Motorized spiral enteroscopy: effectiveness when used for new indications.

Background and study aims: Motorized spiral enteroscopy is proven to be effective in antegrade and retrograde enteroscopy. Nevertheless, little is known about its use in less common indications. The aim of this study was to identify new indications for the motorized spiral enteroscope. Methods: Monocentric retrospective analysis of 115 patients who underwent enteroscopy using PSF-1 motorized spiral enteroscope between January 2020 and December 2022. Results: A total of 115 patients underwent PSF-1 enteroscopy. 44 (38%) were antegrade procedures and 24 (21%) were retrograde procedures in patients with normal gastrointestinal anatomy with conventional enteroscopy indications. The remaining 47 (41%) patients underwent PSF-1 procedures for secondary less conventional indications: n=25 (22%) enteroscopy-assisted ERCP, n=8 (7%) endoscopy of the excluded stomach after Roux-en-Y gastric bypass, n=7 (6%) retrograde enteroscopy after previous incomplete conventional colonoscopy and n=7 (6%) antegrade panenteroscopy of the entire small bowel. In this group of secondary indications, technical success rate was significantly lower (72.5%) as compared to technical success rates in the conventional groups (98-100%, p<0.001 Chi-square). Minor adverse events occurred in 17/115 patients (15%), all treated conservatively (AGREE I and II). Conclusion: This study demonstrates the capabilities of PSF-1 motorized spiral enteroscope for secondary indications. PSF-1 is useful to complete colonoscopy in case of long redundant colon, to reach the excluded stomach after Roux-en-Y gastric bypass, to perform unidirectional pan-enteroscopy and to perform ERCP in patients with surgically altered anatomy. However, technical success rates are lower as compared to conventional antegrade and retrograde enteroscopy procedures, with only minor adverse events.

Cryptogenic multifocal ulcerative stenosing enteritis (CMUSE) diagnosed by retrograde motorized spiral enteroscopy.

We present the case of a 59-years-old woman with a history of abdominal pain and iron-deficiency anemia. Upper and lower gastrointestinal endoscopy turned out negative and further investigation with wireless videocapsule showed an inflammatory stricture in the middle of the small bowel with retention of the videocapsule. Treatment with budesonide was initiated and allowed the spontaneous evacuation of the videocapsule. Retrograde motorized spiral enteroscopy was performed and confirmed an ulcerative stricture 60 cm proximal to the ileocaecal valve. Clinical, iconographic, endoscopic and histological results were compatible with a rare entity described as cryptogenic multifocal ulcerative stenosing enteritis (CMUSE). After the diagnosis budesonide was replaced by azathioprine 100 mg/d as an immunosuppressor. However, azathioprine induced mild pancreatitis and a second course of budesonide was started again. Clinical evolution was favorable.

How to track and register adverse events and incidents related to gastrointestinal endoscopy.

Background and study aims: Gastrointestinal endoscopic procedures have evolved significantly in the last sixty years revolutionising the approach to the diagnostic and therapeutic spheres of medicine. Despite the advantages of using natural orifices to the bowel, adverse events (AE) may occur following endoscopy. Systematic AE registration is an objective in every realm of quality medicine. Despite the obvious advantage as a quality indicator, tracking endoscopy-related AE is not evident. The current study aimed at tracking all AE of all endoscopic procedures during a 3-month period. The three methods used were voluntary reporting by the endoscopist and by the patient in parallel with retrospective data analysis of patients' electronic medical records to allow capture of all AE and comparison of the three methods. Patients and methods: During a 3-month period endoscopists and patients were requested to report any possible AE. At the end of the period, a systematic review of all patient files was performed to track all AE related to the endoscopic procedure or the endoscopyrelated anaesthesia. In total 2668 endoscopic procedures were reviewed. Results: The total AE rate was 1.95%. Only half (51.9%) of all AE were voluntarily reported by endoscopists, the other half were extracted from the electronic medical record. There were no patient-reported AE. Although the majority (66.7%) of unreported AE were mild, these findings illustrate that voluntary AE reporting is unreliable. However, the retrospective tracking process proved to be difficult and time-consuming. Conclusions: The current study highlighted that systematic registration of all endoscopy-related AE is feasible, but challenging because of multiple hurdles. More practical methods are warranted to obtain reliable and long-term data as part of endoscopy quality measures.

