Abstract Background Inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC), are chronic and immune-mediated diseases with a relapsing-remitting trend. The overall incidence of these diseases is increasing. However, it is estimated that more than one third of patients experienced symptoms for more than one year before diagnosis. Delay in IBD diagnosis has several clinical, therapeutic and economic implications. Early diagnosis and proper treatment are the cornerstones for improving the standard of care for these patients. This study aims to evaluate the diagnostic delay (DD) in patients with IBD and to analyze the clinical burden of the delay in IBD diagnosis in patients treated with biological drugs. Methods An observational and retrospective study was performed in IBD patients, regularly followed in four IBD Units. Data regarding delay in IBD diagnosis were assessed through a questionnaire evaluating the disease course. Moreover, data about biologics dispensation were obtained from the medical records in the period 2020-2022 Results 135 IBD patients were enrolled (UC 72, CD 63, M 80, F 55). Median age at diagnosis was 32 years (IQR 22-45); 7% of patients were ≤ 16 years old at diagnosis. Median age on erollement was 47 ( IQR 4-59) Median DD was 12 months (IQR: 6-24). No significant difference was found in median DD between UC [12 months (IQR: 4.5-12.0)] and CD patients [12 months (IQR: 12-48)]. However, the proportion of patients with a DD >24 months was significantly (p=0.007) higher in CD (21/63 = 33%) than in UC patients (10/72=13%). After a median disease duration of 10 years (IQR: 4-17), overall, 67 patients (49.7%) were exposed to one biologic agent, 43 patients (31.8%) were exposed to two biologic agents, 25 (18.5%) to three or more biologic agents. 23% of patients (31/135) underwent surgery. The statistical analysis showed that DD >24 months was not statistically significant associated with history of ≥ 2 biological drugs (p=0.51). Conversely, there was association with surgical treatment (p=0.004). Conclusion The diagnostic delay in IBD represents a challenge with clinical and, therapeutic impact. It’s crucial to cooperate with general practitioner and gastroenterologists not dedicated to IBD in order to reduce the diagnostic delay and guarantee an effective, appropriate and early treatment that will improve the patients’ quality of life and meanwhile reduce the health care system costs.

BACKGROUND:There are little data on the epidemiological and clinical features of adult patients with ulcerative colitis (UC) in the different Italian regions, mainly derived from the absence of a national registry. This prevents correct interpretation of the disease burden.AIM:To assess the main clinical and epidemiological features of adult patients diagnosed with UC in Sardinia, Italy.METHODS:We performed a multicenter, observational, cross-sectional study that included adult patients with UC enrolled in seven gastroenterology unit centers in Sardinia. Data were obtained from the patients' medical records and from a questionnaire administered at the inclusion visit.RESULTS:Four hundred and forty-two patients with UC were included. The median age at diagnosis was 39 years (interquartile range 28-48). After a median disease duration of 10 years, 53 patients experienced proximal extension of proctitis or left-sided colitis. Seventy-five patients developed extraintestinal manifestations. Nineteen patients (4.3%) developed cancer: two with colorectal cancer and seventeen with extracolonic cancers. Mesalazine (5-ASA) remains the mainstay of treatment for UC. Overall, 95 patients (21.5%) were treated with one or more biologic agents, whereas 15 patients (3.4%) underwent surgery, mostly colectomy.CONCLUSION:Our results provide important insights into the clinical and epidemiological features of patients with UC, and while waiting for a national Italian registry, present eligible data on the UC population in Sardinia.

Smell strongly contributes to food choice and intake, influencing energy balance and body weight; its reduction or loss has been related to malnutrition problems. Some patients with inflammatory bowel disease (IBD), mainly Crohn’s disease (CD) and ulcerative colitis (UC), are underweight, while others are overweight. Some studies suggest that changes in eating habits could be linked to specific disorders of the olfactory functions. We assessed the olfactory performance in 199 subjects (healthy control (HC) n = 99, IBD n = 100), based on the olfactory Threshold, Discrimination and Identification score (TDI score), measured with the “Sniffin’ Sticks” test. Subjects were genotyped for the rs2590498 polymorphism of the OBPIIa gene. IBD patients showed both a slightly, but significantly, lower olfactory function and a higher BMI compared to HC subjects. Threshold (in both population) and Discrimination (in IBD patients) olfactory score were affected by the OBPIIa genotype. BMI was influenced by both health status and OBPIIa genotype. A lower olfactory function may delay the satiety sensation and thus increase meal duration and body weight in IBD patients. However, the AA genotype of the OBPIIa seems to “protect” IBD patients from more severe olfactory dysfunction.

