factors associated with survival.ResultsA total of 247 patients were included in the study with a mean (SD) age of 53.3 (15.7) years and a female: male ratio of 1.14:1. The proportions of patients surviving at 1, 2 and 3 years were 65.2% (95% CI: 58.8–70.9), 42.0% (95% CI:35.6–48.3) and 33.3% (95% CI:27.3–39.4) respectively. In multivariate analysis, factors associated with increased mortality included clinical stage II (aHR = 2.44, 95% CI: 1.10–5.41, p=0.028), stage III (aHR=2.65, 95% CI: 1.31–5.39, p=0.007) and stage IV (aHR=5.47, 95% CI: 2.40–12.48, p<0.001). Curative surgery alone (aHR=0.63, 95% CI: 0.39–1.01, p=0.057) and curative surgery with chemotherapy (aHR=0.53, 95% CI: 0.32–0.88, p=0.015) were associated with a better survival.ConclusionThe survival rate among CRC patients in Uganda is low. Advanced stage CRC accelerates mortality, while surgery alone or in combination with chemotherapy improves survival. Implementation of national screening programmes for early diagnosis of CRC and increasing surgery and oncology infrastructure is recommended to improve the CRC survival rate in the Ugandan population.

Colorectal Cancer associated with pediatric inflammatory bowel disease: a case series

BackgroundInflammatory bowel disease (IBD) is associated with an increased risk of Colorectal cancer (CRC), and its most important risk factors are the duration and extent of the disease. Pediatric-onset inflammatory bowel disease has a tendency for a more extensive, more severe, and longer predicted disease duration than adult-onset inflammatory bowel disease. This study aimed to identify the clinical characteristics of patients with CRC related to pediatric-onset IBD and consider the appropriateness of current surveillance endoscopy recommendations for the detection of premalignant lesions and early-stage CRC.MethodsWe searched a research platform based on the SUPREME electronic medical record data-mining system to identify cases of colorectal malignancy in patients with pediatric IBD that presented between 2000 and 2020.ResultsDuring the follow-up, 4 (1.29 per 1000 person years) out of 443 patients with PIBD was diagnosed with CRC. The median age at diagnosis of CRC was 18.5 (range: 15–24) years, and the median period from diagnosis of IBD to CRC was 9.42 (range: 0.44–11.96) years. The sigmoid colon was the most frequent location of CRC (in 3 of the 4 cases). Adenocarcinoma was the most common histological type (in 2 of the 4 cases).ConclusionsPatients with pediatric-onset IBD exhibited a much shorter disease duration than that of adult-onset IBD at the time of diagnosis of CRC, suggesting that surveillance endoscopy for the detection of precancerous lesions and early-stage cancer should be initiated earlier in pediatric patients than in adult patients.

Fecal Microbiota and Gut Microbe-Derived Extracellular Vesicles in Colorectal Cancer.

The human microbiota comprises trillions of microbes, and the relationship between cancer and microbiota is very complex. The impact of fecal microbiota alterations on colorectal cancer (CRC) pathogenesis is emerging. This study analyzed changes in the microbial composition in CRC subjects with both fecal microbiota and gut microbe-derived extracellular vesicles (EVs). From August 2017 to August 2018, 70 CRC patients and 158 control subjects were enrolled in the study. Metagenomic profiling of fecal microbiota and gut microbe-derived EVs in stool was performed using 16S ribosomal DNA sequencing. Relative abundance, evenness, and diversity in both the gut microbiota and gut microbe-derived EVs were analyzed. Additionally, microbial composition changes according to the stage and location of CRC were analyzed. Microbial composition was significantly changed in CRC subjects compared to control subjects, with evenness and diversity significantly lower in the fecal microbiota of CRC subjects. Gut microbe-derived EVs of stool demonstrated significant differences in the microbial composition, evenness, and diversity in CRC subjects compared to the control subjects. Additionally, microbial composition, evenness, and diversity significantly changed in late CRC subjects compared to early CRC subjects with both fecal microbiota and gut microbe-derived EVs. Alistipes-derived EVs could be novel biomarkers for diagnosing CRC and predicting CRC stages. Ruminococcus 2-derived EVs significantly decreased in distal CRC subjects than in proximal CRC subjects. Gut microbe-derived EVs in CRC had a distinct microbial composition compared to the controls. Profiling of microbe-derived EVs may offer a novel biomarker for detecting and predicting CRC prognosis.

