Publications by authors named "Livia Biancone"

116 Publications

Poorly Cohesive Carcinoma of the Nonampullary Small Intestine: A Distinct Histologic Subtype With Prognostic Significance.

Am J Surg Pathol 2021 Oct 11. Epub 2021 Oct 11.

Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia Anatomic Pathology, Fondazione IRCCS San Matteo Hospital Clinical Epidemiology & Biometry Unit, Fondazione IRCCS San Matteo Hospital Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital Medical Oncology Unit, ICS Maugeri-IRCCS SpA SB, Pavia Pathology Unit, Department of Surgical and Diagnostic Sciences (DISC), University of Genoa and Ospedale Policlinico San Martino IRCCS, Genoa Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua Veneto Institute of Oncology, IOV-IRCCS, Padua Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori," Meldola Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese Gatroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco University Hospital Department of Biochemical and Clinical Sciences, University of Milan, Milan Division of General and HPB Surgery, ASST Rhodense, Rho Gatroenterology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey.

Poorly cohesive carcinomas (PCCs) are neoplasms characterized by a dyshesive cell invasion pattern featuring single-cell or cord-like stromal infiltration. Although they have been extensively studied in the stomach and other digestive system organs, limited data regarding nonampullary small bowel poorly cohesive carcinomas (SB-PCCs) are hitherto available. The aims of our study were to analyze the clinicopathologic and immunophenotypical features of SB-PCCs (PCC pattern accounting for >50% of the neoplasm) and to compare them with small bowel adenocarcinomas (SBAs), not otherwise specified (SBAs-NOS) and with cancers with a histologically distinct PCC component accounting for 10% to 50% of the neoplasm (mixed-poorly-cohesive-glandular-SBAs). Fifteen SB-PCCs were identified and compared with 95 SBAs-NOS and 27 mixed-poorly-cohesive-glandular-SBAs. Most SB-PCCs (67%) were composed of <10% of signet-ring cells, and all but 1 SB-PCCs exhibited loss of membranous expression of E-cadherin. Compared with SBAs-NOS, SB-PCCs showed a significantly younger patient age at diagnosis, and a stronger association with Crohn disease, and both SB-PCCs and mixed-poorly-cohesive-glandular-SBAs featured a higher rate of lymphovascular and perineural invasion and a lower percentage of mismatch repair-deficient cases. Importantly, the cancer-specific survival of SB-PCC (hazard ratio: 3.81; 95% confidence interval: 1.90-7.64; P<0.001) and mixed-poorly-cohesive-glandular-SBA (4.12; 2.20-7.71; P<0.001) patients was significantly worse compared with SBAs-NOS cases. This study provides objective evidence to the World Health Organization (WHO) 2019 introduction of SB-PCC as a distinctive subtype of nonampullary SBA, by virtue of its unique clinical and histologic features, and suggests that both SB-PCCs and mixed-poorly-cohesive-glandular-SBAs should be separated from SBAs-NOS.
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http://dx.doi.org/10.1097/PAS.0000000000001821DOI Listing
October 2021

Diagnostic yield of small bowel capsule endoscopy in obscure gastrointestinal bleeding: a real-world prospective study.

Intern Emerg Med 2021 Jun 27. Epub 2021 Jun 27.

Department of Systems Medicine, University "Tor Vergata" of Rome, Vie Montpellier, 1, 00133, Rome, Italy.

Small bowel capsule endoscopy (SBCE) visualizes the small bowel (SB) mucosa. Gastrointestinal (GI) bleeding from SB accounts for the majority of SBCE indications. We aimed to assess, in a "real-world" prospective study, the diagnostic yield of SBCE in a cohort of consecutive patients with obscure gastrointestinal bleeding (OGIB). Secondary end point was to assess the frequency of adverse events and the role of SBCE in determining the diagnostic work-up and clinical outcome. From 2016 to 2018, all patients referred for SBCE examination were enrolled. Indication for SBCE was re-assessed by 2 dedicated gastroenterologists. Inclusion criteria: (1) age ≥ 18 and ≤ 85 years; (2) diagnosis of OGIB; 3) non-diagnostic standard bidirectional endoscopy; (4) informed consent. Exclusion criteria: (1) deglutition impairment; (2) SBCE contraindications; (3) pregnancy. The cohort included 50 patients [males 18 (36%), age 68 (27-83)]. SBCE indication: patients with ongoing overt OGIB (Group A) (n = 11; 22%), previous overt OGIB (Group B) (n = 14; 28%), occult bleeding (with Iron Deficiency Anaemia) (Group C) (n = 25; 50%). SBCE detected clinically relevant lesions in 46 (92%) cases. Clinically relevant lesions were more frequent in Group C (24/25; 96%), followed by Group A (10/11; 91%) and Group B (12/14; 85.5%). After SBCE, treatment was medical (60%); endoscopic (14%), surgical (36%) or conservative (18%). Clinical follow-up showed complete resolution in 63.2%, partial/absent resolution in 18.4% of cases. In a prospective study, the high diagnostic yield of SBCE supports its role as first-line investigation in patients with OGIB. However, this achievement requires an accurate and timely assessment by dedicated gastroenterologists.
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http://dx.doi.org/10.1007/s11739-021-02791-zDOI Listing
June 2021

Efficacy and tolerability of very low-volume bowel preparation in patients with inflammatory bowel diseases.

