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20 pages, 5570 KiB

Open AccessArticle

A Truncated NRIP1 Mutant Amplifies Microsatellite Instability of Colorectal Cancer by Regulating MSH2/MSH6 Expression, and Is a Prognostic Marker of Stage III Tumors

by Pascale Palassin, Marion Lapierre, Samuel Pyrdziak, Antoine Wagner, Régine Stehle, Carole Corsini, Jacqueline Duffour, Sandrine Bonnet, Abdelhay Boulahtouf, Carmen Rodriguez, Alexandre Ho-Pun-Cheung, Evelyne Lopez-Crapez, Florence Boissière-Michot, Frédéric Bibeau, Simon Thezenas, Nabila Elarouci, Janick Selves, Jean-Sébastien Hoffmann, Paul Roepman, Thibault Mazard, Olivier Buhard, Alex Duval, Stéphan Jalaguier, Vincent Cavaillès and Audrey Castet-Nicolas Show full author list Hide full author list

Cancers 2021, 13(17), 4449; https://doi.org/10.3390/cancers13174449 - 3 Sep 2021

Cited by 4 | Viewed by 2947

Abstract

Microsatellite instability (MSI) is related to the alteration of mismatch repair (MMR) genes and plays a key role in colorectal cancer (CRC) pathogenesis. We previously reported that the transcription factor Nuclear Receptor Interacting Protein 1 (NRIP1) is involved in sporadic intestinal tumorigenesis. The [...] Read more.

Microsatellite instability (MSI) is related to the alteration of mismatch repair (MMR) genes and plays a key role in colorectal cancer (CRC) pathogenesis. We previously reported that the transcription factor Nuclear Receptor Interacting Protein 1 (NRIP1) is involved in sporadic intestinal tumorigenesis. The aim of this study was to decipher its role in MSI CRC. By using different mouse models and engineered cell lines, we demonstrated that NRIP1 increased MSH2 and MSH6 MMR gene transcription and mRNA/protein levels. In human CRC cells, NRIP1 expression was associated with decreased MSI and the hypermutator phenotype, and with resistance to chemotherapy drugs. Using a cohort of 194 CRC patients, we detected in 22% of the cases a MSI-induced frameshift mutation in the NRIP1 coding sequence. This genetic alteration generates a truncated protein with a dominant negative activity that increased human CRC cell proliferation and impaired the regulation of MSH2 and MSH6 gene expression. Moreover, the NRIP1 mutant correlated with a decreased overall survival of patients with advanced CRC, especially when MLH1-deficient. By decreasing the expression of MSH2 and MSH6 gene expression, the NRIP1 variant may amplify MLH1-dependent CRC progression and behave as a new prognostic marker of advanced MSI CRC. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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13 pages, 793 KiB

Open AccessArticle

Survival Impact of Chronic Obstructive Pulmonary Disease or Acute Exacerbation on Patients with Rectal Adenocarcinoma Undergoing Curative Resection: A Propensity Score-Matched, Population-Based Cohort Study

by Jiaqiang Zhang, Kuo-Chin Chiu, Wei-Chun Lin and Szu-Yuan Wu

Cancers 2021, 13(16), 4221; https://doi.org/10.3390/cancers13164221 - 22 Aug 2021

Cited by 1 | Viewed by 2305

Abstract

Purpose: The survival effect of current smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with rectal adenocarcinoma undergoing curative resection. Methods: We recruited patients with clinical stage I–IIIC rectal adenocarcinoma from the Taiwan Cancer Registry [...] Read more.

Purpose: The survival effect of current smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with rectal adenocarcinoma undergoing curative resection. Methods: We recruited patients with clinical stage I–IIIC rectal adenocarcinoma from the Taiwan Cancer Registry Database who had received surgery. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into two groups by using propensity score matching based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD). Results: In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.25 (1.04–1.51). The aHRs (95% cis) of all-cause mortality for frequency of ≥1 hospitalizations for COPDAE or ≥2 hospitalizations within 1 year before diagnosis were 1.17 (1.05–1.51) and 1.48 (1.03–2.41) compared with no COPDAE in patients with rectal adenocarcinoma undergoing curative resection. Conclusion: In patients with rectal adenocarcinoma undergoing curative resection, being a current smoker with COPD (Group 1) was associated with worse survival outcomes than being a nonsmoker without COPD (Group 2). Being hospitalized at least once for COPDAE within 1 year before the diagnosis of rectal adenocarcinoma is an independent risk factor for poor overall survival in these patients, and a higher number of hospitalizations for COPDAE within 1 year before diagnosis was associated with poorer survival. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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14 pages, 3038 KiB

