Income differences in time to colon cancer diagnosis.

INTRODUCTION: People with low income have worse outcomes throughout the cancer care continuum; however, little is known about income and the diagnostic interval. We described diagnostic pathways by neighborhood income and investigated the association between income and the diagnostic interval. METHODS: This was a retrospective cohort study of colon cancer patients diagnosed 2007-2019 in Ontario using routinely collected data. The diagnostic interval was defined as the number of days from the first colon cancer encounter to diagnosis. Asymptomatic pathways were defined as first encounter with a colonoscopy or guaiac fecal occult blood test not occurring in the emergency department and were examined separately from symptomatic pathways. Quantile regression was used to determine the association between neighborhood income quintile and the conditional 50th and 90th percentile diagnostic interval controlling for age, sex, rural residence, and year of diagnosis. RESULTS: A total of 64,303 colon cancer patients were included. Patients residing in the lowest income neighborhoods were more likely to be diagnosed through symptomatic pathways and in the emergency department. Living in low-income neighborhoods was associated with longer 50th and 90th-percentile symptomatic diagnostic intervals compared to patients living in the highest income neighborhoods. For example, the 90th percentile diagnostic interval was 15 days (95% CI 6-23) longer in patients living in the lowest income neighborhoods compared to the highest. CONCLUSION: These findings reveal income inequities during the diagnostic phase of colon cancer. Future work should determine pathways to reducing inequalities along the diagnostic interval and evaluate screening and diagnostic assessment programs from an equity perspective.

The value of FPR, FAR, CAR, CPR in the auxiliary diagnosis of colon cancer.

Chronic malnutrition, abnormal blood clotting, and systemic inflammation contribute to the occurrence and progression of colon cancer. This study aimed to assess the diagnostic utility of the 100fibrinogen-to-prealbumin ratio (FPR), 100fibrinogen-to-albumin ratio (FAR), 100C-reactive protein-to-albumin ratio (CAR), and 100C-reactive protein-to-prealbumin ratio (CPR) in aiding the diagnosis of colon cancer. A total of 129 patients with colon cancer were enrolled between April 2015 and August 2022. While 129 patients with colon adenoma were selected as the control group. The serum levels of FAR, FPR, CAR, CPR, CEA, and CA125 in the colon cancer group were significantly higher than those in the colon adenoma group (P < .05). In Logistic regression analysis, high FAR and high FPR were identified as independent risk factors for colon cancer. Receiver operating characteristic (ROC) curve analysis results showed that Among the combined measures, FAR, FPR, CAR, and CPR had the highest diagnostic efficacy in distinguishing colon cancer from colon adenomas (AUC = 0.886, Sen = 80.62%, Spe = 81.40%). Thus, FAR, FPR, CAR, and CPR may serve as valuable biomarkers for the diagnosis of colon cancer, and the combined detection of FAR, FPR, CAR, and CPR can enhance the diagnostic efficiency for both colon cancer and colon adenoma.

Colon cancer diagnosis by means of explainable deep learning.

Early detection of the adenocarcinoma cancer in colon tissue by means of explainable deep learning, by classifying histological images and providing visual explainability on model prediction. Considering that in recent years, deep learning techniques have emerged as powerful techniques in medical image analysis, offering unprecedented accuracy and efficiency, in this paper we propose a method to automatically detect the presence of cancerous cells in colon tissue images. Various deep learning architectures are considered, with the aim of considering the best one in terms of quantitative and qualitative results. As a matter of fact, we consider qualitative results by taking into account the so-called prediction explainability, by providing a way to highlight on the tissue images the areas that from the model point of view are related to the presence of colon cancer. The experimental analysis, performed on 10,000 colon issue images, showed the effectiveness of the proposed method by obtaining an accuracy equal to 0.99. The experimental analysis shows that the proposed method can be successfully exploited for colon cancer detection and localisation from tissue images.

Quantification method of ctDNA using cell-free DNA methylation profile for noninvasive screening and monitoring of colon cancer.