Eur J Gastroenterol Hepatol 2021 07;33(7):977-982

Gastroenterology Unit, Department of Systems Medicine, University of Rome "Tor Vergata".

Objectives: An adequate bowel preparation is essential for a quality colonoscopy. Patients with inflammatory bowel disease (IBD) show low compliance with bowel preparation due to the large volume of lavage solution to be ingested, especially if active symptoms are present, and the frequency of having a colonoscopy. We evaluated the efficacy and tolerability of a very low-volume (VLV) polyethylene glycol (PEG)-based solution in patients with IBD.

Methods: A cohort of 103 consecutive patients, 56 with Crohn's disease and 47 with ulcerative colitis, received a 1-L PEG-based bowel preparation divided into two 500-mL doses taken the evening before and the morning of the colonoscopy, each dose followed by at least another 500-mL of clear fluids. Colon cleansing was scored according to the Boston Bowel Preparation Scale (BBPS) and evaluated in relation to influencing variables.

Results: Bowel cleansing was adequate (BBPS ≥ 6) in 88 patients (85.4%). The time interval between the end of bowel preparation and the beginning of colonoscopy and the disease activity significantly affected colon cleansing. Most patients declared a complete intake of lavage solution (99%), the willingness to repeat the same bowel preparation in a future colonoscopy (86.4%), and a good taste assessment.

Conclusion: The VLV PEG-based bowel preparation is effective and well accepted by IBD patients. As minimizing the volume of lavage solution required, the VLV-bowel preparation here tested could be of choice in subjects who perform periodically colonoscopy or in those who do not tolerate a larger amount of liquids.
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http://dx.doi.org/10.1097/MEG.0000000000002167DOI Listing
July 2021

A Pharmacological Batch of Mongersen that Downregulates Smad7 is Effective as Induction Therapy in Active Crohn's Disease: A Phase II, Open-Label Study.

BioDrugs 2021 May 19;35(3):325-336. Epub 2021 Apr 19.

Dipartimento di Medicina dei Sistemi, Università di Roma "Tor Vergata", Via Montpellier, 1, 00133, Rome, Italy.

Background: A recent phase III trial did not confirm the previous clinical and endoscopic improvements seen in patients with Crohn's disease (CD) receiving Mongersen, an oral Smad7 antisense oligonucleotide. Factors accounting for such a discrepancy are unknown.

Objective: Our objective was to further assess whether Mongersen was effective as induction therapy in active CD and evaluate the in vitro inhibitory effect of various batches of Mongersen used in the previous and present trials on Smad7 expression.

Methods: In a phase II, open-label study, 18 patients with active CD (Crohn's Disease Activity Index [CDAI] score > 220 and evidence of endoscopic lesions) received Mongersen 160 mg/day for 12 weeks. The rates of clinical remission, defined as CDAI < 150, and clinical response, defined as a CDAI score decrease ≥ 100, were evaluated at week 4, 8, and 12. The fraction of circulating CCR9-expressing leukocytes was assessed by flow cytometry. Smad7 expression was evaluated in the human colorectal cancer cell line HCT-116 transfected with different batches of Mongersen using real-time polymerase chain reaction (PCR) and Western blotting, RESULTS: The proportions of patients experiencing clinical remission were 38.9%, 55.6%, and 50.0% at week 4, 8, and 12, respectively. At the same time points, the rates of clinical response were 72.2%, 77.8%, and 77.8%, respectively. Mongersen reduced the percentages of CCR9-expressing CD45+ cells. The batch of Mongersen used in this study, but not two batches used in the phase III study, inhibited Smad7 expression in HCT-116 cells.

Conclusions: The present findings support the clinical benefit of Mongersen in active CD and show that various batches manufactured during the GED0301 program differ in their ability to inhibit in vitro Smad7.

Trial Registration Number: NCT02685683; EudraCT 2015-001693-18.
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http://dx.doi.org/10.1007/s40259-021-00482-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084825PMC
May 2021

Natural History of Ulcerative Colitis with Coexistent Colonic Diverticulosis.

J Clin Med 2021 Mar 12;10(6). Epub 2021 Mar 12.

Gastroenterology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.

Ulcerative colitis (UC) and colonic diverticulosis can co-exist in some patients. However, the natural history of UC associated with colonic diverticulosis is not well known. We here compared the disease characteristics and outcome of UC patients with and without concomitant colonic diverticulosis. Medical records of 347 UC patients were included in an observational, retrospective, nested-matched case-control study. Cases were 92 patients with UC and concomitant colonic diverticulosis, while controls were 255 UC patients without concomitant colonic diverticulosis. A propensity score matching (PSM) was used to homogenate cases (n = 92) and controls (n = 153) for age. UC patients with concomitant colonic diverticulosis were less likely to have an extensive disease (25/92, 27.1%) and to experience steroid dependence (8/92, 8.6%) compared to patients without concomitant colonic diverticulosis (70/153, 45.7% and 48/153, 31.3%, respectively; < 0.001). The use of immunosuppressants (9/92, 9.7% vs. 37/153, 24.1%; = 0.007) or biologics (3/92, 3.2% vs. 26/153, 16.9%, < 0.001) was significantly lower in UC patients with concomitant diverticulosis compared to the control group. On multivariate analysis, steroid dependence and extensive colitis were significantly less frequent in UC patients with concomitant colonic diverticulosis compared to UC patients without diverticula. UC patients with coexisting colonic diverticulosis are less likely to have an extensive disease and to be steroid-dependent.
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http://dx.doi.org/10.3390/jcm10061192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001479PMC
March 2021

Two years follow-up of golimumab treatment in refractory enteropathic spondyloarthritis patients with Crohn disease: A STROBE-compliant study.

