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Chronic Intestinal Inflammation and Cancers

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

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 38804

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Special Issue Editors

Prof. Dr. Livia Biancone

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Guest Editor

1. Gastroenterology Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy
2. Department of Medical Science, University “Tor Vergata” of Rome, 00133 Roma, Italy
Interests: inflammatory bowel disease; IBD-associated cancer.
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. David Laharie

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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 Issues, Collections and Topics in MDPI journals

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 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 2900 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

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Published Papers (13 papers)

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Research

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10 pages, 263 KiB

Open AccessArticle

Treat-to-Target and Regular Surveillance of Inflammatory Bowel Disease Are Associated with Low Incidence and Early-Stage Detection of Malignancies: A Retrospective Cohort Study

by Tommaso Lorenzo Parigi, Mariangela Allocca, Federica Furfaro, Ferdinando D’Amico, Alessandra Zilli, Arianna Dal Buono, Roberto Gabbiadini, Stefanos Bonovas, Alessandro Armuzzi, Silvio Danese and Gionata Fiorino

Cancers 2023, 15(24), 5754; https://doi.org/10.3390/cancers15245754 - 8 Dec 2023

Cited by 2 | Viewed by 1652

Abstract

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), increase the risk of malignancies, particularly colorectal cancer (CRC). We aimed to assess the incidence of malignancies in IBD patients managed using a treat-to-target approach and recommended surveillance. We retrospectively searched the electronic databases of two tertiary IBD centers in Milan from 2010 to 2019 for new diagnoses of malignancy in patients with pre-existing IBD. A total of 5239 patients with a follow-up of 19,820 years were included. In total, 71 malignancies were diagnosed in 70 patients (38 CD, 32 UC) with a mean age of 52.9 years, of whom 64% were former or active smokers. The annual incidence of all malignancies was 358 per 100,000 patient years (95% CI 275–444), and the standardized incidence rate (SIR) was 0.93 (95% CI 0.73–1.16). Gastrointestinal cancers were the most frequent (n = 17, 23.9%), in particular, CRC (n = 9), with an incidence of 45 per 100,000 (95% CI 15–74) and an SIR of 1.18 (95% CI 0.54–2.09). CRC occurred mainly in UC patients (6/8), while small bowel cancer was seen in CD patients (5/9). Melanoma and breast cancer (n = 8 each) were the most common non-GI cancers. No significant difference in incidence was found between CD or UC. Death occurred in nine patients (11%) and was due to cancer in eight of these cases, two of which were IBD-related. Most malignancies included in the surveillance were diagnosed at early (I–II) stages (20 vs. 4, p < 0.05). In patients with IBD, treat-to-target and strict surveillance were associated with a low incidence of cancer, similar to that of the general population, and the detection of malignancies at an early stage. Full article

(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)

14 pages, 1173 KiB

Open AccessArticle

Mucinous and Signet-Ring Cell Colonic Adenocarcinoma in Inflammatory Bowel Disease: A Case–Control Study

by Benedetto Neri, Roberto Mancone, Luca Savino, Sara Schiavone, Vincenzo Formica, Francesca Pizzi, Silvia Salvatori, Michelangela Mossa, Stefano Migliozzi, Mariasofia Fiorillo, Cristina Morelli, Alessandro Moscardelli, Elisabetta Lolli, Emma Calabrese, Giuseppe S. Sica, Giovanni Monteleone and Livia Biancone

Cancers 2023, 15(15), 3803; https://doi.org/10.3390/cancers15153803 - 26 Jul 2023