The history of Acta Gastro-Enterologica Belgica.

The history of Acta Gastro-Enterologica Belgica is long, rich… and cloudy. There is no centralised archive available. However, all currently active gastroenterologists in Belgium have been trained with the journal, have published abstracts or manuscripts in it, or at least know of its existence. Whereas it started as a national society's journal in 1933, it has grown to a competitive international journal with Impact Factor. We felt the need to reconstruct the journal's long history, since this was never done before. This review tried to highlight some of the important milestones, without claiming to be complete. Looking back helps to better foresee and anticipate the future.

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.

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.

Comparison of the pharmacological profile of S-nitrosothiols, nitric oxide and the nitrergic neurotransmitter in the canine ileocolonic junction.

1. In organ bath experiments, hydroquinone (30-100 microM) and hydroxocobalamin (30-100 microM) concentration-dependently inhibited the relaxations induced by NO (0.3-30 microM) but not those by nitroglycerin (GTN, 1 microM) in the canine ileocolonic junction (ICJ). Hydroxocobalamin reduced the relaxation to low frequency (2 Hz) stimulation of the non-adrenergic, non-cholinergic (NANC) nerves, whereas hydroquinone only reduced the NANC nerve-mediated relaxations to electrical stimulation at 16 Hz, 0.5 ms. 2. Relaxations to S-nitroso-L-cysteine (CysNO, 1-30 microM), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1-30 microM) were not inhibited by hydroquinone (30-100 microM), hydroxocobalamin (30-100 microM), pyrogallol (30-100 microM) or L-cysteine (1-3 microM). Hydroquinone (100 microM) only reduced the relaxation to 10 microM CysNO. Hydroxocobalamin, but not hydroquinone, pyrogallol or L-cysteine, potentiated the relaxations to the lowest concentration (1 microM) of S-nitrosoglutathione (GSNO, 1-30 microM). 3. In the superfusion bioassay, hydroquinone (100 microM) and hydroxocobalamin (1 microM) concentration-dependently inhibited the biological activity of authentic NO (1-4 pmol) to the same extent as that of the transferable nitrergic factor, released from the canine ICJ in response to NANC nerve stimulation (8-16 Hz, 2 ms). Responses to GTN (10 pmol) or adenosine 5'-triphosphate (10 nmol) were not affected. 4. In conclusion, the nitrosothiols CysNO, SNAP and GSNO relax the canine ileocolonic junction, but these relaxations, pharmacologically, behave differently from the NANC nerve-mediated relaxations. From the bioassay experiments, we conclude that the nitrergic factor, released in response to NANCnerve stimulation of the canine ICJ, behaves pharmacologically like NO but not like a nitrosothiol.Therefore, we suggest NO, and not CysNO, SNAP or GSNO as the inhibitory NANC neurotransmitter in the canine ICJ.

Effect of adrenergic and nitrergic blockade on experimental ileus in rats.

1. In a rat model of experimental ileus, the effect of blockade of adrenergic and nitrergic neurotransmission was studied on the intestinal transit of Evans blue. 2. Ether anaesthesia and skin incision had no influence on the transit. Laparotomy significantly inhibited the transit of Evans blue. This inhibition was even more pronounced when the small intestine was manipulated. 3. Reserpine (5 mg kg-1), a drug that blocks adrenergic neurotransmission, completely reversed the inhibition of the transit induced by laparotomy but only partially reversed that induced by laparotomy with manipulation of the small intestine. 4. N omega-nitro-L-arginine (L-NOARG, 5 mg kg-1), a nitric oxide synthase inhibitor, completely reversed the reserpine-resistant inhibition induced by laparotomy with manipulation of the small intestine. The effect of L-NOARG was prevented by concomitant administration of L-arginine. L-Arginine itself slightly, but significantly enhanced the inhibition. S-methylisothiourea and aminoguanidine, selective inhibitors of the inducible NO synthase, had no effect on the transit after the three operations. 5. Treatment of the rats with reserpine plus L-NOARG had no additional effect on the transit after laparotomy as compared to reserpine alone. However, reserpine plus L-NNA completely reversed the inhibition of the transit induced by laparotomy with manipulation of the small intestine. 6. These findings support the involvement of adrenergic pathways in the pathogenesis of ileus and suggest that the additional inhibitory effect of mechanical stimulation results from an enhanced release of NO by the constitutive NO synthase.