BACKGROUND: Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer. RESULTS: We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer. Our method initially identified 901 colon cancer-specific hypermethylated (CaSH) regions in the tissues of the 49 cancer patients. We then used these CaSH regions to accurately quantify the amount of circulating tumor DNA (ctDNA) in the blood samples of these same patients, utilizing cell-free DNA methylation profiles. Notably, the methylation profiles of ctDNA in the blood exhibited high sensitivity (82%) and specificity (93%) in distinguishing patients with colon cancer from the control group, with an area under the curve of 0.903. Furthermore, we confirm that our method for ctDNA quantification is effective for monitoring cancer patients and can serve as a valuable tool for postoperative prognosis. CONCLUSIONS: This study demonstrated a successful application of the quantification of ctDNA among cfDNA using the original cancer tissue-derived CaSH region for screening and monitoring colon cancer.

PPIH acts as a potential predictive biomarker for patients with common solid tumors.

BACKGROUND: Our previous studies have indicated that mRNA and protein levels of PPIH are significantly upregulated in Hepatocellular Carcinoma (LIHC) and could act as predictive biomarkers for patients with LIHC. Nonetheless, the expression and implications of PPIH in the etiology and progression of common solid tumors have yet to be explored, including its potential as a serum tumor marker. METHODS: We employed bioinformatics analyses, augmented with clinical sample evaluations, to investigate the mRNA and protein expression and gene regulation networks of PPIH in various solid tumors. We also assessed the association between PPIH expression and overall survival (OS) in cancer patients using Kaplan-Meier analysis with TCGA database information. Furthermore, we evaluated the feasibility and diagnostic efficacy of PPIH as a serum marker by integrating serological studies with established clinical tumor markers. RESULTS: Through pan-cancer analysis, we found that the expression levels of PPIH mRNA in multiple tumors were significantly different from those in normal tissues. This study is the first to report that PPIH mRNA and protein levels are markedly elevated in LIHC, Colon adenocarcinoma (COAD), and Breast cancer (BC), and are associated with a worse prognosis in these cancer patients. Conversely, serum PPIH levels are decreased in patients with these tumors (LIHC, COAD, BC, gastric cancer), and when combined with traditional tumor markers, offer enhanced sensitivity and specificity for diagnosis. CONCLUSION: Our findings propose that PPIH may serve as a valuable predictive biomarker in tumor patients, and its secreted protein could be a potential serum marker, providing insights into the role of PPIH in cancer development and progression.

Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Clinical significance of 18F-FDG-PET/CT for detection of incidental pre-malignant and malignant colonic lesions: correlation with colonoscopic and histopathological results.

BACKGROUND: Incidental colorectal fluorodeoxyglucose (FDG) uptake, observed during positron emission tomography/computed tomography (PET/CT) scans, attracts particular attention due to its potential to represent both benign and pre-malignant/malignant lesions. Early detection and excision of these lesions are crucial for preventing cancer development and reducing mortality. This research aims to evaluate the correlation between incidental colorectal FDG uptake on PET/CT with colonoscopic and histopathological results. METHODS: Retrospective analysis was performed on data from all patients who underwent PET/CT between December 2019 and December 2023 in our hospital. The study included 79 patients with incidental colonic FDG uptake who underwent endoscopy. Patient characteristics, imaging parameters, and the corresponding colonoscopy and histopathological results were studied. A comparative analysis was performed among the findings from each of these modalities. The optimal cut-off value of SUVmax for 18F-FDG PET/CT diagnosis of premalignant and malignant lesions was determined by receiver operating characteristic (ROC) curves. The area under the curve (AUC) of SUVmax and the combined parameters of SUVmax and colonic wall thickening (CWT) were analyzed. RESULTS: Among the 79 patients with incidental colorectal FDG uptake, histopathology revealed malignancy in 22 (27.9%) patients and premalignant polyps in 22 (27.9%) patients. Compared to patients with benign lesions, patients with premalignant and malignant lesions were more likely to undergo a PET/CT scan for primary evaluation (p = 0.013), and more likely to have focal GIT uptake (p = 0.001) and CWT (p = 0.001). A ROC curve analysis was made and assesed a cut-off value of 7.66 SUVmax (sensitivity: 64.9% and specificity: 82.4%) to distinguish premalignant and malignant lesions from benign lesions. The AUCs of the SUVmax and the combined parameters of SUVmax and CWT were 0.758 and 0.832 respectively. CONCLUSION: For patients undergo PET/CT for primary evaluation, imaging features of colorectal focal FDG uptake and CWT were more closely associated with premalignant and malignant lesions. The SUVmax helps determine benign and premalignant/malignant lesions of the colorectum. Moreover, the combination of SUVmax and CWT parameters have higher accuracy in estimating premalignant and malignant lesions than SUVmax.

