Intestinal Cancers and Surgery in Inflammatory Bowel Diseases

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 15181

Special Issue Editors


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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
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Guest Editor
Department of Surgery, University of Tor Vergata, Rome, Italy
Interests: minimally invasive surgery for IBD, including research on the mechanism of recurrence and prevention of recurrence; colon and rectal cancer mechanisms of peritoneal spread and lymph nodes diffusion and technology in surgery

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Guest Editor
Humanitas University Hospital, Milan, Italy
Interests: advanced minimally invasive techniques, included laparoscopic, single-port and transanal surgery (TAMIS, TATME, TTSS); enhanced postoperative patient recovery, sphincter saving procedures for rectal cancer and Inflammatory Bowel Disease (IBD).

Special Issue Information

Crohn Disease (CD) and Ulcerative Colitis (UC) are Inflammatory Bowel Diseases of unknown etiology, characterized by a relapsing clinical course.

Recently, growing attention has been focused in IBD, in relation to the young age at onset of symptoms, to the high h prevalence observed in North America and North Europe, and to the development of several highly effective biologic therapies. These immunomodulators showed a marked clinical efficacy, associated with healing of the lesions in subgroups of patients. Due to the possible induction of side effects, particularly infections, and to the high costs, biologic therapies are currently indicated for treating IBD patients refractory to conventional treatments characterized by severe clinical course. The overarching goal in IBD is to control the immunomodulatory response, to achieve a clinical and possibly endoscopic steroid-free remission, thus improving patients’ quality of life.

Despite the marked efficacy of biologics in IBD, a primary or secondary failure to these treatments may be observed in subgroups of patients (10-30%), thus leading to surgical indication. In IBD, surgical indication includes inefficacy/intolerance to conventional and biological treatments, steroid-dependent disease or complications (obstruction, abscess, perforation, massive bleeding in CD, toxic megacolon in UC). In CD, surgical indication for these indications needs to consider the cost/benefit balance due to the almost ineluctable the post-operative recurrence. Nevertheless, almost 2/3 of CD patients require surgery and almost half of them will need a second resection for CD.  In UC, almost 10-15% of patients require surgery for refractory disease or toxic megacolon,

Additional indication for surgery in IBD is represented by the development of colorectal cancer. Chronic inflammation in the involved bowel has indeed been associated with a higher risk of dysplasia or adenocarcinoma in both CD and in UC. A long-term disease course significantly increases the colorectal cancer risk in IBD. Endoscopic surveillance is therefore indicated in patients with both UC and Crohn’s colitis, which needs to be tailored according to additional individual risk factors (history of CRC/dysplasia, IBD duration, severity of the disease, sclerosing cholangitis). Surgery for CRC in IBD includes the same approach as for non-IBD related cancers. Nevertheless, as the mean age at diagnosis at diagnosis of CRC has been shown to be lower in IBD than in non-IBD patients, surgical techniques may also consider to use a non-invasive approach, when possible. Moreover, whether pre-operatory treatments for CRC need to be reconsidered in IBD, including radiotherapy in patients with rectal adenocarcinoma in patients with IBD involving the rectum is undefined.

The purpose of this special issue is to collect studies from IBD-dedicated gastroenterologists and surgeons, possibly integrated, to discuss over the current indications for surgical treatments in patients with CRC and IBD.  We hope to be able to receive works that can possibly clarify the current risk factors for CRC in IBD, as also the best surgical management of CRC in UC and Crohn’s colitis. All these, in view of the changes in the medical and surgical perspectives in IBD, and with a close eye to the quality of life and cost-effectiveness.

Prof. Livia Biancone
Prof. Giuseppe S. Sica
Prof. Antonino Spinelli
Guest Editors

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Keywords

  • Risk factors for CRC in IBD
  • Endoscopic surveillance for CRC in IBD
  • Surgery for CRC in CD: indications, techniques, morbidity, major challenges
  • Surgery for CRC in UC: indications, techniques, morbidity, major challenges
  • Quality of life in IBD patients after surgery for CRC
  • Analysis of Costs
  • Timing of surgery in IBD patients with CRC

Published Papers (5 papers)

