Gian Eugenio Tontini

Differential diagnosis in inflammatory bowel disease colitis: State of the art and future perspectives

Distinction between Crohns disease of the colon-rectum and ulcerative colitis or inflammatory bowel disease (IBD) type unclassified can be of pivotal importance for a tailored clinical management, as each entity often involves specific therapeutic strategies and prognosis. Nonetheless, no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations. Hence, we have performed a literature search to address the problem of differential diagnosis in IBD colitis, revised current and emerging diagnostic tools and refined disease classification strategies. Nowadays, the differential diagnosis is an untangled issue, and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis. This topic is receiving emerging attention, as medical therapies, surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients. The optimization of standard diagnostic approaches based on clinical features, biomarkers, radiology, endoscopy and histopathology appears to provide only marginal benefits. Conversely, emerging diagnostic techniques in the field of gastrointestinal endoscopy, molecular pathology, genetics, epigenetics, metabolomics and proteomics have already shown promising results. Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD, better reflecting diverse disease behaviors based on specific pathogenic pathways.

Review article: newer optical and digital chromoendoscopy techniques vs. dye-based chromoendoscopy for diagnosis and surveillance in inflammatory bowel disease

Recent innovations in gastrointestinal endoscopy have changed our traditional approach to diagnosis and therapy in patients with inflammatory bowel diseases (IBD). While traditionally used dye‐based chromoendoscopy (DBC) techniques suffer from several limitations that reduce their utility in daily routine practice, newer ‘dye‐less’ chromoendoscopy (DLC) techniques offer a great potential to overcome most of these limitations.

Advanced endoscopic imaging techniques in Crohn's disease.

BACKGROUNDnEndoscopy is of pivotal importance in Crohns disease (CD) patients for diagnosis, surveillance and assessment of disease activity and extent. Device-assisted enteroscopy (DAE) and small-bowel capsule endoscopy (SBCE) have recently changed our endoscopic approach to small-bowel imaging. Furthermore, new advanced endoscopic imaging techniques have been implemented into clinical practice to improve both characterization of mucosal inflammation and detection of dysplastic lesions.nnnAIMnTo provide readers with a review about the concept of advanced endoscopic imaging for the diagnosis and characterization of CD.nnnMETHODSnA literature search on the use of advanced endoscopy techniques in IBD patients was performed.nnnRESULTSnDAE and SBCE allow for deep enteroscopy with high diagnostic yields and low complications rate but their collocation in the diagnostic algorithm is still not clearly defined. Dye-based chromoendoscopy (DBC) and magnification chromoendoscopy improved dysplasias detection in long standing colitis and prediction of inflammatory activity and extent. Dye-less chromoendoscopy (DLC) might offer the potential to replace conventional DBC for surveillance. However, both narrow band imaging and i-scan have already shown to significantly improve activity and extent assessment in comparison to white-light endoscopy. Confocal laser endomicroscopy (CLE) can detect more dysplastic lesions in surveillance colonoscopy and predict neoplastic and inflammatory changes with high accuracy compared to histology. Moreover, CLE-based molecular imaging may anticipate the therapeutic responses to biological therapy. Endocytoscopy can identify in vivo inflammatory mucosal cells harboring a new method to assess the mucosal activity.nnnCONCLUSIONSnRecent progresses in small-bowel enteroscopy offer several potential benefits to improve both diagnosis and characterization of CD. New advanced endoscopic imaging techniques can improve detection of dysplasia and refine mucosal healing assessment, even looking beyond the morphological parameters revealed by conventional endoscopic imaging.

Confocal laser endomicroscopy for the differential diagnosis of ulcerative colitis and Crohn’s disease: a pilot study