Budget Impact Analysis of Circulating Tumor DNA Testing for Colon Cancer in Commercial Health and Medicare Advantage Plans.

Importance: In a randomized clinical trial, treatment guided by tumor-informed circulating tumor (ct)DNA testing reduced adjuvant chemotherapy use without compromising recurrence-free survival in patients with stage II colon cancer. The potential effects of adopting ctDNA testing into routine patient care is unknown. Objective: To compare the total cost of patient care scenarios with and without the adoption of ctDNA testing. Design, Setting, and Participants: This budget impact analysis was conducted from the perspectives of US commercial health and Medicare Advantage payers. A decision-analytical model was populated with age-specific incidence of colon cancer, use of adjuvant chemotherapy, and use of single-agent or multiagent regimens. Total cost was estimated with the costs of ctDNA testing, drug acquisition, administration, surveillance, and adverse events. The analysis was conducted from September 2023 to January 2024. Exposures: The adoption of ctDNA testing. Main Outcomes and Measures: The incremental cost in the first year following the adoption of ctDNA testing, where testing will affect patient treatment and costs. Results: In hypothetical plans with 1 million individuals covered, 35 commercial health plan members and 102 Medicare Advantage members aged 75 years and younger were eligible for ctDNA testing. In the base case with a 50% adoption rate, total cost savings were $221 684 (equivalent to $0.02 per member per month [PMPM]) for a commercial payer and $116 720 (equivalent to $0.01 PMPM) for a Medicare Advantage payer. Cost savings were robust to variations in assumptions of all parameters in the commercial population but sensitive to variations in assumptions of adjuvant chemotherapy use rates in the Medicare Advantage population. The number needed to test to avoid 1 patient receiving adjuvant chemotherapy was 4 in the commercial population and 10 in the Medicare Advantage population. The budget-neutral cost for ctDNA testing was $16 202 for a commercial payer and $5793 for a Medicare Advantage payer. Conclusions and Relevance: Use of tumor-informed ctDNA testing to guide adjuvant chemotherapy in postsurgery patients with stage II colon cancer was projected to result in cost savings for both commercial and Medicare Advantage payers. Adoption of ctDNA testing is therefore advantageous from a budgetary perspective.

Serum ferritin and risk of colonic neoplasia: Implications for the workup and treatment of iron deficiency.

Iron deficiency is the most common extraintestinal sign of colonic neoplasia, including colorectal cancer (CRC) and other lower gastrointestinal pathology. Both upper endoscopy and colonoscopy is usually recommended in the work-up of patients with unexplained iron deficiency, particularly in men and postmenopausal women. As the incidence of early-onset CRC (age <50 years) rises in the United States, there is an increasing need to identify risk predictors to aid in the early detection of CRC. It remains unknown if serum ferritin (SF), and what specific threshold, can be used as a marker to stratify those at risk for CRC and other lower gastrointestinal pathology. In this current review of the literature, we aimed to review guidelines for diagnostic workup of colonic neoplasia in the setting of iron deficiency and examine the association and specific thresholds of SF and risk of CRC by age. Some of the published findings are conflicting, and conclusions specific to younger patients are limited. Though further investigation is warranted, the cumulative findings suggest that SF, in addition to considering the clinical context and screening guidelines, may have potential utility in the assessment of colonic neoplasia.

Design and evaluation of a colon cancer mobile application.