S-nitrosothiols and the nitrergic neurotransmitter in the rat gastric fundus: effect of antioxidants and metal chelation.

1. The effects of the antioxidants ascorbic acid and alpha-tocopherol and of the metal chelator ethylenediaminetetraacetic acid (EDTA) were studied on relaxations in response to S-nitrosothiols, authentic nitric oxide (NO) and nitrergic non-adrenergic non-cholinergic stimulation of the rat gastric fundus. 2. The S-nitrosothiols S-nitrosocysteine (1-100 nM), S-nitrosoglutathione (0.01-3 microM) and S-nitroso-N-acetylpenicillamine (0.01-3 microM) induced concentration-dependent relaxations of the rat gastric fundus muscle strips, which were precontracted with prostaglandin F2alpha. The relaxations to all S-nitrosothiols were concentration-dependently enhanced by the antioxidants ascorbic acid (0.1-3 microM) and alpha-tocopherol (3-30 microM) and inhibited by the metal chelator EDTA (26 microM). 3. Ascorbic acid and alpha-tocopherol alone did not induce a relaxation of the precontracted rat gastric fundus muscle strip. However, when ascorbic acid (1 microM) or alpha-tocopherol (1 microM) were injected in the organ bath 1 minute after S-nitrosoglutathione (0.1 microM) or after S-nitroso-N-acetylpenicillamine (0.1 microM), they induced an immediate, sharp and transient relaxation. This relaxation was inhibited by the superoxide generator pyrogallol (2 microM). Such a relaxation to ascorbic acid or alpha-tocopherol was not observed in the presence of S-nitrosocysteine (10 nM). 4. Electrical field stimulation (0.5-4 Hz) of the precontracted rat gastric fundus strips induced frequency-dependent nitrergic relaxations which were mimicked by authentic NO (3-300 nM) and by acidified sodium nitrite NaNO2 (0.3-10 microM). Ascorbic acid (0.33-3 microM), alpha-tocopherol (3-30 microM) or EDTA (26 microM) did not affect the relaxations to nitrergic stimulation, NO or NaNO2. 5. In summary, relaxations to S-nitrosothiols in the rat gastric fundus are enhanced by the antioxidants ascorbic acid and alpha-tocopherol and inhibited by the metal chelator EDTA. However, relaxations to nitrergic stimulation of the rat gastric fundus or those to authentic NO were not affected by the antioxidants or by the metal chelator. These results indicate that antioxidants and metal chelators have a different effect on the biological activity of S-nitrosothiols and on that of the nitrergic neurotransmitter. Therefore, our results suggest that S-nitrosothiols do not act as intermediate compounds in nitrergic neurotransmission in the rat gastric fundus.

Role of VIP1/PACAP receptors in postoperative ileus in rats.

1. Vasoactive intestinal polypeptide (VIP) is an inhibitory neurotransmitter in the enteric nervous system. We investigated the role of VIP1/PACAP receptors in postoperative ileus in rats. 2. Different degrees of inhibition of the gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy or laparotomy plus mechanical stimulation of the gut. 3. The transit after skin incision or laparotomy was not altered by the VIP1/PACAP receptor antagonist Ac-His1,D-Phe2, K15, R16, VIP(3-7), GRF(8-27)-NH2 nor by the VIP1/PACAP receptor agonist K15, R16, VIP(1-7), GRF(8-27)-NH2 and the VIP2/PACAP receptor agonist RO 25-1553 (5 microg kg(-1)). 4. However, the transit after laparotomy plus mechanical stimulation was significantly enhanced by the VIP1/PACAP receptor antagonist, whereas it was further inhibited by the VIP1/PACAP receptor agonist. The combination of the VIP1/PACAP receptor agonist and antagonist counteracted the effect of both drugs alone. The VIP2/PACAP receptor agonist did not alter the effect of the VIP1/PACAP receptor antagonist. 5. The combination of the VIP1/PACAP receptor antagonist plus the nitric oxide (NO) synthase inhibitor L-nitroarginine had no effect on the transit after laparotomy plus mechanical stimulation, while the transit after skin incision was significantly decreased. 6. These findings suggest the involvement of VIP1/PACAP receptors, next to NO, in the pathogenesis of postoperative ileus. However, the combination of the VIP1/PACAP antagonist and the NO synthase inhibitor abolished the beneficial effect of each drug alone, suggesting the need for one of the inhibitory neurotransmitters to enable normal gastrointestinal transit.