Medicine (Baltimore) 2021 Mar;100(12):e25122

Rheumatology, Allergology and Clinical Immunology.

Abstract: Golimumab is a fully human monoclonal antibody against tumor necrosis factor (TNF) approved for the treatment of ulcerative colitis and not for Crohn disease (CD). Many CD patients experience primary, secondary failure, or intolerance to other TNF inhibitors (TNFi) approved in Italy for CD (adalimumab and infliximab). Spondyloarthritis (SpA) may be associated with CD (enteropathic, ESpA) in up to 50% of patients requiring a multidisciplinary and tailored approach. However, only few data from literature and no formal trials determined the efficacy and safety of golimumab in ESpA patients. We performed a case series on 12 patients affected by active CD and active ESpA were failure or intolerant to previous TNFi approved in Italy for both SpA and CD, infliximab and adalimumab. Golimumab was administered following rheumatologic dosage (subcutaneous 50 mg monthly; 100 mg monthly for patients ≥100 kg). Gastrointestinal and rheumatologic disease activity was evaluated with a follow-up of 2 years. A total of 9 patients were followed for 2 years of golimumab treatment. CD clinical activity ameliorated as shown by the reduction of Harvey-Bradshaw index and Crohn disease activity index (CDAI) at 12 and 24 months of treatment (P = .03 and P = .04, respectively) associated with reduction of C-reactive protein at 12 and 24 months (P = .04 for both comparisons) of treatment. SpA assessment revealed a significant reduction in tender joint count at 6 (P = .03), 12 (P = .03), and 24 months (P = .007) of treatment. Swollen joint count, pain, SpA disease activity, and disability reduced in several patients during the follow-up. No adverse events were registered in the follow-up. We demonstrate good clinical efficacy and safety profile of both gastrointestinal and rheumatologic involvement. This may indicate promising therapeutic option for ESpA patients affected by CD, and non-responsive to other TNFi.
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http://dx.doi.org/10.1097/MD.0000000000025122DOI Listing
March 2021

Update on the therapeutic management of patients with either psoriatic arthritis or ulcerative colitis: focus on the JAK inhibitor tofacitinib.

Ther Adv Musculoskelet Dis 2021 18;13:1759720X20977777. Epub 2021 Feb 18.

Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Lazio, Italy.

Psoriatic arthritis (PsA) and ulcerative colitis (UC) are immune-mediated diseases that cause significant burden worldwide. Recent advances in their management have improved patient outcomes. However, significant unmet needs still remain as not all patients respond to current treatments, and patients may lose responsiveness over time. An improved understanding of the pathophysiology of these diseases has brought about the development of novel disease-modifying agents, including interleukin inhibitors and, more recently, Janus kinase (JAK) inhibitors. With the approval of tofacitinib for the treatment of adults with active PsA and in adult patients with moderately-to-severely active UC, JAK inhibitors have recently entered the treatment armamentarium for PsA and UC. A number of other JAK inhibitors are also undergoing clinical development and are currently in phase III trials. This review provides an overview of the current therapeutic options for PsA and UC, with a focus on the JAK inhibitors.
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http://dx.doi.org/10.1177/1759720X20977777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897839PMC
February 2021

Interleukin-34 Enhances the Tumor Promoting Function of Colorectal Cancer-Associated Fibroblasts.

Cancers (Basel) 2020 Nov 27;12(12). Epub 2020 Nov 27.

Department of Systems Medicine, University of Rome "TOR VERGATA", 00133 Rome, Italy.

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.
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http://dx.doi.org/10.3390/cancers12123537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761053PMC
November 2020

Finger clubbing in inflammatory bowel disease: association with upper small bowel lesions and need of surgery in Crohn's disease.

Eur J Gastroenterol Hepatol 2021 06;33(6):844-851

Department of Systems Medicine, GI Unit, University "Tor Vergata" of Rome.

Objective: Finger clubbing has been associated with inflammatory bowel disease (IBD).

Aims: In a prospective single-center study, we aimed to assess the frequency of finger clubbing in a cohort of IBD patients. Whether finger clubbing is associated with clinical characteristics of IBD was also investigated.

Methods: IBD patients with a detailed clinical history were enrolled. Finger clubbing was assessed by visual inspection. Data were expressed as median (range), chi-square, t-test. Multivariate logistic regression analysis was used to assess risk factors for finger clubbing, when considering demographic and clinical characteristics, smoking habits and chronic pulmonary diseases (CPD).