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Research

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16 pages, 1571 KiB  
Article
Incident Colorectal Cancer in Inflammatory Bowel Disease
by Benedetto Neri, Maria Lia Scribano, Alessandro Armuzzi, Fabiana Castiglione, Renata D’Incà, Ambrogio Orlando, Stefano Festa, Gabriele Riegler, Walter Fries, Gianmichele Meucci, Patrizia Alvisi, Filippo Mocciaro, Claudio Papi, Michelangela Mossa, Giorgia Sena, Luisa Guidi, Anna Testa, Sara Renna, Iris Frankovic, Anna Viola, Marta Patturelli, Carlo Chiaramonte, Livia Biancone and on behalf of IG-IBD (Italian Group for the Study of Inflammatory Bowel Disease)add Show full author list remove Hide full author list
Cancers 2022, 14(3), 721; https://doi.org/10.3390/cancers14030721 - 30 Jan 2022
Cited by 6 | Viewed by 2705
Abstract
Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed [...] Read more.
Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed in our multicenter study, including a cohort of 56 IBD patients with incident CRC. The clinical and histopathological features of IBD patients and of CRC were recorded. Incident CRC in IBD occurred at a young age (≤40 years) in 25% of patients (median age 55.5 (22–76)). Mucinous signet-ring carcinoma was detected in 6 out of the 56 (10.7%) patients, including 4 with Ulcerative Colitis (UC) and 2 with Crohn’s disease (CD). CRC was more frequently diagnosed by colonoscopy in UC (85.4% vs. 50%; p = 0.01) and by imaging in Crohn’s Disease CD (5.8% vs. 31.8%; p = 0.02). At onset, CRC-related symptoms occurred in 29 (51.9%) IBD patients. The time interval from the diagnosis of IBD to CRC was shorter in UC and CD patients with >40 years (p = 0.002; p = 0.01). CRC-related death occurred in 10 (29.4%) UC and in 6 (27.2%) CD patients (p = 0.89), with a short time interval from CRC to death (UC vs. CD: 6.5 (1–68) vs. 14.5 (8–40); p = 0.85; IBD: 12 months (1–68)). CRC occurring at a young age, a short time interval from the diagnosis of IBD to CRC-related death in the elderly, CRC-symptoms often mimicking IBD relapse and the observed high mortality rate may support the need of closer surveillance intervals in subgroups of patients. Full article
(This article belongs to the Special Issue Intestinal Cancers and Surgery in Inflammatory Bowel Diseases)
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15 pages, 3892 KiB  
Article
Interleukin-34 Enhances the Tumor Promoting Function of Colorectal Cancer-Associated Fibroblasts
by Eleonora Franzè, Antonio Di Grazia, Giuseppe Sigismondo Sica, Livia Biancone, Federica Laudisi and Giovanni Monteleone
Cancers 2020, 12(12), 3537; https://doi.org/10.3390/cancers12123537 - 27 Nov 2020
Cited by 17 | Viewed by 2522
Abstract
The stromal compartment of colorectal cancer (CRC) is marked by the presence of large numbers of fibroblasts, termed cancer-associated fibroblasts (CAFs), which promote CRC growth and progression through the synthesis of various molecules targeting the neoplastic cells. Interleukin (IL)-34, a cytokine over-produced by [...] Read more.
The stromal compartment of colorectal cancer (CRC) is marked by the presence of large numbers of fibroblasts, termed cancer-associated fibroblasts (CAFs), which promote CRC growth and progression through the synthesis of various molecules targeting the neoplastic cells. Interleukin (IL)-34, a cytokine over-produced by CRC cells, stimulates CRC cell growth. Since IL-34 also regulates the function of inflammatory fibroblasts, we hypothesized that it could regulate the tumor promoting function of colorectal CAFs. By immunostaining and real-time PCR, we initially showed that IL-34 was highly produced by CAFs and to lesser extent by normal fibroblasts isolated from non-tumoral colonic mucosa of CRC patients. CAFs and normal fibroblasts expressed the functional receptors of IL-34. IL-34 induced normal fibroblasts to express α-SMA, vimentin and fibroblast activation protein and enhanced fibroblast growth, thus generating a cellular phenotype resembling that of CAFs. Consistently, knockdown of IL-34 in CAFs with an antisense oligonucleotide (AS) decreased expression of such markers and inhibited cell proliferation. Co-culture of CRC cells with IL-34 AS-treated CAFs supernatants resulted in less cancer cell proliferation and migration. Among CAF-derived molecules known to promote CRC cell growth/migration, only netrin-1 and basic-fibroblast growth factor were induced by IL-34. Data suggest a role for IL-34 in the control of colorectal CAF function. Full article
(This article belongs to the Special Issue Intestinal Cancers and Surgery in Inflammatory Bowel Diseases)
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14 pages, 5627 KiB  
Article
Small Bowel Adenocarcinomas Featuring Special AT-Rich Sequence-Binding Protein 2 (SATB2) Expression and a Colorectal Cancer-Like Immunophenotype: A Potential Diagnostic Pitfall
by Giuseppe Neri, Giovanni Arpa, Camilla Guerini, Federica Grillo, Marco Vincenzo Lenti, Paolo Giuffrida, Daniela Furlan, Fausto Sessa, Erica Quaquarini, Alessandra Viglio, Cristina Ubezio, Alessandra Pasini, Stefano Ferrero, Gianluca Sampietro, Sandro Ardizzone, Giovanni Latella, Claudia Mescoli, Massimo Rugge, Fabiana Zingone, Valeria Barresi, Rachele Ciccocioppo, Paolo Pedrazzoli, Gino Roberto Corazza, Ombretta Luinetti, Enrico Solcia, Marco Paulli, Antonio Di Sabatino and Alessandro Vanoliadd Show full author list remove Hide full author list
Cancers 2020, 12(11), 3441; https://doi.org/10.3390/cancers12113441 - 19 Nov 2020
Cited by 7 | Viewed by 3118
Abstract
Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small [...] Read more.
Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn’s disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and alpha-methylacyl-CoA racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7−/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7−/CK20- SBAs were enriched with MMR-deficient cases (71%) and patients with CK7−/CK20− or CK7−/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20− or CK7+/CK20+ cancers (p = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7−/CK20− cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup. Full article
(This article belongs to the Special Issue Intestinal Cancers and Surgery in Inflammatory Bowel Diseases)
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24 pages, 1648 KiB  
Review
Challenges in Crohn’s Disease Management after Gastrointestinal Cancer Diagnosis
by Claudio Fiorillo, Carlo Alberto Schena, Giuseppe Quero, Vito Laterza, Daniela Pugliese, Giuseppe Privitera, Fausto Rosa, Tommaso Schepis, Lisa Salvatore, Brunella Di Stefano, Luigi Larosa, Laura Maria Minordi, Luigi Natale, Giampaolo Tortora, Alessandro Armuzzi and Sergio Alfieri
Cancers 2021, 13(3), 574; https://doi.org/10.3390/cancers13030574 - 02 Feb 2021
Cited by 6 | Viewed by 3781
Abstract
Crohn’s disease (CD) is a chronic inflammatory bowel disease with a progressive course, potentially affecting the entire gastrointestinal tract from mouth to anus. Several studies have shown an increased risk of both intestinal and extra-intestinal cancer in patients with CD, due to long-standing [...] Read more.
Crohn’s disease (CD) is a chronic inflammatory bowel disease with a progressive course, potentially affecting the entire gastrointestinal tract from mouth to anus. Several studies have shown an increased risk of both intestinal and extra-intestinal cancer in patients with CD, due to long-standing transmural inflammation and damage accumulation. The similarity of symptoms among CD, its related complications and the de novo onset of gastrointestinal cancer raises difficulties in the differential diagnosis. In addition, once a cancer diagnosis in CD patients is made, selecting the appropriate treatment can be particularly challenging. Indeed, both surgical and oncological treatments are not always the same as that of the general population, due to the inflammatory context of the gastrointestinal tract and the potential exacerbation of gastrointestinal symptoms of patients with CD; moreover, the overlap of the neoplastic disease could lead to adjustments in the pharmacological treatment of the underlying CD, especially with regard to immunosuppressive drugs. For these reasons, a case-by-case analysis in a multidisciplinary approach is often appropriate for the best diagnostic and therapeutic evaluation of patients with CD after gastrointestinal cancer onset. Full article
(This article belongs to the Special Issue Intestinal Cancers and Surgery in Inflammatory Bowel Diseases)
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Other