Cited by 8 | Viewed by 1856

Abstract

A higher frequency of mucinous and signet-ring cell colonic adenocarcinoma has been reported in inflammatory bowel disease (IBD). The primary aim was to investigate the frequency of mucinous and signet-ring cell colorectal adenocarcinoma in patients with IBD (Cases) versus age-matched non-IBD Controls. The secondary aims were to compare the characteristics of these two histotypes of colorectal cancer (CRC) in IBD patients vs. Controls and to search for specific risk factors in IBD. In a case–control study, all IBD patients with CRC diagnosed from 2000 to 2022 were enrolled and matched for age (1:2) with non-IBD Controls with CRC. The study population included 120 CRC patients (40 IBD, 80 Controls). In IBD, CRC included standard adenocarcinoma in 23 (57.5%) patients mucinous/signet-ring cell adenocarcinoma in 17 (42.5%) patients. The proportion of mucinous/signet-ring cell adenocarcinoma was higher in IBD than in Controls (17 [42.5%] vs. 18 [22.5%]; p = 0.03). In rectal CRC, the proportion of mucinous/signet-ring cell adenocarcinoma was higher than standard adenocarcinoma in IBD (8 [47.1%] vs. 4 [17.4%]; p = 0.04) but not in Controls (4 [22.2%] vs. 20 [32.2%]; p = 0.59). In rectal CRC, the proportion of these two histotypes was higher in Cases than in Controls (8/12 [66.6%] vs. 4/24 [16.6%]; p = 0.008), with no risk factors identified in IBD. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in age-matched non-IBD Controls. In IBD, these two CRC histotypes were more frequent in the rectum. Full article

(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)

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21 pages, 9214 KiB

Open AccessArticle

by Muhammad G. Kibriya, Farzana Jasmine, Joel Pekow, Aaron Munoz, Christopher Weber, Maruf Raza, Mohammed Kamal, Habibul Ahsan and Marc Bissonnette

Cancers 2023, 15(11), 2921; https://doi.org/10.3390/cancers15112921 - 26 May 2023

Cited by 2 | Viewed by 2518

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 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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16 pages, 1020 KiB

Open AccessArticle

Preoperative Predictors of Neoplasia in Patients Undergoing Small Bowel Resection for Complicated Crohn’s Disease: A Multicentre Case-Control Study

by Capucine Chappe, Cecile Salut, Aurelien Amiot, Delphine Gaye, Nora Frulio, Bruno Lapuyade, Lucine Vuitton, Romain Altwegg, Cyrielle Gilletta, Mathurin Fumery, Guillaume Bouguen, Melanie Serrero, Maria Nachury, Nicolas de Suray, Ludovic Caillo, Mireille Simon, David Laharie, Pauline Rivière and Florian Poullenot

Cancers 2023, 15(7), 2004; https://doi.org/10.3390/cancers15072004 - 28 Mar 2023

Cited by 2 | Viewed by 1527

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 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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10 pages, 571 KiB

Open AccessArticle

Clinical Presentation, Management, and Evolution of Lymphomas in Patients with Inflammatory Bowel Disease: An ENEIDA Registry Study

by Ivan Guerra, Luis Bujanda, Miriam Mañosa, Isabel Pérez-Martínez, María José Casanova, Luisa de la Peña, Marina de Benito, Montserrat Rivero, Pilar Varela, Lorena Bernal, Ana Carolina Franco, Yolanda Ber, Marta Piqueras, Carlos Tardillo, Ángel Ponferrada, Sonsoles Olivares, Alfredo J. Lucendo, Pau Gilabert, Mónica Sierra Ausín, María Bellart, Amaia Herrarte, Margalida Calafat, Ruth de Francisco, Javier P. Gisbert, Jordi Guardiola, Eugeni Domènech and Fernando Bermejo Show full author list Hide full author list

Cancers 2023, 15(3), 750; https://doi.org/10.3390/cancers15030750 - 25 Jan 2023

Cited by 3 | Viewed by 2739

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. 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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12 pages, 1074 KiB

Open AccessArticle

Endoscopic Predictors of Neoplastic Lesions in Inflammatory Bowel Diseases Patients Undergoing Chromoendoscopy

by Elisabetta Lolli, Elena De Cristofaro, Irene Marafini, Edoardo Troncone, Benedetto Neri, Francesca Zorzi, Livia Biancone, Emma Calabrese and Giovanni Monteleone

