A Comparative Study for Methodologies and Algorithms Used In Colon Cancer Diagnoses and Detection

Rates of New or Missed Colorectal Cancers After Colonoscopy and Their Risk Factors: A Population-Based Analysis

The ACPGBI has been at the forefront in developing guidelines, position statements and national training programs related to both common, and complex, colorectal pathology. These initiatives often serve as a global reference in this challenging field. The Association of Coloproctology of Great Britain and Ireland (ACPGBI) 2007 Colorectal Cancer Management Guidelines have been the basis for continuous evolution in the way these cancers are managed. The current update aims to clarify many recent developments on the multidisciplinary management of colorectal cancer and to provide links to relevant publications. The recommendations made within these guidelines have been graded according to the Oxford Centre for Evidence-based Medicine – levels of evidence (www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/). We hope that these guidelines will offer a framework for clinicians and MDT's to tailor treatments to suit individual patients. We also hope to direct future research and debate in a rapidly evolving field. A substantial part of the workload of colorectal units is to not only exclude diagnosis of cancer but to manage cancer of the colon, rectum and anal canal. Access to information through technology, and particularly the internet, has changed perceptions and expectations of cancer patients, their carers and clinicians. The general public and healthcare providers continue to shift focus towards cancer prevention and early diagnosis. At the other end of the spectrum, patients with locally advanced, recurrent or metastatic cancer are increasingly being considered for tailored multimodal therapy, based on molecular biology and pharmaceutical advances. In the UK, through the NCRI Colorectal Cancer Clinical Trials Group and numerous other research organizations, we are proud of our record of being at the forefront of designing and completing many internationally acclaimed oncological and surgical trials. These have been instrumental in shaping our current clinical practice. We must continue to build on this foundation by developing and recruiting into new trials to further improve treatment. Over the last few decades, multidisciplinary teams (MDTs) have evolved, and consolidated, in individual units to manage colorectal cancer. At the MDT meeting, the clinical nurse specialist, with the attending surgeon, are best positioned to act as the patients’ advocates and ensure crucial decisions are made with a first-hand knowledge of the patient and their wishes. It is pertinent that MDT recommendations are based on the available information and recommendations may, or may not be appropriate, or acceptable to the individual patient. Clinicians should support patients requesting second opinions and guide them with appropriate pathways. Current MDTs should look to extend their role in training junior surgeons, radiologists, histopathologists and oncologists, and mentoring new members of the core team. Personal-audits and regular feedback between core members should be an integral part of the development of the MDT. Ongoing sub-specialization has encouraged development of specialist MDTs in a number of areas including anal cancer, early rectal cancer, ‘beyond’-TME and recurrent pelvic cancers, and cytoreductive surgery. Teams treating colorectal disease need to recognize the spectrum of disease, diversity of treatments and develop care pathways to access specialist MDT's. Public awareness campaigns and the NHS Bowel Cancer Screening Program have impacted positively on the diagnosis of early stage disease, and polyp detection and clearance are likely to reduce colorectal cancer incidence. Introduction of Faecal Immunochemical Test and Bowel Scope Screening will further improve the stage at diagnosis of colon and rectal cancer. Bowel cancer screening has added to the challenge of treating polyp cancers and early rectal cancer; oncological adequacy of minimally invasive interventions (polypectomy and local excisions) vs morbidity and mortality risk of resection surgery. The ongoing SPECC (Significant Polyp Early Colorectal Cancer) Pelican/ACPGBI Program aims to stimulate discussion and training in these areas. Robust risk stratification tools to help MDTs and patients make informed decisions, especially in an older and frailer population, are needed. Clinical trials, such as the recently completed NCRI TREC-1 and the new NCRI STAR-TREC in early rectal cancer will add to this knowledge. The Laparoscopic Colorectal Surgery (LAPCO) program, which was a joint initiative between the ACPGBI and NHS England, delivered high quality accreditation training in laparoscopic surgery to NHS colorectal surgeons. This initiative, together with increasing public awareness of laparoscopic surgery, has resulted in a steady year-on-year increase in the proportion of cases treated by minimal access, whilst achieving good oncological outcomes in addition to the short-term early benefits, particularly in colon cancer but less so in rectal cancer. Introduction of ERAS on the background of minimally invasive surgery has improved