Open AccessArticle

Colorectal Cancer Patients Have Four Specific Bacterial Species in Oral and Gut Microbiota in Common—A Metagenomic Comparison with Healthy Subjects

by Yoshinori Uchino, Yuichi Goto, Yusuke Konishi, Kan Tanabe, Hiroko Toda, Masumi Wada, Yoshiaki Kita, Mahiro Beppu, Shinichiro Mori, Hiroshi Hijioka, Takao Otsuka, Shoji Natsugoe, Eiji Hara and Tsuyoshi Sugiura

Cancers 2021, 13(13), 3332; https://doi.org/10.3390/cancers13133332 - 2 Jul 2021

Cited by 25 | Viewed by 6795

Abstract

Oral microbiota is reportedly associated with gut microbiota and influences colorectal cancer (CRC) progression; however, the details remain unclear. This study aimed to evaluate the role of oral microbiota in CRC progression. Fifty-two patients with CRC and 51 healthy controls were included. Saliva [...] Read more.

Oral microbiota is reportedly associated with gut microbiota and influences colorectal cancer (CRC) progression; however, the details remain unclear. This study aimed to evaluate the role of oral microbiota in CRC progression. Fifty-two patients with CRC and 51 healthy controls were included. Saliva and stool samples were collected, and microbiota were evaluated using 16S rRNA analysis and next-generation sequencing. Comparative analysis was performed on both groups. Linear discriminant analysis effect size (LEfSe) revealed the presence of indigenous oral bacteria, such as Peptostreptococcus, Streptococcus, and Solobacterium spp., at a significantly higher relative abundance in saliva and stool samples of CRC patients compared with controls. Next, CRC patients were divided into early stage (Stage I, II; n = 26; 50%) and advanced stage (Stage III, IV; n = 26; 50%) disease. LEfSe revealed that S. moorei was present at a significantly higher relative abundance in the advanced-stage group compared with the early-stage group, again consistent for both saliva and stool samples. Among bacterial species with significantly higher relative abundance in CRC patients, P. stomatis, S. anginosus, S. koreensis, and S. moorei originated from the oral cavity, suggesting indigenous oral bacteria may have promoted initiation of CRC carcinogenesis. Furthermore, S. moorei may influence CRC progression. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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10 pages, 463 KiB

Open AccessArticle

Right and Left Colorectal Cancer: Differences in Post-Surgical-Care Outcomes and Survival in Elderly Patients

by Irene Mirón Fernández, Santiago Mera Velasco, Jesús Damián Turiño Luque, Iván González Poveda, Manuel Ruiz López and Julio Santoyo Santoyo

Cancers 2021, 13(11), 2647; https://doi.org/10.3390/cancers13112647 - 28 May 2021

Cited by 7 | Viewed by 2578

Abstract

(1) There is evidence of the embryological, anatomical, histological, genetic and immunological differences between right colon cancer (RCC) and left colon cancer (LCC). This research has the general objective of studying the differences in outcome between RCC and LCC. (2) A longitudinal analytical [...] Read more.

(1) There is evidence of the embryological, anatomical, histological, genetic and immunological differences between right colon cancer (RCC) and left colon cancer (LCC). This research has the general objective of studying the differences in outcome between RCC and LCC. (2) A longitudinal analytical study with prospective follow-up of the case–control type was conducted from 1 January 2010 to 31 December 2017 including 398 patients with 1:1 matching, depending on the location of the tumor. Inclusion criteria: programmed colectomies, 15 cm above the anal margin, adults and R0 surgery. (3) Precisely 6.8% of the exitus occurred in the first 6 months of the intervention. At 6 months, patients with LCC presented a mean survival of 7 months higher than RCC (p = 0.028). In the first stages, it can be observed that most of the exitus are for patients with RCC (stage I p = 0.021, stage II p = 0.014). In the last stages, the distribution of the deaths does not show differences between locations (stage III p = 0.683, stage IV p = 0.898). (4) The results show that RCC and LCC are significantly different in terms of evolution, progression, complications and survival. Patients with RCC have a worse prognosis, even in the early stages of the disease, due to more advanced N stages, larger tumor size, more frequently poorly differentiated tumors and a greater positivity of lymphovascular invasion than LCC. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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17 pages, 858 KiB

