Accuracy of optical diagnosis with narrow band imaging in the surveillance of ulcerative colitis: a prospective study comparing Kudo, Kudo-IBD and NICE classifications.

PURPOSE: The diagnostic accuracy of Narrow Band Imaging (NBI) in the endoscopic surveillance of ulcerative colitis (UC) has been disappointing in most trials which used the Kudo classification. We aim to compare the performance of NBI in the lesion characterization of UC, when applied according to three different classifications (NICE, Kudo, Kudo-IBD). METHODS: In a prospective, real-life study, all visible lesions found during consecutive surveillance colonoscopies with NBI (Exera-II CV-180) for UC were classified as suspected or non-suspected for neoplasia according to the NICE, Kudo and Kudo-IBD criteria. The sensitivity (SE), specificity (SP), positive (+LR) and negative (-LR) likelihood ratios of the three classifications were calculated, using histology as the reference standard. RESULTS: 394 lesions (mean size 6 mm, range 2-40 mm) from 84 patients were analysed. Twenty-one neoplastic (5%), 49 hyperplastic (12%), and 324 inflammatory (82%) lesions were found. The diagnostic accuracy of the NICE, Kudo and Kudo-IBD classifications were, respectively: SE 76%-71%-86%; SP 55-69%-79% (p < 0.05 Kudo-IBD vs. both Kudo and NICE); +LR 1.69-2.34-4.15 (p < 0.05 Kudo-IBD vs. both Kudo and NICE); -LR 0.43-0.41-0.18. CONCLUSION: The diagnostic accuracy of NBI in the differentiation of neoplastic and non-neoplastic lesions in UC is low if used with conventional classifications of the general population, but it is significantly better with the modified Kudo classification specific for UC.

Effect of Tofacitinib on One-Year Colectomy Risk in Anti-TNF Refractory Ulcerative Colitis: A Prospective Multicenter Italian Study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). AIMS: Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks. METHODS: From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. RESULTS: We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. CONCLUSIONS: In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.

Timing of proper introduction, optimization and maintenance of anti-TNF therapy in IBD: Results from a Delphi consensus.

BACKGROUND: Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBDs) with a rapidly growing worldwide incidence. The last decades presented rapid progress in pharmacological treatment leading in many cases to clinical and endoscopic remission, including biological treatment with anti-TNF agents. AIM: The exact timing of introduction, optimization and maintenance of anti-TNF therapy in IBDs is not thoroughly covered in current guidelines. METHODS: We used the Delphi panel methodology to gather the IBD experts' views and achieve consensus for clinical recommendations on introducing and maintaining anti-TNF therapy for patients with IBDs. RESULTS: Twelve recommendations achieved a high level of consensus in two assessment rounds by 52 (1st round) and 47 (2nd round) IBD experts. CONCLUSION: In many clinical situations, the early use of anti-TNF therapy is recommended. Nowadays, the cost-efficacy profile of anti-TNF biosimilars makes them the first-line drug in a substantial proportion of patients, thus providing the opportunity to increase access to biological therapy.

IDH1-mutated Crohn's disease-associated small bowel adenocarcinomas: Distinctive pathological features and association with MGMT methylation and serrated-type dysplasia.

AIMS: Patients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD-SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1-mutated CrD-SBAs. METHODS AND RESULTS: An international multicentre series of surgically resected CrD-SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6-methylguanine-DNA methyltransferase (MGMT) and long interspersed nuclear element-1 (LINE-1) methylation were compared between IDH1-mutated and IDH1 wild-type CrD-SBAs. Ten (20%) of the 49 CrD-SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild-type cases, IDH1-mutated CrD-SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1-mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non-conventional subtype (two serrated dysplastic lesions and one goblet cell-deficient dysplasia). In particular, non-conventional serrated dysplasia was significantly associated with IDH1-mutated CrD-SBAs (P = 0.029). No significant cancer-specific survival difference between IDH1-mutated CrD-SBA patients and IDH1 wild-type CrD-SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16-1.89; P = 0.313). CONCLUSIONS: IDH1-mutated CrD-SBAs, which represent approximately one-fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1-mutated non-conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD-SBAs.

Severe chronic diarrhoea caused by hereditary transthyretin amyloidosis.