short-term outcomes including length of stay. Optimal results have been reported using a combination of ERAS and minimal access techniques. The concepts from colorectal surgical ERAS programs have been adopted by other surgical fields and have benefited a wider group of patients. The Low Rectal Cancer Development (LOREC) program is another joint initiative between the ACPGBI and NHS England, providing training to MDTs on the overall management of cancers arising at, or below, the level of the insertion of the levator muscles, including the appropriate use of extralevator abdominoperineal excision (ELAPE). The longer-term oncological outcomes and the associated morbidity of this initiative are yet to be reported. High quality radiology and detailed histopathology reporting is crucial, as it underpins MDT decision making. This provides quality assurance to patients and clinicians on management decisions. Radiology and pathology provide valuable prognostic indicators in colon and rectal cancer, which helps to determine further management. Advances in imaging and use of biomarkers have initiated individualized treatment strategies to be developed in all stages of disease. We predict that these advances will expand exponentially in the next decade. The use of preoperative radiotherapy, with or without chemotherapy in addition to surgery in ‘operable’ rectal cancer reduces local recurrence rates, but much of the published evidence predates modern imaging, making it difficult to quantify the exact benefits. Together with ongoing improvements in surgical techniques, such as ELAPE for advanced low rectal cancer, and an increasing awareness of immediate and long-term toxicity, the risk-benefit of using radiotherapy in rectal cancer, either to downstage disease or to reduce local recurrence needs careful consideration on an individual basis. There remains significant variation in the use of radiotherapy nationally, but with further refinements in imaging and expansion of knowledge, this will allow more selective utilization. However the role of optimal surgery remains crucial. Further advances in the use of adjuvant chemotherapy, with the addition of new targeted agents have failed to materialize. The focus has shifted to earlier use of systemic therapy in the neoadjuvant setting for colon and rectal cancers, as well as reducing the duration and toxicity of adjuvant therapies. There is increasing worldwide interest in the potential for non-operative management of rectal cancers of all stages. Ongoing trials to improve pathological complete response rates (pCR) and translational studies to develop new predictive markers, together with high-quality observational trials such as the NCRI Deferral of Surgery, may allow for safe deferral and hopefully, complete avoidance of surgery in selected patients who have potentially achieved pCR after preoperative chemoradiotherapy (CRT). The National Bowel Cancer Audit (NBOCA) has evolved from being a voluntary audit when first launched in 2000, to currently being a quality assurance tool for individual surgeons and NHS Trusts. Although it has provided invaluable data to drive up the standards of care delivered nationally, there remain opportunities to further improve the quality of data collected. Through NBOCA, the publication of individual colorectal surgeons’ outcomes has empowered patients, by providing online information about volumes and outcomes of individual surgeons and NHS Trusts. Individual surgeon outcome reporting is contentious and unit data may be more meaningful and is the subject of ongoing discussion. Most importantly, treatment of colorectal cancer should take into account individual preferences, and be delivered with dignity, compassion and respect. Patients need to understand that the management of their cancer is individualized and complex. They should be given an explanation for the perceived delays in commencing treatment, such as the need for further investigations or MDT discussion. Response to treatment is often unpredictable, as are many of the acute and late toxicities. These uncertainties should be openly discussed and patients should be able to make informed choices about their care, in partnership with their healthcare professionals. These decisions should be subject to regular review at appropriate key points during treatment, to accommodate any changes in circumstances and to allow the patient the opportunity for further discussion or reconsideration. Healthcare professionals must not underestimate the psychological and social impact of a diagnosis of colorectal cancer on the individual as well as family, carers and supporters. There is wide variation in their reactions, their ability to cope and their recall of information received, which may be subject to strong emotions and anxiety. Communication and listening skills for such patients need to be exemplary as they form a vital part of the patient journey, from undergoing treatment, to recovery and eventual readjustment to life beyond hospital. These guidelines offer an updated framework for colorectal cancer clinicians and MDTs. They will continue to evolve and require updating in light of ongoing developments and emerging evidence. None of the authors have any conflicts to declare.