Open AccessArticle

Comprehensive Genomic Characterization of Fifteen Early-Onset Lynch-Like Syndrome Colorectal Cancers

by Mariano Golubicki, Marcos Díaz-Gay, Laia Bonjoch, Sebastià Franch-Expósito, Jenifer Muñoz, Miriam Cuatrecasas, Teresa Ocaña, Soledad Iseas, Guillermo Mendez, Marcela Carballido, Juan Robbio, Daniel Cisterna, Enrique Roca, Antoni Castells, Francesc Balaguer, Sergi Castellví-Bel and Marina Antelo

Cancers 2021, 13(6), 1259; https://doi.org/10.3390/cancers13061259 - 12 Mar 2021

Cited by 6 | Viewed by 3168

Abstract

Lynch-like syndrome (LLS) is an increasingly common clinical challenge with an underlying molecular basis mostly unknown. To shed light onto it, we focused on a very young LLS early-onset colorectal cancer (CRC) cohort (diagnosis ≤ 40 y.o.), performing germline and tumor whole-exome sequencing [...] Read more.

Lynch-like syndrome (LLS) is an increasingly common clinical challenge with an underlying molecular basis mostly unknown. To shed light onto it, we focused on a very young LLS early-onset colorectal cancer (CRC) cohort (diagnosis ≤ 40 y.o.), performing germline and tumor whole-exome sequencing (WES) of 15 patients, and additionally analyzing their corresponding tumor mutational burden (TMB) and mutational signatures. We identified four cases (27%) with double somatic putative variants in mismatch repair (MMR) core genes, as well as three additional cases (20%) with double MSH3 somatic alterations in tumors with unexplained MSH2/MSH6 loss of expression, and two cases (13%) with POLD1 potential biallelic alterations. Average TMB was significantly higher for LLS cases with double somatic alterations. Lastly, nine predicted deleterious variants in genes involved in the DNA repair functions and/or previously associated with CRC were found in nine probands, four of which also showed MMR biallelic somatic inactivation. In conclusion, we contribute new insights into LLS CRC, postulating MSH3 and POLD1 double somatic alterations as an underlying cause of a microsatellite instability (MSI) phenotype, proposing intrinsic biological differences between LLS with and without somatic alterations, and suggesting new predisposing candidate genes in this scenario. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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12 pages, 1071 KiB

Open AccessArticle

Long-Term Incidence of Advanced Colorectal Neoplasia in Patients with Serrated Polyposis Syndrome: Experience in a Single Academic Centre

by Daniel Rodríguez-Alcalde, Guillermo Castillo-López, Jorge López-Vicente, Luis Hernández, Mercedes Lumbreras-Cabrera and Diego Moreno-Sánchez

Cancers 2021, 13(5), 1066; https://doi.org/10.3390/cancers13051066 - 3 Mar 2021

Cited by 3 | Viewed by 2404

Abstract

Serrated polyposis syndrome (SPS) implies a slightly elevated risk of colorectal cancer (CRC) during endoscopic follow-up, but its natural course is still not well known. The main objective of this study was to describe the long-term risk of developing advanced neoplasia (AN) in [...] Read more.