BACKGROUND AND STUDY AIMnThe differential diagnosis of ulcerative colitis from Crohns disease is of pivotal importance for the management of inflammatory bowel diseases, as both entities involve specific therapeutic management strategies. Confocal laser endomicroscopy (CLE) allows on-demand, in vivo characterization of architectural and cellular details during endoscopy. The aim of this study was to assess the efficacy of CLE to differentiate between ulcerative colitis and Crohns disease.nnnPATIENTS AND METHODSnThis was a prospective study involving consecutive patients with a well-established diagnosis of ulcerative colitis or Crohns disease who underwent colonoscopy with fluorescein-aided confocal imaging.nnnRESULTSnOverall, 79 patients were included (40 Crohns disease, 39 ulcerative colitis). CLE findings in patients with Crohns disease, showed significantly more discontinuous inflammation (87.5u200a% vs. 5.1u200a%), focal cryptitis (75.0u200a% vs. 12.8u200a%), and discontinuous crypt architectural abnormality (87.5u200a% vs. 10.3u200a%) than in ulcerative colitis (Pu200a<u200a0.0001). Conversely, ulcerative colitis was associated with severe, widespread crypt distortion (87.2u200a% vs. 17.5u200a% in Crohns disease), decreased crypt density (79.5u200a% vs. 22.5u200a%), and frankly irregular surface (89.7u200a% vs. 17.5u200a%; Pu200a<u200a0.0001 for all comparisons). Statistically significant differences were not seen for heavy, diffuse lamina propria cell increase or mucin preservation. No granulomas were visible. Based on these findings, a CLE scoring system was developed that revealed excellent accuracy (93.7u200a%) when compared with the historical clinical diagnosis and the histopathological gold standard.nnnCONCLUSIONSnCLE could visualize several disease-specific microscopic features, which are conventionally used in standard histopathology to differentiate between ulcerative colitis and Crohns disease. However, because of the limited penetration depth of CLE, submucosal details or granulomas were not visible. The new scoring system may allow in vivo diagnosis of ulcerative colitis or Crohns disease. Trial registered at ClinicalTrials.gov: NCT 02238665.

Microscopic Colitis and Colorectal Neoplastic Lesion Rate in Chronic Nonbloody Diarrhea: A Prospective, Multicenter Study

Background:Lymphocytic and collagenous colitis are emerging as common findings in subjects undergoing colonoscopy for chronic non-bloody diarrhea (CNBD). Data concerning microscopic colitis (MC) are still limited and affected by controversial epidemiological evidences. Recent converging lines of evidence suggest that MC correlates a lower risk of colorectal neoplasia. Accordingly, we prospectively assessed MC prevalence in a multicenter cohort of subjects submitted to colonoscopy for CNBD, thereby defining whether MC influences the risk of colorectal neoplasia. Methods:Consecutive patients with CNBD of unknown origin underwent pan-colonoscopy with multiple biopsies. The prevalence of neoplastic patients in MC was compared with that observed in negative CNBD subjects. Results:Among 8006 colonoscopy, 305 subjects were enrolled for CNBD. Patients with CNBD were more likely to be women than men (odds ratio = 1.5; P = 0.001). Histopathology detected high prevalence of MC (16%) with a clear predominance of collagenous colitis (70%). A striking age-dependent rise in MC-associated risk was observed, depicting outstanding differences among varying age groups, as in the number needed to screen 1 new case. Gender distribution was balanced within MC patients (Female/Male = 1.5/1), especially among lymphocytic colitis (Female/Male = 1.2/1). MC patients were negatively associated with the risk of neoplastic polyps compared with negative CNBD subjects (odds ratio = 0.22; P = 0.035). Conclusions:MC is the first cause of CNBD in subjects submitted to colonoscopy. Multiple biopsies are strongly recommended, even in the case of uneventful endoscopic inspection, especially for age ≥40 years. MC has a reduced risk of colorectal neoplasia, suggesting that this model of chronic inflammation plays a protective effect against colorectal carcinogenesis.

Endoscopic scoring systems for inflammatory bowel disease: pros and cons

Endoscopy plays a pivotal role for diagnosis and assessment of disease activity and extent in patients with inflammatory bowel diseases. International guidelines recommend the use of endoscopic scoring systems for evaluation of the prognosis and efficacy of medical treatments. Ideal scoring systems are easy to use, reproducible, reliable, responsive to changes, and validated in different clinical settings in order to guide therapeutic strategies. However, currently available endoscopic scoring systems often appear as complex for routine endoscopy and suffer from insufficient interobserver agreement and lack of formal validation which often limit their use in clinical trials. Here, we describe the role of endoscopic scoring systems in inflammatory bowel diseases focusing on pros and cons in the era of advanced endoscopic imaging and mucosal healing.

