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  • 1
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    Online Resource
    Liver-Specific Contrast-Enhanced Magnetic Resonance Cholangio-Pancreatography (Ce-MRCP) in Non-Invasive Diagnosis of Iatrogenic Biliary Leakage
    MDPI AG ; 2023
    In:  Diagnostics Vol. 13, No. 10 ( 2023-05-09), p. 1681-
    Details
    In: Diagnostics, MDPI AG, Vol. 13, No. 10 ( 2023-05-09), p. 1681-
    Abstract: Current non-invasive diagnostic modalities of iatrogenic bile leak (BL) are not particularly sensitive and often fail to localise the BL origin. Percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP) are considered the gold standard, yet are invasive studies with potential complications. Ce-MRCP has been not comprehensively studied in this setting but may prove particularly helpful given its non-invasive nature and the anatomical dynamic detail. This paper reports a monocentric retrospective study of BL patients referred between January 2018 and November 2022 submitted to Ce-MRCP followed by PTC. The primary outcome was the accuracy of Ce-MRCP in detecting and localising BL compared to PTC and ERCP. Blood tests, coexisting cholangitis features and time for leak resolution were also investigated. Thirty-nine patients were included. Liver-specific contrast-enhanced MRCP detected BL in 69% of cases. The BL localisation was 100% accurate. Total bilirubin above 4 mg/dL was significantly associated with false negative results of Ce-MRCP. Ce-MRCP is highly accurate in detecting and localising BL, but sensitivity is significantly reduced by a high bilirubin level. Ce-MRCP may be very useful in early BL diagnosis and in accurate pre-treatment planning, but can only be reliably used in selected patients with TB 〈 4 mg/dL. Non-surgical techniques, both radiological and endoscopic, are proven to be effective in terms of leak resolution.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics13101681
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662336-5
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  • 2
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    Online Resource
    Role of TGF-Beta and Smad7 in Gut Inflammation, Fibrosis and Cancer
    MDPI AG ; 2020
    In:  Biomolecules Vol. 11, No. 1 ( 2020-12-27), p. 17-
    Details
    In: Biomolecules, MDPI AG, Vol. 11, No. 1 ( 2020-12-27), p. 17-
    Abstract: The human gastrointestinal tract contains the largest population of immune cells in the body and this is a reflection of the fact that it is continuously exposed to a myriad of dietary and bacterial antigens. Although these cells produce a variety of inflammatory cytokines that could potentially promote tissue damage, in normal conditions the mucosal immune response is tightly controlled by counter-regulatory factors, which help induce and maintain gut homeostasis and tolerance. One such factor is transforming growth factor (TGF)-β1, a cytokine produced by multiple lineages of leukocytes, stromal cells and epithelial cells, and virtually targets all the gut mucosal cell types. Indeed, studies in animals and humans have shown that defects in TGF-β1 production and/or signaling can lead to the development of immune-inflammatory pathologies, fibrosis and cancer in the gut. Here, we review and discuss the available evidence about the role of TGF-β1 and Smad7, an inhibitor of TGF-β1 activity, in gut inflammation, fibrosis and cancer with particular regard to the contribution of these two molecules in the pathogenesis of inflammatory bowel diseases and colon cancer.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom11010017
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2701262-1
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  • 3
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    Online Resource
    Frequency and Predictors of Dysplasia in Pseudopolyp-like Colorectal Lesions in Patients with Long-Standing Inflammatory Bowel Disease
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 13 ( 2023-06-27), p. 3361-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 13 ( 2023-06-27), p. 3361-
    Abstract: Current endoscopic surveillance programs do not consider inflammatory bowel disease (IBD)-associated post-inflammatory polyps (pseudopolyps) per se clinically relevant, even though their presence seems to increase the risk of colorectal cancer (CRC). However, it remains unclear whether the link between pseudopolyps and CRC is indirect or whether some subsets of pseudopolyp-like lesions might eventually undergo neoplastic transformation. This study aimed to assess the frequency and predictors of dysplasia in pseudopolyp-like lesions in a population with long-standing colonic IBD. This was a retrospective, single-center study including patients with a colonic IBD (median disease duration of 192 months) and at least a pseudopolyp-like lesion biopsied or resected in the period from April 2021 to November 2022. One hundred and five pseudopolyps were identified in 105 patients (80 with ulcerative colitis and 25 with Crohn’s disease). Twenty-three out of 105 pseudopolyp samples (22%) had dysplastic foci, and half of the dysplastic lesions were hyperplastic. Multivariate analysis showed that the age of the patients (odds ratio (OR) 1.1; p = 0.0012), size (OR 1.39; p = 0.0005), and right colonic location (OR 5.32; p = 0.04) were independent predictors of dysplasia, while previous exposure to immunosuppressors/biologics and left colonic location of the lesions were inversely correlated to dysplasia (OR 0.11; p = 0.005, and OR 0.09; p = 0.0008, respectively). No differences were seen between ulcerative colitis and Crohn’s disease patients. Lesions with a size greater than 5 mm had a sensitivity of 87% and a specificity of 63% to be dysplastic. These data show that one-fourth of pseudopolyp-like lesions evident during surveillance colonoscopy in patients with longstanding IBD bear dysplastic foci and suggest treating such lesions properly.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15133361
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 4
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    Online Resource
    Difficult Biliary Stones: A Comprehensive Review of New and Old Lithotripsy Techniques
    MDPI AG ; 2022
    In:  Medicina Vol. 58, No. 1 ( 2022-01-13), p. 120-
    Details
    In: Medicina, MDPI AG, Vol. 58, No. 1 ( 2022-01-13), p. 120-
    Abstract: Biliary stones represent the most common indication for therapeutic endoscopic retrograde cholangiopancreatography. Many cases are successfully managed with biliary sphincterotomy and stone extraction with balloon or basket catheters. However, more complex conditions secondary to the specific features of stones, the biliary tract, or patient’s needs could make the stone extraction with the standard techniques difficult. Traditionally, mechanical lithotripsy with baskets has been reported as a safe and effective technique to achieve stone clearance. More recently, the increasing use of endoscopic papillary large balloon dilation and the diffusion of single-operator cholangioscopy with laser or electrohydraulic lithotripsy have brought new, safe, and effective therapeutic possibilities to the management of such challenging cases. We here summarize the available evidence about the endoscopic management of difficult common bile duct stones and discuss current indications of different lithotripsy techniques.
