Cancers

Research

12 pages, 811 KiB

Open AccessArticle

Somatic Mutations in Exon 7 of the TP53 Gene in Index Colorectal Lesions Are Associated with the Early Occurrence of Metachronous Adenoma

by Tereza Hálková, Renata Ptáčková, Anastasiya Semyakina, Štěpán Suchánek, Eva Traboulsi, Ondřej Ngo, Kateřina Hejcmanová, Ondřej Májek, Jan Bureš, Miroslav Zavoral, Marek Minárik and Lucie Benešová

Cancers 2022, 14(12), 2823; https://doi.org/10.3390/cancers14122823 - 7 Jun 2022

Viewed by 2260

Abstract

(1) Background: this prospective study was focused on detailed analysis of the mutation heterogeneity in colorectal lesions removed during baseline (index) colonoscopy to identify patients at high risk of early occurrence of metachronous adenomas. (2) Methods: a total of 120 patients after endoscopic [...] Read more.

(1) Background: this prospective study was focused on detailed analysis of the mutation heterogeneity in colorectal lesions removed during baseline (index) colonoscopy to identify patients at high risk of early occurrence of metachronous adenomas. (2) Methods: a total of 120 patients after endoscopic therapy of advanced colorectal neoplasia size ≥10 mm (index lesion) with subsequent surveillance colonoscopy after 10–18 months were included. In total, 143 index lesions and 84 synchronous lesions in paraffin blocks were divided into up to 30 samples. In each of them, the detection of somatic mutations in 11 hot spot gene loci was performed. Statistical analysis to correlate the mutation profiles and the degree of heterogeneity of the lesions with the risk of metachronous adenoma occurrence was undertaken. (3) Results: mutation in exon 7 of the TP53 gene found in the index lesion significantly correlated with the early occurrence of metachronous adenoma (log-rank test p = 0.003, hazard ratio 2.73, 95% confidence interval 1.14–6.56). We did not find an association between the risk of metachronous adenomas and other markers monitored. (4) Conclusions: the findings of this study could lead to an adjustment of existing recommendations for surveillance colonoscopies in a specific group of patients with mutations in exon 7 of the TP53 gene in an index lesion, where a shortening of surveillance interval may be warranted. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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16 pages, 1787 KiB

Open AccessArticle

Impact of Age on Multimodality Treatment and Survival in Locally Advanced Rectal Cancer Patients

by Lindsey C. F. De Nes, Thea C. Heil, Rob H. A. Verhoeven, Valery E. P. P. Lemmens, Harm J. Rutten, Johannes H. W. De Wilt and Pauline A. J. Vissers

Cancers 2022, 14(11), 2741; https://doi.org/10.3390/cancers14112741 - 31 May 2022

Cited by 2 | Viewed by 2035

Abstract

Background: Optimal treatment for locally advanced rectal cancer is neoadjuvant (chemo)radiation followed by radical surgery. This is challenging in the aging population because of frequently concomitant comorbidity. We analyzed whether age below and above 70 years is associated with differences in treatment strategy [...] Read more.

Background: Optimal treatment for locally advanced rectal cancer is neoadjuvant (chemo)radiation followed by radical surgery. This is challenging in the aging population because of frequently concomitant comorbidity. We analyzed whether age below and above 70 years is associated with differences in treatment strategy and outcome in this population-based study. Methods: Data between 2008 and 2016 were extracted from the Netherlands Cancer Registry with follow-up until 2021. Differences in therapy, referral and outcome were analyzed using χ² tests, multivariable logistic regression and relative survival analysis. Results: In total, 6524 locally advanced rectal cancer patients were included. A greater proportion of patients <70 years underwent resection compared to older patients (89% vs. 71%). Patients ≥70 years were more likely treated with neoadjuvant radiotherapy (OR 3.4, 95% CI 2.61–4.52), than with chemoradiation (OR 0.3, 95% CI 0.23–0.37) and less often referred to higher volume hospitals for resection (OR 0.7, 95% CI 0.51–0.87). Five-year relative survival after resection following neoadjuvant therapy was comparable and higher for both patients <70 years and ≥70 years (82% and 77%) than after resection only. Resection only was associated with worse survival in the elderly compared to younger patients (56% vs. 75%). Conclusion: Elderly patients with locally advanced rectal cancer received less intensive treatment and were less often referred to higher volume hospitals for surgery. Relative survival was good and comparable after optimal treatment in both age groups. Effort is necessary to improve guideline adherence, and multimodal strategies should be tailored to age, comorbidity and performance status. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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19 pages, 6941 KiB