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14 pages, 7002 KiB  
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Management of Low Rectal Cancer Complicating Ulcerative Colitis: Proposal of a Treatment Algorithm
by Bruno Sensi, Giulia Bagaglini, Vittoria Bellato, Daniele Cerbo, Andrea Martina Guida, Jim Khan, Yves Panis, Luca Savino, Leandro Siragusa and Giuseppe S. Sica
Cancers 2021, 13(10), 2350; https://doi.org/10.3390/cancers13102350 - 13 May 2021
Cited by 5 | Viewed by 2426
Abstract
Low rectal Carcinoma arising at the background of Ulcerative Colitis poses significant management challenges to the clinicians. The complex decision-making requires discussion at the multidisciplinary team meeting. The published literature is scarce, and there are significant variations in the management of such patients. [...] Read more.
Low rectal Carcinoma arising at the background of Ulcerative Colitis poses significant management challenges to the clinicians. The complex decision-making requires discussion at the multidisciplinary team meeting. The published literature is scarce, and there are significant variations in the management of such patients. We reviewed treatment protocols and operative strategies; with the aim of providing a practical framework for the management of low rectal cancer complicating UC. A practical treatment algorithm is proposed. Full article
(This article belongs to the Special Issue Intestinal Cancers and Surgery in Inflammatory Bowel Diseases)
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