Efficacy of mast cell directed therapies in irritable bowel syndrome: a systematic review.

Background and study aim: Lately, mast cells (MCs) are increasingly implicated in the pathophysiology of irritable bowel syndrome (IBS). The aim of this systematic review was to assess the efficacy of mast cell directed therapies in reducing the main symptoms of IBS: abdominal pain and changes in stool frequency or consistency. Patients and methods: Pubmed, Web of Science and Scopus were searched until December 19, 2022. Trials evaluating the efficacy of mast cell directed therapies, compared to placebo or any form of control group, were included. Trial selection was performed in two stages: screening titles and abstracts and reviewing full papers identified as relevant, taking into account the inclusion criteria. Results: The search strategy identified a total of 1.384 citations. Eleven trials on 943 IBS patients and 197 controls were included: ten randomized controlled trials, two of which cross-over trials, and one cohort study. Of the 11 studies included in the systematic review, only three studies were found to be at low risk of bias. This limited evidence suggests a significant overall improvement in the key symptoms after treatment with disodium cromoglycate, ebastine, ketotifen or palmitoylethanolamide-polydatin compared to control groups. Conclusions: Mast cell modulating therapies could be of significant value in therapy for IBS patients. Further high-quality research is needed to establish the therapeutic efficacy of mast cell targeted therapies in order to draw robust conclusions and improve the clinical management of irritable bowel syndrome.

Epidemiological characteristics of a population visiting a patient-centered informative website about irritable bowel syndrome.

Background and aims: Irritable bowel syndrome (IBS) is a chronic disorder characterized by abdominal pain and an altered bowel habit. The aim of this study was to evaluate the characteristics of a population visiting a patient-centered informative website about IBS. Methods: Five digital surveys were used to assess the Rome IV criteria, red flag symptoms, healthcare use, psychological comorbidities, quality of life, symptom severity, diet, physical activity. Patients were divided into a Rome positive and negative population with the Rome positive population being further subtyped based on dominant stool pattern. Results: Red flag symptoms (42%) and comorbid psychological disorders (65% anxiety and 39% depression) were common. Despite consulting health care professionals and therapy, most patients (96%) still experienced moderate to severe symptoms with an average impact on quality of life. 73% performed regular physical exercise and 25% of the Rome positive population followed the FODMAP diet. Almost all participants consulted a health care professional at one point in time and used some form of therapy. 54% of the patients believed there is generally sufficient information available and 57% thinks that their physician takes IBS seriously. However, only 41% thinks that their physician has sufficient knowledge about IBS. Conclusions: This study underlines the importance of a thorough characterization of IBS patients. Furthermore, patients expressed an urgent need for high quality information and education for both health care professionals and patients.

Endoscopic diagnosis of a colonic localisation of a mantle cell lymphoma.

Extra-nodal localisations of mantle cell lymphomas are most frequently found in the gastrointestinal tract. It is therefore important for an endoscopist to be familiar with the endoscopic image of a mantle cell lymphoma. In this case series of three patients with colonic involvement of mantle cell lymphoma, we discuss the endoscopic diagnosis.

Diagnosis and screening for anal intraepithelial neoplasia in Belgium: position statement.

Anal cancer is an uncommon malignancy, comprising only 2.5% of all gastrointestinal malignancies and similar to cervical cancer, the human papillomavirus (HPV) is responsible for the majority of anal cancers. Over the last decades there has been an up to 3-fold increased incidence seen in specific populations at risk such as persons living with HIV (PLWH), men who have sex with men (MSM), woman diagnosed with HPV-related gynaecological precancerous lesions or cancer, solid organ transplant recipients (SOTR) and patients with autoimmune diseases. Although international practice is evolving increasingly towards active screening for and treatment of anal cancer precursors in at-risk groups, currently no organised screening program is in effect in Belgium. Currently, differerent screening options as well as treatment modalities are available. Before commencing a nationwide organised screening program, essential decisions on screening strategies need to be made, based on both scientific as well as financial and logistical facts.

Belgian consensus on irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. METHODS: A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. RESULTS: Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. CONCLUSIONS: A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.

The role of neuromodulation in chronic functional constipation: a systematic review.