Serrated polyposis syndrome (SPS) implies a slightly elevated risk of colorectal cancer (CRC) during endoscopic follow-up, but its natural course is still not well known. The main objective of this study was to describe the long-term risk of developing advanced neoplasia (AN) in these patients. Until October 2020, individuals who fulfilled 2010 WHO criteria I and/or III for SPS were retrospectively recruited. We selected those under endoscopic surveillance after resection of all lesions >3 mm in a high-quality colonoscopy. We excluded patients with total colectomy at diagnosis and those with any interval between colonoscopies >3.5 years. We defined AN as advanced serrated polyp (≥10 mm and/or with dysplasia), advanced adenoma, or CRC. In 109 patients, 342 colonoscopies were performed (median = 3, median interval = 1.8 years) during a median follow-up after colonic clearance of 5.0 years. Five-year cumulative incidences of AN were 21.6% globally, and 5.6%, 10.8%, and 50.8% in patients who fulfilled criterion I, III, and both, respectively (p < 0.001). No CRC was diagnosed and only 1 (0.9%) patient underwent surgery. In conclusion, cumulative incidences of AN could be lower than previously described, at least in patients who fulfil the 2010 WHO criterion III alone. Therefore, low-risk individuals might benefit from less stringent surveillance. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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13 pages, 1908 KiB

Open AccessEditor’s ChoiceArticle

Feedforward Artificial Neural Network-Based Colorectal Cancer Detection Using Hyperspectral Imaging: A Step towards Automatic Optical Biopsy

by Boris Jansen-Winkeln, Manuel Barberio, Claire Chalopin, Katrin Schierle, Michele Diana, Hannes Köhler, Ines Gockel and Marianne Maktabi

Cancers 2021, 13(5), 967; https://doi.org/10.3390/cancers13050967 - 25 Feb 2021

Cited by 57 | Viewed by 4270

Abstract

Currently, colorectal cancer (CRC) is mainly identified via a visual assessment during colonoscopy, increasingly used artificial intelligence algorithms, or surgery. Subsequently, CRC is confirmed through a histopathological examination by a pathologist. Hyperspectral imaging (HSI), a non-invasive optical imaging technology, has shown promising results [...] Read more.

Currently, colorectal cancer (CRC) is mainly identified via a visual assessment during colonoscopy, increasingly used artificial intelligence algorithms, or surgery. Subsequently, CRC is confirmed through a histopathological examination by a pathologist. Hyperspectral imaging (HSI), a non-invasive optical imaging technology, has shown promising results in the medical field. In the current study, we combined HSI with several artificial intelligence algorithms to discriminate CRC. Between July 2019 and May 2020, 54 consecutive patients undergoing colorectal resections for CRC were included. The tumor was imaged from the mucosal side with a hyperspectral camera. The image annotations were classified into three groups (cancer, CA; adenomatous margin around the central tumor, AD; and healthy mucosa, HM). Classification and visualization were performed based on a four-layer perceptron neural network. Based on a neural network, the classification of CA or AD resulted in a sensitivity of 86% and a specificity of 95%, by means of leave-one-patient-out cross-validation. Additionally, significant differences in terms of perfusion parameters (e.g., oxygen saturation) related to tumor staging and neoadjuvant therapy were observed. Hyperspectral imaging combined with automatic classification can be used to differentiate between CRC and healthy mucosa. Additionally, the biological changes induced by chemotherapy to the tissue are detectable with HSI. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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20 pages, 2697 KiB

Open AccessArticle

Germline and Somatic Whole-Exome Sequencing Identifies New Candidate Genes Involved in Familial Predisposition to Serrated Polyposis Syndrome

by Yasmin Soares de Lima, Coral Arnau-Collell, Marcos Díaz-Gay, Laia Bonjoch, Sebastià Franch-Expósito, Jenifer Muñoz, Leticia Moreira, Teresa Ocaña, Miriam Cuatrecasas, Cristina Herrera-Pariente, Sabela Carballal, Lorena Moreno, Aránzazu Díaz de Bustamante, Antoni Castells, Luis Bujanda, Joaquín Cubiella, Daniel Rodríguez-Alcalde, Francesc Balaguer and Sergi Castellví-Bel

Cancers 2021, 13(4), 929; https://doi.org/10.3390/cancers13040929 - 23 Feb 2021

Cited by 15 | Viewed by 4633

Abstract

The serrated polyposis syndrome (SPS) is the most common and yet underdiagnosed colorectal polyposis syndrome. It is characterized by multiple and/or large colonic serrated polyps and a higher associated risk for colorectal cancer (CRC). The main objective of this study was to identify [...] Read more.