Results: Finger clubbing was searched in 470 IBD patients: 267 Crohn's disease and 203 ulcerative colitis. Finger clubbing was more frequent in Crohn's disease than in ulcerative colitis: 45/267 (16.8%) vs. 15/203 (7.3%) [odds ratio (OR), 2.54 (1.37-4.70); P = 0.003]. Crohn's disease involved the ileum (59.9%), colon (4.5%), ileum-colon (25.8%) and upper gastrointestinal (GI) (9.8%). Ulcerative colitis extent included proctitis (E1) (13.4%), left-sided (E2) (43.3%) and pancolitis (E3) (43.3%). Upper GI lesions, but not other Crohn's disease localizations, were more frequent in patients with finger clubbing [9/45 (20%) vs. 17/222 (7.7%); P = 0.032]. Crohn's disease-related surgery was more frequent in patients with finger clubbing [36/45 (80%) vs. 107/222 (48.1%); P < 0.001]. In Crohn's disease, the only risk factors for finger clubbing were upper GI lesions and Crohn's disease-related surgery [OR, 2.58 (1.03-6.46), P = 0.04; OR, 4.07 (1.86-8.91), P = 0.006]. Ulcerative colitis extent was not associated with finger clubbing [E1: OR, 0.27 (0.02-3.44), P = 0.33; E2: OR, 0.93 (0.24-3.60), P = 0.92; E3:OR, 0.64 (0.22-1.86), P = 0.59]. In ulcerative colitis, but not in Crohn's disease, finger clubbing was more frequent in smokers [13/15 (86.6%) vs. 99/188 (52.6%); P = 0.01] and in patients with CPD [5/15 (33.3%) vs. 16/188 (8.5%); P = 0.002]. Smoking and CPD were the only risk factors for finger clubbing in ulcerative colitis [OR, 7.18 (1.44-35.78), P = 0.01; OR, 10.93 (2.51-47.45), P = 0.001].

Conclusion: In the tested IBD population, finger clubbing was more frequent in Crohn's disease than in ulcerative colitis. In Crohn's disease, upper GI lesions and history of Crohn's disease-related surgery were risk factors for finger clubbing, suggesting the possible role of finger clubbing as a subclinical marker of Crohn's disease severity.
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http://dx.doi.org/10.1097/MEG.0000000000001966DOI Listing
June 2021

High Smad7 in the early post-operative recurrence of Crohn's disease.

J Transl Med 2020 10 19;18(1):395. Epub 2020 Oct 19.

Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Roma, Italy.

Background: In Crohn's disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-β1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD.

Methods: Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Smad7 was examined by immunohistochemistry and cytokine expression was analysed by flow-cytometry.

Results: Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of Smad7-expressing cells in both the epithelial and lamina propria compartments. Transition from this stage to endoscopic recurrence was marked by persistence of high number of Smad7-positive cells, which reduced significantly in the late stages of the disease, where Smad7 expression remained, however, greater than that seen in normal controls. In samples with early lesions, Smad7 expression positively correlated with the number of interferon-γ-secreting cells.

Conclusions: Smad7 induction is an early event in the inflammatory sequence occurring in CD, thus suggesting that knockdown of Smad7 can help prevent post-operative recurrence.
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http://dx.doi.org/10.1186/s12967-020-02558-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574182PMC
October 2020

Histological scores in inflammatory bowel disease.

J Dig Dis 2021 Jan;22(1):9-22

Department of Systems Medicine, Unit of Gastroenterology, Tor Vergata University, Rome, Italy.

The role of histology in inflammatory bowel disease (IBD) has not yet been well defined. Endoscopic mucosal healing has been proposed as a predictor of the clinical course of IBD and it is indeed considered one of the main therapeutic targets. However, it does not necessarily imply histological healing. Histological remission has been reported to be associated with a better clinical outcome than endoscopic remission only in IBD patients. These observations support the view that histology plays a role as a potential therapeutic target in Crohn's disease and ulcerative colitis. Histological scores being able to quantify the degree of microscopic activity are needed for this purpose. In the era of biologics, indication for proper treatment may benefit from the assessment of clinical and endoscopic activity, as well as histological scores. Such scores may allow us to quantify the microscopic mucosal response to treatment and to define complete healing in IBD. A validated histological score in IBD may lead to the definition of microscopic activity in clinical practice, trials and investigational settings. Several attempts to develop such scores have been reported, but few are currently used and none is applied worldwide in clinical practice. The present review summarizes the main histological scores currently used for assessing IBD activity.
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http://dx.doi.org/10.1111/1751-2980.12937DOI Listing
January 2021

Observational study on the evaluation of quality of life in patients affected by enteropathic spondyloarthritis.

Musculoskeletal Care 2020 12 20;18(4):527-534. Epub 2020 Aug 20.

Rheumatology Unit, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Background: Enteropathic spondyloarthritis (ESpA) and inflammatory bowel diseases (IBD) have high impact on physical and psychological health but health-related quality of life (HRQoL) has never been evaluated in ESpA patients.

Purpose: Cross-sectional multidisciplinary study was performed to evaluate HRQoL, state of health, and well-being in IBD and ESpA patients.

Methods: Consecutive IBD and ESpA outpatients were enrolled. Disease activity, inflammatory parameters, function, and quality of life (EuroQol questionnaire) were assessed at visit time and compared with 12 months ago.

Results: Two hundred fifty-three IBD patients were evaluated. Ninety-five patients met inclusion criteria. ESpA was established in 65.3% IBD patients. Most ESpA patients had discreet or good health perception (65.3% and 22.5%, respectively), similar to IBD group (64.6% and 20.7%, respectively). In both groups, no patients had exceptional state of general well-being. Compared with previous 12 months, ESpA group showed improved state of health in 12% of patients, worsening in 28% and stable state of health in 60%. Similar results were obtained in IBD group. Emotional and psychological problems (anxiety, depression, and feeling of loneliness and isolation) were reported: In ESpA patients, these feelings were observed in 58.1%, 40.57%, and 29% of cases, respectively; IBD patients showed slightly lower percentage. More than half of ESpA and IBD patients reported an embarrassment about their condition and worry about disease's future progression and physical pain.