BACKGROUND: Colorectal cancer (CRC) is the third leading cause of cancer and the second cause of cancer-related deaths in the world. Despite the infrastructure and the availability of organized screening programs, participation in their screening programs is less than the set goals. Considering the importance of informing the society about the prevention and early detection of colorectal cancer symptoms and the positive impact of mobile health technologies, the present research was conducted with the aim of designing and evaluating a colon cancer mobile application. METHODS: The present research was conducted in two phases: software design and evaluation. In the first phase, the software was prepared using the cascade method. First, all the educational content related to colorectal cancer was collected through an expert panel with the participation of 10 specialists. Then the software was evaluated with alpha and beta testing, and the initial version was approved by users in terms of simplicity and usability. In the second phase, a parallel clinical randomized trial study was conducted with the aim of investigating the effect of a colon cancer mobile application on the early detection of colorectal cancer. In this stage, 204 volunteers participated; inclusion criteria were age 18-85 years, owning a smartphone and the ability to read and write. Participants were randomized into control and intervention groups. The intervention group was educated with the colon cancer application for education about colorectal cancer, and the control group was educated with a pamphlet. After education, both groups were screened for colorectal cancer symptoms, and the results were compared. RESULTS: In the software evaluation phase, the application was used by 204 users. In this stage, 84 (41.2%) women and 120 (58.8%) men, with an average (Standard Deviation) age of 47.53 (13.68) participated. Participants were randomized in two groups, 103 people with an average (Standard Deviation) age of 47.62 (14.65) in intervention group and 101 people with an average (Standard Deviation) age of 47.44 (12.70) in control group. There were no significant differences between the demographic characteristics of age, gender, marriage, occupation, instruction level, digestive disease history, cancer history, cancer risk factors, and family history of cancer between the two groups (P > 0.05). The Mann-Whitney U test indicated that there is a significant difference between the two groups of participants in self-assessment, willingness to do the screening, and the results of the assessment of colorectal cancer (P < 0.05). CONCLUSION: The results of the research indicated the positive impact of the Colon Cancer Application on the abilities of the users of self-assessment of colon cancer. Therefore, based on the findings, it can be concluded that the use of the colon cancer mobile application is effective for colon cancer prevention and self-care. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials ( https://irct.behdasht.gov.ir ) on 13/2/2024, with the IRCT ID: IRCT20210131050189N9.

Characterizing colon lipomas: Insights from a retrospective analysis of clinical presentation and management strategies.

This retrospective study aims to examine the characteristics and treatment approaches of colon lipomas, which are benign tumors found in the colon. We analyzed a cohort of 25 patients, focusing on demographic characteristics, clinical presentation, location and size of the lipoma, concomitant pathologies, and treatment methods. The average age of the patients was 67.3 years, with 36% being male and 64% female. The majority of lipomas were located in the ascending colon (52%), and their median size was 2 cm. The predominant presenting symptom was constipation, affecting 83.3% of the symptomatic patients. Surgical resection was undertaken in only 1 patient due to obstruction. Statistically significant differences were observed between symptomatic and asymptomatic patients regarding various parameters, including the size of the lipoma (P = .033). Colon lipomas are generally benign and frequently asymptomatic but may necessitate different treatment approaches depending on their size, location, and the presence of symptoms. Further studies are imperative to refine treatment strategies and enhance patient care outcomes.

Identification of extracellular matrix-related biomarkers in colon adenocarcinoma by bioinformatics and experimental validation.

Backgrounds: Extracellular matrix (ECM) is an important component of tumor microenvironment, and its abnormal expression promotes tumor formation, progression and metastasis. Methods: Weighted gene co-expression network analysis (WGCNA) was used to identify ECM-related hub genes based on The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) data. COAD clinical samples were used to verify the expression of potential biomarkers in tumor tissues, and siRNA was used to explore the role of potential biomarkers in cell proliferation and epithelial-mesenchymal transition (EMT). Results: Three potential biomarkers (LEP, NGF and PCOLCE2) related to prognosis of COAD patients were identified and used to construct ERGPI. Immunohistochemical analysis of clinical samples showed that the three potential biomarkers were highly expressed in tumor tissues of COAD patients. Knockdown of LEP, NGF or PCOLCE2 inhibited COAD cell proliferation and EMT. Dictamnine inhibited tumor cell growth by binding to these three potential biomarkers based on molecular docking and transplanted tumor model. Conclusion: The three biomarkers can provide new ideas for the diagnosis and targeted therapy of COAD patients.

Inappropriate Ordering of Multitarget Stool DNA Tests for Colon Cancer Screening.

BACKGROUND: CRC screening is recommended for adults aged 45-75. Mt-sDNA is indicated for asymptomatic individuals between the ages of 45 and 85, but not for those with rectal bleeding, iron deficiency anemia, adenomatous polyps, previous colonoscopy within 10 years, family history of CRC, positive results from CRC screening tests within the past 6 months, or age less than 45 and greater than 85. We aimed to determine the prevalence of mt-sDNA use when not indicated and factors associated with inappropriate testing. METHODS: 7,345 patients underwent mt-sDNA testing and were randomized using EMERSE. Charts for the first 500 patients were reviewed to determine whether mt-sDNA was ordered appropriately according to the USPSTF criteria. Seven patients were excluded due to having more than one inappropriate ordering for mt-sDNA. RESULTS: Of 500 patients, 22.2% had an inappropriately ordered mt-sDNA test. The most common reason for inappropriate ordering was having a previous colonoscopy done within the past 10 years. Rates of inappropriate testing significantly varied by race and the specialty of the ordering provider, with internal medicine providers ordering the most mt-sDNA tests. Rates of inappropriate testing did not significantly vary by sex or type of insurance. DISCUSSION: Our study suggests that providers may not be familiar with guidelines for the indicated use of mtsDNA, leading to inappropriate referrals and increased costs. Patients at increased CRC risk would benefit from a more sensitive procedure such as a colonoscopy. Future studies could understand the motivation to order testing outside approved indications through provider surveys and interviews.

