Usefulness of Bisacodyl Testing on Therapeutic Outcomes in Refractory Constipation.

BACKGROUND: Although chronically constipated patients usually respond to medical treatment, there is a subgroup with scarce/no response, generally labeled as refractory or intractable. However, whether this lack of response is real or due to ancillary causes (suboptimal dosage, lack of compliance etc.) is unknown. AIMS: To see whether a pharmacologic test (bisacodyl colonic intraluminal infusion during manometric assessment) may predict the therapeutic outcome. METHODS: Data of patients undergoing 24/h colonic manometry for severe intractable constipation in whom the bisacodyl test (10 ml of drug dissolved into saline and injected through the more proximal recording port) had been carried out were retrieved and analysed, and correlations with the therapeutic outcome made. RESULTS: Overall, charts from 38 patients (5 men) were available; of these, only 21% displayed naive high-amplitude propagated contractions (average, less than 2/24 h), mostly meal-induced, during the recordings. A bisacodyl response was present in 31.6% patients, with a mean number of events of 1.8 per patient. After bisacodyl testing, 47.3% patients underwent intensive medical treatment, 44.7% surgery (medical failures), and 8% transanal irrigation, a procedure employed to treat refractory patients. The presence of naive propulsive contractions significantly correlated with the response to bisacodyl infusion (p < 0.0001), and with a favourable outcome to intensive medical treatment (p < 0.0001). CONCLUSIONS: The bisacodyl test may be clinically useful to better categorize constipated patients erroneously labelled as intractable and to exclude true colonic inertia, thus avoiding surgery in more than 30% of these subjects.

Chronic constipation diagnosis and treatment evaluation: the "CHRO.CO.DI.T.E." study.

BACKGROUND: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. METHODS: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. RESULTS: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. CONCLUSIONS: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity.

Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management: Delphi consensus study.

BACKGROUND: Gastro-esophageal reflux disease (GERD) may affect the upper digestive tract; up to 20% of population in Western nations are affected by GERD. Antacids, histamine H2-receptor antagonists, and Proton Pump Inhibitors (PPIs) are considered the referring medications for GERD. Nevertheless, PPIs must be managed carefully because their use, especially chronic, could be linked with some adverse effects. An effective and safe alternative pharmacological tool for GERD is needed. After the identification of potentially new medications to flank PPIs, it is mandatory to revise and improve good clinical practices even through a consensus process. AIM: To optimize diagnosis and treatment guidelines for GERD through a consensus based on Delphi method. METHODS: The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel, subject of the consensus, is the basic prerequisite for the consensus itself. A modified Delphi process was used to reach a consensus among a panel of Italian GERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of GERD. The Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations: Gastroenterology, otolaryngology, geriatrics, and general medicine. A scientific committee analyzed the literature, determined areas that required investigation (in agreement with the multiple-choice questionnaire results), and identified two topics of interest: (1) GERD disease; and (2) GERD treatment. Statements for each of these topics were then formulated and validated. The Delphi process involved two rounds of questioning submitted to the panel experts using an online platform. RESULTS: According to their routinary GERD practice and current clinical evidence, the panel members provided feedback to each questionnaire statement. The experts evaluated 15 statements and reached consensus on all 15. The statements regarding the GERD disease showed high levels of agreement, with consensus ranging from 70% to 92%. The statements regarding the GERD treatment also showed very high levels of agreement, with consensus ranging from 90% to 100%. This Delphi process was able to reach consensus among physicians in relevant aspects of GERD management, such as the adoption of a new approach to treat patients with GERD based on the overlapping between PPIs and Nux vomica-Heel. The consensus was unanimous among the physicians with different specializations, underlying the uniqueness of the agreement reached to identify in the overlapping approach between PPIs and Nux vomica-Heel a new intervention model for GERD management. The results support that an effective approach to deprescribe PPIs through a progressive decalage timetable (reducing PPIs administration to as-needed use), should be considered. CONCLUSION: Nux vomica-Heel appears to be a valid opportunity for GERD treatment to favor the deprescription of PPIs and to maintain low disease activity together with the symptomatology remission.

The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis - Definition, Clinical Presentation and Diagnosis.

Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis-Current Treatment and Monitoring.