Cancers 2022, 14(18), 4426; https://doi.org/10.3390/cancers14184426 - 12 Sep 2022

Cited by 2 | Viewed by 1639

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. 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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24 pages, 2035 KiB

Open AccessReview

Inflammation-Associated Stem Cells in Gastrointestinal Cancers: Their Utility as Prognostic Biomarkers and Therapeutic Targets

by Beauty Kumari, Aniket Tiwari, Sakshi Meena and Dinesh Kumar Ahirwar

Cancers 2024, 16(18), 3134; https://doi.org/10.3390/cancers16183134 - 12 Sep 2024

Viewed by 1645

Abstract

Stem cells are critical for the development and homeostasis of the gastrointestinal (GI) tract. Inflammatory molecules are known to regulate the activity of stem cells. A comprehensive review specifically describing the role of inflammatory molecules in the regulation of stem cells within the GI tract and in GI cancers (GICs) is not available. This review focuses on understanding the role of inflammatory molecules and stem cells in maintaining homeostasis of the GI tract. We further discuss how inflammatory conditions contribute to the transformation of stem cells into tumor-initiating cells. We also describe the molecular mechanisms of inflammation and stem cell-driven progression and metastasis of GICs. Furthermore, we report on studies describing the prognostic value of cancer stem cells and the clinical trials evaluating their therapeutic utility. This review provides a detailed overview on the role of inflammatory molecules and stem cells in maintaining GI tract homeostasis and their implications for GI-related malignancies Full article

(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)

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11 pages, 296 KiB

Open AccessReview

Inflammatory Bowel Disease and Colorectal Cancer: Epidemiology, Etiology, Surveillance, and Management

by Yoshihiro Sato, Shingo Tsujinaka, Tomoya Miura, Yoh Kitamura, Hideyuki Suzuki and Chikashi Shibata

Cancers 2023, 15(16), 4154; https://doi.org/10.3390/cancers15164154 - 17 Aug 2023

Cited by 38 | Viewed by 4778

Abstract

Patients with inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn’s disease, have an increased risk of developing colorectal cancer (CRC). Although advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have contributed to a decreased incidence of CRC in patients with IBD, the rate of CRC remains higher in patients with IBD than in individuals without chronic colitis. Patients with IBD-related CRCs exhibit a poorer prognosis than those with sporadic CRCs, owing to their aggressive histological characteristics and lower curative resection rate. In this review, we present an updated overview of the epidemiology, etiology, risk factors, surveillance strategies, treatment recommendations, and prognosis of IBD-related CRCs. Full article

(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)

33 pages, 1204 KiB

Open AccessReview

Extraintestinal Cancers in Inflammatory Bowel Disease: A Literature Review

by Alessandro Massano, Luisa Bertin, Fabiana Zingone, Andrea Buda, Pierfrancesco Visaggi, Lorenzo Bertani, Nicola de Bortoli, Matteo Fassan, Marco Scarpa, Cesare Ruffolo, Imerio Angriman, Cristina Bezzio, Valentina Casini, Davide Giuseppe Ribaldone, Edoardo Vincenzo Savarino and Brigida Barberio

Cancers 2023, 15(15), 3824; https://doi.org/10.3390/cancers15153824 - 27 Jul 2023

Cited by 6 | Viewed by 3591

Abstract

Background: Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn’s disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis. Aims: The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs. Results: IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy. Conclusions: Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists. Full article

(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)

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25 pages, 767 KiB

Open AccessReview

Tumorigenesis in Inflammatory Bowel Disease: Microbiota-Environment Interconnections

by Irene Mignini, Maria Elena Ainora, Silvino Di Francesco, Linda Galasso, Antonio Gasbarrini and Maria Assunta Zocco

Cancers 2023, 15(12), 3200; https://doi.org/10.3390/cancers15123200 - 15 Jun 2023