The serrated polyposis syndrome (SPS) is the most common and yet underdiagnosed colorectal polyposis syndrome. It is characterized by multiple and/or large colonic serrated polyps and a higher associated risk for colorectal cancer (CRC). The main objective of this study was to identify new candidate genes involved in the germline predisposition to SPS/CRC. Thirty-nine SPS patients from 16 families (≥2 patients per family) were recruited without alterations in well-known hereditary CRC genes, and germline and somatic whole-exome sequencing were performed. Germline rare variants with plausible pathogenicity, located in genes involved in cancer development, senescence and epigenetic regulation were selected. Somatic mutational profiling and signature analysis was pursued in one sample per family, when possible. After data filtering, ANXA10, ASXL1, CFTR, DOT1L, HIC1, INO80, KLF3, MCM3AP, MCM8, PDLIM2, POLD1, TP53BP1, WNK2 and WRN were highlighted as the more promising candidate genes for SPS germline predisposition with potentially pathogenic variants shared within families. Somatic analysis characterized mutational profiles in advanced serrated polyps/tumors, revealing a high proportion of hypermutated samples, with a prevalence of clock-like mutational signatures in most samples and the presence of DNA mismatch repair-defective signatures in some cases. In conclusion, we identified new candidate genes to be involved in familial SPS. Further functional studies and replication in additional cohorts are required to confirm the selected candidates. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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12 pages, 1294 KiB

Open AccessArticle

Delayed Surgery after Neoadjuvant Treatment for Rectal Cancer Does Not Lead to Impaired Quality of Life, Worry for Cancer, or Regret

by Vincent Maurice Meyer, Richtje R Meuzelaar, Yvonne Schoenaker, Jan-Willem de Groot, Edwin de Boer, Onno Reerink, Wouter de Vos tot Nederveen Cappel, Geerard L Beets and Henderik L van Westreenen

Cancers 2021, 13(4), 742; https://doi.org/10.3390/cancers13040742 - 11 Feb 2021

Cited by 7 | Viewed by 2433

Abstract

Non operative management of complete clinical responders after neoadjuvant treatment for rectal cancer enjoys an increasing popularity because of the increased functional outcome results. Even a near complete response can evolve in a cCR, and therefore further delaying response assessment is accepted. However, [...] Read more.

Non operative management of complete clinical responders after neoadjuvant treatment for rectal cancer enjoys an increasing popularity because of the increased functional outcome results. Even a near complete response can evolve in a cCR, and therefore further delaying response assessment is accepted. However, up to 40% of patients will develop a regrowth and will eventually require delayed surgery. It is presently unknown if and to what extent quality of life of these patients is affected, compared to patients who undergo immediate surgery. Between January 2015-May 2020, 200 patients were treated with neoadjuvant therapy of whom 94 received TME surgery. Fifty-one (59%) of 87 alive patients returned the questionnaires: 33 patients who underwent immediate and 18 patients who underwent delayed surgery. Quality of life was measured through the QLQ-C30, QLQ-CR29, and Cancer Worry Scale questionnaires. Regret to participate in repeated response assessment protocol was assessed through the Decision Regret Scale. Exploratory factor analysis (EFA) and a ‘known groups comparison’ was performed to assess QLQ questionnaires validity in this sample. Higher mean physical function scores (89.2 vs. 77.6, p = 0.03) were observed in the immediate surgery group, which lost significance after correction for operation type (p = 0.25). Arousal for men was higher in the delayed surgery group (20.0 vs. 57.1, p = 0.02). There were no differences between surgical groups for the other questionnaire items. Worry for cancer was lower in the delayed surgery group (10.8 vs. 14.0, p = 0.21). Regret was very low (12–16%). EFA reproduced most QLQ C-30 and CR29 subscales with good internal consistency. Quality of life is not impaired in patients undergoing delayed TME surgery after neoadjuvant treatment for rectal cancer. Moreover, there is very low regret and no increase in worry for cancer. Therefore, from a quality of life perspective, this study supports a repeated response assessment strategy after CRTx for rectal carcinoma to identify all complete responders. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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15 pages, 2311 KiB

Open AccessArticle

Histopathological Chromogranin A-Positivity Is Associated with Right-Sided Colorectal Cancers and Worse Prognosis

by Zoltan Herold, Magdolna Dank, Magdolna Herold, Peter Nagy, Klara Rosta and Aniko Somogyi

Cancers 2021, 13(1), 67; https://doi.org/10.3390/cancers13010067 - 29 Dec 2020

Cited by 7 | Viewed by 2637

Abstract

Background: Colorectal cancer (CRC) is known to be affected by paraneoplastic thrombocytosis and chromogranin A-positive neuroendocrine-cell differentiation (CgA⁺). Their combined effect has never been previously investigated. Methods: A prospective cohort pilot study of 42 CRC patients and 42 age- and sex-matched [...] Read more.