    Type of Medium: Online Resource
    ISSN: 1648-9144
    URL: Article
    DOI: 10.3390/medicina58010120
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2088820-X
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  • 5
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    Online Resource
    Endoscopic Gallbladder Drainage: A Comprehensive Review on Indications, Techniques, and Future Perspectives
    MDPI AG ; 2024
    In:  Medicina Vol. 60, No. 4 ( 2024-04-14), p. 633-
    Details
    In: Medicina, MDPI AG, Vol. 60, No. 4 ( 2024-04-14), p. 633-
    Abstract: In recent years, therapeutic endoscopy has become a fundamental tool in the management of gallbladder diseases in light of its minimal invasiveness, high clinical efficacy, and good safety profile. Both endoscopic transpapillary gallbladder drainage (TGBD) and endoscopic ultrasound (EUS)-guided gallbladder drainage (EUS-GBD) provide effective internal drainage in patients with acute cholecystitis unfit for cholecystectomy, avoiding the drawbacks of external percutaneous gallbladder drainage (PGBD). The availability of dedicated lumen-apposing metal stents (LAMS) for EUS-guided transluminal interventions contributed to the expansion of endoscopic therapies for acute cholecystitis, making endoscopic gallbladder drainage easier, faster, and hence more widely available. Moreover, EUS-GBD with LAMS opened the possibility of several cholecystoscopy-guided interventions, such as gallstone lithotripsy and clearance. Finally, EUS-GBD has also been proposed as a rescue drainage modality in malignant biliary obstruction after failure of standard techniques, with encouraging results. In this review, we will describe the TBGD and EUS-GBD techniques, and we will discuss the available data on clinical efficacy in different settings in comparison with PGBD. Finally, we will comment on the future perspectives of EUS-GBD, discussing the areas of uncertainty in which new data are more strongly awaited.
    Type of Medium: Online Resource
    ISSN: 1648-9144
    URL: Article
    DOI: 10.3390/medicina60040633
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
    detail.hit.zdb_id: 2088820-X
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  • 6
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    Online Resource
    A Novel Smad7 Genetic Variant Mapping on the Genomic Region Targeted by Mongersen Is Associated with Crohn’s Disease
    MDPI AG ; 2020
    In:  Biomedicines Vol. 8, No. 8 ( 2020-07-22), p. 234-
    Details
    In: Biomedicines, MDPI AG, Vol. 8, No. 8 ( 2020-07-22), p. 234-
    Abstract: Background: Down-regulation of Smad7 with a specific Smad7 antisense (AS) oligonucleotide-containing oral drug (Mongersen) was effective in pre-clinical studies and initial clinical trials in Crohn’s disease (CD) patients. A recent phase 3 trial was discontinued due to an apparent inefficacy of the drug, but factors contributing to the failure of this study remain unknown. Here, we analysed the frequency in CD of rs144204026 C/T single nucleotide polymorphism (SNP), which maps on the corresponding region targeted by the Smad7 AS contained in the Mongersen formulation and examined whether such a variant allele affects the ability of Smad7 AS to knockdown Smad7. Methods: rs144204026 SNP frequency was evaluated in two independent Italian cohorts of Crohn’s disease patients and normal controls. Genotyping was performed by allelic discrimination assay. Smad7 expression was evaluated in wild-type or heterozygous PBMCs treated with Smad7 AS. Results: No TT genotype was seen in CD patients and controls. Heterozygous genotype was more frequent in CD patients of both cohort 1 (11/235, 4.68%) and cohort 2 (8/122, 6.56%) as compared to controls (6/363, 1.65%; p = 0.029 and p = 0.01 respectively). Overall, a statistically significant association was observed between the T variant allele and CD patients’ susceptibility (p = 0.008; OR = 3.28, 95%CI: 1.3–8.3). Smad7 AS down-regulated Smad7 RNA independently of the presence of the variant allele. Conclusions: This is the first study to show an association between Smad7 rs144204026 SNP and CD patients. Data indicate that such a variant does not negatively influence the in vitro inhibitory effect of Smad7 AS on Smad7.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines8080234
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720867-9
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  • 7
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    Online Resource
    Endoscopic Predictors of Neoplastic Lesions in Inflammatory Bowel Diseases Patients Undergoing Chromoendoscopy
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 18 ( 2022-09-12), p. 4426-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 18 ( 2022-09-12), p. 4426-
    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.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14184426
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 8
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    Online Resource
    Endoscopic Ultrasound Plus Endoscopic Retrograde Cholangiopancreatography Based Tissue Sampling for Diagnosis of Proximal and Distal Biliary Stenosis Due to Cholangiocarcinoma: Results from a Retrospective Single-Center Study