New biologic agents (vedolizumab, ustekinumab and tofacitinib) represent an effective treatment for inflammatory bowel diseases and have been recently approved. However, with a rapidly evolving complement of advanced targeted therapies, new concerns about their potentially undesirable effects on liver function emerge. In particular, little is known about safety data in patients with hepatitis B virus, hepatitis C virus chronic infections, cirrhosis and in transplanted patients who are accumulating. In addition, these new agents have also been associated with drug-induced liver injury. Limited data on the efficacy of vedolizumab in patients with primary sclerosing cholangitis are also available. This article reviews available data about hepatic safety concerns in patients receiving vedolizumab, ustekinumab and tofacitinib with and without preexistent hepatic diseases.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract resulting from interactions among various factors with diet being one of the most significant. IBD-related dietary behaviors are not clearly related to taste dysfunctions. We analyzed body mass index (BMI) and perception of six taste qualities and assessed effects of specific taste genes in IBD patients and healthy subjects (HC). BMI in IBD patients was higher than in HC subjects. Taste sensitivity to taste qualities was reduced in IBD patients, except for sour taste, which was higher than in HC subjects. Genetic variations were related to some taste responses in HC subjects, but not in IBD patients. Frequencies of genotype AA and allele A in CD36 polymorphism (rs1761667) were significantly higher in IBD patients than in HC subjects. The taste changes observed could be explained by the oral pathologies and microbiome variations known for IBD patients and can justify their typical dietary behaviors. The lack of genetic effects on taste in IBD patients indicates that IBD might compromise taste so severely that gene effects cannot be observed. However, the high frequency of the non-tasting form of CD36 substantiates the fact that IBD-associated fat taste impairment may represent a risk factor for IBD.

Abstract Background & Aims Malnutrition with the accumulation of fat tissue and nonalcoholic fatty liver disease (NAFLD) are conditions associated with inflammatory bowel disease (IBD). Visceral fat and NAFLD-related liver dysfunction can both worsen intestinal inflammation. Because the Mediterranean diet (Md) has been shown to ameliorate both obesity and NAFLD, the aim of this study was to analyze the impact of Md on the nutritional state, liver steatosis, clinical disease activity, and quality of life (QoL) in IBD patients. Methods Patients with IBD, both Crohn’s disease (CD) and ulcerative colitis (UC), followed Md for 6 months. Their body mass index (BMI), body tissue composition, liver steatosis and function, serum lipid profile, clinical disease activity, and inflammatory biomarkers (C-reactive protein and fecal calprotectin) were collected at baseline (T0) and compared with those obtained after 6 months (T180) to evaluate the impact of Md. Results One hundred forty-two IBD patients, 84 UC and 58 CD, followed Md for 6 months. At T180, diet-adherent CD and UC improved BMI (UC −0.42, P = 0.002; CD −0.48, P = 0.032) and waist circumference (UC −1.25 cm, P = 0.037; CD −1.37 cm, P = 0.041). Additionally, the number of patients affected by liver steatosis of any grade was significantly reduced in both groups (UC T0 31 of 84 [36.9%] vs T180 18 of 84 [21.4%], P = 0.0016; CD T0 27 of 58 [46.6%] vs T180 18 of 58 [31.0%], P < 0.001) after dietary intervention. Finally, after 6 months of the diet, fewer UC and CD patients with stable therapy had active disease (UC T0 14 of 59 [23.7%] vs T180 4 of 59 [6.8%], P = 0.004; CD T0 9 of 51 [17.6%] vs T180 2 of 51 [3.0%], P = 0.011) and elevated inflammatory biomarkers. Mediterranean diet improved QoL in both UC and CD, but neither serum lipid profile nor liver function were modified by the diet. Conclusions A significant reduction of malnutrition-related parameters and liver steatosis was observed in both CD and UC patients after short-term dietary intervention based on the adoption of Md, and this was associated with a spontaneous improvement of disease activity and inflammatory markers.

