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Colorectal Cancer Early Detection, Diagnosis, and Staging

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (15 August 2022) | Viewed by 17778

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Prof. Dr. Holger Rumpold

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Gastrointestinal Cancer Center, Ordensklinikum Linz, Seilerstaette 4, 4010 Linz, Austria
Interests: gastrointestinal cancer; epidemiology; real-life data; molecular oncology; rare cancers

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is the third most common cancer worldwide. It develops from precursor lesions, making it a sensitive disease for surveillance and early detection programs. Techniques for early detection have been under development in the last years and, especially with the introduction of novel methods, and can be divided into invasive and non-invasive procedures. Once detected, the spread of the disease, along with other prognostic markers, have to be defined so as to provide necessary information for tailored treatment concepts.

Several issues are of interest in this context, namely:

What impact does nutrition and associated factors (i.e., the microbiome or small circulating DNA-fragments) have on the development of colorectal cancer
What is the sensitivity and specificity of established screening methods like colonoscopy and occult blood test? What is the impact of these methods in reducing mortality caused by colorectal cancer?
What are the most promising new non-invasive methods (methylation, microbiome, etc.) for the early detection of adenomas and/or early colorectal cancer?
What are the limits of staging for colorectal cancer? What role does MR play in the staging of rectal cancer (over-/under-staging); what is the role of FDG-PET-CT and, associated with this issue, is there a measurable stage migration leading to different treatment decision due to FDG-PET-CT?
What are the biomarkers defining the prognosis for early colorectal cancer, especially new markers like ctDNA?

Prof. Dr. Holger Rumpold
Guest Editor

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Keywords

prevention
early detection
cancer surveillance
staging

Published Papers (7 papers)

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Research

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18 pages, 1524 KiB

Open AccessArticle

Prognostic Value of Combined Hematological/Biochemical Indexes and Tumor Clinicopathologic Features in Colorectal Cancer Patients—A Pilot Single Center Study

by Vladica Cuk, Aleksandar Karamarkovic, Jovan Juloski, Dragana Arbutina, Radosav Radulovic, Ljiljana Milic, Bojan Kovacevic, Silvio De Luka and Jelena Grahovac

Cancers 2023, 15(6), 1761; https://doi.org/10.3390/cancers15061761 - 14 Mar 2023

Cited by 1 | Viewed by 1280

Abstract

Colorectal cancer (CRC) is a significant public health problem. There is increasing evidence that the host’s immune response and nutritional status play a role in the development and progression of cancer. The aim of our study was to examine the prognostic value of clinical markers/indexes of inflammation, nutritional and pathohistological status in relation to overall survival and disease free-survival in CRC. The total number of CRC patients included in the study was 111 and they underwent laboratory analyses within a week before surgery. Detailed pathohistological analysis and laboratory parameters were part of the standard hospital pre-operative procedure. Medical data were collected from archived hospital data. Data on the exact date of death were obtained by inspecting the death registers for the territory of the Republic of Serbia. All parameters were analyzed in relation to the overall survival and survival period without disease relapse. The follow-up median was 42 (24−48) months. The patients with the III, IV and V degrees of the Clavien–Dindo classification had 2.609 (HR: 2.609; 95% CI: 1.437−4.737; p = 0.002) times higher risk of death. The modified Glasgow prognostic score (mGPS) 2 and higher lymph node ratio carried a 2.188 (HR: 2.188; 95% CI: 1.413−3.387; p < 0.001) and 6.862 (HR: 6.862; 95% CI: 1.635−28.808; p = 0.009) times higher risk of death in the postoperative period, respectively; the risk was 3.089 times higher (HR: 3.089; 95% CI: 1.447−6.593; p = 0.004) in patients with verified tumor deposits. The patients with tumor deposits had 1.888 (HR: 1.888; 95% CI: 1024−3481; p = 0.042) and 3.049 (HR: 3.049; 95% CI: 1.206−7.706; p = 0.018) times higher risk of disease recurrence, respectively. The emphasized peritumoral lymphocyte response reduced the risk of recurrence by 61% (HR: 0.391; 95% CI: 0.196−0.780; p = 0.005). Standard perioperative laboratory and pathohistological parameters, which do not present any additional cost for the health system, may provide information on the CRC patient outcome and lay the groundwork for a larger prospective examination. Full article