What can hospital emergency admissions prior to cancer diagnosis tell us about socio-economic inequalities in cancer diagnosis? Evidence from population-based data in England.

BACKGROUND: More deprived cancer patients are at higher risk of Emergency Presentation (EP) with most studies pointing to lower symptom awareness and increased comorbidities to explain those patterns. With the example of colon cancer, we examine patterns of hospital emergency admissions (HEAs) history in the most and least deprived patients as a potential precursor of EP. METHODS: We analysed the rates of hospital admissions and their admission codes (retrieved from Hospital Episode Statistics) in the two years preceding cancer diagnosis by sex, deprivation and route to diagnosis (EP, non-EP). To select the conditions (grouped admission codes) that best predict emergency admission, we adapted the purposeful variable selection to mixed-effects logistic regression. RESULTS: Colon cancer patients diagnosed through EP had the highest number of HEAs than all the other routes to diagnosis, especially in the last 7 months before diagnosis. Most deprived patients had an overall higher rate and higher probability of HEA but fewer conditions associated with it. CONCLUSIONS: Our findings point to higher use of emergency services for non-specific symptoms and conditions in the most deprived patients, preceding colon cancer diagnosis. Health system barriers may be a shared factor of socio-economic inequalities in EP and HEAs.

Colonoscopy-assisted laparoscopic wedge resection for a large symptomatic colonic lipoma.

A colonic lipoma is an uncommon lesion that is linked with clinical symptoms in only a small portion of patients. Patients with large lipomas are often referred for major surgery, which is associated with significant morbidity and mortality. In this case, we described a female patient with recurrent episodes of gastrointestinal blood loss, abdominal pain and colocolic intussusceptions due to a large, lumen-filling, obstructive lipoma in the splenic flexure. On abdominal CT, a lesion of 3.6 cm was visualised with a fat-like density without solid components. Considering its benign nature, we intended to preserve the colon by deroofing the upper part of the lesion and then performing a colonoscopy-assisted laparoscopic wedge resection. During reassessment, auto-amputation of part of the lesion was observed, most likely as a result of long-lasting mechanical effects, which made it possible to perform solely a wedge resection with an excellent outcome.

Endoscopic ultrasound-guided fine needle biopsy diagnosis of circumferentially extraluminal mucosa-associated lymphoid tissue lymphoma in the transverse colon: a case report.

A 61-year-old man present to us with continued abdominal pain without abdominal tenderness for 1 month. Blood testing showed elevated biliary enzymes and inflammation. Contrast-enhanced computed tomography (CT) revealed thickening of the transverse colon with relatively strong enhancement but no bile duct dilatation. Colonoscopy revealed localized edema and granular mucosa in the transverse colon. Fluoroscopic endoscopy exhibited the absence of haustra. Multiple biopsies were performed, but differentiation between mild inflammation and mucosa-associated lymphoid tissue (MALT) lymphoma was inconclusive. To establish a definitive diagnosis, transgastric endoscopic ultrasound-guided fine needle biopsy of the hypoechoic mass was performed. Histopathological analysis exhibited the proliferation of small-sized lymphocytes. Fluorescence in situ hybridization revealed the characteristic API2-MALT1 translocation of MALT lymphoma. We performed liver biopsy to investigate biliary enzyme elevation. Histopathology confirmed lymphocytic infiltration within Glisson's capsule. Immunohistochemistry showed positive for CD20 and negative for CD3 and CD5, signifying the infiltration of MALT lymphoma in the liver. Based on these findings, we diagnosed MALT lymphoma, Lugano classification Stage IV. We performed bendamustine-rituximab (BR)-combined therapy. After six courses of BR-combined therapy, colonoscopy revealed improvement in the lead pipe sign and CT revealed disappearance of the mass.