Statin Use After Diagnosis of Colon Cancer and Patient Survival

Ulcerative colitis with low-grade dysplasia

Acute Leukemias Following a Diagnosis of Colorectal Cancer: Are They Therapy-Related?

BackgroundDifferences in the prognosis after colorectal cancer (CRC) by socioeconomic position (SEP) have been reported previously; however, most studies focused on survival differences at a particular time since diagnosis. We...

Guidelines on genetic evaluation and management of Lynch syndrome: A consensus statement by the U.S. Multi-Society Task Force on Colorectal Cancer

Previous studies demonstrated that cancer sera contain antibodies, which react with a unique group of autologous cellular antigens called tumour-associated antigens (TAAs). This study determines whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in colon cancer detection and diagnosis. The mini-array of multiple TAAs was composed of five TAAs including Imp1, p62, Koc, p53 and c-myc full-length recombinant proteins. Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against these five TAAs in 46 sera from patients with colon cancer and also 58 sera from normal individuals. Antibody frequency to any individual TAA in colon cancer was variable and ranged from 15.2% to 23.9%. With the successive addition of TAAs to a final total of five antigens, there was a stepwise increase of positive antibody reactions reaching a sensitivity of 60.9% and a specificity of 89.7% in colon cancer. Positive and negative likelihood ratio was 5.91 and 0.43 respectively, which showed that the clinical diagnostic value of parallel assay of five TAAs was high. Positive and negative predictive values were respectively 82.4% and 74.3% indicating that parallel assay of five TAAs raised the diagnostic precision greatly. Agreement rate and Kappa value were 76.9% and 0.52 respectively, which indicated that the observed value of this assay had middle range coincidence with actual value. The data from this study further support our previous hypothesis that detection of autoantibodies for diagnosis of certain type of cancer can be enhanced by using a mini-array of several TAAs as target antigens. In 19 colon cancer sera with carcinoembryonic antigen (CEA) negative, 11 (57.9%) were found to have anti-TAA antibodies. When CEA and anti-TAAs were used together as markers in colon cancer detection, the diagnostic sensitivity could be raised from 60.9% to 82.6%. A customized antigen mini-array using a panel of appropriately selected TAAs can enhance autoantibody detection in immunodiagnosis of colon cancer. Anti-TAA and CEA were independent markers and the simultaneous use of these two markers significantly raised the sensitivity of colon cancer detection.

Previous Commission on Cancer studies have examined time trends in stage of disease, treatment patterns, and survival for colorectal cancer. Reported herein are the most current 1993 National Cancer Data Base (NCDB) data on colorectal cancer. Two "calls for data," one in 1990 and one in 1991, have yielded a total of 71,560 colon cancer reports and 33,409 rectal cancer reports from hospital registries across the country. For colon cancer, continuation of the time trend toward proximal migration was reported. For both colon and rectal cancer, American Joint Committee on Cancer staging was used increasingly as the standard of appropriate cancer diagnosis. Increased use of multimodal treatment was reported for both colon and rectal cancers. African-American and non-Hispanic white, low-income patients were reported to have later stages of both colon and rectal cancers. The NCDB provides a useful longitudinal perspective on the diagnosis and treatment of colon and rectal cancers.

Simple SummaryColorectal cancer is increasingly recognized as two separate diseases: colon cancer and rectal cancer, each with its own causes and outcomes. We included 674 patients with colorectal cancer, with pre-surgery collected blood samples, and patient follow up for an average of 4.4 years. Ninety-three patients (14%) died from various causes including 60 patients with colon cancer and 33 patients with rectal cancer. Higher levels of plasma creatinine increased the risk of death by 39% in patients with rectal but not colon cancer. We further identified a biological pathway (e.g., roadmaps inside our bodies that guide various processes) related to starch and sucrose metabolism, which was linked to worse clinical outcomes in colon cancer but not rectal cancer. There is some evidence, that resistant starch, which resists digestion in the small intestine, may offer protection against colon cancer. Understanding the distinct causes and outcomes of colon and rectal cancer is crucial for tailoring effective treatments. In conclusion, personalized treatment strategies should consider colon cancer and rectal cancer separately and are essential for improving patient outcomes in the future.Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates AbsoluteIDQ p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I–III) colon (n = 394) or rectal cancer (n = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23–1.72, pFDR = 0.03; but not colon cancer: pFDR = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments.