Dual-focus narrow band imaging for the detection of intestinal metaplasia and atrophic gastritis

Gastric cancer is one of the most common neoplastic diseases in developed Western countries, and is characterized by a poor prognosis when diagnosed at a late stage [1]. Atrophic gastritis and gastric intestinal metaplasia (GIM) are well-known risk factors for the development of gastric cancer. For this reason, endoscopy with multiple biopsies is recommended in patients with atrophic gastritis or GIM, to exclude preneoplastic or neoplastic tissue [1]. Magnifying endoscopy with narrow band imaging (NBI) has been shown to be reliable for in vivo diagnosis of atrophic gastritis and GIM [1–4]. However, while magnifying endoscopy is routinely used by Asian endoscopists, it is not established in most European and Northern American endoscopy centers. Recently, a novel endoscope with NBI and dual-focus capability has been introduced to improve the quality of endoscopic imaging [5]. Dual focus allows the user to select between two focus settings by pushing a button on the scope. This results in an optimized close view of the tissue up to an 80-fold optical magnification. To the best of our knowledge, no reports exist so far on the use of this new technique for the detection and characterization of gastric lesions. We report a case in which dual-focus narrow band imaging was used to diagnose atrophic gastritis with intestinal metaplasia and obtain targeted biopsies in the same session. A 57-year-old woman with dyspeptic symptoms was referred for esophagogastroduodenoscopy. Physical examination was unremarkable and laboratory parameters were within reference ranges. Highdefinition white-light endoscopy (Olympus, Tokyo, Japan) showed extensive absence of gastric rugae and visible vessels upon the gastric mucosa, consistent with macroscopic signs of atrophic gastritis (● Fig.1). Additionally, NBI revealed the presence of blue-whitish patchy areas on the distal corpus (● Fig.2). Dual-focus NBI revealed isolated flat lesions up to 2mm in diameter with a subtle villous-like morphology and the appearance of light blue crests on the epithelial surface (● Fig.3). Accordingly, an invivodiagnosis of atrophic gastritis with intestinal metaplasia was made and targeted biopsies were obtained, which confirmed the in vivo diagnosis of atrophic gastritis with foci of intestinal metaplasia. This case is interesting as it demonstrates for the first time the potential of dual-focusNBI fordiagnosis ofearlygastric lesions. The potential benefits of this new technique are that in vivo diagnosis of suspect lesions could be performed in real time without any time delay, and that targetedbiopsies could be performed for subsequent histopathological analysis, thereby allowing the assignment of proper surveillance intervals. As dual focus is combined with an automatic algorithm (Prefreeze) which selects the sharpest image when the image is frozen by the user, high-magnification imaging becomes feasible even for nonexpert users. Larger trials on the potential of this technique for early diagnosis and surveillance of patients with early gastric lesions are now warranted.

Prediction of clinical outcomes in Crohn’s disease by using confocal laser endomicroscopy: results from a prospective multicenter study

BACKGROUND AND AIMSnAssessment of prognostic factors in patients with Crohns disease (CD) is of pivotal importance for early intervention and treat-to-target strategies. Confocal laser endomicroscopy (CLE) enables on-demand inxa0vivo characterization of mucosal inflammatory and architectural changes during endoscopy. We prospectively assessed the value of CLE for prediction of clinical outcome parameters in CD.nnnMETHODSnConsecutive patients with CD undergoing colonoscopy were included in a multicenter study. Confocal imaging focused on 2 highly reproducible histologic hallmarks of active colonic inflammation: focal cryptitis and crypt architectural abnormality. We evaluated whether CLE, CD endoscopic index of severity (CDEIS), serum C-reactive protein (CRP), and CD activity index (CDAI) were associated with the risk of medical treatment escalation, transmural adverse events, and CD-related hospitalization or surgery during a 4-year follow-up.nnnRESULTSnAmong 49 patients (53% men, median age, 39 years), baseline CRP wasxa0≥5 mg/L in 47%, CDEISxa0≥3 in 75%, and CDAI >150 in 51%. Focal cryptitis and crypt architectural abnormality were observed in 63% (CLE+ group). CLE+ patients showed an increased incidence of medical treatment escalation (Pxa0< .001; relative risk [RR]xa0= 3.27) and transmural lesions (Pxa0= .025; RRxa0= 1.70), whereas patients with CRPxa0≥5 mg/L had increased CD-related hospitalization and surgery (Pxa0= .020, RRxa0= 2.71) at 1-year follow-up. No further association with prognostic clinical outcomes was found over the 1-year follow-up as well as for CDEIS and CDAI at any time.nnnCONCLUSIONSnCLE reveals CD-related features of mucosal inflammation and allows for early prediction of relevant clinical outcomes. Further studies should now address whether this promising prognostic tool could refine the timing of treatment strategies in patients with CD.