Conclusions: Well-being, quality of life, and psychological problems were described in ESpA and IBD patients. Disease management should include also social, mental, and psychological impacts, in terms of QoL.
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http://dx.doi.org/10.1002/msc.1500DOI Listing
December 2020

Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas.

Ann Surg Oncol 2021 Feb 5;28(2):1167-1177. Epub 2020 Aug 5.

Unit of Pathology, Cervello Hospital, Palermo, Italy.

Background: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer.

Patients And Methods: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability.

Results: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status.

Conclusions: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.
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http://dx.doi.org/10.1245/s10434-020-08926-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801310PMC
February 2021

Ustekinumab for treating ulcerative colitis: an expert opinion.

Expert Opin Biol Ther 2020 11 24;20(11):1321-1329. Epub 2020 Jul 24.

IBD UNIT AO, "Villa Sofia-Cervello" Hospital , Palermo, Italy.

Introduction: Biologic agents have revolutionized the therapeutic management of ulcerative colitis. Anti-tumor necrosis factor agents were the first biologic drugs used to induce and maintain remission in this inflammatory bowel disease. Recently, another biologic option, ustekinumab, has become available for the treatment of moderate-to-severe ulcerative colitis.

Areas Covered: In this article, the authors review the literature on the efficacy and safety of ustekinumab in the context of current biologic agents used for the management of this disease. The potential role of ustekinumab in the treatment paradigm of the disease is also discussed. : The UNIFI trial has demonstrated the efficacy and safety of ustekinumab in induction and maintenance phases of treatment for ulcerative colitis. Ustekinumab may provide clinical benefit in a range of settings in patients with ulcerative colitis, even for those with multiple treatment failures, which are relatively common in daily clinical practice. Future clinical trials should compare the efficacy of ustekinumab with existing biologic agents in the management of ulcerative colitis.
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http://dx.doi.org/10.1080/14712598.2020.1792882DOI Listing
November 2020

Effect of Vedolizumab on Anemia of Chronic Disease in Patients with Inflammatory Bowel Diseases.

J Clin Med 2020 Jul 6;9(7). Epub 2020 Jul 6.

Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.

Background: Anemia of Chronic Disease (ACD) can negatively influence the clinical course of Inflammatory Bowel Disease (IBD) patients. The aim of this study was to evaluate the effect of Vedolizumab on ACD in IBD.

Methods: Clinical data of 75 IBD patients (25 Crohn's disease (CD) and 50 Ulcerative Colitis (UC)) receiving Vedolizumab in a tertiary referral IBD center were retrospectively evaluated and the effect of the drug on ACD was ascertained at weeks 14 and 24.

Results: ACD was diagnosed in 35 (11 CD and 24 UC) out of 75 (47%) IBD patients. At both week 14 and week 24, improvements and resolutions of ACD were achieved by 13/35 (37%) and 11/35 (31%) patients, respectively. Baseline demographic/clinical characteristics did not differ between patients with ACD improvements/resolutions and those with persistent ACD. Clinical response occurred more frequently in patients who achieved ACD resolution (10/11, 91%) than in those without ACD improvement (5/11, 45%, = 0.022). When analysis was restricted to anemic patients, ACD resolution was documented in 10/22 patients (45%) achieving clinical response and 1/13 of non-responders (8%; = 0.02).

Conclusions: ACD occurs in half of the IBD patients and, in nearly two thirds of them, Vedolizumab treatment associates with ACD resolution/improvement.
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http://dx.doi.org/10.3390/jcm9072126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408734PMC
July 2020

Low frequency of COVID-19 in inflammatory bowel diseases.

Dig Liver Dis 2020 11 13;52(11):1234-1235. Epub 2020 Jun 13.

Department of Systems Medicine, University of Rome "TOR VERGATA", Rome, Italy; IBD group of Tor Vergata University Hospital, Rome, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.dld.2020.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293454PMC
November 2020

The impact of COVID-19 pandemic in the colorectal cancer prevention.

Int J Colorectal Dis 2020 Oct 4;35(10):1951-1954. Epub 2020 Jun 4.

Gastroenterology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.

Background: The coronavirus disease 2019 (COVID-19) has led to a policy of severe restrictions in almost all countries strongly involved by the pandemic. National Health System is among activities suffering from the COVID-19 and the lockdown.

Aim: To evaluate the impact of COVID-19 in colorectal cancer (CRC) prevention.

Methods: We report the change in the hospital organization to meet the growing healthcare needs determined by COVID-19. The limitations of CRC prevention secondary to COVID-19 and their effects on the healthcare are analyzed considering the features of the CRC screening programs in the average-risk population and endoscopic surveillance in patients with inflammatory bowel diseases (IBD).

Results: The interruption of CRC prevention may lead to a delayed diagnosis of CRC, possibly in a more advanced stage. The economic burden and the impact on workload for gastroenterologists, surgeons, and oncologists will be greater as long as the CRC prevention remains suspended. To respond to the increased demand for colonoscopy once COVID-19 will be under control, we should optimize the resources. It will be necessary to stratify the CRC risk and reach an order of priority. It should be implemented the number of health workers, equipment, and spaces dedicated to performing colonoscopy for screening purpose and in subjects with alarm symptoms in the shortest time. To this aim, the funds earmarked for healthcare should be increased.

