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1.
What does not look like celiac disease and instead it is.
Villanacci, V, Del Sordo, R, Setti, O, Zanini, B, Casella, G
Gastroenterology and hepatology from bed to bench. 2023;(2):230-233
Abstract
The celiac disease (CD) diagnosis sometimes is challenging and diagnostic process cannot always follow a simple algorithm but it requires a close collaboration between histo-pathologists, clinicians, laboratory and genetic experts. The genetic predisposition for CD is related to HLA-DQ2 and/or DQ8 but other HLA haplotypes and non-HLA genes may be involved in genetic predisposition. In particular DQ7 may represent an additive and independent CD risk associated haplotype. We describe an unusual case of a female 42 year old with a previous diagnosis of Hodgkin lymphoma, who has a clinical presentation suggestive for CD with negativity for anti-transglutaminase and anti-endomysium antibodies and HLA-DQ7 positivity.
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2.
Nutritional intervention with TGF-beta enriched food for special medical purposes (TGF-FSMP) is associated with a reduction of malnutrition, acute GVHD, pneumonia and may improve overall survival in patients undergoing allogeneic hematopoietic stem transplantation.
Morello, E, Brambilla, G, Bernardi, S, Villanacci, V, Carlessi, M, Farina, M, Radici, V, Samarani, E, Pellizzeri, S, Polverelli, N, et al
Transplant immunology. 2023;:101954
Abstract
Malnutrition in allogeneic stem cell transplant (allo-SCT) is associated with poor outcomes. Supplementation with Foods for Special Medical Purposes may be a valid alternative to enteral nutrition or total parental nutrition to reduce malnutrition in allo-SCT. In this study, 133 patients consecutively allo-transplanted were assessed for nutritional status by Patient- Generated Subjective Global Assessment (PG-SGA) and supplemented with TGF-beta enriched Food for Special Medical Purposes (TGF-FSMP). PG-SGA, gold standard for nutritional assessment in oncologic patients, was assessed at admission and on day 0, +7, +14, +21, and + 28 from transplant and categorized as follows: A = good nutritional status; B = moderate malnutrition; C = severe malnutrition. TGF-FSMP (Modulen-IBD) is currently used in Inflammatory Bowel Diseases (IBD) as primary nutritional support and in this study the dose was calculated according to BMI and total daily energy expenditure (TDEE). The patients assuming ≥50% of the prescribed TGF-FSMP dose were classified in Group A; the patients who received < 50% were included in Group B per protocol. The primary endpoint of the study was the assessment of the malnourished patients in Group A and B at day+28 after transplantation, according to the criteria of PG-SGA C categorization. At day +28 after transplant: i) patients in Group A were significantly less severely malnourished than patients in the Group B (21/76,28% vs 42/53, 79% respectively, OR 2.86 - CI 1.94-4.23 -, p = 0.000); ii) the incidence of severe (MAGIC II-IV) aGVHD and of any grade gastrointestinal (GI) aGVHD was higher in Group B than in Group A, (43% vs 21% p = 0.003) and (34.5% vs 9.2% p = 0.001); iii) Pneumonia was more frequent in the malnourished patients of Group B than in well/moderate nourished patients of Group A (52.7% vs 27.6% p = 0.002). In group A parenteral nutrition was avoided more frequently than in group B (67.5% vs 33.3% p = 0.000) and a median hospital stay of 27 days in comparison to 32 was reported (p = 0.006). The estimated median overall survival (OS) of the population was 33 months in Group A and 25.1 months in group B (p = 0.03). By multivariate and ANN analysis, TGF-FSMP TR < 50% assumption was significantly correlated with malnutrition, severe and GI aGVHD, pneumonia and reduced OS.
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3.
hERG1 Potassium Channel Expression in Colorectal Adenomas: Comparison with Other Preneoplastic Lesions of the Gastrointestinal Tract.
