Noninvasive early diagnosis of intestinal diseases based on artificial intelligence in genomics and microbiome.

The maturing development in artificial intelligence (AI) and genomics has propelled the advances in intestinal diseases including intestinal cancer, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). On the other hand, colorectal cancer is the second most deadly and the third most common type of cancer in the world according to GLOBOCAN 2020 data. The mechanisms behind IBD and IBS are still speculative. The conventional methods to identify colorectal cancer, IBD, and IBS are based on endoscopy or colonoscopy to identify lesions. However, it is invasive, demanding, and time-consuming for early-stage intestinal diseases. To address those problems, new strategies based on blood and/or human microbiome in gut, colon, or even feces were developed; those methods took advantage of high-throughput sequencing and machine learning approaches. In this review, we summarize the recent research and methods to diagnose intestinal diseases with machine learning technologies based on cell-free DNA and microbiome data generated by amplicon sequencing or whole-genome sequencing. Those methods play an important role in not only intestinal disease diagnosis but also therapy development in the near future.

Progress in Screening for Barrett's Esophagus: Beyond Standard Upper Endoscopy.

The rapid increase in the incidence of esophageal adenocarcinoma in Western populations over the past 4 decades and its associated poor prognosis, unless detected early has generated great interest in screening for the precursor lesion Barrett's esophagus (BE). Recently, there have been significant developments in imaging-based modalities and esophageal cell-sampling devices coupled with biomarker assays. In this review, the authors discuss the rationale for screening for BE and the factors to consider for targeting the at-risk population. They also explore future avenues for research in this area.

Wide-area transepithelial sampling in adjunct to forceps biopsy increases the absolute detection rates of Barrett's oesophagus and oesophageal dysplasia: a meta-analysis and systematic review.

BACKGROUND: Wide-area transepithelial sampling (WATS) is a new technique that uses an abrasive brush to obtain samples from a larger surface area of the oesophagus. Studies have shown promising results that WATS in adjunct to forceps biopsy (FB) increases the detection rate of Barrett's oesophagus (BE) as well as oesophageal dysplasia (ED). We conducted a systematic review and meta-analysis to compare the detection rates of BE and ED between FB and WATS in adjunct to FB. METHODS: A Literature search was done using electronic databases, including PubMed, Embase, Scopus, Cochrane and CINAHL from inception to 26 April 2020. A meta-analysis comparing detection rates of WATS in adjunct to FB versus FB using the random-effects model was done using RevMan V.5.3. RESULTS: Pooled data from 20 392 endoscopies across 11 studies showed an absolute increase in detection of 16% (95% CI 0.10% to 0.22%, p<0.00001). A relative increase of 1.62 was seen in detection rates of BE (95% CI 1.28 to 2.05, p<0.0001) when WATS was used with FB with the number needed to test (NNT) of 6.1 patients. For ED, a 2% absolute increase (95% CI 0.01 to 0.03, p=0.001) in additional diagnostic yield from WATS. A relative increase of 2.05 was seen in the detection rate of ED (95% CI 1.42 to 2.98, p=0.0001) yielding an NNT of 50 patients. CONCLUSION: Our study shows that WATS, as an adjunct to FB, improves both the absolute detection rate and relative detection rate of both BE and ED as compared to FB alone.

Diagnosis and management of jejunoileal diverticular haemorrhage: An update on the experience in a single centre.

INTRODUCTION: Jejunoileal diverticular haemorrhage is a rare disease that is difficult to diagnose and treat. Despite advances in endoscopic technology, recommendations on diagnosis and management for jejunoileal diverticular haemorrhage have remained unchanged and these new options have not been compared against traditional surgical management. MATERIALS AND METHODS: We retrospectively reviewed the diagnosis, management, and outcome for jejunoileal diverticular haemorrhage cases at our institution over the past 20 years. Data were organized and analysed by chi-square test, student t-test and Kaplan-Meier survival analysis. RESULTS: The most utilised diagnostic procedure was computed tomography, followed by enteroscopy, angiography, small bowel flow-through and surgery. Primary treatments included, in a decreasing order, medical therapy, surgery, endoscopy and radiology. Surgical treatment was not associated with rebleeding, but it did result in longer hospital stays and larger blood transfusions than non-surgical treatments. The bleeding-related mortality rate was very low. Notably, there was also little change in the diagnosis and treatment between decades. CONCLUSION: We presented our experience with the diagnosis and management of jejunoileal diverticular haemorrhage, as well as long-term follow-up after treatments that have not been reported previously. Surgical treatment continues to dominate management for jejunoileal diverticular haemorrhage, but we support increasing the role of endoscopy for select patient groups.