Pre- and postjunctional protective effect of neocuproine on the nitrergic neurotransmitter in the mouse gastric fundus.

1. Electrical field stimulation (EFS) of non-adrenergic non-cholinergic nerves of the mouse gastric fundus induced frequency-dependent transient relaxations which were mimicked by nitric oxide (NO), added as acidified NaNO(2). The NO donors S-nitrosocysteine, S-nitrosoglutathione, SIN-1 and hydroxylamine induced sustained concentration-dependent relaxations. The NO synthase blocker L-nitro arginine (L-NOARG; 300 microM) abolished the relaxations to EFS without affecting the relaxations to NO. 2. The copper(I) chelator neocuproine (10 microM) enhanced the relaxations to EFS and NO but inhibited those to S-nitrosocysteine and S-nitrosoglutathione. Neocuproine potentiated the relaxations to SIN-1, which releases NO extracellularly, without affecting the relaxations to hydroxylamine, which releases NO intracellularly. 3. The potentiating effect of neocuproine on the relaxations to EFS was more pronounced after inhibition of catalase with 3-amino-1,2,4-triazole (1 mM) but not after inhibition of Cu/Zn superoxide dismutase (SOD) with diethyl dithiocarbamic acid (DETCA, 1 mM). The potentiating effect of neocuproine on relaxations to NO was not altered by 3-amino-1,2,4-triazole or DETCA treatment. 4. The relaxations to EFS were significantly inhibited by the oxidants hydrogen peroxide (70 microM) and duroquinone (10 microM) but only after inhibition of catalase with 3-amino-1,2,4-triazole or after inhibition of Cu/ZnSOD with DETCA respectively. 5. Our results suggest that neocuproine can act as an antioxidant in the mouse gastric fundus and that both catalase and Cu/ZnSOD protect the nitrergic neurotransmitter from oxidative breakdown. Since inhibition of catalase but not inhibition of Cu/ZnSOD potentiated the effect of neocuproine on relaxations to EFS without affecting the relaxations to NO, catalase may protect the nitrergic neurotransmitter mainly at a prejunctional site whereas Cu/ZnSOD protects at a postjunctional site.

Disturbance of the prejunctional modulation of cholinergic neurotransmission during chronic granulomatous inflammation of the mouse ileum.

The effect of chronic granulomatous inflammation of the intestine was studied on the prejunctional modulation of cholinergic nerve activity in the mouse ileum. Contractions to carbachol (0.01 - 0.3 microM) and to electrical field stimulation (EFS, 0.25 - 8 Hz) of enteric neurons were higher in inflamed ileum as compared to control ileum. However, when the neurally-mediated contractions to EFS were expressed as percentage of the direct smooth muscle contraction to carbachol, the responses to EFS were similar in control and inflamed ileum. Atropine (1 microM) abolished all contractions to EFS and carbachol in control and inflamed ileum. DMPP (3 - 30 microM), a nicotinic receptor agonist, induced concentration-dependent contractions that were more pronounced in inflamed ileum as compared to control ileum. Hexamethonium (100 microM), a nicotinic receptor blocker, significantly inhibited the contractions to EFS in inflamed ileum but not in control ileum. In control ileum, histamine (10 - 100 microM) and the histamine H(1) receptor agonist HTMT (3 - 10 microM) inhibited the contractions to EFS concentration-dependently without affecting the contractions to carbachol. The inhibitory effect of histamine and HTMT was prevented by the histamine H(1) antagonist mepyramine (5 - 10 microM) but not by the H(2)- and H(3)-receptor antagonists cimetidine and thioperamide (both 10 microM). In chronically inflamed ileum however, histamine (10 - 100 microM) and HTMT (3 - 10 microM) failed to inhibit the contractions to EFS. The histamine H(2) and H(3) receptor agonists dimaprit and R(-)-alpha-methylhistamine did not affect the contractions to EFS in control and inflamed ileum. The alpha(2)-receptor agonist UK 14.304 (0.01 - 0.1 microM) inhibited the contractions to EFS in control and inflamed ileum without affecting the contractions to carbachol. The effect of UK 14.304 was reversed by the alpha(2)-receptor antagonist yohimbine (1 microM). The inhibitory effect of UK 14.304 on contractions to EFS was of similar potency in control and inflamed ileum. Our results suggest that the prejunctional modulation of cholinergic nerve activity by nicotinic and histaminic H(1) receptors is disturbed during chronic intestinal inflammation whereas the modulation by alpha(2)-receptors is preserved. Such a disturbance of cholinergic nerve activity may contribute to the motility disturbances that are often observed during chronic intestinal diseases in humans.