BACKGROUND: Chronic functional constipation is a highly prevalent disorder in which, when conservative measures fail to relieve symptoms, surgical interventions are sometimes indicated. In recent years, neuromodulation for the treatment of functional constipation has gained interest but its role and effectiveness are still unclear. The purpose of this review is to provide a systematic overview on the current literature on the different modalities of neurostimulation and their effect on chronic functional constipation in adults as reported in the literature. METHODS: A search in the literature for articles concerning the effect of different types of neuromodulation on constipation was performed in PubMed using extensive search terms for the different modalities of neuromodulation. Studies and trials were checked for eligibility. For all types of neuromodulation together, 27 articles were included. RESULTS: 17 studies were included on SNM (sacral nerve modulation). Although multiple studies show positive results on the effect of SNM in constipation, double-blind crossover RCT's (randomised controlled trials) showed no significant effect. 3 studies were included for tSNS (transcutaneous sacral nerve stimulation), 2 for PTNS (percutaneous tibial nerve stimulation) and 2 for TTNS (transcutaneous tibial nerve stimulation). Studies and trials on these modalities of neuromodulation reported ambiguous results on statistical significance of the effect. For transcutaneous IFC (interferential current therapy) 2 studies were included, which both reported a statistically significant effect on all outcomes. CONCLUSION: The beneficial effect of neuromodulation in chronic functional constipation remains questionable. However, neuro-modulation might be worth considering in patients refractory to treatment before turning to more invasive measures. Future research should shed more light on the effects of neuromodulation in constipation.

Belgian consensus guideline on the management of hemorrhoidal disease.

Introduction: Hemorrhoidal disease is a common problem that arises when hemorrhoidal structures become engorged and/or prolapse through the anal canal. Both conservative and invasive treatment options are diverse and guidance to their implementation is lacking. Methods: A Delphi consensus process was used to review current literature and draft relevant statements. These were reconciliated until sufficient agreement was reached. The grade of evidence was determined. These guidelines were based on the published literature up to June 2020. Results: Hemorrhoids are normal structures within the anorectal region. When they become engorged or slide down the anal canal, symptoms can arise. Every treatment for symptomatic hemorrhoids should be tailored to patient profile and expectations. For low-grade hemorrhoids, conservative treatment should consist of fiber supplements and can include a short course of venotropics. Instrumental treatment can be added case by case : infrared coagulation or rubber band ligation when prolapse is more prominent. For prolapsing hemorrhoids, surgery can be indicated for refractory cases. Conventional hemorrhoidectomy is the most efficacious intervention for all grades of hemorrhoids and is the only choice for non-reducible prolapsing hemorrhoids. Conclusions: The current guidelines for the management of hemorrhoidal disease include recommendations for the clinical evaluation of hemorrhoidal disorders, and their conservative, instrumental and surgical management.

A case series of 3 patients with acute colonic pseudo-obstruction after vincristine administration.

Acute colonic pseudo-obstruction (ACPO) or Ogilvie's syndrome is characterized by acute colonic dilatation in the absence of mechanical obstruction. It usually occurs in hospitalized patients with acute illness or following surgical procedures, but several medications such as cytotoxic chemotherapy can also induce ACPO. We report three cases of patients with Ogilvie's syndrome after induction therapy with vincristine-containing chemotherapy. Conservative management failed in all three cases. Awareness for this syndrome is necessary when administrating vincristine, because delay in diagnosis may lead to colonic ischaemia and perforation.

Rectal cancer surgery : what's in a name?

The field of rectal cancer treatment is a dynamic and changing field, due to better understanding of the pathology and new medical treatment options, but perhaps mostly due to innovations in the surgical approach. Surgery is the cornerstone for rectal cancer treatment. Currently, Total Mesorectal Excision is the gold standard. After evolution towards laparoscopic TME, improving technology has led to the development of platforms that allow transanal TME and robotic TME. In addition, local excision can be performed safer and more accurately by means of Transanal Endoscopic Microsurgery (TEM), TransAnal Minimally Invasive Surgery or Endoscopic Submucosal Dissection (ESD), possibly avoiding TME. The aim of this review is to summarize the different surgical techniques and approaches for rectal cancer in function of tumor stage and describe the specifics of the technique.

Manometric and ultrasonographic characteristics of patients with coexisting fecal incontinence and constipation.