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 7 ( 2022-03-29), p. 1730-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 7 ( 2022-03-29), p. 1730-
    Abstract: Differentiating between benign and malignant biliary stenosis (BS) is challenging, where tissue diagnosis plays a crucial role. Endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling and endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) or biopsy (FNB) are used to obtain tissue specimens from BS. The aim of this retrospective study was to evaluate the diagnostic yield of EUS-FNA/B plus ERCP with brushing or forceps biopsy in BS. All endoscopic procedures performed in patients with BS at our gastroenterology unit were reviewed. The gold standard for diagnosis was histopathology of surgical specimens or the progression of the malignancy at radiological or clinical follow-up. A total of 70 endoscopic procedures were performed in 51 patients with BS. Final endoscopic diagnosis was reached in 96% of the patients and was malignant in 61.7% and benign in 38.3% of cases. Sensitivity, specificity, and diagnostic accuracy were 73.9%, 100%, and 80%, respectively, for EUS-FNA/B; 66.7%, 100%, and 82.5% for ERCP; and 83.3%, 100%, and 87.5% for both procedures carried out in the same session. The combination of EUS and ERCP tissue sampling seems to increase diagnostic accuracy in defining the etiology of BS. Performing both procedures in a single session reduces the time required for diagnostic work-up and optimizes resources.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14071730
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 9
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    Online Resource
    Role of Interleukin-34 in Cancer
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 1 ( 2020-01-20), p. 252-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 1 ( 2020-01-20), p. 252-
    Abstract: Cross-talk between cancer cells and the immune cells occurring in the tumor microenvironment is crucial in promoting signals that foster tumor growth and metastasis. Both cancer cells and immune cells secrete various interleukins (IL), which, either directly or indirectly, stimulate cancer-cell proliferation, survival, and diffusion, as well as contribute to sculpt the immune microenvironment, thereby amplifying tumorigenic stimuli. IL-34, a cytokine produced by a wide range of cells, has been initially involved in the control of differentiation, proliferation, and survival of myeloid cells. More recent studies documented the overexpression of IL-34 in several cancers, such as hepatocarcinoma, osteosarcoma, multiple myeloma, colon cancer, and lung cancer, and showed that tumor cells can produce and functionally respond to this cytokine. In this review, we summarize the multiple roles of IL-34 in various cancers, with the aim to better understand the relationship between the expression of this cytokine and cancer behavior and to provide new insights for exploring a new potential therapeutic target.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12010252
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 10
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    Online Resource
    Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 8 ( 2021-04-10), p. 3922-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 8 ( 2021-04-10), p. 3922-
    Abstract: In physiological conditions, the human intestinal mucosa is massively infiltrated with various subsets of immune cells, the activity of which is tightly regulated by several counter-regulatory factors. One of these factors is transforming growth factor-β1 (TGF-β1), a cytokine produced by multiple cell types and targeting virtually all the intestinal mucosal cells. Binding of TGF-β1 to its receptors triggers Smad2/3 signaling, thus culminating in the attenuation/suppression of immune–inflammatory responses. In patients with Crohn’s disease and patients with ulcerative colitis, the major human inflammatory bowel diseases (IBD), and in mice with IBD-like colitis, there is defective TGF-β1/Smad signaling due to high levels of the intracellular inhibitor Smad7. Pharmacological inhibition of Smad7 restores TGF-β1 function, thereby reducing inflammatory pathways in patients with IBD and colitic mice. On the other hand, transgenic over-expression of Smad7 in T cells exacerbates colitis in various mouse models of IBD. Smad7 is also over-expressed in other inflammatory disorders of the gut, such as refractory celiac disease, necrotizing enterocolitis and cytomegalovirus-induced colitis, even though evidence is still scarce and mainly descriptive. Furthermore, Smad7 has been involved in colon carcinogenesis through complex and heterogeneous mechanisms, and Smad7 polymorphisms could influence cancer prognosis. In this article, we review the data about the expression and role of Smad7 in intestinal inflammation and cancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22083922
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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