Open AccessArticle

Metformin and ICG-001 Act Synergistically to Abrogate Cancer Stem Cells-Mediated Chemoresistance in Colorectal Cancer by Promoting Apoptosis and Autophagy

by Souvick Roy, Yinghui Zhao, Yate-Ching Yuan and Ajay Goel

Cancers 2022, 14(5), 1281; https://doi.org/10.3390/cancers14051281 - 2 Mar 2022

Cited by 10 | Viewed by 3286

Abstract

Colorectal cancer (CRC) remains the third most frequently diagnosed cancer in the United States. The current treatment regimens for CRC include surgery followed by 5FU-based chemotherapy. Cancer stem-like cells (CSCs) have been implicated in 5FU-mediated chemoresistance, which leads to poor prognosis. In this [...] Read more.

Colorectal cancer (CRC) remains the third most frequently diagnosed cancer in the United States. The current treatment regimens for CRC include surgery followed by 5FU-based chemotherapy. Cancer stem-like cells (CSCs) have been implicated in 5FU-mediated chemoresistance, which leads to poor prognosis. In this study, we used metformin along with ICG-001, a Wnt signaling inhibitor, to abrogate CSC-mediated chemoresistance in CRC. We observed that 5FU-resistant (5FUR) CRC cells exhibited increased expression of CSC markers and enhanced spheroid formation. Genome-wide transcriptomic profiling analysis revealed that Wnt signaling, colorectal cancer metastasis signaling, etc., were enriched in 5FUR CRC cells. Accordingly, selective targeting of Wnt signaling using ICG-001 along with metformin abrogated CSC-mediated chemoresistance by decreasing the expression of CSC markers and promoting autophagy and apoptosis in a synergistic manner. We also observed that metformin and ICG-001 exhibited anti-tumor activity in CRC patient-derived tumor organoids. In conclusion, our study highlights that metformin and ICG-001 act synergistically and can be used as part of a therapeutic strategy to overcome 5FU-mediated therapeutic resistance in CRC. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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12 pages, 787 KiB

Open AccessArticle

Efficacy of Retreatment with Oxaliplatin-Based Regimens in Metastatic Colorectal Cancer Patients: The RETROX-CRC Retrospective Study

by Alessio Amatu, Gianluca Mauri, Federica Tosi, Katia Bencardino, Erica Bonazzina, Viviana Gori, Lorenzo Ruggieri, Sabrina Arena, Alberto Bardelli, Silvia Marsoni, Salvatore Siena and Andrea Sartore-Bianchi

Cancers 2022, 14(5), 1197; https://doi.org/10.3390/cancers14051197 - 25 Feb 2022

Cited by 11 | Viewed by 2761

Abstract

Background: oxaliplatin with fluoropyrimidine is a “mainstay” regarding the upfront treatment of metastatic colorectal cancer (mCRC). In contrast, the efficacy and safety of oxaliplatin-based regimens in late-care settings have been poorly reported. Methods: we identified a real-world mCRC patient cohort who were re-treated [...] Read more.