Amyloidosis includes a heterogeneous group of diseases caused by the extracellular deposition of insoluble fibrillar proteins, leading to multiple organ dysfunction and a poor life expectancy. In the early stages of amyloidosis, gastrointestinal (GI) symptoms are uncommon. We describe a rare case of hereditary transthyretin amyloidosis (ATTRv) with involvement of the heart, nervous system and GI tract. A man in his 60s was hospitalised due to chronic diarrhoea, orthostatic hypotension, malabsorption and weight loss. An organic origin for the diarrhoea was suspected, but the most common causes were ruled out. The review of GI biopsies and an abdominal fat aspirate confirmed the diagnosis of amyloidosis. The diagnosis of ATTRv amyloidosis with GI presentation is challenging, especially in the early stages, and misdiagnosis is common. The recent approval of therapies emphasises the importance of early diagnosis to prevent irreversible organ damage.

Relevance of sonographic parameters for inflammatory bowel disease in children.

PURPOSE: Intestinal ultrasound (IUS) is widely used as the first exam in patients with suspected inflammatory bowel disease (IBD). This study investigated the accuracy of several IUS parameters, including increased bowel wall thickening (BWT), in detecting IBD in a paediatric population. METHODS: The study included an unselected series of 113 patients aged 2-18 years (mean age 10.8 years, 65 male), referred for recurrent abdominal pain or altered bowel habits, without known organic diseases, to perform an IUS as first investigation of a diagnostic workup. Patients with full systematic IUS examination, clinical and biochemical exams, and ileocolonoscopy or an uneventful follow-up at least one year follow up were eligible. RESULTS: 23 IBD patients (20.4%; 8 ulcerative colitis, 12 Crohn's disease and 3 indeterminate colitis) were diagnosed. We found that increased BWT > 3 mm (OR 5.4), altered IUS bowel pattern (IUS-BP, OR 9.8) and mesenteric hypertrophy (MH, OR 5.2) accurately identified IBD at the multivariate analysis. IUS-BP, MH and BWT > 3 mm had a sensitivity of 78.3%, 65.2% and 69.6% and a specificity of 93.3%, 92.2% and 96.7%, respectively. The combination of these three alterations increased the specificity up to 100%, whilst decreased sensitivity to 56.5%. CONCLUSION: Among several US parameters suggestive of IBD, the increased BWT, MH and altered echopattern are independent predictors of IBD. The ultrasonographic diagnosis of IBD could be more accurate if relied on combination of different sonographic parameters, than on the sole BWT evaluation.

SARS-CoV-2 infection in patients with inflammatory bowel disease: comparison between the first and second pandemic waves.

BACKGROUND: In Italy, the incidence of SARS-CoV-2 infection peaked in April and November 2020, defining two pandemic waves of coronavirus disease 2019 (COVID-19). This study compared the characteristics and outcomes of patients with inflammatory bowel disease (IBD) and SARS-CoV-2 infections between pandemic waves. METHODS: Observational longitudinal study of IBD patients with SARS-CoV-2 infection. Patients with established diagnoses of IBD and of SARS-CoV-2 infection were consecutively enrolled in two periods: (i) first wave, from 1 March 2020 to 31 May 2020; and (ii) second wave, from 15 September to 15 December 2020. RESULTS: We enrolled 937 IBD patients (219 in the first wave, 718 in the second wave). Patients of the first wave were older (mean ± SD: 46.3 ± 16.2 vs. 44.1 ± 15.4 years, p = 0.06), more likely to have ulcerative colitis (58.0% vs. 44.4%, p < 0.001) and comorbidities (48.9% vs. 38.9%; p < 0.01), and more frequently residing in Northern Italy (73.1% vs. 46.0%, p < 0.001) than patients of the second wave. There were no significant differences between pandemic waves in sex (male: 54.3% vs. 53.3%, p = 0.82) or frequency of active IBD (44.3% vs. 39.0%, p = 0.18). The rates of negative outcomes were significantly higher in the first than second wave: pneumonia (27.8% vs. 11.7%, p < 0.001), hospital admission (27.4% vs. 9.7%, p < 0.001), ventilatory support (11.9% vs. 5.4%, p < 0.003) and death (5.5% vs. 1.8%, p < 0.007). CONCLUSION: Between the first and second SARS-CoV-2 pandemic waves, demographic, clinical and geographical features of IBD patients were different as were the symptoms and outcomes of infection. These differences are likely due to the different epidemiological situations and diagnostic possibilities between the two waves.