(This article belongs to the Special Issue Colorectal Cancer Early Detection, Diagnosis, and Staging)

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9 pages, 901 KiB

Open AccessArticle

The Spectrum of Co-Diagnoses in Patients with Colorectal Cancer: A Retrospective Cohort Study of 17,824 Outpatients in Germany

by Sven H. Loosen, David Schöler, Simon Labuhn, Alexander Mertens, Markus S Jördens, Mark Luedde, Karel Kostev, Tom Luedde and Christoph Roderburg

Cancers 2022, 14(15), 3825; https://doi.org/10.3390/cancers14153825 - 06 Aug 2022

Cited by 2 | Viewed by 1737

Abstract

Background: The prognosis of colorectal cancer (CRC) patients is determined to a decisive extent by comorbidities. On the other hand, anti-cancer treatments for CRC are associated with relevant toxicities and may therefore cause additional comorbidities. Methods: This retrospective cohort study assessed the prevalence of various diseases in patients 12 months before and 12 months after an initial diagnosis of colorectal cancer (ICD-10: C18, C20) in 1274 general practices in Germany between January 2000 and December 2018. The study is based on the Disease Analyzer database (IQVIA), which contains drug prescriptions, diagnoses, and basic medical and demographic data. Patients with and without CRC were matched by sex, age, and index year. Results: We identified several diagnoses with a significantly higher prevalence among CRC patients 12 months prior to the index date compared to controls. These diagnoses included gastrointestinal hemorrhage, hemorrhoids, perianal venous thrombosis, and abdominal and pelvic pain, as well as functional intestinal disorders. In contrast, the prevalence of lipid metabolism disorder, depression, hypertension, coronary heart disease, or acute bronchitis was significantly lower in CRC cases. After diagnosis of CRC, we found a significantly higher prevalence of anemia, polyneuropathies, functional intestinal disorders, and chronic kidney disease among CRC patients compared to the control group, while the prevalence of acute upper respiratory infections of multiple and unspecified sites and acute bronchitis was significantly lower in CRC patients compared to non-CRC patients. Conclusions: In the present study, we identified a variety of diseases occurring at higher or lower frequencies in CRC patients compared to matched controls without CRC. This might help to select patients for early CRC screening and improve the clinical management of CRC patients. Full article

(This article belongs to the Special Issue Colorectal Cancer Early Detection, Diagnosis, and Staging)

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13 pages, 537 KiB

Open AccessArticle

The Risk Analyses of Lymph Node Metastasis and Recurrence for Submucosal Invasive Colorectal Cancer: Novel Criteria to Skip Completion Surgery

by Takanori Ozeki, Takaya Shimura, Tomonori Ozeki, Masahide Ebi, Hiroyasu Iwasaki, Hiroyuki Kato, Shingo Inaguma, Yusuke Okuda, Takahito Katano, Hirotada Nishie, Satoru Takahashi and Hiromi Kataoka

