Special Issue "Chronic Intestinal Inflammation and Cancers"

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Epidemiology and Prevention".

Deadline for manuscript submissions: 31 August 2023 | Viewed by 4767

Special Issue Editors

Dr. Livia Biancone
E-Mail Website
Guest Editor
GI Unit, Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Interests: inflammatory bowel disease; IBD-associated cancer
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. David Laharie
E-Mail Website
Guest Editor
CHU de Bordeaux, Centre Médico-chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, 33000 Bordeaux, France
Interests: inflammatory bowel disease

Special Issue Information

Dear Colleagues,

It is well known that inflammation-associated colorectal cancer shows different clinicopathological characteristics compared to sporadic colorectal cancer. These include: a younger age at diagnosis, a worse outcome, and a different molecular pathway (which more frequently includes mutation on the TP53 gene). Moreover, in inflammatory bowel disease,  higher frequencies of signet rings and mucinous adenocarcinomas have been suggested. Furthermore, when focusing on precancerous chronic inflammation-associated lesions, it has been shown that these are more frequently non-polypoid in patients with inflammatory bowel diseases and are thus more difficult to detect during screening colonoscopies. Chromoendoscopy, able to enhance polyp detection, currently represents the gold standard technique for colorectal cancer screening in these patients, thus allowing a better characterization of the lesions. A wider application of advanced endoscopic resection techniques is therefore reached by using this technique.

Chronic inflammation leading to small bowel cancer has also been described in the development of cancers complicating coeliac disease and Crohn’s disease. Different molecular pathways and risk factors have been described in these conditions.

The role of immunomodulators in determining the risk of cancer in patients with a  prior history of cancer is still debated, particularly in inflammatory bowel disease, in patients often requiring conventional immunosuppressives, or biologic therapies for the underlying chronic intestinal inflammation.

We are pleased to invite you to contribute to the Special Issue “Chronic intestinal inflammation and cancers”.

The aim of the present Special Issue is to summarize current evidences and possibly to increase knowledge in the field of intestinal cancers associated with chronic inflammation. We aim to report and to investigate evidences regarding inflammation-associated intestinal cancers from its precursors to patient’s outcome. For this purpose, we will collect at least 10 articles. The Special Issue may be printed in book form if this number is reached.

This Special Issue aims to deepen knowledge in the field of intestinal cancers associated with chronic inflammation.

Accepted article types are original articles and reviews.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Intestinal cancers associated with chronic inflammation and outcome;
  • Intestinal cancer associated with chronic inflammation: molecular pathway;
  • Colorectal cancer associated with chronic inflammation and cancer precursors: diagnosis and management;
  • Immunomodulators in patients with a prior history of cancer;
  • Intestinal cancers associated with chronic inflammation: epidemiology and histological characterization;
  • Colorectal cancer and small bowel cancer in Inflammatory Bowel Disease;
  • Small intestinal cancer and coeliac disease.

We look forward to receiving your contributions.

Dr. Livia Biancone
Prof. Dr. David Laharie
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • colorectal cancer
  • chronic inflammation
  • inflammatory bowel disease
  • inflammation-associated dysplasia
  • outcomes
  • cancer molecular pathways

Published Papers (6 papers)