BACKGROUND: The treatment of fecal incontinence (FI) depends upon the dominant pathophysiology: impaired sphincter contractility or overflow due to pelvic floor dyssynergia and insufficient rectal emptying. In this study, we aimed to define the manometric and anorectal ultrasound characteristics in FI patients with and without constipation. METHODS: We did a retrospective study of 365 anal manometries, performed between October 2012 and July 2015, in patients with FI. Clinical information was obtained from questionnaires. In 220 of these patients an anorectal ultrasound was also available. Key results : A high prevalence of self-reported constipation was seen in the total population of FI patients (66%). This number was lower (31%) when Rome IV criteria were applied. A very high percentage of manometric pelvic floor dyssynergia was seen in the total population with FI (81%). However, patients with FI and constipation did not show pelvic floor dyssynergia more often than patients without constipation. Anal resting pressure, squeeze pressure and anorectal pressure sensitivity were not different when comparing patients without and with constipation. The prevalence of a functional defecation disorder (FDD) in our study population of FI patients was 20%. Wexner score in this subgroup was lower compared with patients without FDD. Anal sphincter defects were more prevalent in women than men, and were associated with diminished sphincter contractility. CONCLUSION AND INFERENCES: A very high percentage of FI patients showed manometric pelvic floor dyssynergia. The coexistence of fecal incontinence and constipation did not increase this percentage. KEY MESSAGES: Constipation is a frequent and underestimated cause of FI. A correct diagnosis has a major impact on treatment. We aimed to characterize the manometric and transrectal ultrasound profile of FI patients with and without signs of coexisting constipation. - A very high percentage of incontinent patients showed pelvic floor dyssynergia, however no significant difference between the group with and the group without constipation was seen. Anal resting pressure, squeeze pressure and anorectal pressure sensitivity did not differ significantly either.

Comparison of side-viewing duodenoscope and single-balloon enteroscope to perform ERCP in patients with Billroth II gastrectomy.

Endoscopic retrograde cholangiopancreatography (ERCP) in Billroth II patients is challenging and different endoscopes can be used. We retrospectively analysed 67 ERCP procedures in 38 Billroth II patients focussing on endoscope type and respective technical success and adverse event rate. 33 (49.2 %) ERCPs were performed using a duodenoscope, 87.9 % were successful and 3 were completed with the single-balloon enteroscope. 28 (41.8 %) ERCPs were performed with the single-balloon enteroscope, 82.1 % were successful and 2 were completed with a paediatric colonoscope. For 6 (9.0 %) ERCPs a paediatric colonoscope was used but only 3 (50.0 %) were successful. Overall technical success rate was 82.1 % without difference between the success rate of the duodenoscope and the single-balloon enteroscope. Overall adverse event rate was 10.5 %: 6.1 % duodenoscope,10.7 % single-balloon enteroscope, 33.3 % paediatric colonoscope. The duodenoscope allowed all conventional ERCP procedures, whereas the singleballoon enteroscope required dedicated ERCP catheters and did not allow metallic stent placement. However, the single-balloon enteroscope facilitated access to the papilla and sphincteroplasty allowed direct cholangioscopy. ERCP indications were bile duct stones (53.7 %), cholangitis (20.9 %), chronic pancreatitis (20.9 %), pancreatic cancer (1.5 %) and liver transplantation (3%). Therapeutic ERCP success rate is high in patients with Billroth II gastrectomy using either a conventional duodenoscope or the single-balloon enteroscope, with an acceptable and comparable adverse event rate. The choice of endoscope may depend on local experience, post-operative anatomy and therapeutic indication.

Case series of Cryptogenic Multifocal Ulcerating Stenosing Enteritis (CMUSE).

BACKGROUND AND STUDY AIMS: Small bowel ulceration poses a limited, but difficult differential diagnosis. The most common causes are Crohn's disease (CD), NSAID-associated enteritis, lymphoma, cytomegaly virus infection and tuberculosis. A less known and relatively novel differential diagnosis is cryptogenic multifocal ulcerative stenosing enteritis (CMUSE). PATIENTS AND METHODS: ive patients referred for balloon-assisted enteroscopy for various reasons showed endoscopic features of CMUSE. These findings and, when available, medical imaging were reviewed in order to increase general knowledge on CMUSE. RESULTS: Five patients, 3 males and 2 females, with a mean age of 39±5 years, underwent balloon-assisted enteroscopy. Typical short, circular, ulcerative stenoses were detected in the jejunum in 2 and in the ileum in 3 patients. The number of stenoses ranged from 1 to 7 per patient. Histopathology revealed nonspecific granulocyte inflammation without specific CD findings. Stenoses were often missed on pre-enteroscopy CT or MRI enteroclysis due to their short length. Treatment consisted of endoscopic balloon dilation in 3, corticosteroids in 3, azathioprine in 1 and anti-TNFα biologicals in 3 patients. 3 patients needed additional surgery because of ongoing symptomatic small bowel stenosis or retained wireless videocapsule. CONCLUSION: In patients with short, ulcerative small intestinal stenoses CMUSE is an important but often neglected differential diagnosis. The pathophysiology and relationship to CD are subject of ongoing debate, but specific endoscopic characteristics, different histopathological findings and lack of clear abnormalities on CT or MRI enterography suggest that CMUSE is a distinct albeit rare chronic inflammatory bowel disease.