Conclusion: The economic impact will be dramatic, but COVID-19 is the demonstration that healthcare has to be the primary goal of humans.
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http://dx.doi.org/10.1007/s00384-020-03635-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271141PMC
October 2020

Minimal Open Access Ileocolic Resection in Complicated Crohn's Disease of the Terminal Ileum.

Gastroenterol Res Pract 2020 28;2020:6019435. Epub 2020 Feb 28.

Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Umberto I Hospital-Via Lancisi 2, 00155 Rome, Italy.

The objective of this study was to evaluate the possibility to undertake an ileocolic resection in complex Crohn's disease using a minimal open abdominal access using standard laparoscopic instruments. The incision was carried out over the previous McBurney scar, with a mean length of 6 cm. Seventy-two patients with complicated Crohn's disease underwent IC resection in the considered period; 12 patients had a McBurney scar due to a previous appendectomy and represented the group of study. Feasibility and safety of the procedure were evaluated. Clinical data and outcome were compared with a control arm of 15 patients who had a standard laparoscopic IC resection, pooled out from our database among those who had a McBurney incision as service incision. Mean operative time and postoperative stay were significantly shorter in the study group. Blood loss and operative costs were also lower in the study group but did not reach statistical significance. Minimal open access ileocolic resection (MOAIR) through a small McBurney incision seems safe and feasible in complex Crohn's disease. Some advantages over standard laparoscopic surgery could be found in surgical outcomes and costs.
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http://dx.doi.org/10.1155/2020/6019435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064858PMC
February 2020

Impact of surgery on quality of life in Crohn's disease: short- and mid-term follow-up.

Updates Surg 2020 Sep 17;72(3):773-780. Epub 2020 Mar 17.

Gastrointestinal Surgery Unit, Tor Vergata University Hospital, Viale Oxford 81, 00133, Rome, Italy.

Active Crohn's disease has a substantial impact on Quality of Life (QoL). Medical management could be associated to side effects, hospitalization, long treatment period and requires patient's compliance, impacting QoL. Ileocecal resection (ICR) is often required, open or laparoscopic. Aim of the study was to assess Health-Related (HR) QoL changes following ICR, and to identify factors impacting on QoL in the short and mid-term. From a single institution, we created a prospective database of patients undergoing ICR from 01/2009 to 12/2015. HRQoL was analysed with Cleveland Global Quality of Life (CGQL) score, Overall Quality of Happiness (OQH), and asking patients if they would have surgery again. QoL scores were recorded at 30 days, 6, 12 and 36 months postoperatively and compared according to follow-up timing, technique, medical treatment and demographics. Statistical analysis included 187 patients. Mean follow-up was 3.8 ± 2.9 years. Both at 30 days and 6 months postoperatively, CGQL, its items and OQH increased significantly (p < 0.001). Increased values were also recorded at 1 and 3 years; 88% of patients would undergo surgery again. Laparoscopy was associated with improved CGQL scores, while preoperative steroids with worsen data. Young female patients, with penetrating pattern, experienced greater HRQoL improvements. Surgery is associated with improvements of HRQoL and patients' happiness in the short and mid-term. Laparoscopy, steroid-free and young patients showed the best results. ICR should be considered a reasonable alternative to non-operative strategies in selected cases.
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http://dx.doi.org/10.1007/s13304-020-00738-1DOI Listing
September 2020

PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.

Mod Pathol 2020 07 17;33(7):1398-1409. Epub 2020 Feb 17.

Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1 immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1 cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1 microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.
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http://dx.doi.org/10.1038/s41379-020-0497-0DOI Listing
July 2020

Response Assessed by Ultrasonography as Target of Biological Treatment for Crohn's Disease.

Clin Gastroenterol Hepatol 2020 08 20;18(9):2030-2037. Epub 2019 Dec 20.

Gastroenterology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. Electronic address:

Background & Aims: Mucosal healing, determined by ileocolonoscopy, is a goal for treatment of Crohn's disease (CD), but this is an invasive assessment procedure. We investigated whether response to tumor necrosis factor (TNF) antagonists, determined by small-intestine contrast ultrasonography, associates with long-term outcomes.

Methods: We performed observational study of 80 patients with CD treated with anti-TNF agents for at least 1 year who underwent serial small intestine contrast ultrasonography (SICUS) at the University of Rome, in Italy. SICUS was used to evaluate disease site (based on bowel wall thickness), extent of lesions, and presence of complications. Inclusion criteria required pre-therapy SICUS with follow-up SICUS after 18 months. At second SICUS, patients were assigned to categories of complete or partial responder or non-responder. CD-related outcomes (corticosteroid need, hospitalization, and surgery) were assessed at 1 year from the second SICUS, using multivariate models, and were analyzed after long term follow up (5 years) using Kaplan-Meier survival analysis.

Results: Based on SICUS, after a median of 18 months, 36 patients (51%) were complete responders, 30 were partial responders (34%), and 13 were non-responders (15%). At 1 year from the second SICUS, no patients with a complete response, based on ultrasonography, underwent surgery, in comparison to partial responders (P = .0003) or non-responders (P = .001). Complete responders used smaller amounts of corticosteroids than partial responders (P = .0001) or non-responders (P < .0001). Complete responders required fewer hospitalizations than non-responders (P = .001). Kaplan-Meier survival analysis of long-term follow up data demonstrated a lower cumulative probability of need for surgery, hospitalization, and need for steroids among SICUS-categorized complete responders (P < .0001, P = .003 and P = .0001 respectively) than SICUS-categorized non-responders.