Background: Colorectal cancer (CRC) is known to be affected by paraneoplastic thrombocytosis and chromogranin A-positive neuroendocrine-cell differentiation (CgA⁺). Their combined effect has never been previously investigated. Methods: A prospective cohort pilot study of 42 CRC patients and 42 age- and sex-matched controls was carried out. Plasma interleukin-6, thrombopoietin, and serum chromogranin A and -B were measured; furthermore, tumor tissue was immunohistochemically stained for CgA⁺. Results: Twenty-seven and 15 patients were assigned to the chromogranin A-negative (CgA⁻) and CgA⁺ groups, respectively. Within the CgA⁺ group, right-sided tumors were more frequent (18.5% vs. 53.3%), no stage I cancer was found, and patients of this group were in worse general condition. Compared to control subjects, chromogranin A level was higher in the CgA⁺ group (p = 0.0086), thrombopoietin (p = 0.0040) and chromogranin B (p = 0.0070) in the CgA⁻ group, while interleukin-6 was high in both tumor groups (p ≤ 0.0090). Survival was significantly worse in the CgA⁺ group (hazard ratio: 5.73; p = 0.0378). Conclusions: Different thrombopoietin levels indicated distinct thrombocytosis types. Within the two CRC groups, serum levels of chromogranins changed in different directions suggesting two well-distinguishable pathophysiologies. Based on these observations we propose a new subtype of CRC, which can be characterized by chromogranin A-positive neuroendocrine-cell differentiation. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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19 pages, 829 KiB

Open AccessArticle

pT1 Colorectal Cancer Detected in a Colorectal Cancer Mass Screening Program: Treatment and Factors Associated with Residual and Extraluminal Disease

by Joaquín Cubiella, Antía González, Raquel Almazán, Elena Rodríguez-Camacho, Juana Fontenla Rodiles, Carmen Domínguez Ferreiro, Coral Tejido Sandoval, Cristina Sánchez Gómez, Natalia de Vicente Bielza, Isabel Peña-Rey Lorenzo and Raquel Zubizarreta

Cancers 2020, 12(9), 2530; https://doi.org/10.3390/cancers12092530 - 6 Sep 2020

Cited by 8 | Viewed by 3115

Abstract

The aim of this study is to describe the treatment of pT1 colorectal cancer (CRC) in a mass screening program, the surgery-related complications and the factors associated with residual disease after endoscopic resection and extraluminal disease after surgery. We included in this retrospective [...] Read more.