Diagnosing coeliac disease: Out with the old and in with the new?

Coeliac disease (CD) is a complex condition resulting from an interplay between genetic and environmental factors. When diagnosing the condition, serological testing and genotyping are useful in excluding CD, although the gold standard of testing is currently histopathological examination of the small intestine. There are drawbacks associated with this form of testing however and because of this, novel forms of testing are currently under investigation. Before we develop completely novel tests though, it is important to ask whether or not we can simply use the data we gather from coeliac patients more effectively and build a more accurate snapshot of CD through statistical analysis of combined metrics. It is clear that not one single test can accurately diagnose CD and it is also clear that CD patients can no longer be defined by discrete classifications, the continuum of patient presentation needs to be recognised and correctly captured to improve diagnostic accuracy. This review will discuss the current diagnostics for CD and then outline novel diagnostics under investigation for the condition. Finally, improvements to current protocols will be discussed with the need for a holistic "snapshot" of CD using a number of metrics simultaneously.

Modern Esophageal Function Testing and Gastroesophageal Reflux Disease in Morbidly Obese Patients.

BACKGROUND: The implementation of high-resolution manometry (HRM) and the Lyon Consensus statement facilitate evaluation of gastroesophageal reflux disease and motility disorders in morbidly obese patients. Therefore, we aimed to investigate prevalence and phenotype of (borderline) GERD and esophageal motility disorders in this population. METHODS: Consecutive morbidly obese (BMI ≥ 35 kg/m2) patients were offered evaluation by means of HRM, ambulatory 24-h pH impedance monitoring, endoscopy, and a clinical examination at our tertiary academic center. Data were collected prospectively. RESULTS: Out of 448 eligible individuals, 147 patients (females = 75, 51%) with a median age of 41.6 (33.4; 52.3) years and a BMI of 44 (40.9; 49.4) kg/m2 were included during the study period. The Chicago Classification revealed motility disorders in 50 (34%) patients, dominated by outflow obstruction (18.4%, n = 27) and a novel disorder (7.5%, n = 11), nicknamed jackhammer esophagus (JE). According to the Lyon Consensus, 52 (35.4%) patients had evidence of true GERD, whereas borderline GERD was noted in another 60 (40.8%). Hypersensitive esophagus was observed in 6.8% (n = 10). Sensitivity and specificity of symptoms for GERD were 53.8% and 68.4%, respectively. CONCLUSIONS: The current gold standard of assessment revealed that the prevalence of esophageal motility disorders and (borderline) GERD is high in the morbidly obese population. Further longitudinal data are needed to delineate the natural course of novel motility disorders like JE in obesity and to identify risk factors for adverse outcomes following bariatric surgery.

Current trends in the management of Mirizzi Syndrome: A review of literature.

Mirizzi Syndrome is a rare and challenging clinical entity to manage. However, recent advances in technology have provided surgeons with new options for more effective diagnosis and treatment of this condition. This paper reviews these new diagnostic modalities and treatment approaches for the management of Mirizzi Syndrome.An online search language was performed using PubMed and Web of Science for literature published in English between 2012 and 2017 using the search terms "Mirizzi Syndrome" and "Mirizzi." In total, 16 case series and 11 case reports were identified and analyzed.The most frequently used diagnostic modalities were ultrasound, computed tomography (CT); magnetic resonance cholangiopancreaticography (MRCP); endoscopic retrograde cholangiopancreaticography (ERCP). A combination of ≥2 diagnostic modalities was frequently used to detect Mirizzi Syndrome. Literature shows that the specific type of Mirizzi Syndrome determined the type of treatment chosen. Open surgery was the preferred option, although there are documented cases of the use of minimally-invasive techniques, even in advanced cases. Laparoscopic, endoscopic or robot-assisted surgery, used individually or in combination with lithotripsy, were all associated with a favorable outcome.As yet, there are no internationally-accepted guidelines for the management of Mirizzi Syndrome. Laparotomy is the preferred surgical technique of choice, although an increasing number of surgeons are beginning to opt for minimally-invasive techniques. The number of papers in the existing literature describing diagnostic and treatment procedures is relatively small at present, thus making it difficult to reasonably propose an evidence-based standard of care for Mirizzi Syndrome.