Background: oxaliplatin with fluoropyrimidine is a “mainstay” regarding the upfront treatment of metastatic colorectal cancer (mCRC). In contrast, the efficacy and safety of oxaliplatin-based regimens in late-care settings have been poorly reported. Methods: we identified a real-world mCRC patient cohort who were re-treated with oxaliplatin, and in which clinicopathological features were retrospectively analyzed to identify efficacy–predictive determinants (RETROX-CRC study). Results: of 2606 patients, 119 fulfilled the eligibility criteria. Oxaliplatin retreatment response rate (RR) and disease control rate (DCR) were 21.6% (CI 14.4–31.0%), and 57.8% (CI 47.7–67.4). A trend towards better RR and DCR was observed among patients who had first oxaliplatin in an adjuvant setting; a poorer outcome was observed if two or more intervening treatments were delivered. Median progression-free survival (PFS) was 5.1 months (95%CI 4.3–6.1), reducing to 4.0 months (95%CI 3.07–5.13) if oxaliplatin was readministered beyond third-line (HR 2.02; 1.25–3.25; p = 0.004). Safety data were retrieved in 65 patients (54.6%); 18.5% (12/65) and 7.7% (5/65) had G3–4 toxicities. Toxicities led to discontinuation in 34/119 (28.6%). Conclusions: oxaliplatin retreatment produced further RR in around one-fifth of patients and DCR 57.8%. Efficacy decreased in more pre-treated patients and around one-third of patients discontinued treatment due to adverse events. Translational studies improving patient selection are warranted. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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12 pages, 979 KiB

Open AccessArticle

Diagnostic Performance of a Fecal Immunochemical Test-Based Colorectal Cancer Screening Program According to Ambient Temperature and Humidity

by Gemma Ibáñez-Sanz, Núria Milà, Núria Vives, Carmen Vidal, Gemma Binefa, Judith Rocamora, Carmen Atencia, Víctor Moreno, Rebeca Sanz-Pamplona, Montse Garcia and on behalf of the MSIC-SC Research Group

Cancers 2022, 14(5), 1153; https://doi.org/10.3390/cancers14051153 - 23 Feb 2022

Cited by 1 | Viewed by 2281

Abstract

Exposure of the fecal immunochemical test (FIT) to different ambient temperatures and humidity is unavoidable in population-based screening programs in Southern European countries, and it could lead to a decrease in target colorectal lesions. The objective was to evaluate the effect of ambient [...] Read more.

Exposure of the fecal immunochemical test (FIT) to different ambient temperatures and humidity is unavoidable in population-based screening programs in Southern European countries, and it could lead to a decrease in target colorectal lesions. The objective was to evaluate the effect of ambient temperature and humidity on the FIT sensitivity in a population-based screening program for colorectal cancer (CRC) using an ecological design. The retrospective cohort included individuals aged 50–69 years who participated in CRC screening (Barcelona) from 2010–2015, and were followed until 2017 to identify interval CRCs. The positivity rate, and detection rates for advanced polyps and CRC were compared according to ambient temperature, humidity, and quarters of the year. A positive FIT was defined as the detection of ≥20 μg Hb/g in feces. The monthly ambient temperature and humidity were recorded on the day that the FIT was performed. In total, 92,273 FIT results from 53,860 participants were analyzed. The FIT positivity rate was lower at >24 °C than at ≤24 °C (p = 0.005) but was not affected by humidity. The temperature’s impact on positivity did not lead to a decrease in the FIT detection rate for advanced neoplasia or the interval cancer detection rate in a program where the samples were refrigerated until the analysis and screening invitations were discontinued in July and August. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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13 pages, 870 KiB

Open AccessArticle

Interplay between Genome, Metabolome and Microbiome in Colorectal Cancer

by Koldo Garcia-Etxebarria, Marc Clos-Garcia, Oiana Telleria, Beatriz Nafría, Cristina Alonso, Marta Iruarrizaga-Lejarreta, Andre Franke, Anais Crespo, Agueda Iglesias, Joaquín Cubiella, Luis Bujanda and Juan Manuel Falcón-Pérez

Cancers 2021, 13(24), 6216; https://doi.org/10.3390/cancers13246216 - 10 Dec 2021

Cited by 17 | Viewed by 5027

Abstract

Background: Colorectal cancer (CRC), a major health concern, is developed depending on environmental, genetic and microbial factors. The microbiome and metabolome have been analyzed to study their role in CRC. However, the interplay of host genetics with those layers in CRC remains unclear. [...] Read more.