Lastraioli, E, Iorio, J, Petrelli, F, Tomezzoli, A, Battista, S, Ambrosio, MR, Chiudinelli, M, De Salvatore, F, Messerini, L, Villanacci, V, et al
Current issues in molecular biology. 2022;(3):1326-1331
Abstract
Preneoplastic lesions represent a useful target for early diagnosis and follow-up of gastrointestinal malignancies. hERG1 channel expression was tested by immunohistochemistry (IHC) in a cohort of colorectal adenoma samples belonging to Italian subjects. Overall, hERG1 was expressed in 56.5% of cases with both high staining intensity and a high percentage of positive cells. Moreover, hERG1 was expressed in a higher percentage of dysplastic adenomas with respect to hyperplastic lesions, and the proportion of positive samples further increased in patients with high-grade dysplasia. Comparing hERG1 expression in other preneoplastic lesions of the GI tract (gastric dysplasia and Barrett's esophagus), it emerged that in all the conditions, hERG1 was expressed with a diffused pattern, throughout the cell, with variable staining intensity within the samples. The highest expression was detected in gastric dysplasia samples and the lowest in Barrett's esophagus at similar levels observed in colorectal adenomas. Our results show that hERG1 is aberrantly expressed in human preneoplastic lesions of the gastrointestinal tract and has a different pattern of expression and role in the different sites. Overall, the detection of hERG1 expression in preneoplastic lesions could represent a novel diagnostic or prognostic marker of progression in the gastrointestinal tract.
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4.
Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.
Rostami, K, Ensari, A, Marsh, MN, Srivastava, A, Villanacci, V, Carroccio, A, Asadzadeh Aghdaei, H, Bai, JC, Bassotti, G, Becheanu, G, et al
Nutrients. 2022;(12)
Abstract
Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.
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5.
Histopathology of intestinal villi in neonatal and paediatric age: main features with clinical correlation - Part II.
Rossi, C, Simoncelli, G, Arpa, G, Stracuzzi, A, Parente, P, Fassan, M, Vanoli, A, Villanacci, V
Pathologica. 2022;(1):22-31
Abstract
In this paper, we will continue the description of histological findings of infantile and paediatric small bowel alterations with the main clinical pictures and differential diagnosis. We emphasise once again the need to evaluate the biopsies in an adequate clinical contest and with a systematic approach, including epithelial alterations, lamina propria changes, mucosal architecture, and the distribution of inflammation, together with other morphological signs more specific of certain diseases. We describe the histological findings of coeliac and Crohn's disease, gastrointestinal food allergic diseases, Langerhans cell histiocytosis, nutritional deficiencies and infections. Finally, we suggest the principal issues in the drafting the pathological report for appropriate interpretation and usefulness in clinical practice.
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6.
Non-celiac wheat sensitivity: rationality and irrationality of a gluten-free diet in individuals affected with non-celiac disease: a review.
Sergi, C, Villanacci, V, Carroccio, A
BMC gastroenterology. 2021;(1):5
Abstract
Non-celiac gluten or wheat sensitivity (NCWS) is a "clinical entity induced by the ingestion of wheat leading to intestinal and/or extraintestinal symptoms that improve once the wheat-containing foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded". This mostly accepted definition raises several points that remain controversial on this condition. In the present review, the authors summarize the most recent advances in the clinic and research on NCWS through an accurate analysis of different studies. We screened PubMed, Medline, Embase, and Scopus using the keywords "non-celiac gluten sensitivity", "non-celiac wheat sensitivity", and "diagnosis". We would like to emphasize two main points, including (A) the controversial clinical and etiological aspects in different trials and experiences with particular attention to the Salerno criteria for the diagnosis of NCWS and (B) the histological aspects. The etiology of NCWS remains controversial, and the relationship with irritable bowel syndrome is obscure. Histologically, the duodenal mucosa may show a variable pattern from unremarkable to a slight increase in the number of T lymphocytes in the superficial epithelium of villi. The endorsement of this disease is based on a positive response to a gluten-free diet for a limited period, followed by the reappearance of symptoms after gluten challenge. The Salerno expert criteria may help to diagnose NCWS accurately. Social media and inaccurate interpretation of websites may jeopardize the diagnostic process if individuals self-label as gluten intolerant.
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7.
Neonatal Nav1.5 Protein Expression in Human Colorectal Cancer: Immunohistochemical Characterization and Clinical Evaluation.