Distal esophageal spasm and the Chicago classification: is timing everything?

BACKGROUND: According to the Chicago classification of esophageal motility disorders, distal esophageal spasm (DES) is defined as premature esophageal contractions (distal latency [DL] <4.5 s) for ≥20% of swallows, in the presence of a normal mean integral relaxation pressure (IRP). However, some patients with symptoms of DES have rapid contractions with a normal DL. The aim of this study was to characterize these patients and compare their clinical characteristics to those of patients classified as DES. METHODS: We retrospectively compared clinical characteristics and high-resolution manometry findings of patients with rapid contractions with normal latency to those meeting the Chicago classification criteria for DES. KEY RESULTS: Over a 3-year period, nine patients were diagnosed with DES and 14 showed rapid contractions in the distal esophagus with normal latency. The latter were younger than DES patients (60 ± 4 vs 72 ± 3 years, p < 0.05). Dysphagia and retrosternal pain occurred to a similar degree in both groups. Weight loss and abnormal barium esophagogram tended to be more frequent in DES patients. There was no difference in contractile front velocity (CFV) and in distal contractile integral (DCI) between patients with DES and rapid contractions with normal latency. Lower esophageal sphincter pressures were not different between groups. However, IRP was significantly higher in DES compared to rapid contractions with normal latency (11.7 ± 0.6 mmHg vs 7.6 ± 1.2 mmHg, p < 0.05), albeit still within the normal range. CONCLUSIONS & INFERENCES: These data suggest that patients with simultaneous contractions with normal latency represent a group of patients with many features similar to DES.

Mechanisms contributing to visceral hypersensitivity: focus on splanchnic afferent nerve signaling.

BACKGROUND: Visceral hypersensitivity is a main characteristic of functional bowel disorders and is mediated by both peripheral and central factors. We investigated whether enhanced splanchnic afferent signaling in vitro is associated with visceral hypersensitivity in vivo in an acute and postinflammatory rat model of colitis. METHODS: Trinitrobenzene sulfonic acid (TNBS)-colitis was monitored individually by colonoscopy to confirm colitis and follow convalescence and endoscopic healing in each rat. Experiments were performed in controls, rats with acute colitis and in postcolitis rats. Colonic afferent mechanosensitivity was assessed in vivo by quantifying visceromotor responses (VMRs), and by making extracellular afferent recordings from splanchnic nerve bundles in vitro. Multiunit afferent activity was classified into single units identified as low threshold (LT), wide dynamic range (WDR), high threshold (HT), and mechanically insensitive afferents (MIA). KEY RESULTS: During acute TNBS-colitis, VMRs were significantly increased and splanchnic nerve recordings showed proportionally less MIA and increased WDR and HT afferents. Acute colitis gave rise to an enhanced spontaneous activity of both LT and MIA and augmented afferent mechanosensitivity in LT, WDR and HT afferents. Postcolitis, VMRs remained significantly increased, whereas splanchnic nerve recordings showed that the proportion of LT, WDR, HT and MIA had normalized to control values. However, LT and MIA continued to show increased spontaneous activity and WDR and HT remained sensitized to colorectal distension. CONCLUSIONS & INFERENCES: Visceral hypersensitivity in vivo is associated with sensitized splanchnic afferent responses both during acute colitis and in the postinflammatory phase. However, splanchnic afferent subpopulations are affected differentially at both time points.

Impact of spatial resolution on results of esophageal high-resolution manometry.

BACKGROUND: The Chicago classification for esophageal motility disorders was designed for a 36-channel manometry system with sensors spaced at 1 cm. However, many motility laboratories outside the USA use catheters with a lower resolution in the segments outside the esophagogastric junction. Our aim was to investigate the effect of spatial resolution on the Chicago metrics and diagnosis. METHODS: In 20 healthy volunteers and 47 patients with upper gastrointestinal symptoms, high-resolution manometric studies of the esophagus were retrospectively reanalyzed using the original 1-cm spacing in the segments outside the 7-cm esophagogastric junction segment, and again after manually increasing the spacing between sensors to 2, 3, and 4 cm (above the lower esophageal sphincter region). Measurements were analyzed in random order and the investigator was blinded to the outcome of the analyses performed in another resolution of the same patient. Intra-class correlation coefficients (ICC) and Kappa values were determined. KEY RESULTS: There was a very strong correlation between the 1-cm and 2-cm analysis for all Chicago metrics studied in healthy volunteers (ICCs: distal contractile integral 0.998; contractile front velocity (CFV) 0.964; distal latency 0.919; peristaltic break size 0.941). The 2-cm spacing analysis also correlated very well with the 1-cm analysis for the different Chicago diagnoses obtained in the patients (Kappa values ranging from 0.665 to 1.000). When the sensor spacing was increased to 3 and 4 cm, the correlation was reduced to moderate for the Chicago metrics, especially for break size and CFV of peristalsis. CONCLUSIONS & INFERENCES: The Chicago classification for esophageal motility disorders is still valid and the same normal values can be used when catheters with a slightly lower resolution are used (i.e., 2-cm vs 1-cm spacing). For larger sensor intervals, the classification and the normal values will need to be adjusted.