An 82-year-old man presented with jaundice and evidence of a stricture in the mid common bile duct (CBD), with wall thickening detected on CT scan (Fig. 1). The patient underwent endoscopic ultrasound that showed a hypoechoic, endoductal, hypovascularized lesion of the mid CBD measuring 12.7 mm in diameter. EUS-guided fine-needle biopsy was performed in this area, and histocytopathologic evaluation results were inconclusive. An ERCP with sphincterotomy brushing and subsequent positioning of a fully covered self-expandable metal stent (FC-SEMS), 10 × 80 mm, was performed with progressive resolution of jaundice. Nevertheless, cytologic and histologic analysis revealed inconclusive results. Thus, 15 days later, a second ERCP was performed for repeat tissue acquisition for a possible definitive diagnosis. After removing the biliary FC-SEMS, the fluoroscopic images showed persistence of the stricture in the mid CBD (Fig. 2). Dilation of the distal CBD created by the indwelling FC-SEMS previously placed allowed us to perform direct peroral cholangioscopy using a slim (8.5-mm diameter, 2.8-mm working channel; Fujifilm EG 530FP, Tokyo, Japan) endoscope with free-hand technique under CO2 insufflation to prevent air embolism. The endoscope is manipulated to assume a “J” configuration by left torch to maintain a stable position in front of the papilla. A concentric, obstructing lesion with dilated and tortuous vessels in the mid CBD was revealed (Fig. 3). Under direct endoscopic visualization, multiple targeted biopsy specimens were obtained with regular forceps for histopathologic analysis (Figs. 4 and 5). Finally, an FC-SEMS, 10 × 60 mm, was placed. No adverse events occurred during the procedure or at the subsequent follow-up. Histologic analysis revealed a cholangiocarcinoma (Fig. 6). Therefore, the patient was scheduled for surgery (Video 1, available online at www.VideoGIE.org).Figure 3Appearance of the lesion on direct peroral cholangioscopy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 4Direct peroral cholangioscopy view of targeted biopsy specimens obtained with regular forceps.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 5Fluoroscopic image showing position of the endoscope during direct peroral cholangioscopy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 6Histologic image showing a cholangiocarcinoma.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Indeterminate biliary strictures of the mid and distal CBD are often managed with temporary FC-SEMS placement.1Viesca M.F.Y. Arvanitakis M. Early diagnosis and management of malignant distal biliary obstruction: a review on current recommendations and guidelines.Clin Exp Gastroenterol. 2019; 12: 415-432Crossref PubMed Scopus (10) Google Scholar The histologic characterization of this condition remains a challenge, even at centers with significant ERCP and EUS expertise. Intraductal biliary imaging can help in diagnostic work-up and subsequent therapeutic management.2Gerges C. Beyna T. Tang R.S.Y. et al.Digital single-operator peroral cholangioscopy-guided biopsy versus ERCP-guided brushing for indeterminate biliary strictures: a prospective, randomized multicenter trial (with video).Gastrointest Endosc. 2020; 91: 1105-1113Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar, 3Nishikawa T. Tsuyuguchi T. Sakai Y. et al.Comparison of the diagnostic accuracy of peroral video-cholangioscopic visual findings and cholangioscopy-guided forceps biopsy findings for indeterminate biliary lesions: a prospective study.Gastrointest Endosc. 2013; 77: 219-226Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 4Anderloni A. Fugazza A. Auriemma F. et al.Intrabiliary resection of metastasis originating from colorectal carcinoma during direct peroral cholangioscopy: a new tool for biliary palliation.Endoscopy. 2018; 50: E96-E98PubMed Google Scholar The presence of a previously placed FC-SEMS has been usually considered an impediment for subsequent tissue acquisition (during EUS-guided fine-needle biopsy, ERCP, or cholangioscopy). Immediate stent expansion at the time of stent deployment affects short-term outcomes, and chronic resistant force against tissue compression affects long-term outcomes. The SEMSs partially expand immediately after deployment and then gradually expand to their full extent. Nevertheless, if removed after at least 2 weeks, they might achieve good distal CBD dilatation to allow direct peroral cholangioscopy with a slim gastroscope, without need for specifically designed instruments or devices. This approach could represent a useful additional strategy for the assessment of malignancy in indeterminate biliary strictures that can be performed by expert operators at a tertiary referral center. Dr Repici is a consultant for Boston Scientific and Fujifilm. Dr Anderloni is a consultant for Boston Scientific and Olympus. All other authors disclosed no financial relationships. https://www.videogie.org/cms/asset/55c64778-3124-48c3-a825-4f53fa451e0c/mmc1.mp4Loading ... Download .mp4 (41.97 MB) Help with .mp4 files Video 1Direct peroral cholangioscopy after dilation of distal common bile duct with a fully covered self-expandable metal stent for the assessment of indeterminate biliary stricture.