Lastraioli, E, Fraser, SP, Guzel, RM, Iorio, J, Bencini, L, Scarpi, E, Messerini, L, Villanacci, V, Cerino, G, Ghezzi, N, et al
Cancers. 2021;(15)
Abstract
Voltage-gated Na+ channels (VGSCs) are expressed widely in human carcinomas and play a significant role in promoting cellular invasiveness and metastasis. However, human tissue-based studies and clinical characterization are lacking. In several carcinomas, including colorectal cancer (CRCa), the predominant VGSC is the neonatal splice variant of Nav1.5 (nNav1.5). The present study was designed to determine the expression patterns and clinical relevance of nNav1.5 protein in human CRCa tissues from patients with available clinicopathological history. The immunohistochemistry was made possible by the use of a polyclonal antibody (NESOpAb) specific for nNav1.5. The analysis showed that, compared with normal mucosa, nNav1.5 expression occurred in CRCa samples (i) at levels that were significantly higher and (ii) with a pattern that was more delineated (i.e., apical/basal or mixed). A surprisingly high level of nNav1.5 protein expression also occurred in adenomas, but this was mainly intracellular and diffuse. nNav1.5 showed a statistically significant association with TNM stage, highest expression being associated with TNM IV and metastatic status. Interestingly, nNav1.5 expression co-occurred with other biomarkers associated with metastasis, including hERG1, KCa3.1, VEGF-A, Glut1, and EGFR. Finally, univariate analysis showed that nNav1.5 expression had an impact on progression-free survival. We conclude (i) that nNav1.5 could represent a novel clinical biomarker ('companion diagnostic') useful to better stratify CRCa patients and (ii) that since nNav1.5 expression is functional, it could form the basis of anti-metastatic therapies including in combination with standard treatments.
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8.
Insulinoma Identified in Puerperium: Association with Pregnancy and Literature Review.
Orabona, R, Zanardini, C, Lojacono, A, Zatti, S, Cappelli, C, Tiberio, GA, Villanacci, V, Sartori, E
European journal of case reports in internal medicine. 2020;(4):001556
Abstract
UNLABELLED Postpartum hypoglycemia in non-diabetic women is a rare condition. We report the case of a 34-year-old woman who experienced neuroglycopenia 2 days after delivery. Corresponding to severe hypoglycemia, we found inappropriately elevated insulin and C-peptide levels. Following magnetic resonance imaging a lesion of 10×8 mm was detected in the head of the pancreas. An ultrasound-guided fine needle aspiration of the mass confirmed the diagnostic suspicion of a pancreatic neuroendocrine tumor. Complete surgical enucleation of the insulinoma resulted in immediate and permanent resolution of the hypoglycemia. The postoperative course was uneventful. Histopathological and immunohistochemical analyses were consistent with insulinoma. The diagnostic approach to postpartum hypoglycemia represents a challenge for multidisciplinary teamwork. LEARNING POINTS Although insulinomas are extremely rare during pregnancy, most cases are recognized or become symptomatic during the first trimester.Symptoms of insulinomas may be initially masked due to changes in glucose metabolism and insulin resistance associated with pregnancy.In pregnancy, surgical treatment should be avoided whenever possible because of the risks to both mother and fetus; conservative treatment, including dietary intake, intravenous glucose and glucagon, should be initiated to control the hypoglycemia symptoms.
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9.
hERG1 and HIF-2α Behave as Biomarkers of Positive Response to Bevacizumab in Metastatic Colorectal Cancer Patients.
Iorio, J, Lastraioli, E, Tofani, L, Petroni, G, Antonuzzo, L, Messerini, L, Perrone, G, Caputo, D, Francesconi, M, Amato, MM, et al
Translational oncology. 2020;(3):100740
Abstract
BACKGROUND In search of novel biomarkers of response to bevacizumab in metastatic colorectal cancer (mCRC), we analyzed the expression and prognostic role of several proteins related to angiogenesis. METHODS A retrospective, multicenter study on 80 surgical samples from mCRC patients treated in first line with bevacizumab plus chemotherapy was accomplished. The following proteins were analyzed by immunohistochemistry: hERG1 potassium channel, β1-integrin, pAKT, NFkB, HIF-1α, HIF-2α, p53, VEGF-A, GLUT-1, and CA-IX. Data were analyzed in conjunction with the clinicopathological characteristics of the patients, KRAS status, response to bevacizumab, and follow-up. RESULTS (1) All the proteins were expressed in the samples, with statistically significant associations between HIF-1α and gender, HIF-2α and left colon, hERG1 and VEGF-A, β1-integrin and HIF-2α, GLUT-1 and both HIF-1α and HIF-2α, and CA-IX and VEGF-A. (2) At the univariate analysis, positivity for hERG1, VEGF-A, and the active form of HIF-2α (aHIF-2α), and the G3 histological grade showed a positive impact on progression-free survival (PFS). (3) hERG1 and aHIF-2α maintained their positive impact on PFS at the multivariate analysis. (4) hERG1 behaved as a protective factor for PFS independently on KRAS status. CONCLUSIONS hERG1 and aHIF-2α might help to identify patients who would benefit from bevacizumab treatment.
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10.
PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.
Giuffrida, P, Arpa, G, Grillo, F, Klersy, C, Sampietro, G, Ardizzone, S, Fociani, P, Fiocca, R, Latella, G, Sessa, F, et al
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2020;(7):1398-1409
Abstract
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.