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Research

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Article
Pathways Related to Colon Inflammation Are Associated with Colorectal Carcinoma: A Transcriptome- and Methylome-Wide Study
Cancers 2023, 15(11), 2921; https://doi.org/10.3390/cancers15112921 - 26 May 2023
Viewed by 289
Abstract
The association of chronic inflammation with colorectal carcinoma (CRC) development is well known in ulcerative colitis (UC). However, the role of inflammatory changes in sporadic CRC pathogenesis is less widely appreciated. In this study, in the first step using RNA-seq, we identified gene-pathway-level [...] Read more.
The association of chronic inflammation with colorectal carcinoma (CRC) development is well known in ulcerative colitis (UC). However, the role of inflammatory changes in sporadic CRC pathogenesis is less widely appreciated. In this study, in the first step using RNA-seq, we identified gene-pathway-level changes in UC-associated CRC (UC CRC, n = 10) and used the changes as a proxy for inflammation in human colon to ask if there were associations of inflammatory pathway dysregulations in sporadic CRC pathogenesis (n = 8). We found down-regulations of several inflammation-related metabolic pathways (nitrogen metabolism, sulfur metabolism) and other pathways (bile secretion, fatty acid degradation) in sporadic CRC. Non-inflammation-related changes included up-regulation of the proteasome pathway. In the next step, from a larger number of paired samples from sporadic CRC patients (n = 71) from a geographically and ethnically different population and using a different platform (microarray), we asked if the inflammation-CRC association could be replicated. The associations were significant even after stratification by sex, tumor stage, grade, MSI status, and KRAS mutation status. Our findings have important implications to widen our understanding of inflammatory pathogenesis of sporadic CRC. Furthermore, targeting of several of these dysregulated pathways could provide the basis for improved therapies for CRC. Full article
(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)
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Article
Preoperative Predictors of Neoplasia in Patients Undergoing Small Bowel Resection for Complicated Crohn’s Disease: A Multicentre Case-Control Study
Cancers 2023, 15(7), 2004; https://doi.org/10.3390/cancers15072004 - 28 Mar 2023
Viewed by 470
Abstract
Crohn’s disease (CD) is associated with an increased risk of small bowel neoplasia (SBN). We aimed to assess preoperative predictors of SBN in CD patients. We conducted a retrospective case-control study including CD patients who underwent surgery: cases were diagnosed with SBN on [...] Read more.
Crohn’s disease (CD) is associated with an increased risk of small bowel neoplasia (SBN). We aimed to assess preoperative predictors of SBN in CD patients. We conducted a retrospective case-control study including CD patients who underwent surgery: cases were diagnosed with SBN on histopathological analysis and controls had no neoplasia. Preoperative cross-sectional imaging was reviewed by a panel of blinded expert radiologists. Fifty cases were matched to one hundred and fifty consecutive controls. In multivariable analysis, predictors of SBN were age ≥ 50 years (OR = 28, 95% CI = 5.05–206), median CD duration ≥ 17.5 years (OR = 4.25, 95% CI = 1.33–14.3), and surgery for stricture (OR = 5.84, 95% CI = 1.27–35.4). The predictors of small bowel adenocarcinoma were age ≥ 50 years (OR = 5.14, 95% CI = 2.12–12.7), CD duration ≥ 15 years (OR = 5.65, 95% CI = 2.33–14.3), and digestive wall thickening > 8 mm (OR = 3.79, 95% CI = 1.45–11.3). A predictive score based on the aforementioned factors was constructed. Almost 73.7% of patients with a high score had SBA. Old age, long small bowel CD duration, and stricture predicted the presence of SBN, particularly adenocarcinoma when patients have digestive wall thickening > 8 mm on preoperative imaging. Full article
(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)
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Article
Clinical Presentation, Management, and Evolution of Lymphomas in Patients with Inflammatory Bowel Disease: An ENEIDA Registry Study
Cancers 2023, 15(3), 750; https://doi.org/10.3390/cancers15030750 - 25 Jan 2023
Cited by 1 | Viewed by 934
Abstract
An increased risk of lymphoma has been described in patients with inflammatory bowel disease (IBD). The aims of our study were to determine the clinical presentation, the previous exposure to immunosuppressive and biologic therapies, and the evolution of lymphomas in patients with IBD. [...] Read more.
An increased risk of lymphoma has been described in patients with inflammatory bowel disease (IBD). The aims of our study were to determine the clinical presentation, the previous exposure to immunosuppressive and biologic therapies, and the evolution of lymphomas in patients with IBD. IBD patients with diagnosis of lymphoma from October 2006 to June 2021 were identified from the prospectively maintained ENEIDA registry of GETECCU. We identified 52 patients (2.4 cases of lymphoma/1000 patients with IBD; 95% CI 1.8–3.1). Thirty-five were men (67%), 52% had ulcerative colitis, 60% received thiopurines, and 38% an anti-TNF drug before lymphoma diagnosis. Age at lymphoma was lower in those patients treated with thiopurines (53 ± 17 years old) and anti-TNF drugs (47 ± 17) than in those patients not treated with these drugs (63 ± 12; p < 0.05). Five cases had relapse of lymphoma (1.7 cases/100 patient-years). Nine patients (17%) died after 19 months (IQR 0–48 months). Relapse and mortality were not related with the type of IBD or lymphoma, nor with thiopurines or biologic therapies. In conclusion, most IBD patients had been treated with thiopurines and/or anti-TNF agents before lymphoma diagnosis, and these patients were younger at diagnosis of lymphoma than those not treated with these drugs. Relapse and mortality of lymphoma were not related with these therapies. Full article
(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)
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Article
Endoscopic Predictors of Neoplastic Lesions in Inflammatory Bowel Diseases Patients Undergoing Chromoendoscopy
Cancers 2022, 14(18), 4426; https://doi.org/10.3390/cancers14184426 - 12 Sep 2022
Viewed by 754
Abstract
Dye-based chromoendoscopy (DCE) with targeted biopsies is recommended for surveillance of patients with long-standing inflammatory bowel diseases (IBD), but endoscopic features that predict dysplasia are not fully clarified. We here aimed at identifying predictive factors of dysplastic/neoplastic lesions in IBD patients undergoing DCE. [...] Read more.
Dye-based chromoendoscopy (DCE) with targeted biopsies is recommended for surveillance of patients with long-standing inflammatory bowel diseases (IBD), but endoscopic features that predict dysplasia are not fully clarified. We here aimed at identifying predictive factors of dysplastic/neoplastic lesions in IBD patients undergoing DCE. Two-hundred-and-nineteen patients were consecutively and prospectively enrolled from October 2019 to March 2022. One-hundred-and-forty-five out of 219 patients underwent DCE, and 148 lesions were detected in 79/145 (54%) patients. Thirty-nine lesions (26%) were dysplastic and one of them contained a CRC. Among these lesions, 7 (17.9%) had Kudo pit pattern I-II and 32 (82.1%) had a neoplastic pit pattern (Kudo III-IV). Multivariate analysis showed that neoplastic lesions Kudo III-IV (OR: 5.8, 95% CI: 2.3–14.6; p = 0.0002), lesion’s size (OR 1.16, 95% CI: 1.06–1.26; p = 0.0009), and polypoid lesions according to Paris Classification (OR 7.4, 95% CI: 2.7–20.2; p = 0.0001) were independent predictors of dysplasia. A cut-off of lesion’s size > 7 mm was identified as the best predictor of dysplasia. Among such features, Kudo pit pattern III-IV had the highest sensitivity and specificity to predict dysplasia (79% and 80%, respectively). Lesions with all three endoscopic features had a sensitivity of 90% and specificity of 100% to predict dysplasia. In contrast, non-polypoid lesions were inversely associated with dysplasia (OR 0.13, 95% CI: 0.05–0.36; p = 0.0001). These findings indicate that, in IBD patients, DCE-evidenced polypoid lesions with Kudo pit pattern III-IV and size > 7 mm are frequently dysplastic. Full article
(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)
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Review