Cancers 2022, 14(3), 822; https://doi.org/10.3390/cancers14030822 - 06 Feb 2022

Cited by 13 | Viewed by 2006

Abstract

(1) Background: Additional surgical resection after endoscopic resection (ER) is recommended for patients with submucosal invasive colorectal cancer (pT1 CRC) who have risk factors for lymph node metastasis (LNM) (high-risk pT1 CRC). This study aimed to identify risk factors for LNM and metastatic recurrence and to determine the low-risk population for whom additional surgery can be omitted among high-risk pT1 CRCs. (2) Methods: We retrospectively identified 404 patients with pT1 CRC who underwent ER or surgery, and patients were divided into three groups: low-risk (n = 79); high-risk pT1 with ER (n = 40); and high-risk with surgery (n = 285). We also enrolled another 64 patients with high-risk pT1 CRC in an independent validation cohort. (3) Results: In the high-risk with surgery group, LNM was seen in 11.2%, and vascular and lymphatic invasions were significantly independent risk factors for LNM on multivariate analysis. No LNMs were observed in pT1 CRCs with a negative vertical margin and SM invasion depth ≤2000 µm that had no other risk factors except for budding. Five patients developed metastatic recurrence in the high-risk with surgery group, and rectal cancer and undifferentiated histology were significantly independent risk factors for poor relapse-free survival. No LNM or recurrent cases were seen in high-risk pT1 CRCs that met these criteria: differentiated adenocarcinoma, no lymphovascular invasion, colon cancer, SM invasion depth ≤2000 μm, and a negative vertical margin, which were validated in an independent validation cohort. (4) Conclusions: Completion surgery may be skipped for high-risk pT1 CRCs that meet our proposed criteria. Full article

(This article belongs to the Special Issue Colorectal Cancer Early Detection, Diagnosis, and Staging)

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33 pages, 21157 KiB

Open AccessArticle

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

by Evan Maestri, Kalina Duszka and Vladimir A. Kuznetsov

Cancers 2021, 13(13), 3180; https://doi.org/10.3390/cancers13133180 - 25 Jun 2021

Viewed by 2792

Abstract

Systems cancer biology analysis of calorie restriction (CR) mechanisms and pathways has not been carried out, leaving therapeutic benefits unclear. Using metadata analysis, we studied gene expression changes in normal mouse duodenum mucosa (DM) response to short-term (2-weeks) 25% CR as a biological model. Our results indicate cancer-associated genes consist of 26% of 467 CR responding differential expressed genes (DEGs). The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest telomeric maintenance misbalance and metabolic pathway activation playing dual (anti-cancer and pro-oncogenic) roles. The aberrant DEG profile of DM epithelial cells is found within CR-induced overexpression of Paneth cells and is coordinated significantly across GI tract tissues mucosa. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor-immune surveillance. CR induces metabolic reprogramming, suppressing immune mechanics and activating oncogenic pathways. We introduce and argue for our network pro-oncogenic model of the mucosa multicellular tissue response to CR leading to aberrant transcription and pre-malignant states. These findings change the paradigm regarding CR’s anti-cancer role, initiating specific treatment target development. This will aid future work to define critical oncogenic pathways preceding intestinal lesion development and biomarkers for earlier adenoma and colorectal cancer detection. Full article

(This article belongs to the Special Issue Colorectal Cancer Early Detection, Diagnosis, and Staging)

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Review

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16 pages, 1687 KiB

Open AccessReview

Lynch-like Syndrome: Potential Mechanisms and Management

by Alejandro Martínez-Roca, Mar Giner-Calabuig, Oscar Murcia, Adela Castillejo, José Luis Soto, Anabel García-Heredia and Rodrigo Jover

Cancers 2022, 14(5), 1115; https://doi.org/10.3390/cancers14051115 - 22 Feb 2022

Cited by 10 | Viewed by 4012

Abstract

Lynch syndrome is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) system genes, such as MLH1, MSH2, MSH6, or PMS2. It is the most common hereditary colorectal cancer syndrome. Screening is regularly performed by using microsatellite instability (MSI) or immunohistochemistry for the MMR proteins in tumor samples. However, in a proportion of cases, MSI is found or MMR immunohistochemistry is impaired in the absence of a germline mutation in MMR genes, BRAF mutation, or MLH1 hypermethylation. These cases are defined as Lynch-like syndrome. Patients with Lynch-like syndrome represent a mixture of truly hereditary and sporadic cases, with a risk of colorectal cancer in first-degree relatives that is between the risk of Lynch syndrome in families and relatives of sporadic colon cancer cases. Although multiple approaches have been suggested to distinguish between hereditary and sporadic cases, a homogeneous testing protocol and consensus on the adequate classification of these patients is still lacking. For this reason, management of Lynch-like syndrome and prevention of cancer in these families is clinically challenging. This review explains the concept of Lynch-like syndrome, potential mechanisms for its development, and methods for adequately distinguishing between sporadic and hereditary cases of this entity. Full article