Assessing Old and New Diagnostic Tests for Gastroesophageal Reflux Disease.

A detailed critique of objective measurements of gastroesophageal reflux disease (GERD) would improve management of patients suspecting of having reflux, leading to rational selection of treatment and better outcomes. Many diagnostic tests for GERD have been developed over the past decades. We analyze their development, positive- and negative-predictive values, and ability to predict response to treatment. These features are important for development of medical, surgical, and endoscopic therapies for GERD. We discuss the value of available diagnostic tests and review their role in management of patients with persistent reflux symptoms despite adequate medical or surgical treatment. This is becoming a significant health economic problem, due to the widespread use of proton pump inhibitors. GERD is believed to cause nonesophageal symptoms, such as those provoked by ear, nose, throat, or respiratory disorders. We analyze the value of GERD diagnostic tests in evaluation of these troublesome, nonesophageal symptoms.

Recent advances in diagnostic testing for gastroesophageal reflux disease.

INTRODUCTION: Gastroesophageal reflux disease (GERD) has a large economic burden with important complications that include esophagitis, Barrett's esophagus, and adenocarcinoma. Despite endoscopy, validated patient questionnaires, and traditional ambulatory pH monitoring, the diagnosis of GERD continues to be challenging. Areas covered: This review will explore the difficulties in diagnosing GERD with a focus on new developments, ranging from basic fundamental changes (histology and immunohistochemistry) to direct patient care (narrow-band imaging, impedance, and response to anti-reflux surgery). We searched PubMed using the noted keywords. We included data from full-text articles published in English. Further relevant articles were identified from the reference lists of review articles. Expert commentary: Important advances in novel parameters in intraluminal impedance monitoring such as baseline impedance monitoring has created some insight into alternative diagnostic strategies in GERD. Recent advances in endoscopic assessment of esophageal epithelial integrity via mucosal impedance measurement is questioning the paradigm of prolonged ambulatory testing for GERD. The future of reflux diagnosis may very well be without the need for currently employed technologies and could be as simple as assessing changes in epithelia integrity as a surrogate marker for GERD. However, future studies must validate such an approach.

A Laboratory Diagnostic Approach to Hepatobiliary Disease in Small Animals.

Routine biochemical tests generally include serum enzymes, proteins, and other markers useful for identifying hepatobiliary disease in dogs and cats. Obtaining results outside the reference intervals can occur with direct hepatocellular injury, enzyme induction by hepatocytes or biliary epithelium, or decreased hepatic function. However, detection of biochemical abnormalities does not necessarily indicate clinically significant disease. For a comprehensive approach to detection and treatment of hepatobiliary disease, the laboratory results must be correlated with the history and physical examination findings, diagnostic imaging results, and other assays.

Diagnosis of Small Intestinal Disorders in Dogs and Cats.

Laboratory tests are an important part of the workup of small intestinal diseases in dogs and cats. Especially in chronic cases, when extragastrointestinal causes need to be ruled out, it is important to adhere to a systematic workup. This article details the newest available data on tests to aid this diagnostic process. Once the diagnosis of a chronic enteropathy is made, there are many laboratory tests that can help in monitoring the disease and providing prognostic information. Several new tests being evaluated for clinical usefulness are discussed.

Ingestible gastrointestinal sampling devices: state-of-the-art and future directions.

Despite the significant contribution of gastrointestinal diseases to the global disease burden and the increasing recognition of the role played by the intestinal microbiota in human health and disease states, conventional methods of exploring and collecting samples from the gastrointestinal tract remain invasive, resource intensive, and often unable to capture all the information contained in these heterogeneous samples. A new class of gastrointestinal sampling capsules is emerging in the literature, which contains the components required for an autonomous intra-luminal device and preserves the spatial and temporal information of the gastrointestinal samples. In this paper, we identify the primary design requirements for gastrointestinal sampling capsules, and we review the state-of-the-art for different components and functionalities. We also suggest two design concepts, and we highlight future directions for this class of biomedical devices.

Diagnostic and therapeutic challenges in pediatric eosinophilic esophagitis: past, present and future.