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Review
Inflammation-Driven Colorectal Cancer Associated with Colitis: From Pathogenesis to Changing Therapy
Cancers 2023, 15(8), 2389; https://doi.org/10.3390/cancers15082389 - 20 Apr 2023
Viewed by 1008
Abstract
Patients affected by inflammatory bowel disease (IBD) have a two-fold higher risk of developing colorectal cancer (CRC) than the general population. IBD-related CRC follows a different genetic and molecular pathogenic pathway than sporadic CRC and can be considered a complication of chronic intestinal [...] Read more.
Patients affected by inflammatory bowel disease (IBD) have a two-fold higher risk of developing colorectal cancer (CRC) than the general population. IBD-related CRC follows a different genetic and molecular pathogenic pathway than sporadic CRC and can be considered a complication of chronic intestinal inflammation. Since inflammation is recognised as an independent risk factor for neoplastic progression, clinicians strive to modulate and control disease, often using potent therapy agents to achieve mucosal healing and decrease the risk of colorectal cancer in IBD patients. Improved therapeutic control of inflammation, combined with endoscopic advances and early detection of pre-cancerous lesions through surveillance programs, explains the lower incidence rate of IBD-related CRC. In addition, current research is increasingly focused on translating emerging and advanced knowledge in microbiome and metagenomics into personalised, early, and non-invasive CRC screening tools that guide organ-sparing therapy in IBD patients. This review aims to summarise the existing literature on IBD-associated CRC, focusing on new insights into the alteration of the intestinal barrier and the interactions with the gut microbiome as the initial promoter. In addition, the role of OMIC techniques for precision medicine and the impact of the available IBD therapeutic armamentarium on the evolution to CRC will be discussed. Full article
(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)
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Review
Management of Inflammatory Bowel Disease in Patients with Current or Past Malignancy
Cancers 2023, 15(4), 1083; https://doi.org/10.3390/cancers15041083 - 08 Feb 2023
Viewed by 849
Abstract
Immunomodulators, conventional immunosuppressants, and/or biologics are used more often, earlier, and longer than before in patients with inflammatory bowel disease (IBD). Along with this, the lifetime risk for cancer is estimated to be 33% in the general population in Europe. Thus, physicians face [...] Read more.
Immunomodulators, conventional immunosuppressants, and/or biologics are used more often, earlier, and longer than before in patients with inflammatory bowel disease (IBD). Along with this, the lifetime risk for cancer is estimated to be 33% in the general population in Europe. Thus, physicians face therapeutic choices in an increasing number of IBD patients with current or past malignancy. Few data are available so far for managing this IBD subpopulation and this clinical concern still remains a critical situation for four reasons: (i) risk of reactivation of dormant micrometastasis with immunomodulators is of major concern, (ii) there is a knowledge gap about the safety of the most recent molecules, (iii) current guidelines do not recommend the use of immunomodulators within 2–5 years after a diagnosis of cancer, (iv) patients with previous cancers are excluded from clinical trials. There is a lack of scientific evidence supporting the non-use of immunomodulators in IBD patients with previous cancer. Indeed, accumulative data suggest that the risk for recurrent and new cancer in patients with a history of cancer is not increased by thiopurines and anti-TNF agents. Most recently, cohort studies have found no differences in incident cancer rates in IBD patients with prior malignancy treated with vedolizumab or ustekinumab compared to those treated with anti-TNF agents. Therefore, decisions should be shared by the oncologist and the patient, considering the natural history of cancer, the time elapsed since cancer diagnosis, and IBD prognosis. Full article
(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)
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