(This article belongs to the Special Issue Colorectal Cancer Early Detection, Diagnosis, and Staging)

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11 pages, 1493 KiB

Open AccessViewpoint

A Scoring Model and Protocol to Adapt Universal Screening for Lynch Syndrome to Identify Germline Pathogenic Variants by Next Generation Sequencing from Colorectal Cancer Patients and Cascade Screening

by Ramadhani Chambuso, Barbara Robertson and Raj Ramesar

Cancers 2022, 14(12), 2901; https://doi.org/10.3390/cancers14122901 - 12 Jun 2022

Cited by 1 | Viewed by 1864

Abstract

Identification of germline pathogenic variants (PV) predisposing to Lynch syndrome (LS) is an important step for effective use of cascade screening of extended at-risk lineages, leading to reduced morbidity and mortality due to colorectal cancer (CRC). As a general rule, however, next generation sequencing (NGS, either of gene panels or whole exomes) is relatively expensive and unaffordable for general clinical use. In resource-poor settings, performing NGS testing on an entire cohort of CRC patients, even if limited to those under 50 or 60 years of age, still places an enormous burden on limited resources. Although family history can be a good indicator for LS testing, identifying at-risk family members and offering cascade screening may not benefit many patients/probands without an obvious family history. This article presents a novel program called Modified Ascertainment and follow-up Program (MAP) with a scoring model for LS ascertainment and molecular screening by NGS with diagnosis confirmation of PV and cascade screening. The goal is to improve LS ascertainment in light of the growing burden of early-onset CRC, particularly in low- and middle-income countries. Through MAP, judiciously applied molecular genetics will improve identification of PV predisposing to LS and cascade screening. Full article

(This article belongs to the Special Issue Colorectal Cancer Early Detection, Diagnosis, and Staging)

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12 pages, 2104 KiB

Open AccessSystematic Review

A Global Evaluation of the Performance Indicators of Colorectal Cancer Screening with Fecal Immunochemical Tests and Colonoscopy: A Systematic Review and Meta-Analysis

by Hanyue Ding, Jiaye Lin, Zijun Xu, Xiao Chen, Harry H. X. Wang, Liwen Huang, Junjie Huang, Zhijie Zheng and Martin C. S. Wong

Cancers 2022, 14(4), 1073; https://doi.org/10.3390/cancers14041073 - 21 Feb 2022

Cited by 14 | Viewed by 3036

Abstract

(1) Background: To summarize the achievements of the performance indicators of colorectal cancer (CRC) screening programs that used the fecal immunochemical test (FIT) as a primary screening modality and colonoscopy as a subsequent confirmatory test. (2) Methods: PubMed, Ovid MEDLINE, Embase, and Cochrane were searched from inception to September 2020. We included original articles published in English, and performed hand searching for relevant national reports. We generated pooled achievement estimates of the performance indicators by “metaprop” (R software 3.6.3). Meta-regression analyses and subgroup analyses were also conducted. (3) Results: We included 93 studies involving nearly 90 million people-times. The participation rate ranged from 6.80% to 95.98%, which was associated with study type, continents, FIT number, age, and round. The pooled FIT invalid rate and positivity rate were 1.08% and 7.28%, respectively. The pooled estimates of FIT detection were 2.26% for adenoma, 1.26% for advanced adenoma, and 0.28% for CRC. In addition, only seven studies reported that their colonoscopy compliance rate reached 90% among 69 studies. The colonoscopy completion rate (21/40 studies > 95%) and the complication rate (18/27 studies < 0.5%) were acceptable. (4) Conclusions: Our findings could help to identify the areas that could be improved and finally optimize the CRC screening programs. Full article

(This article belongs to the Special Issue Colorectal Cancer Early Detection, Diagnosis, and Staging)

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