Echo-Endoscopy Combined with Virtual Reality: A Whole Perspective of Laparoscopic Common Bile Duct Exploration in Children.

Introduction: Endoscopic procedures are performed more frequently in children due to technological advances that can be safely performed in an adequate setting with a support of a multidisciplinary team. Pediatric indications for ERCP (endoscopic retrograde cholangiopancreatography) and EUS (endoscopic ultrasound) occur mainly due to congenital malformations. In a pediatric case series, we report the application of EUS combined with duodenoscopy, eventually associated with ERCP and minimally invasive surgery, highlighting the importance of defining a tailored dedicated management pathway for each patient. Patients and methods: A series of 12 patients, managed at our Center in the last three years, were evaluated, and their management was discussed. Results: EUS was performed in eight patients and permitted the differential diagnosis of duplication cysts and the visualization of the biliary tree and pancreatic anatomy. ERCP was attempted in five patients: in one case, it permitted the preservation of pancreatic tissue, postponing surgery and in three patients, it was technically unfeasible. MIS (minimally invasive surgery) was performed in seven patients, two with laparoscopic common bile duct exploration (LCBDE). Precise anatomical definition and the possibility of surgical simulation and team sharing were evaluated under VR HMD (Virtual Reality Head Mounted Display) in four cases. Conclusions: Exploration of the common bile duct in children differs from that of the adult population and combines echo-endoscopy and ERCP. The integrated use of minimally invasive surgery in the pediatric area is necessary for the whole management perspective in complex malformations and small patients. The introduction in the clinical practice of a preoperative study with Virtual Reality allows a better survey of the malformation and a tailored treatment.

Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.

Ultrasonographic and Functional Features of Symptomatic Uncomplicated Diverticular Disease.

INTRODUCTION: To evaluate the ability of intestinal ultrasound (IUS) in discriminating symptomatic uncomplicated diverticular disease (SUDD) among patients with abdominal symptoms including irritable bowel syndrome (IBS). METHODS: This observational, prospective study included consecutive patients classified into the following categories: (i) SUDD; (ii) IBS; (iii) unclassifiable abdominal symptoms; and (iv) controls, including asymptomatic healthy subjects and diverticulosis. The IUS evaluation of the sigmoid: assessed the presence of diverticula, thickness of the muscularis propria, and IUS-evoked pain, namely the intensity of pain evoked by compression with the ultrasound probe on sigmoid colon compared with an area of the left lower abdominal quadrant without underlying sigmoid colon. RESULTS: We enrolled 40 patients with SUDD, 20 patients with IBS, 28 patients with unclassifiable abdominal symptoms, 10 healthy controls, and 20 patients with diverticulosis. Patients with SUDD displayed significantly ( P < 0.001) greater muscle thickness (2.25 ± 0.73 mm) compared with patients with IBS (1.66 ± 0.32 mm), patients with unclassifiable abdominal pain, and healthy subjects, but comparable with that of patients with diverticulosis (2.35 ± 0.71 mm). Patients with SUDD showed a greater (not significant) differential pain score than other patients. There was a significant correlation between the thickness of the muscularis propria and the differential pain score only for patients with SUDD ( r = 0.460; P : 0.01). Sigmoid diverticula were detected by colonoscopy in 40 patients (42.4%) and by IUS with a sensitivity of 96.0% and a specificity of 98.5%. DISCUSSION: IUS could represent a useful diagnostic tool for SUDD, potentially useful in characterizing the disease and appropriately address the therapeutic approach.

Therapeutic Management of Adults with Inflammatory Bowel Disease and Malignancies: A Clinical Challenge.