Successful over-the-scope clip (OTSC) treatment for severe bleeding due to anastomotic dehiscence

Postanastomotic complications of the gastrointestinal tract, including leakage and bleeding, are rare but critical conditions requiring prompt treatment. Most anastomotic problems are managed surgically [1], but endoscopic therapy is considered as the first choice of treatment for bleeding and treatment of an incomplete anastomotic dehiscence with no peritoneal involvement [1,2]. Here we report the case of a 71-year-old woman presenting with an acute fall in hemoglobin level (11.7 to 9.1g/dL), hypotension (90/50mmHg), and melena. Physical examination revealed skin pallor and tachycardia (130 beats per min). The patient had undergone laparotomic debridement with a Billroth I gastroenteral anastomosis 3 weeks before for an advanced ovarian tumor with massive peritoneal carcinomatosis. Emergent esophagogastroduodenoscopy (EGD) revealed oozing bleeding from an anastomotic dehiscence at the posterior wall (● Fig.1). The dehiscence extended over half the circumference of the anastomosis, with a diameter of about 25mm (● Fig.2). Based on the size and position of the leak, we decided to use an over-the-scope clip (OTSC) for sealing the dehiscence. The procedure commenced with injection of epinephrine 1:10000 to reduce the active bleeding (● Fig.3). Then scope was withdrawn and the “atraumatic” version of OTSC (with blunt teeth) was mounted on the tip as previously described [2,3]. Next, the Twin Grasper (Ovesco, Tübingen, Germany) was advanced through the working channel of the endoscope to access the leak margins. Maneuvering the tip of the scope with gentle axial rotation allowed placement of the OTSC correctly over the dehiscence. The Twin Grasper was pulled into the distal cap of the OTSC system under continuous suction. The OTSC was deployed after the clear distal capwas filled tomore than half its volume with tissue. OTSC placement took about 2 minutes and the subsequent endoscopic examination revealed complete closure of the leak and stable hemostasis (● Fig.4). The patient’s clinical condition stabilized and she was discharged 5 days later. This case is interesting for several reasons. First, we have demonstrated how OTSC use can aid emergent endoscopic therapy when other hemostatic and leak sealing techniques are deemed unsuitable due to technical problems such as right target position in a 5 o’clock oriented working channel, large leak (10–25mm), andmassive bleeding [1–4]. Second, we have provided a detailed description of the procedure, which may assist further use of the technique. Third, we have shown successful use of the OTSC for treatment of a larger anastomotic leak [1,2]. Finally, our report adds to the growing literature on potential applications of the OTSC [1– 5]. Altogether, the recently introduced OTSC system provides a practical solution to difficult endoscopic treatment where standard clipping techniques may not be appropriate. The OTSC should be considered as the first choice for sealing of intermediate leaks.

Extensive small-bowel diverticulosis identified with the newly introduced On Demand Enteroscopy system

The recently introduced On Demand Enteroscopy system (ODE;NaviAid AB, Smart Medical Systems, Ra’anana, Israel) enables deep small-bowel enteroscopy using standard endoscopic equipment. The ODE device consists of a disposable balloon that is advanced through the working channel of a standard endoscope equipped with a working channel of at least 3.8mm (● Fig.1). To the best of our knowledge, there are currently no published reports on the use of this new technique. A64-year-oldmanpresentedwith abdominal pain, anemia and positive hemoccult. His physical examination was unremarkable and the laboratory parameters were within thenormal reference ranges, except for a low hemoglobin level (10.2g/dL). Celiac disease and lactose intolerance had already been ruled out and previous esophagogastroduodenoscopy (EGD) and colonoscopy had not revealed any bleeding source. In view of the positive hemoccult but negative upper and lower endoscopic examinations, a decision was made to use ODE deep small-bowel enteroscopy. The endoscope was advanced into the distal duodenum, and the ODE systemwas inserted through the working channel of the endoscope (Pentax i10L, Tokyo, Japan) and advanced ahead of the endoscope inside the small intestine. Next, the balloon at the distal tip of the ODE device was inflated. Once the balloon was completely inflated, the endoscope was pushed forward while the anchored balloon was pulled gently backwards. The small-bowel was straightenedwith the inflated balloon placed at the distal tip of the endoscope while the endoscope was gently pulled backwards. This approach allowed us to introduce the endoscope within 12 minutes to a maximum length of 180cm from the pyloric region. The next advancement step revealed a huge (20-mm diameter) diverticulum (● Fig.2) which had come to be situated next to the inflated balloon during the last pulling operation, however, there were no signs of mucosal damage. The endoscope was carefully advanced and several more large-sized diverticula were found at approximately 200cm from the pyloric region (● Fig.3 and● Video1). Fig.1 a The disposable parts of the On Demand Enteroscopy (ODE) system for balloon-assisted enteroscopy. b The disposable, inflated ODE balloon at the tip of the scope.