The Comparison of Fecal Microbiota in Left-Side and Right-Side Human Colorectal Cancer

Introduction: Microbiomes play a vital role in the development and progression of cancer. The clinical status, including prognosis, genetic mutations, and sensitivity to chemotherapy, differs depending on the location of colorectal cancer (CRC); however, the association between gut microbiota and the location of CRC is not entirely understood. This study was conducted to evaluate the differences in the gut microbiota in patients with CRC according to the location of the tumor. Methods: Fifty-six patients who underwent surgery for CRC between August 2018 and November 2019 were included in the study. Three patients who had received neoadjuvant therapy or antibiotic treatment within 1 month before surgery were excluded. The metagenomes of microbiota in preoperative feces were assessed using the V3–V4 region of 16s rRNA amplicon sequences. Results: The beta diversity of the Bray-Curtis distance was significantly higher in left-sided than in right-sided CRC. Fusobacterium predominated in left-sided CRC according to the linear discriminant analysis effect size method. Blautia, Eryspelotrichales, Holdemanella, Faecalibacterium, Subdoligranulum, and Dorea constituted the dominant intestinal flora in right-sided CRC. Pathway analysis revealed that L-lysine fermentation and cob(II)yrinate a,c-diamide biosynthesis I were predominant in left-sided CRC. Discussion: This study demonstrated that fecal microbiota in left-sided CRC constitutionally and functionally differ from those in right-side CRC. These results will help to elucidate the biological differences according to tumor location and develop treatments for human CRC.

Impact of preoperative antibiotics and other variables on integrated microbiome-host transcriptomic data generated from colorectal cancer resections.

BACKGROUNDIntegrative multi-omic approaches have been increasingly applied to discovery and functional studies of complex human diseases. Short-term preoperative antibiotics have been adopted to reduce site infections in colorectal cancer (CRC) resections. We hypothesize that the antibiotics will impact analysis of multi-omic datasets generated from resection samples to investigate biological CRC risk factors.AIMTo assess the impact of preoperative antibiotics and other variables on integrated microbiome and human transcriptomic data generated from archived CRC resection samples.METHODSGenomic DNA (gDNA) and RNA were extracted from prospectively collected 51 pairs of frozen sporadic CRC tumor and adjacent non-tumor mucosal samples from 50 CRC patients archived at a single medical center from 2010-2020. The 16S rRNA gene sequencing (V3V4 region, paired end, 300 bp) and confirmatory quantitative polymerase chain reaction (qPCR) assays were conducted on gDNA. RNA sequencing (IPE, 125 bp) was performed on parallel tumor and non-tumor RNA samples with RNA Integrity Numbers scores ≥ 6.RESULTSPERMANOVA detected significant effects of tumor vs nontumor histology (P = 0.002) and antibiotics (P = 0.001) on microbial β-diversity, but CRC tumor location (left vs right), diabetes mellitus vs not diabetic and Black/African Ancestry (AA) vs not Black/AA, did not reach significance. Linear mixed models detected significant tumor vs nontumor histology*antibiotics interaction terms for 14 genus level taxa. QPCR confirmed increased Fusobacterium abundance in tumor vs nontumor groups, and detected significantly reduced bacterial load in the (+)antibiotics group. Principal coordinate analysis of the transcriptomic data showed a clear separation between tumor and nontumor samples. Differentially expressed genes obtained from separate analyses of tumor and nontumor samples, are presented for the antibiotics, CRC location, diabetes and Black/AA race groups.CONCLUSIONRecent adoption of additional preoperative antibiotics as standard of care, has a measurable impact on -omics analysis of resected specimens. This study still confirmed increased Fusobacterium nucleatum in tumor.