Patients with chronic inflammatory bowel diseases (IBD) have increased risk of developing intestinal and extraintestinal cancers. However, once a diagnosis of malignancy is made, the therapeutic management of Crohn's disease (CD) and ulcerative colitis (UC) can be challenging as major guidelines suggest discontinuing the ongoing immunosuppressant and biological therapies for at least 2-5 years after the end of cancer treatment. Recently, new molecules such as vedolizumab and ustekinumab have been approved for IBD and limited data exist on the real risk of new or recurrent cancer in IBD patients with prior cancer, exposed to immunosuppressants and biologic agents. Thus, a multidisciplinary approach and case-by-case management is the preferred choice. The primary aim of our review was to summarize the current evidence about the safety of reintroducing an immunosuppressant or biologic agent in patients with a history of malignancy and to compare the different available therapies, including gut-selective agents. The secondary aim was to evaluate the clinical course of the IBD patients under cancer treatment who do not receive any specific immunosuppressant treatment after the diagnosis of cancer.

Continuous clinical remission with biologics in ulcerative colitis: the 'AURORA' comparison study.

OBJECTIVES: Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR). METHODS: In a retrospective, multicentre study, all UC patients treated with adalimumab, infliximab biosimilar, golimumab or vedolizumab between 2014 and 2019 were included. All drugs were compared to each other according to the 1-year CCR rate, defined as Mayo partial score ≤2, with bleeding subscore = 0, without any relapse or optimization with dose escalation, topical treatments or steroid use after first clinical remission. RESULTS: Four-hundred sixteen patients (adalimumab = 90, infliximab biosimilar = 105, golimumab = 79, vedolizumab = 142) were included. CCR was achieved in similar percentages among the groups (33%, 37%, 28%, 37%, respectively). All drugs were equivalent in biologic-naive patients, while vedolizumab was better than a second anti-TNFα in prior anti-TNFα agent failures. No differences were found according to type of adverse events or severe adverse events. CONCLUSIONS: Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year. Changing to vedolizumab is more effective than switching to another anti-TNFα in TNFα failures.

The impact of biologic therapies on extra-intestinal manifestations in inflammatory bowel disease: A multicenter study.

Introduction: Patients with inflammatory bowel disease (IBD) have a high risk of developing extra-intestinal manifestations (EIMs). We aimed to assess the cumulative incidence and clinical course of EIMs in patients treated with Vedolizumab (VDZ) and non-gut selective biologic drugs. Materials and methods: In this multicenter observational study, we enrolled 1,182 patients with IBD under biologic treatment in tertiary care centers, collecting the rate of new-onset EIMs and the clinical course of new and pre-existing EIMs since the introduction of the ongoing biologic drug (259 VDZ vs. 923 non-gut selective agents, median time 3 vs. 4 years). Results: Among 1,182 patients with IBD (median age of 46 years; 55% men) on biologics, the overall cumulative incidence of new onset EIMs was 4.1% (49/1,182), in particular 6.6% (17/259) on VDZ vs. 3.5% (32/923) on non-gut selective biologics (p = 0.02). Among 224 patients reporting new or pre-existing EIMs, those on VDZ showed a higher rate of clinical worsening compared with non-gut selective therapies (15.5 vs. 7.3%, p = 0.08). However, both showed a similar rate of modification of the therapeutic regimen. Female gender [hazard ratio (HR) 2.18], a longer course of ongoing biologic therapy (HR 1.18), ulcerative colitis (UC) (HR 1.83), and VDZ therapy (HR 1.85) were significant risk factors for developing new EIMs. Discussion: Our study suggests that the type of biologic treatment might affect the risk of developing EIMs, with a slightly higher risk in patients on gut-selective therapies. However, a similar clinical course is observed in the two groups.

Segmental Versus Total Colectomy for Crohn's Disease in the Biologic Era: Results From The SCOTCH International, Multicentric Study.