Effect of 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced ileitis on the motor function of non-inflamed rat gastric fundus.

During intestinal inflammation, motility disturbances are not restricted to inflamed regions, but may also occur in remote non-inflamed sites of the gastrointestinal tract. Our aim was to investigate the motor function of the gastric fundus after the induction of terminal ileitis in the rat. Ileal inflammation was induced by intraluminal installation of 2,4,6-trinitrobenzenesulphonic acid (TNBS) into the ileum. Inflammation was assessed both histologically and biochemically. Contractions and relaxations of longitudinal muscle strips from the gastric fundus were studied 36 h and 1 week later. During the acute phase of ileal inflammation (36 h), the non-inflamed stomach was distended. The contractility of longitudinal muscle strips of the gastric fundus was decreased due to a post-receptor defect. In addition, nonadrenergic noncholinergic (NANC) relaxations were inhibited due to neuronal dysfunction. Aortic contractility remained normal and the mere presence of food in the stomach did not account for the disturbed neuromuscular function in the gastric fundus. Ablation of extrinsic primary afferent neurones by capsaicin further impaired gastric fundus contractility. Transection and re-anastomosis of the jejunum reversed the effect of TNBS-induced ileitis on the neuromuscular function of the gastric fundus. One week after TNBS, cholinergic neurotransmission was increased in the gastric fundus. During acute ileitis, smooth muscle cell contractility and inhibitory NANC neurotransmission are inhibited in the non-inflamed gastric fundus. This phenomenon may be mediated by intrinsic connections within the enteric nervous system.

Inhibition of non-adrenergic non-cholinergic relaxations by nitric oxide donors.

The effects of pretreatment with the nitric oxide (NO)-releasing substances 3-morpholino-sydnoninime (SIN-1) and nitroglycerin were investigated on relaxations induced by non-adrenergic non-cholinergic (NANC) nerve stimulation, authentic NO and vasoactive intestinal polypeptide (VIP) in the rat gastric fundus. Short periods of electrical stimulation (0.5-16 Hz, 1 ms, pulse trains of 10 s) induced frequency-dependent transient relaxations, previously shown to be mainly mediated by NO. Both SIN-1 (10-100 microM) and nitroglycerin (0.5 mM) pretreatment significantly reduced these electrically induced responses to a similar extent as the inhibitor of the NO biosynthesis L-nitroarginine (30-300 microM). Prolonged periods of electrical stimulation (16 Hz, 1 ms, pulse trains of 180 s) induced a sustained relaxation, previously shown to be mediated by NO and VIP. L-Nitroarginine (30-300 microM) or pretreatment with SIN-1 (100 microM) or nitroglycerin (0.5 mM) did not affect the amplitude of this relaxation but slowed down its onset. Authentic NO (0.01-10 microM) and VIP (0.01-10 nM) induced respectively transient and sustained concentration-dependent relaxations. SIN-1 or nitroglycerin pretreatment had no effect on the concentration-response curves to NO and VIP. These results indicate that prolonged exposure to NO donors inhibits electrically induced nerve-mediated NANC relaxations without affecting the postjunctional response to NO and VIP. As similar results are obtained with NO biosynthesis inhibitors, our results illustrate a prejunctional inhibitory effect of NO on the NANC nerves of the rat gastric fundus and suggest the presence of an autoregulatory mechanism for the nitrergic innervation.