Background: Colorectal cancer (CRC), a major health concern, is developed depending on environmental, genetic and microbial factors. The microbiome and metabolome have been analyzed to study their role in CRC. However, the interplay of host genetics with those layers in CRC remains unclear. Methods: 120 individuals were sequenced and association analyses were carried out for adenoma and CRC risk, and for selected components of the microbiome and metabolome. The epistasis between genes located in cholesterol pathways was analyzed; modifiable risk factors were studied using Mendelian randomization; and the three omic layers were used to integrate their data and to build risk prediction models. Results: We detected genetic variants that were associated to components of metabolome or microbiome and adenoma or CRC risk (e.g., in LINC01605, PROKR2 and CCSER1 genes). In addition, we found interactions between genes of cholesterol metabolism, and HDL cholesterol levels affected adenoma (p = 0.0448) and CRC (p = 0.0148) risk. The combination of the three omic layers to build risk prediction models reached high AUC values (>0.91). Conclusions: The use of the three omic layers allowed for the finding of biological mechanisms related to the development of adenoma and CRC, and each layer provided complementary information to build risk prediction models. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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10 pages, 847 KiB

Open AccessArticle

Faecal Diagnostic Biomarkers for Colorectal Cancer

by Andrea Cruz, Carla M. Carvalho, Alexandra Cunha, Anais Crespo, Águeda Iglesias, Laura García-Nimo, Paulo P. Freitas and Joaquín Cubiella

Cancers 2021, 13(21), 5568; https://doi.org/10.3390/cancers13215568 - 7 Nov 2021

Cited by 9 | Viewed by 2892

Abstract

Background: Colorectal cancer (CRC) is a major cause of cancer-related death worldwide. Cancer progression, including invasion and metastasis, is a major cause of death among CRC patients. Current methods for CRC screening commonly consist of a combination of faecal immunochemical test (FIT) for [...] Read more.

Background: Colorectal cancer (CRC) is a major cause of cancer-related death worldwide. Cancer progression, including invasion and metastasis, is a major cause of death among CRC patients. Current methods for CRC screening commonly consist of a combination of faecal immunochemical test (FIT) for stool occult blood detection and invasive procedures such as colonoscopy. Considering the slow progression of CRC, and that symptoms usually emerge at advanced stages, its early diagnostic can limit cancer’s spread and provide a successful treatment. Biomarkers have a high potential for the diagnosis of CRC in either blood or stool samples. Methods: In this study, we analysed the diagnostic value of six different biomarkers in stool samples of patients with CRC, advanced adenomas, other lesions and healthy individuals. We have also assessed the overall performance of the combination of these biomarkers for CRC detection. Results: The results indicate that haemoglobin (Hb) and M2-pyruvate kinase (M2-PK) levels were increased in CRC patients in comparison to the controls. Conversely, the concentrations of matrix metalloproteinase (MMP)-2, MMP-9, and tumour necrosis factor-alpha (TNF-α) were not significantly different between the tested groups. Conclusion: The combination of FIT-Hb with the M2-PK levels increased the specificity or sensitivity for CRC detection and thus present potential as faecal diagnostic biomarkers for CRC. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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12 pages, 2628 KiB

Open AccessArticle

Compound Endoscopic Morphological Features for Identifying Non-Pedunculated Lesions ≥20 mm with Intramucosal Neoplasia

by João Pedro da Costa-Seixas, María López-Cerón, Anna Arnau, Òria Rosiñol, Miriam Cuatrecasas, Alberto Herreros-de-Tejada, Ángel Ferrández, Miquel Serra-Burriel, Óscar Nogales, Luisa de Castro, Jorge López-Vicente, Pablo Vega, Marco A. Álvarez-González, Jesús M. González-Santiago, Marta Hernández-Conde, Pilar Diez-Redondo, Liseth Rivero-Sánchez, Antonio Z. Gimeno-García, Aurora Burgos, Francisco Javier García-Alonso, Marco Bustamante-Balén, Eva Martínez-Bauer, Beatriz Peñas, Daniel Rodríguez-Alcalde, Maria Pellisé and Ignasi Puig Show full author list Hide full author list

Cancers 2021, 13(21), 5302; https://doi.org/10.3390/cancers13215302 - 22 Oct 2021

Cited by 3 | Viewed by 2694

Abstract

Background: The major limitation of piecemeal endoscopic mucosal resection (EMR) is the inaccurate histological assessment of the resected specimen, especially in cases of submucosal invasion. Objective: To classify non-pedunculated lesions ≥20 mm based on endoscopic morphological features, in order to identify those that [...] Read more.