Association Between Body Size and Colorectal Adenoma Recurrence

Purpose: Our pilot study in a small cohort by ELISA showed that the levels and positive rates of serum IgG autoantibodies against p53, HRAS and NSG1, and IgA autoantibody against TIF1γ in early colon cancer (CC) group were significantly higher than that of colon benign lesion (CBL) group / healthy control (HC) group (P <0.01), which suggested that four autoantibodies might be valuable for the diagnosis of patients with CC at early stage. On the basis of pilot study, we intend to comprehensively elucidate the performance of four autoantibodies for the early diagnosis of CC in a large sample cohort, and explore the optimal panel of autoantibodies in the diagnosis of patients with CC at early stage.Methods: Western blot was used to define the ELISA results of serum anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA. The performances of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA were evaluated by ELISA for the early diagnosis of CC with 601 serum samples of 157 patients with CC at early stage, 144 patients with CC at advanced stage, 130 patients with CBL, and 170 HC, and then the performances of different combinations of four autoantibodies were analyzed for the development of an optimal panel for the early diagnosis of CC.Results: The results of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA in western blotting were consistent with that in ELISA. The levels and positive rates of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA in early CC group were significantly higher than that in CBL group/HC group (P <0.01), while had no significant difference from that in advanced CC group (P >0.05), of which anti-TIF1γ-IgA showed the highest area under the receiver operating characteristic curve (AUC) of 0.716 for the patients with CC at early stage, with 25.5% sensitivity and specificity at 96.7%. Additionally, a panel of anti-p53, HRAS-IgG and anti-TIF1γ-IgA showed the highest AUC among all possible combinations of four autoantibodies, up to 0.737, with 47.1% sensitivity at 92.0% specificity.Conclusions: Serum IgG autoantibodies against p53, HRAS and NSG1, and IgA autoantibody against TIF1γ show the diagnostic value for the patients with CC at early stage, of which anti-TIF1γ-IgA is demonstrated to be a preferable biomarker, and an optimal panel comprised of anti-p53, HRAS-IgG and anti-TIF1γ-IgA might contribute to the further improvement of early diagnosis for CC.

Worldwide, colon cancer is the third most frequent malignancy and the second most common cause of death. Although it can strike anybody at any age, colon cancer mostly affects the elderly. Small, non-cancerous cell clusters inside the colon, commonly known as polyps, are typically where colon cancer growth starts. But over time, if left untreated, these benign polyps may develop into malignant tissues and develop into colon cancer. For the diagnosis of colon cancer, with routine inspection of the colon region for polyps, several techniques, including colonoscopy and cancer scanning, are used. In the case identifying the polyps in the colon area, efforts are being taken to surgically remove the polyps as quickly as possible before they become malignant. If the polyps become malignant, then colon cancer treatment strategies, such as surgery, chemotherapy, targeted therapy, and immunotherapy, are applied to the patients. Despite the recent improvements in diagnosis and prognosis, the treatment of colorectal cancer (CRC) remains a challenging task. The objective of this review was to discuss how CRC is initiated, and its various developmental stages, pathophysiology, and risk factors, and also to explore the current state of colorectal cancer diagnosis and treatment, as well as recent advancements in the field, such as new screening methods and targeted therapies. We examined the limitations of current methods and discussed the ongoing need for research and development in this area. While this topic may be serious and complex, we hope to engage and inform our audience on this important issue.

Introduction:Asian developing countries share the burden of colorectal cancer (CRC) with rising mortality rates. This prospective study aims to apprehend the clinical relevance of age, gender, lifestyle choices (dietary habits and addiction) and body mass index (BMI) to the occurrence and progression of colon cancer (CC).Methods:A cohort of non-cancer (NC) and CC patients of South-Central Asian origin registered for screening colonoscopy or surgery at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC), Lahore, Pakistan, from 2015 to 2020 was identified. BMI (Kg/m2) was classified according to the World Health Organization criteria as underweight (<18.5 Kg/m2), normal weight (18.5–24.9 Kg/m2) and overweight (≥25 Kg/m2).Results:Among 236 participants, 99 (41.9%) belonged to the NC group, and 137 (58.1 %) participants had CC Overall, participants included 74 women and 162 men aged 20–85 years (mean ± SD; 49.9 ± 14.9). Notably, 46.0% of cancer patients had a family history of cancer. There was a direct relationship between CC with abnormal BMI (underweight and overweight), positive smoking history and positive family history of cancer.Conclusion:Being underweight or overweight is a potential risk factor for CC patients. The overall survival in patients with CC is clinically associated with lifestyle choices before CC diagnosis. A balanced diet, walking and other forms of exercise should be strongly recommended to the community and those undergoing screening colonoscopy.

UK Fifth National Colorectal Cancer Consensus Meeting 2010