Cited by 5 | Viewed by 2357

Abstract

Colo-rectal cancer (CRC) is undoubtedly one of the most severe complications of inflammatory bowel diseases (IBD). While sporadic CRC develops from a typical adenoma-carcinoma sequence, IBD-related CRC follows different and less understood pathways and its pathophysiological mechanisms were not completely elucidated. In contrast to chronic inflammation, which is nowadays a well-recognised drive towards neoplastic transformation in IBD, only recently was gut microbiota demonstrated to interfere with both inflammation processes and immune-mediated anticancer surveillance. Moreover, the role of microbiota appears particularly complex and intriguing when also considering its multifaceted interactions with multiple environmental stimuli, notably chronic pathologies such as diabetes and obesity, lifestyle (diet, smoking) and vitamin intake. In this review, we presented a comprehensive overview on current evidence of the influence of gut microbiota on IBD-related CRC, in particular its mutual interconnections with the environment. Full article

(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)

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18 pages, 1913 KiB

Open AccessReview

Inflammation-Driven Colorectal Cancer Associated with Colitis: From Pathogenesis to Changing Therapy

by Olga Maria Nardone, Irene Zammarchi, Giovanni Santacroce, Subrata Ghosh and Marietta Iacucci

Cancers 2023, 15(8), 2389; https://doi.org/10.3390/cancers15082389 - 20 Apr 2023

Cited by 33 | Viewed by 6649

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 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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13 pages, 975 KiB

Open AccessReview

Management of Inflammatory Bowel Disease in Patients with Current or Past Malignancy

by Florian Poullenot and David Laharie

Cancers 2023, 15(4), 1083; https://doi.org/10.3390/cancers15041083 - 8 Feb 2023

Cited by 6 | Viewed by 3953

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 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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13 pages, 504 KiB

Open AccessSystematic Review

Liver Fibrosis in Non-Alcoholic Fatty Liver Disease and Progression to Hepatocellular Carcinoma in Patients with Inflammatory Bowel Disease: A Systematic Review

by Samuel J. Martínez-Domínguez, Sandra García-Mateo, Viviana Laredo, Carla J. Gargallo-Puyuelo, Beatriz Gallego Llera, Julia López de la Cruz and Fernando Gomollón

Cancers 2023, 15(13), 3367; https://doi.org/10.3390/cancers15133367 - 27 Jun 2023

Cited by 6 | Viewed by 2825

Abstract

The aim of the systematic review is to assess the prevalence and risk factors of liver fibrosis in patients with Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD) and to discuss the role of liver fibrosis in the progression to hepatocellular carcinoma (HCC). We performed a structured search in PubMed, Web of Science, Embase, and Scopus up to 3 March 2023 to identify observational studies reporting liver fibrosis in patients with NAFLD and IBD. Quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) score. A total of 23 studies met our inclusion criteria, including 629,781 patients. A total of 10 cross-sectional, 3 case-control, and 10 cohort studies were included. Fourteen studies had a NOS score ≥ 7 points. NAFLD was diagnosed in 2162/6332 (34.1%) IBD participants. However, NAFLD diagnosis was established in 924/2962 (31.2%) healthy individuals without IBD. Advanced liver fibrosis was found in 116 (11.6%) of 992 IBD patients with NAFLD. Most studies found an association between NAFLD and classic cardiovascular risk factors such as older age, male sex, higher BMI, diabetes, hypertension and dyslipidemia. In addition, metabolic syndrome features were also associated with an increased risk of significant and advanced liver fibrosis. Although no strong association between NAFLD and IBD therapy was reported, some studies associated NAFLD with IBD diagnosis, Crohn’s Disease, a complicated course of IBD, disease activity, and IBD duration. Advanced liver fibrosis was also associated with Crohn’s disease in several studies. In conclusion, NAFLD and advanced liver fibrosis are prevalent and clinically relevant extraintestinal manifestations, so its diagnosis and potential progression to HCC should be carefully considered in daily clinical practice. Full article

(This article belongs to the Special Issue Chronic Intestinal Inflammation and Cancers)

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