Background: The major limitation of piecemeal endoscopic mucosal resection (EMR) is the inaccurate histological assessment of the resected specimen, especially in cases of submucosal invasion. Objective: To classify non-pedunculated lesions ≥20 mm based on endoscopic morphological features, in order to identify those that present intramucosal neoplasia (includes low-grade neoplasia and high-grade neoplasia) and are suitable for piecemeal EMR. Design: A post-hoc analysis from an observational prospective multicentre study conducted by 58 endoscopists at 17 academic and community hospitals was performed. Unbiased conditional inference trees (CTREE) were fitted to analyse the association between intramucosal neoplasia and the lesions’ endoscopic characteristics. Result: 542 lesions from 517 patients were included in the analysis. Intramucosal neoplasia was present in 484 of 542 (89.3%) lesions. A conditional inference tree including all lesions’ characteristics assessed with white light imaging and narrow-band imaging (NBI) found that ulceration, pseudodepressed type and sessile morphology changed the accuracy for predicting intramucosal neoplasia. In ulcerated lesions, the probability of intramucosal neoplasia was 25% (95%CI: 8.3–52.6%; p < 0.001). In non-ulcerated lesions, its probability in lateral spreading lesions (LST) non-granular (NG) pseudodepressed-type lesions rose to 64.0% (95%CI: 42.6–81.3%; p < 0.001). Sessile morphology also raised the probability of intramucosal neoplasia to 86.3% (95%CI: 80.2–90.7%; p < 0.001). In the remaining 319 (58.9%) non-ulcerated lesions that were of the LST-granular (G) homogeneous type, LST-G nodular-mixed type, and LST-NG flat elevated morphology, the probability of intramucosal neoplasia was 96.2% (95%CI: 93.5–97.8%; p < 0.001). Conclusion: Non-ulcerated LST-G type and LST-NG flat elevated lesions are the most common non-pedunculated lesions ≥20 mm and are associated with a high probability of intramucosal neoplasia. This means that they are good candidates for piecemeal EMR. In the remaining lesions, further diagnostic techniques like magnification or diagnostic +/− therapeutic endoscopic submucosal dissection should be considered. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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12 pages, 1408 KiB

Open AccessArticle

Validation of Gene Expression-Based Predictive Biomarkers for Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

by Tomoyuki Momma, Hirokazu Okayama, Yasuyuki Kanke, Satoshi Fukai, Hisashi Onozawa, Shotaro Fujita, Wataru Sakamoto, Motonobu Saito, Shinji Ohki and Koji Kono

Cancers 2021, 13(18), 4642; https://doi.org/10.3390/cancers13184642 - 16 Sep 2021

Cited by 8 | Viewed by 2522

Abstract

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is widely used for patients with locally advanced rectal cancer. However, response to nCRT varies substantially among patients, highlighting the need for predictive biomarkers that can distinguish non-responsive from responsive patients before nCRT. This study aimed [...] Read more.