Conclusions: In patients with CD, response to anti-TNF agents, determined by SICUS, is associated with better long-term outcomes than partial or no response. Ultrasonographic assessment therefore provides a relatively non-invasive method for monitoring response to treatment in patients with CD.
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http://dx.doi.org/10.1016/j.cgh.2019.10.042DOI Listing
August 2020

Inflammatory bowel disease versus Chlamydia trachomatis infection: a case report and revision of the literature.

Eur J Gastroenterol Hepatol 2020 03;32(3):454-457

Department of Systems Medicine, Unit of Gastroenterology, University 'Tor Vergata' of Rome.

Infectious proctitis may mimic inflammatory bowel disease, particularly when limited to the rectum. The present case report includes findings from a 50-year-old man, soldier, referring to our Inflammatory Bowel Disease Unit with a diagnosis of rectal Crohn's disease, refractory to conventional treatments. Mild anemia, hypergammaglobulinemia and HIV-antibodies seronegativity were detected. Entero-MRI and stool examinations were negative. Ileocolonoscopy detected few rectal ulcers with irregular edges. Endosonography showed marked thickening of the rectal wall and enlarged perirectal lymphnodes. Nodal and rectal fine needle aspirate did not show atypia (PAN CK-). Rectal biopsies showed flogistic granular tissue (PAN CK-): Warthin-Starry stain was negative. Previous Treponema pallidum infection was detected. Clinical history revealed habits at risk for sexually transmitted infection. Rectal swabs for RT-PCR for Chlamydia trachomatis, Neisseria gonorrhoeae, and Herpes Simplex Virus 1-2 lead to a diagnosis of lymphogranuloma venereum. Doxycycline 100 mg and Azitromicyn 500 mg t.i.d. were given for 21 days, followed by negativity for RT-PCR for Chlamydia trachomatis at rectal swabs. Complete disappearance of symptoms and mucosal healing occurred. Due to the increased frequency of infectious diseases, sexually transmitted infection (including lymphogranuloma venereum) should be considered as possible differential diagnosis when assessing patients with inflammatory bowel disease limited to the rectum.
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http://dx.doi.org/10.1097/MEG.0000000000001605DOI Listing
March 2020

ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment.

J Crohns Colitis 2020 Feb;14(2):155-168

Department of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical University Hospital, Department of Internal Medicine, Riga Stradiņš University, Riga, Latvia.

This article is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of previous guidelines.
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http://dx.doi.org/10.1093/ecco-jcc/jjz187DOI Listing
February 2020

Multiplex gene expression profile in inflamed mucosa of patients with Crohn's disease ileal localization: A pilot study.

World J Clin Cases 2019 Sep;7(17):2463-2476

Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Firenze, Firenze 50134, Italy.

Background: Crohn's disease (CD) is a complex disorder resulting from the interaction of genetic, environmental, and microbial factors. The pathogenic process may potentially affect any segment of the gastrointestinal tract, but a selective location in the terminal ileum was reported in 50% of patients.

Aim: To characterize clinical sub-phenotypes (colonic and/or ileal) within the same disease, in order to identify new therapeutic targets.

Methods: 14 consecutive patients undergoing surgery for ileal CD were recruited for this study. Peripheral blood samples from each patient were collected and the main polymorphisms of the gene (R702W, G908R, and 1007fs) were analyzed in each sample. In addition, tissue samples were taken from both the tract affected by CD and from the apparently healthy and disease-free margins (internal controls). We used a multiplex gene assay in specimens obtained from patients with ileal localization of CD to evaluate the simultaneous expression of 24 genes involved in the pathogenesis of the disease. We also processed surgery gut samples with routine light microscopy (LM) and transmission electron microscopy (TEM) techniques to evaluate their structural and ultrastructural features.

Results: We found a significant increase of Th17 (IL17A and IL17F, IL 23R and CCR6) and Th1 (IFN-γ) gene expression in inflamed mucosa compared to non-inflamed sites of 14 CD patients. and , two genes coding for antimicrobial peptides, were also strongly activated in inflamed ileal mucosa, suggesting the overwhelming stimulation of epithelial cells by commensal microbiota. IFN-γ and CCR6 were more expressed in inflamed mucosa of CD patients with ileal localization compared with patients with colonic localization suggesting a more aggressive inflammation process in this site. Morphological analysis of the epithelial lining of Lieberkün crypts disclosed enhanced release activity from goblet mucocytes, whereas the propria contained numerous cells pertaining to various lines.

Conclusion: We observed that the expression of ileal genes related to Th1 and Th17 activity is strongly activated as well as the expression of genes involved in microbiota regulation.
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http://dx.doi.org/10.12998/wjcc.v7.i17.2463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745337PMC
September 2019

Cancer Risk in Inflammatory Bowel Disease: A 6-Year Prospective Multicenter Nested Case-Control IG-IBD Study.

Inflamm Bowel Dis 2020 02;26(3):450-459

Department of Systems Medicine, GI Unit, Università degli Studi di Roma "Tor Vergata", Rome, Italy.

Background: In a 6-year, multicenter, prospective nested case-control study, we aimed to evaluate risk factors for incident cancer in inflammatory bowel disease (IBD), when considering clinical characteristics of IBD and immunomodulator use. The secondary end point was to provide characterization of incident cancer types.