Differential role of tachykinin NK3 receptors on cholinergic excitatory neurotransmission in the mouse stomach and small intestine.

BACKGROUND AND PURPOSE: Tachykinin NK(3) receptors are widely expressed in the mouse gastrointestinal tract but their functional role in enteric neuromuscular transmission remains unstudied in this species. We investigated the involvement of NK(3) receptors in cholinergic neurotransmission in the mouse stomach and small intestine. EXPERIMENTAL APPROACH: Muscle strips of the mouse gastric fundus and ileum were mounted in organ baths for tension recordings. Effects of NK(3) agonists and antagonists were studied on contractions to EFS of enteric nerves and to carbachol. KEY RESULTS: EFS induced frequency-dependent tetrodotoxin-sensitive contractions, which were abolished by atropine. The cholinergic contractions to EFS in the stomach were enhanced by the NK(3) antagonist SR142801, but not affected by the NK(3) agonist senktide or neurokinin B. The cholinergic contractions to EFS in the small intestine were not affected by SR142801, but dose-dependently inhibited by senktide and neurokinin B. This inhibitory effect was prevented by SR142801 but not by hexamethonium. SR142801, senktide or neurokinin B did not induce any response per se in the stomach and small intestine and did not affect contractions to carbachol. CONCLUSIONS AND IMPLICATIONS: NK(3) receptors modulate cholinergic neurotransmission differently in the mouse stomach and small intestine. Blockade of NK(3) receptors enhanced cholinergic transmission in the stomach but not in the intestine. Activation of NK(3) receptors inhibited cholinergic transmission in the small intestine but not in the stomach. This indicates a physiological role for NK(3) receptors in mouse stomach contractility and a pathophysiological role in mouse intestinal contractility.

TRPV1 receptors on unmyelinated C-fibres mediate colitis-induced sensitization of pelvic afferent nerve fibres in rats.

Patients with inflammatory bowel disease often suffer from gastrointestinal motility and sensitivity disorders. The aim of the current study was to investigate the role of transient receptor potential of the vanilloid type 1 (TRPV1) receptors in the pathophysiology of colitis-induced pelvic afferent nerve sensitization. Trinitrobenzene sulphate (TNBS) colitis (7.5 mg, 30% ethanol) was induced in Wistar rats 72 h prior to the experiment. Single-fibre recordings were made from pelvic nerve afferents in the decentralized S1 dorsal root. Fibres responding to colorectal distension (CRD) were identified in controls and rats with TNBS colitis. The effect of the TRPV1 antagonist N-(4-tertiarybutylphenyl)-4-(3-chlorophyridin-2-yl)tetrahydropyrazine-1(2H)carboxamide (BCTC; 0.25-5 mg kg(-1)) or its vehicle (hydroxypropyl-beta-cyclodextrin) was tested on the afferent response to repetitive distensions (60 mmHg). Immunocytochemical staining of TRPV1 and NF200, a marker for A-fibre neurons, was performed in the dorsal root ganglia L6-S1. TNBS colitis significantly increased the response to colorectal distension of pelvic afferent C-fibres. BCTC did not significantly affect the C-fibre response in controls, but normalized the sensitized response in rats with colitis. TNBS colitis increased the spontaneous activity of C-fibres, an effect which was insensitive to administration of BCTC. TNBS colitis had no effect on Adelta-fibres, nor was their activity modulated by BCTC. TNBS colitis caused an immunocytochemical up-regulation of TRPV1 receptors in the cell bodies of pelvic afferent NF200 negative neurons. TRPV1 signalling mediates the colitis-induced sensitization of pelvic afferent C-fibres to CRD, while Adelta-fibres are neither sensitized by colitis nor affected by TRPV1 inhibition.