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is widely used for patients with locally advanced rectal cancer. However, response to nCRT varies substantially among patients, highlighting the need for predictive biomarkers that can distinguish non-responsive from responsive patients before nCRT. This study aimed to build novel multi-gene assays for predicting nCRT response, and to validate our signature and previously-reported signatures in multiple independent cohorts. Methods: Three microarray datasets of pre-therapeutic biopsies containing a total of 61 non-responders and 53 responders were used as the discovery cohorts to screen for genes that were consistently associated with nCRT response. The predictive values of signatures were tested in a meta-analysis using six independent datasets as the validation cohorts, consisted of a total of 176 non-responders and 99 responders. Results: We identified four genes, including BRCA1, GPR110, TNIK, and WDR4 in the discovery cohorts. Although our 4-gene signature and nine published signatures were evaluated, they were unable to predict nCRT response in the validation cohorts. Conclusions: Although this is one of the largest studies addressing the validity of gene expression-based classifiers using pre-treatment biopsies from patients with rectal cancer, our findings do not support their clinically meaningful values to be predictive of nCRT response. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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16 pages, 34852 KiB

Open AccessArticle

Impact of Race and Socioeconomics Disparities on Survival in Young-Onset Colorectal Adenocarcinoma—A SEER Registry Analysis

by Mark M. Aloysius, Hemant Goyal, Niraj J. Shah, Kumar Pallav, Nimy John, Mahesh Gajendran, Abhilash Perisetti and Benjamin Tharian

Cancers 2021, 13(13), 3262; https://doi.org/10.3390/cancers13133262 - 29 Jun 2021

Cited by 9 | Viewed by 2327

Abstract

Introduction: We aimed to assess the impact of socio-economic determinants of health (SEDH) on survival disparities within and between the ethnic groups of young-onset (<50 years age) colorectal adenocarcinoma patients. Patients and Methods: Surveillance, epidemiology, and end results (SEER) registry was used to [...] Read more.

Introduction: We aimed to assess the impact of socio-economic determinants of health (SEDH) on survival disparities within and between the ethnic groups of young-onset (<50 years age) colorectal adenocarcinoma patients. Patients and Methods: Surveillance, epidemiology, and end results (SEER) registry was used to identify colorectal adenocarcinoma patients aged between 25–49 years from 2012 and 2016. Survival analysis was performed using the Kaplan–Meir method. Cox proportional hazards model was used to determine the hazard effect of SEDH. American community survey (ACS) data 2012–2016 were used to analyze the impact of high school education, immigration status, poverty, household income, employment, marital status, and insurance type. Results: A total of 17,145 young-onset colorectal adenocarcinoma patients were studied. Hispanic (H) = 2874, Non-Hispanic American Indian/Alaskan Native (NHAIAN) = 164, Non-Hispanic Asian Pacific Islander (NHAPI) = 1676, Non-Hispanic black (NHB) = 2305, Non-Hispanic white (NHW) = 10,126. Overall cancer-specific survival was, at 5 years, 69 m. NHB (65.58 m) and NHAIAN (65.67 m) experienced worse survival compared with NHW (70.11 m), NHAPI (68.7), and H (68.31). High school education conferred improved cancer-specific survival significantly with NHAPI, NHB, and NHW but not with H and NHAIAN. Poverty lowered and high school education improved cancer-specific survival (CSS) in NHB, NHW, and NHAPI. Unemployment was associated with lowered CSS in H and NAPI. Lower income below the median negatively impacted survival among H, NHAPI NHB, and NHW. Recent immigration within the last 12 months lowered CSS survival in NHW. Commercial health insurance compared with government insurance conferred improved CSS in all groups. Conclusions: Survival disparities were found among all races with young-onset colorectal adenocarcinoma. The pattern of SEDH influencing survival was unique to each race. Overall higher income levels, high school education, private insurance, and marital status appeared to be independent factors conferring favorable survival found on multivariate analysis. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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Review

Jump to: Research, Other

17 pages, 855 KiB

Open AccessReview

Copy Number Alterations as Novel Biomarkers and Therapeutic Targets in Colorectal Cancer

by Elaine S. Tan, Todd C. Knepper, Xuefeng Wang, Jennifer B. Permuth, Liang Wang, Jason B. Fleming and Hao Xie

Cancers 2022, 14(9), 2223; https://doi.org/10.3390/cancers14092223 - 29 Apr 2022

Cited by 10 | Viewed by 3593

Abstract

In colorectal cancer, somatic mutations have played an important role as prognostic and predictive biomarkers, with some also functioning as therapeutic targets. Another genetic aberration that has shown significance in colorectal cancer is copy number alterations (CNAs). CNAs occur when a change to [...] Read more.