In this paper, we will discuss the nuances of pediatric eosinophilic esophagitis based on symptoms, diagnostics and therapy. The diagnostics will include endoscopy, histology and anesthesia. Therapeutics will include the diet, drugs and 'distress'. Future directions in terms of clinical presentation and diagnostics will be discussed and important issues such as repeated exposure to anesthetic agents and effects of therapy on growth and psychological distress will be listed.

Early detection of biliary atresia: past, present & future.

The age threshold at the time of Kasai hepatic portoenterostomy associated with a prognosis of biliary atresia (BA) is becoming clearer as 10-year native liver survival data become more frequent in the recent literature, whereas the age at diagnosis has not dramatically decreased during the last 3 decades. A stool color card screening implemented in 1994 in Japan is now expanding worldwide. However, the contribution of this modality will probably be limited because of the nature of this disease, for example, 'progressive obliterative cholangiopathy'. A cholic stool was actually observed only in 50% before diagnosis according to the Japanese BA Registry data. Thus, color card screening does not appear to be instrumental in detecting patients with BA early enough before 1 month of age. A highly sensitive, adequately specific, noninvasive and quantitative method may be expensive, but the overall cost would be lower than that of liver transplant.

Screening and surveillance for Barrett's esophagus: current issues and future directions.

PURPOSE OF REVIEW: Our article discusses the current understanding of screening and surveillance options for Barrett's esophagus and emerging concepts that have the potential to improve the effectiveness and cost-effectiveness of surveillance. RECENT FINDINGS: Although endoscopic surveillance of patients with Barrett's esophagus is commonly practiced in order to detect high-grade dysplasia and early esophageal adenocarcinoma (EAC), the reported incidence of EAC in Barrett's esophagus patients varies widely. Recent studies found the risk of progression from Barrett's esophagus to EAC to be significantly lower than previously reported, raising concerns regarding the limitations of current surveillance strategies. Advances in imaging techniques and their enhanced diagnostic accuracy may improve the value of endoscopic surveillance. Additionally, various efforts are ongoing to identify biomarkers that identify individuals at higher risk of cancer, possibly allowing for individual risk stratification. SUMMARY: These new data highlight some of the opportunities to revise and improve surveillance in patients with Barrett's esophagus. The incorporation of new advances such as imaging techniques and biomarkers has the potential to improve the effectiveness and cost-effectiveness of new surveillance regimens.

Changes in diagnostic and treatment strategies of oesophageal cancer in the period from 2001 to 2009: a survey in the Netherlands.

BACKGROUND: In 2005, national guidelines on the diagnosis, staging and treatment of oesophageal cancer were published. We investigated whether staging and treatment strategies of oesophageal cancer had changed over the last decade and indeed followed these guidelines. MATERIALS AND METHODS: In 2001, a questionnaire investigating staging and treatment strategies for oesophageal cancer was sent to Dutch clinicians (response rate 64%). In 2009, the same questionnaire (response rate 41%) was repeated, thus enabling comparison of staging and treatment strategies for oesophageal cancer between 2001 and 2009 and comparing this with the nationwide guidelines of 2005. RESULTS: The advice to use endoscopic ultrasound for staging was followed by the majority of clinicians [84% in 2009 compared with 58% in 2001 (P<0.001)], whereas positron emission tomography scanning was used by almost half of clinicians (44% in 2009, not asked in 2001). There was a strong support for the use of neoadjuvant chemoradiation in 2009 (68% preferred this treatment for a young patient in good condition without metastases), whereas the Dutch guidelines did not recommend routine use of neoadjuvant treatment in 2005. Stent placement for palliation of dysphagia was reduced [from 92% in 2001 to 27% in 2009 (P<0.001)] due to an increased use of other palliative measures, including brachytherapy. An increased use of chemotherapy (19%) or chemoradiation (39%) was noticed in younger patients (<55 years) with metastatic disease. CONCLUSION: Major changes in staging and treatment strategies were observed in patients with oesophageal cancer over the last decade. Although these changes in staging strategies were in concordance to the guidelines introduced in 2005, treatment strategies with curative intent were more often diverse in 2009 and not following guidelines. This suggests that in a rapidly evolving field as oncology, guideline recommendations on treatment should be updated frequently to reflect state-of-the-art knowledge with implementation of results of clinical studies.