The aim of this study is to describe the treatment of pT1 colorectal cancer (CRC) in a mass screening program, the surgery-related complications and the factors associated with residual disease after endoscopic resection and extraluminal disease after surgery. We included in this retrospective analysis all the pT1 CRC detected in the Galician CRC screening program between May 2013 and June 2019. We determined which variables were independently associated with the outcomes of the study through a multivariable logistic regression analysis. We included 370–354 pT1 N0(X), 16 pT1N1- out of the 971 CRC detected; 277 (74.9%) were resected endoscopically and 162 (43.8%) were not referred to surgery. There were surgical complications in 30.7% and 16.3% of the patients during hospitalization and after discharge. Residual disease was detected in 12 (4.3%) after endoscopic resection and extraluminal disease in 18 (8.6%) patients after surgery. The variables independently associated with initial endoscopic resection were a pedunculated morphology (OR 33.1, 95% CI 4.3–254), a diameter ≥ 20 mm (OR 3.94, 95% CI 1.39–11.18) and a Site–Morphology–Size–Access score < 9 (OR 428, 95% CI 42–4263). The variables related with surgery rescue were a piecemeal resection (OR 4.48, 95% CI 1.48–13.6), an infiltrated/nonevaluable resection border (OR 7.44, 95% CI 2.12–26.0), a non-well-differentiated histology (OR 4.76, 95% CI 1.07–20.0), vascular infiltration (OR 8.24, 95% CI 2.72–25.0) and a Haggitt 4 infiltration of the submucosa (OR 5.68, 95% CI 2.62–12.3). Residual disease after endoscopic resection was associated with an infiltrated/nonevaluable resection border (OR 34.9, 95% CI 4.08–298), a non-well-differentiated histology (OR 6.67, 95% CI 1.05–50.0), and the vascular infiltration of the submucosa (OR 7.61, 95% CI 1.55–37.4). The variables related with extraluminal disease after surgical resection were no endoscopic resection (OR 4.34, 95% CI 1.26–14.28), a non-well-differentiated histology (OR 4.35, 95% CI 1.39–14.29) and the lymphatic infiltration of the submucosa (OR 4.8, 95% CI 1.32–17.8). In a CRC screening program, although most of pT1 CRC are candidates for endoscopic treatment, surgery is a safe procedure. We have defined some easy to evaluate variables that can be used in the decision-making process. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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14 pages, 807 KiB

Open AccessArticle

Colorectal Cancer Survival in 50- to 69-Year-Olds after Introducing the Faecal Immunochemical Test

by María Angeles Gutierrez-Stampa, Vanessa Aguilar, Cristina Sarasqueta, Joaquín Cubiella, Isabel Portillo and Luis Bujanda

Cancers 2020, 12(9), 2412; https://doi.org/10.3390/cancers12092412 - 25 Aug 2020

Cited by 9 | Viewed by 2355

Abstract

Population screening has improved early diagnosis of colorectal cancer (CRC). Nonetheless, most cases are diagnosed in symptomatic patients. Faecal immunochemical testing has been recommended for assessing patients with lower gastrointestinal symptoms, but whether it improves patient survival is unknown. Our objective was to [...] Read more.

Population screening has improved early diagnosis of colorectal cancer (CRC). Nonetheless, most cases are diagnosed in symptomatic patients. Faecal immunochemical testing has been recommended for assessing patients with lower gastrointestinal symptoms, but whether it improves patient survival is unknown. Our objective was to compare CRC survival in 50- to 69-year-olds between asymptomatic screen-detected patients and symptomatic patients by route to diagnosis. Methods: We identified all cases of CRC diagnosed in 50-to 69-year-olds between 2009 and 2016, in Donostialdea (Gipuzkoa, Spain). Three groups were created: 1-screen-detected CRC; 2-CRC detected in symptomatic patients after a positive faecal immunochemical test(FIT); and 3-CRC detected in symptomatic patients without a FIT or after a negative result. We analysed survival using the Kaplan-Meier method and log-rank tests. Results: Of 930 patients diagnosed with CRC, 433 cases were detected through screening and 497 in symptomatic patients, 7.9% after a positive FIT and 45.5% by other means. The 3-year CRC survival was significantly lower in group 3 (69.5%) than groups 1 (93%; p = 0.007) or 2 (87.5%; p = 0.02). The risk of death was lower in groups 1 (HR 0.42, 95% CI 0.30–0.58) and 2 (HR 0.51; 95% CI 0.29–0.87). Conclusion: Half of CRC cases in 50- to 69-year-olds are diagnosed outside screening. Use of the FIT as a diagnostic strategy in symptomatic patients may improve survival. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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Review

Jump to: Research

38 pages, 1793 KiB

Open AccessReview

Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer

by Viktoriia Cherkasova, Olga Kovalchuk and Igor Kovalchuk

Cancers 2021, 13(17), 4353; https://doi.org/10.3390/cancers13174353 - 28 Aug 2021

Cited by 9 | Viewed by 4578

Abstract

Despite the multiple preventive measures and treatment options, colorectal cancer holds a significant place in the world’s disease and mortality rates. The development of novel therapy is in critical need, and based on recent experimental data, cannabinoids could become excellent candidates. This review [...] Read more.