Methods: All incident cases of cancer occurring in IBD patients from December 2011-2017 were prospectively recorded in 16 Italian Group for the Study of Inflammatory Bowel Disease units. Each of the IBD patients with a new diagnosis of cancer was matched with 2 IBD patients without cancer, according to IBD phenotype (ulcerative colitis [UC] vs Crohn's disease [CD]), age (±5 years), sex. Risk factors were assessed by multivariate logistic regression analysis.

Results: Cancer occurred in 403 IBD patients: 204 CD (CD cases), 199 UC (UC cases). The study population included 1209 patients (403 IBD cases, 806 IBD controls). Cancer (n = 403) more frequently involved the digestive system (DS; 32%), followed by skin (14.9%), urinary tract (9.7%), lung (6.9%), genital tract (6.5%), breast (5.5%), thyroid (1.9%), lymphoma (2.7%, only in CD), adenocarcinoma of the small bowel (SBA; 3.9%, 15 CD, 1 pouch in UC), other cancers (15.9%). Among cancers of the DS, colorectal cancer (CRC) more frequently occurred in UC (29% vs 17%; P < 0.005), whereas SBA more frequently occurred in CD (13% vs 6.3% P = 0.039). In CD, perforating (B3) vs non-stricturing non-perforating (B1) behavior represented the only risk factor for any cancer (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.33-4.11). In CD, risk factors for extracolonic cancer (ECC) were a B3 vs B1 and a stricturing (B2) vs B1 behavior (OR, 2.95; 95% CI, 1.62-5.43; OR, 1.79; 95% CI, 1.09-2.98). In UC, risk factors for ECC and for overall cancer were abdominal surgery for UC (OR, 4.63; 95% CI, 2.62-8.42; OR, 3.34; 95% CI, 1.88-5.92) and extensive vs distal UC (OR, 1.73; 95% CI, 1.10-2.75; OR, 1.99; 95% CI, 1.16-3.47). Another risk factor for ECC was left-sided vs distal UC (OR, 1.68; 95% CI, 1.00-2.86). Inflammatory bowel disease duration was a risk factor for skin and urinary tract cancers.

Conclusions: Perforating CD, extensive UC, and abdominal surgery for UC were identified as risk factors for overall incident cancer and for ECC. The clinical characteristics associated with severe IBD may increase cancer risk.
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http://dx.doi.org/10.1093/ibd/izz155DOI Listing
February 2020

Separation of Low- Versus High-grade Crohn's Disease-associated Small Bowel Carcinomas is Improved by Invasive Front Prognostic Marker Analysis.

J Crohns Colitis 2020 Mar;14(3):295-302

IBD, San Filippo Neri Hospital, Rome, Italy.

Background And Aims: Crohn's disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a minority of cases displaying a relatively favourable behaviour, thus outlining the need to improve the histopathological prediction of Crohn's disease-associated small bowel carcinoma prognosis.

Methods: As in recent studies on colorectal cancer, a substantial improvement in prognostic evaluations has been provided by the histological analysis of the tumour invasive front; we therefore systematically analysed the tumour budding and poorly differentiated clusters in the invasive front of 47 Crohn's disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium.

Results: Both tumour budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn's disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favourable small bowel carcinoma behaviour. In particular, association of tumour budding and poorly differentiated clusters in a combined invasive front score allowed identification of a minor subset of cancers [12/47, 25%] characterised by combined invasive front low grade coupled with a glandular histology and a low stage [I or II] and showing no cancer-related death during a median follow-up of 73.5 months.

Conclusions: The improved distinction of lower- from higher-grade Crohn's disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms.
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http://dx.doi.org/10.1093/ecco-jcc/jjz140DOI Listing
March 2020

Fecal and Mucosal Microbiota Profiling in Irritable Bowel Syndrome and Inflammatory Bowel Disease.

Front Microbiol 2019 17;10:1655. Epub 2019 Jul 17.

Unit of Digestive Disease, Campus Bio-Medico University, Rome, Italy.

An imbalance in the bacterial species resulting in the loss of intestinal homeostasis has been described in inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). In this prospective study, we investigated whether IBD and IBS patients exhibit specific changes in richness and distribution of fecal and mucosal-associated microbiota. Additionally, we assessed potential 16S rRNA gene amplicons biomarkers for IBD, IBS, and controls (CTRLs) by comparison of taxonomic composition. The relative abundance of bacteria, at phylum and genus/species levels, and the bacterial diversity were determined through 16S rRNA sequence-based fecal and mucosal microbiota analysis. Linear discriminant analysis effect size (LEfSe) was used for biomarker discovery associated to IBD and IBS as compared to CTRLs. In fecal and mucosal samples, the microbiota richness was characterized by a microbial diversity reduction, going from CTRLs to IBS to IBD. β-diversity analysis showed a clear separation between IBD and CTRLs and between IBD and IBS with no significant separation between IBS and CTRLs. β-diversity showed a clear separation between mucosa and stool samples in all the groups. In IBD, there was no difference between inflamed and not inflamed mucosa. Based upon the LEfSe data, the and Ruminococcaceae were identified as the most differentially abundant bacterial taxa in CTRLs. Erysipelotrichi was identified as potential biomarker for IBS, while Gammaproteobacteria, , and Enterococcaceae for IBD. This study provides an overview of the alterations of microbiota and may aid in identifying potential 16S rRNA gene amplicons mucosal biomarkers for IBD and IBS.
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http://dx.doi.org/10.3389/fmicb.2019.01655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650632PMC
July 2019
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