In colorectal cancer, somatic mutations have played an important role as prognostic and predictive biomarkers, with some also functioning as therapeutic targets. Another genetic aberration that has shown significance in colorectal cancer is copy number alterations (CNAs). CNAs occur when a change to the DNA structure propagates gain/amplification or loss/deletion in sections of DNA, which can often lead to changes in protein expression. Multiple techniques have been developed to detect CNAs, including comparative genomic hybridization with microarray, low pass whole genome sequencing, and digital droplet PCR. In this review, we summarize key findings in the literature regarding the role of CNAs in the pathogenesis of colorectal cancer, from adenoma to carcinoma to distant metastasis, and discuss the roles of CNAs as prognostic and predictive biomarkers in colorectal cancer. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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25 pages, 2559 KiB

Open AccessReview

Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies

by Md. Sanower Hossain, Hidayah Karuniawati, Ammar Abdulrahman Jairoun, Zannat Urbi, Der Jiun Ooi, Akbar John, Ya Chee Lim, K. M. Kaderi Kibria, A.K. M. Mohiuddin, Long Chiau Ming, Khang Wen Goh and Muhammad Abdul Hadi

Cancers 2022, 14(7), 1732; https://doi.org/10.3390/cancers14071732 - 29 Mar 2022

Cited by 321 | Viewed by 43791

Abstract

Colorectal cancer (CRC) is the second most deadly cancer. Global incidence and mortality are likely to be increased in the coming decades. Although the deaths associated with CRC are very high in high-income countries, the incidence and fatalities related to CRC are growing [...] Read more.

Colorectal cancer (CRC) is the second most deadly cancer. Global incidence and mortality are likely to be increased in the coming decades. Although the deaths associated with CRC are very high in high-income countries, the incidence and fatalities related to CRC are growing in developing countries too. CRC detected early is entirely curable by surgery and subsequent medications. However, the recurrence rate is high, and cancer drug resistance increases the treatment failure rate. Access to early diagnosis and treatment of CRC for survival is somewhat possible in developed countries. However, these facilities are rarely available in developing countries. Highlighting the current status of CRC, its development, risk factors, and management is crucial in creating public awareness. Therefore, in this review, we have comprehensively discussed the current global epidemiology, drug resistance, challenges, risk factors, and preventive and treatment strategies of CRC. Additionally, there is a brief discussion on the CRC development pathways and recommendations for preventing and treating CRC. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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23 pages, 759 KiB

Open AccessReview

Use of Omics Technologies for the Detection of Colorectal Cancer Biomarkers

by Marina Alorda-Clara, Margalida Torrens-Mas, Pere Miquel Morla-Barcelo, Toni Martinez-Bernabe, Jorge Sastre-Serra, Pilar Roca, Daniel Gabriel Pons, Jordi Oliver and Jose Reyes

Cancers 2022, 14(3), 817; https://doi.org/10.3390/cancers14030817 - 6 Feb 2022

Cited by 8 | Viewed by 3817

Abstract

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers with high mortality rates, especially when detected at later stages. Early detection of CRC can substantially raise the 5-year survival rate of patients, and different efforts are being put into developing enhanced [...] Read more.

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers with high mortality rates, especially when detected at later stages. Early detection of CRC can substantially raise the 5-year survival rate of patients, and different efforts are being put into developing enhanced CRC screening programs. Currently, the faecal immunochemical test with a follow-up colonoscopy is being implemented for CRC screening. However, there is still a medical need to describe biomarkers that help with CRC detection and monitor CRC patients. The use of omics techniques holds promise to detect new biomarkers for CRC. In this review, we discuss the use of omics in different types of samples, including breath, urine, stool, blood, bowel lavage fluid, or tumour tissue, and highlight some of the biomarkers that have been recently described with omics data. Finally, we also review the use of extracellular vesicles as an improved and promising instrument for biomarker detection. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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21 pages, 1179 KiB

Open AccessReview

Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis

by Diana Haimov, Sari Lieberman, Sergi Castellvi-Bel, Maartje Nielsen and Yael Goldberg

Cancers 2022, 14(3), 628; https://doi.org/10.3390/cancers14030628 - 26 Jan 2022

Cited by 2 | Viewed by 5756

Abstract

Genetic diagnosis of affected individuals and predictive testing of their at-risk relatives, combined with intensive cancer surveillance, has an enormous cancer-preventive potential in these families. A lack of awareness may be part of the reason why the underlying germline cause remains unexplained in [...] Read more.