Despite the multiple preventive measures and treatment options, colorectal cancer holds a significant place in the world’s disease and mortality rates. The development of novel therapy is in critical need, and based on recent experimental data, cannabinoids could become excellent candidates. This review covered known experimental studies regarding the effects of cannabinoids on intestinal inflammation and colorectal cancer. In our opinion, because colorectal cancer is a heterogeneous disease with different genomic landscapes, the choice of cannabinoids for tumor prevention and treatment depends on the type of the disease, its etiology, driver mutations, and the expression levels of cannabinoid receptors. In this review, we describe the molecular changes of the endocannabinoid system in the pathologies of the large intestine, focusing on inflammation and cancer. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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22 pages, 1407 KiB

Open AccessReview

Osteopontin as a Regulator of Colorectal Cancer Progression and Its Clinical Applications

by Katyana Amilca-Seba, Michèle Sabbah, Annette K. Larsen and Jérôme A. Denis

Cancers 2021, 13(15), 3793; https://doi.org/10.3390/cancers13153793 - 28 Jul 2021

Cited by 22 | Viewed by 3875

Abstract

A high expression of the phosphoprotein osteopontin (OPN) has been associated with cancer progression in several tumor types, including breast cancer, hepatocarcinoma, ovarian cancer, and colorectal cancer (CRC). Interestingly, OPN is overexpressed in CRC and is associated with a poor prognosis linked to [...] Read more.

A high expression of the phosphoprotein osteopontin (OPN) has been associated with cancer progression in several tumor types, including breast cancer, hepatocarcinoma, ovarian cancer, and colorectal cancer (CRC). Interestingly, OPN is overexpressed in CRC and is associated with a poor prognosis linked to invasion and metastasis. Here, we review the regulation and functions of OPN with an emphasis on CRC. We examine how epigenetic and genetic regulators interact with the key signaling pathways involved in this disease. Then, we describe the role of OPN in cancer progression, including proliferation, survival, migration, invasion, and angiogenesis. Furthermore, we outline the interest of using OPN as a clinical biomarker, and discuss if and how osteopontin can be implemented as a routine assay in clinical laboratories for monitoring CRC patients. Finally, we discuss the use of OPN an attractive, but challenging, therapeutic target. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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13 pages, 5242 KiB

Open AccessReview

Subcellular Expression of Maspin in Colorectal Cancer: Friend or Foe

by Simona Gurzu and Ioan Jung

Cancers 2021, 13(3), 366; https://doi.org/10.3390/cancers13030366 - 20 Jan 2021

Cited by 23 | Viewed by 2721

Abstract

In this review the authors aimed to emphasize the practical value of nuclear expression of the mammary serine protease inhibitor (maspin), also known as serpin B5 protein, in colorectal carcinoma (CRC), from pre-malignant disorders to carcinogenesis and metastasis. As the role of maspin [...] Read more.

In this review the authors aimed to emphasize the practical value of nuclear expression of the mammary serine protease inhibitor (maspin), also known as serpin B5 protein, in colorectal carcinoma (CRC), from pre-malignant disorders to carcinogenesis and metastasis. As the role of maspin is controversial and not yet understood, the present update highlights the latest data revealed by literature which were filtrated through the daily experience of the authors, which was gained at microscopic examination of maspin expression in CRCs and other tumors for daily diagnosis. Data regarding the subcellular localization of maspin, in correlation with the microsatellite status, grade of tumor dedifferentiation, and epithelial-mesenchymal transition (EMT) phenomenon of the tumor buds were presented with details. An original observation refers to the maspin capacity to mark the tumor cells which are “at the point of budding” that were previously considered as having “hybrid EMT phenotype”. It refers to the transitional status of tumor cell that is between “epithelial status” and “mesenchymal status”. The second original hypothesis highlights the possible role of maspin in dysregulating the intestinal microbiota, in patients with idiopathic inflammatory bowel diseases (IBD) and inducing IBD-related CRC. The dynamic process of budding and EMT of tumor buds, possible mediated by maspin, needs further investigation and validation in many human CRC samples. The histological and molecular data reveal that synthesis of maspin-based therapeutics might represent a novel individualized therapeutic strategy for patients with CRC. Full article

(This article belongs to the Special Issue New Insights into Colorectal Cancer)

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