BACKGROUND: The extent of resection in colonic Crohn's disease [cCD] is still a topic of debate, depending on the number of locations, the risk of recurrence and permanent stoma, and the role of medical therapy. METHODS: The Segmental COlecTomy for CroHn's disease [SCOTCH] international study is a retrospective analysis on six tertiary centre prospective databases, comprising all consecutive, unselected patients operated on between 2000 and 2019 with segmental colectomy [SC] or total colectomy [TC] for cCD. The primary aim was long-term surgical recurrence. Secondary aims were perioperative complications, stoma formation and predictors of recurrence. RESULTS: Among 687 patients, SC was performed in 285 [41.5%] and TC in 402 [58.5%]. Mean age at diagnosis and surgery, disease duration, and follow-up were 30 ±â€…15.8, 40.4 ±â€…15.4, 10.4 ±â€…8.6 and 7.1 ±â€…5.2 years respectively. Isolated cCD, inflammatory pattern, perianal CD, younger age, longer disease duration and preoperative maximal therapy were more frequent in TC, while SC presented more small bowel locations and perforating disease, required fewer 90-day re-admissions, and fewer temporary and definitive stomas. Morbidity and mortality were similar. The 15-year surgical recurrence was 44% in TC and 27% in SC [p = 0.006]. In patients with one to three diseased segments, recurrence risk was related to the omission of biological therapy (hazard ratio [HR] 5.6), the number of segments [HR 2.5], perianal disease [HR 1.9] and paediatric diagnosis [HR 2.8]. CONCLUSION: When technically feasible, SC is safe and reduces temporary and permanent stoma. Young age, number of locations and perianal disease adversely affect, but postoperative biological therapy significantly reduces, the long-term surgical recurrence.

Gastrointestinal tuberculosis presenting as acute abdomen: a case report.

Intestinal tuberculosis (ITB) represents an important diagnostic challenge in the clinical setting, as it generally can occur as a chronic condition often mimicking other diseases such as Crohn's disease (CD), and can present itself with acute onset, which can be life-threatening. A 29-years-old Chinese woman coming to ER with abdominal pain, fever and weight loss. Computed tomography and colonoscopy images were not diagnostic. Despite medical therapy, the patient progressively worsened developing sepsis requiring emergency surgery. Pathological and microbiological examination of the colon both pointed towards gastrointestinal tuberculosis involvement. Although ITB is generally a chronic-wasting condition, it can also occur as acute abdomen representing an absolute surgical emergency. Although caseation and necrosis in granulomas can be used for diagnosis of ITB, preoperative diagnosis is still challenging. Endoscopic biopsies targeted to ulcerous lesions could be an essential diagnostic tool, contrary to those targeted to the ulcers' edges as performed in CD.

Pathophysiology and therapeutic management of anemia in gastrointestinal disorders.

INTRODUCTION: Anemia is a common complication of gastrointestinal (GI) disorders, with a prevalence up to 60% in celiac disease (CeD) and inflammatory bowel disease (IBD). Iron deficiency anemia (IDA) is the most prevalent form of anemia in these conditions, but chronic inflammation and vitamin B12 deficiency represent other common contributing mechanisms, especially in IBD. AREAS COVERED: We discuss the pathogenesis of anemia in various medical GI disorders, the sometime problematic distinction between IDA, anemia of inflammation (AI) and the association of the two, and therapeutic and preventive measures that can be useful for the management of anemia in GI disorders. Unfortunately, with the exception of IDA and AI in IBD, large RCT concerning the treatment of anemia in GI disorders are lacking. EXPERT OPINION: Anemia management strategies in GI disorders are outlined, with a focus on the main prevention, diagnostic, and therapeutic measures. Specific problems and situations such as the role of gluten-free diet for IDA treatment in CeD, the choice between oral and parenteral supplementation of iron or vitamin B12 in carential anemias, the use of endoscopic procedures to stop bleeding in intestinal angiodysplasia and preventive/treatment strategies for NSAID-associated GI bleeding are discussed.

An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis.

The main goals of Ulcerative Colitis (UC) treatment are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications such as dysplasia and colorectal carcinoma and improve quality of life. Although a curative medical treatment for UC has not yet been found, new therapeutic strategies addressing specific pathogenetic mechanisms of disease are emerging. Notwithstanding these novel therapies, non-biological conventional drugs remain a mainstay of treatment. The aim of this review is to summarize current therapeutic strategies used as treatment for ulcerative colitis and to briefly focus on emerging therapeutic strategies, including novel biologic therapies and small molecules. To date, multiple therapeutic approaches can be adopted in UC and the range of available compounds is constantly increasing. In this era, the realization of well-designed comparative clinical trials, as well as the definition of specific therapeutic models, would be strongly suggested in order to achieve personalized management for UC patients.

Endoscopic management of recurrent cholangitis following EUS-guided choledochoduodenostomy.

Video 1Endoscopic management of recurrent cholangitis after EUS-guided choledochoduodenostomy.