Genetic diagnosis of affected individuals and predictive testing of their at-risk relatives, combined with intensive cancer surveillance, has an enormous cancer-preventive potential in these families. A lack of awareness may be part of the reason why the underlying germline cause remains unexplained in a large proportion of patients with CRC. Various extracolonic features, mainly dermatologic, ophthalmic, dental, endocrine, vascular, and reproductive manifestations occur in many of the cancer predisposition syndromes associated with CRC and polyposis. Some are mediated via the WNT, TGF-β, or mTOR pathways. However the pathogenesis of most features is still obscure. Here we review the extracolonic features of the main syndromes, the existing information regarding their prevalence, and the pathways involved in their pathogenesis. This knowledge could be useful for care managers from different professional disciplines, and used to raise awareness, enable diagnosis, and assist in the process of genetic testing and interpretation. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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Other

Jump to: Research, Review

16 pages, 618 KiB

Open AccessSystematic Review

Robotic-Assisted vs. Standard Laparoscopic Surgery for Rectal Cancer Resection: A Systematic Review and Meta-Analysis of 19,731 Patients

by Kamil Safiejko, Radoslaw Tarkowski, Maciej Koselak, Marcin Juchimiuk, Aleksander Tarasik, Michal Pruc, Jacek Smereka and Lukasz Szarpak

Cancers 2022, 14(1), 180; https://doi.org/10.3390/cancers14010180 - 30 Dec 2021

Cited by 51 | Viewed by 4409

Abstract

Robotic-assisted surgery is expected to have advantages over standard laparoscopic approach in patients undergoing curative surgery for rectal cancer. PubMed, Cochrane Library, Web of Science, Scopus and Google Scholar were searched from database inception to 10 November 2021, for both RCTs and observational [...] Read more.

Robotic-assisted surgery is expected to have advantages over standard laparoscopic approach in patients undergoing curative surgery for rectal cancer. PubMed, Cochrane Library, Web of Science, Scopus and Google Scholar were searched from database inception to 10 November 2021, for both RCTs and observational studies comparing robotic-assisted versus standard laparoscopic surgery for rectal cancer resection. Where possible, data were pooled using random effects meta-analysis. Forty-Two were considered eligible for the meta-analysis. Survival to hospital discharge or 30-day overall survival rate was 99.6% for RG and 98.8% for LG (OR = 2.10; 95% CI: 1.00 to 4.43; p = 0.05). Time to first flatus in the RG group was 2.5 ± 1.4 days and was statistically significantly shorter than in LG group (2.9 ± 2.0 days; MD = −0.34; 95%CI: −0.65 to 0.03; p = 0.03). In the case of time to a liquid diet, solid diet and bowel movement, the analysis showed no statistically significant differences (p > 0.05). Length of hospital stay in the RG vs. LG group varied and amounted to 8.0 ± 5.3 vs. 9.5 ± 10.0 days (MD = −2.01; 95%CI: −2.90 to −1.11; p < 0.001). Overall, 30-days complications in the RG and LG groups were 27.2% and 19.0% (OR = 1.11; 95%CI: 0.80 to 1.55; p = 0.53), respectively. In summary, robotic-assisted techniques provide several advantages over laparoscopic techniques in reducing operative time, significantly lowering conversion of the procedure to open surgery, shortening the duration of hospital stay, lowering the risk of urinary retention, improving survival to hospital discharge or 30-day overall survival rate. Full article

(This article belongs to the Special Issue Recent Advances in Colorectal Cancer Diagnostics and Treatments)

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