There are few data on epidemiological and clinical features of adult ulcerative colitis (UC) patients in Sardinia (Italy), mainly derived from administrative sources such as Hospital Discharge Register. The aim of this study was to assess the main clinical and epidemiological features of adult patients diagnosed with ulcerative colitis (UC) in Sardinia, Italy. We evaluated the main clinical features of UC patients followed-up in 7 Gastroenterology/Endoscopy Units in Sardinia, Italy. Data were obtained from medical patients’ records and from a questionnaire administered at inclusion visit. 374 patients with UC were included: 52.9% were female, with a female-to-male ratio of 1.125. Eleven per cent of patients were active smokers and 36.4% were former smokers. Mean age at diagnosis was 39.2 years (SD 15.4). Only 4.3% of patients were < 16 years old at diagnosis; 53.2% were diagnosed at age ranging from 17 to 40 and 42.5% at age >40. About three quarters of patients were diagnosed between 17 and 49 years old (23.7% between 17 and 29, 25.8% between 30 and 39 and 22.8% between 40 and 49). Disease extent at diagnosis was proctitis in 18.2% of patients, left-sided colitis in 38.8% and extensive colitis in 41.2% (missing data in 1.9% of patients). After a median disease duration of 9 years (IQR 13.8), proximal extension of proctitis or left-sided colitis (from E1 to E2/E3 or from E2 to E3) occurred in 12% of patients. 17.9% of patients developed extraintestinal manifestations, the most frequent being articular (11.8%). There were six patients (1.6%) with concomitant primary sclerosing cholangitis. Two patients developed colorectal cancer. This multi-centre study provides important preliminary clinical data on UC in Sardinia.

BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is a frequently reported condition in patients with inflammatory bowel disease (IBD). Both intestinal inflammation and metabolic factors are believed to contribute to the pathogenesis of IBD-associated NAFLD.AIM:To evaluate the prevalence of steatosis and liver fibrosis (LF) in a cohort of IBD patients and the identification of metabolic- and IBD-related risk factors for NAFLD and LF.METHODS:IBD patients were consecutively enrolled from December 2016 to January 2018. Demographic, anthropometric and biochemical data were collected so as eating habits. Abdominal ultrasound and transient elastography were performed to evaluate the presence of NAFLD and LF respectively.RESULTS:A total of 178 consecutive patients were enrolled and included in the analysis (95 Ulcerative colitis, 83 Crohn's disease). NAFLD was detected by imaging in 72 (40.4%) patients. Comparison between patients with and without NAFLD showed no significant differences in terms of IBD severity, disease duration, location/extension, use of IBD-related medications (i.e., steroids, anti-TNFs, and immunomodulators) and surgery. NAFLD was significantly associated with the presence of metabolic syndrome [MetS; odds ratio (OR): 4.13, P = 0.001] and obesity defined by body mass index (OR: 9.21, P = 0.0002). IBD patients with NAFLD showed higher caloric intake and lipid consumption than those without NAFLD, regardless disease activity. At the multivariate analysis, male sex, advanced age and high lipid consumption were independent risk factors for the development of NAFLD. An increased liver stiffness was detected in 21 patients (16%) and the presence of MetS was the only relevant factor associated to LF (OR: 3.40, P = 0.01).CONCLUSION:In this study, we demonstrate that risk factors for NAFLD and LF in the IBD population do not differ from those in the general population.

Olfactory function varies by several orders of magnitude among healthy individuals, who may exhibit a reduced sensitivity (hyposmia), a high sensitivity (hyperosmia), or an olfactory blindness (anosmia). Environmental and genetic factors seem to account for this variability. Most of odorant molecules are hydrophobic and it has been suggested that odorants are transported to the olfactory receptors by means of odorant binding proteins (OBPs). Aim of this study was to evaluate the presence of a relationship between the olfactory performance of healthy subjects and the polymorphism in the odor binding-protein (OBPIIa) gene, the only OBP found in the olfactory epithelium of humans. Using the "Sniffin' Sticks" Extended Test we assessed the olfactory performance in 69 subjects, who were genotyped for the rs2590498 polymorphism of the OBPIIa gene, whose major allele A has been associated with a higher retronasal perception as compared to the minor allele G. We found that subjects homozygous for the A-allele exhibited threshold scores higher than subjects homozous for the G-allele or heterozygous. In addition, subjects classified as normosmic and hyposmic differed on the basis of genotype distribution and allelic frequencies. In fact, a normosmic condition was associated with genotype AA and allele A and a hyposmic condition was associated with genotype GG and allele G. In conclusion, our results show that a relationship exists between the physiological variations of olfactory performance and the OBPIIa gene polymorphism.

How to cite this article: Magrì S, Paduano D, Cappai M, Pollino V. Primary pancreatic actinomycosis: A case report and literature review. Endosc Ultrasound 2019;8:354-5. This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.