The present document constitutes Part 2 of the EoETALY Consensus Statements guideline on the diagnosis and management of eosinophilic esophagitis (EoE) developed by experts in the field of EoE across Italy (i.e., EoETALY Consensus Group). Part 1 was published as a different document, and included three chapters discussing 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history and 3) diagnosis of EoE. The present work provides guidelines on the management of EoE in two final chapters: 4) treatment and 5) monitoring and follow-up, and also includes considerations on knowledge gaps and a proposed research agenda for the coming years. The guideline was developed through a Delphi process, with grading of the strength and quality of the evidence of the recommendations performed according to accepted GRADE criteria.This document has received the endorsement of three Italian national societies including the Italian Society of Gastroenterology (SIGE), the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). The guidelines also involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

Efficacy of an enterovaccine in recurrent episodes of diarrhea in the dog: a pilot study.

Recurrent episodes of self-limiting diarrhea in the dog, due to sudden dietary changes and to stressful or exciting situations, are conditions sometimes difficult to treat. Colifagina(®), a commercially available bacterial enterovaccine, showed, in previous studies performed on experimentally induced colitis in mice, to be able to improve both disease activity index and histological appearance, increase colonic secretion of IgA, and reduce inflammatory chemokine secretion. In the present study Colifagina(®) was administered to five dogs presenting recurrent episodes of self-limiting diarrhea and to one dog presenting chronic diarrhea. During the follow-up period, almost all patients decreased the number of episodes of abnormal defecation and the fecal score of such episodes improved in five out of six dogs. Even if further studies are needed to understand the exact potential of the compound, in dogs presenting recurrent episodes of self-limiting diarrhea due to sudden dietary changes and/or stressing or exciting situations, Colifagina(®) seems to be helpful in managing most of these patients.

Doxofylline for Pediatric Asthma Steps 1-4. Pediatric Asthma: New Role for an Old Drug.

The panoply of anti-asthma drugs for children between 6 and 18 years is not limited to those reported in the guidelines. In this review, we will re-assess the role of doxofylline, a xanthine characterized by a much higher handling than that of theophylline, as add-on treatment in pediatric asthma grade 1-4. Ten studies evaluated doxofylline in the treatment of asthma of patients non-responsive to the first-line inhaled corticosteroids. Of these, two included children and one was exclusively pediatric. According to their results, doxofylline exerts a powerful bronchodilator and anti-inflammatory activity, which can be exploited when the inhaled oral corticosteroids are not sufficient to get the desired effect of reducing symptoms. Unlike theophylline, doxofylline does not require blood testing. It can be administered together with or as an alternative to a series of other drugs considered in additional therapy.

Recent advances in the treatment of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder which presents with abdominal pain and altered bowel habits. It affects about 20% of the general population, mainly women, and has a considerable impact on the quality of life and health care costs. Four different entities of IBS have been identified: IBS with constipation (IBS­ C), IBS with diarrhea (IBS D), IBS with a mixed pattern of constipation and diarrhea, and unclassified IBS. Although the precise pathogenesis of IBS remains unclear, its multifactorial nature is evident and includes environmental and host factors. Management of patients with this disease is challenging and a personalized approach is required. A strong, reassuring physician­ patient relationship is crucial, followed by patient education, dietary advice, and stress reduction. For nonresponding patients, the therapeutic approach may include nonpharmacological therapies and / or pharmacotherapy. The choice of pharmacological treatment is based on the predominant symptom and a prespecified time point should be planned for effectiveness evaluation and dose adjustment. In patients with IBS­ D, the therapeutic options include mainly antibiotics, such as rifaximin, peripheral opioid agonists, mixed opioid agonists / antagonists, bile acid sequestrants, and antagonists of serotonin 5­ hydroxytryptamine type 3 receptors. Bulking agents and osmotic laxatives represent the first line therapy for IBS­ C, while lubiprostone and linaclotide should be reserved for difficult to treat patients. The involvement of gastrointestinal microbiota constitutes a fascinating field of exploration as it offers the potential to be modulated by the use of probiotics, prebiotics, synbiotics as well as fecal microbiota transplantation. This review offers an updated overview on the recent advances in the treatment of IBS.

Nissen fundoplication and dyspeptic symptoms: is the water load test useful?

BACKGROUND: The water load test is a simple, cheap and standardized method to evaluate gastric distension and gastric motility responses. We have previously shown that in patients with mild erosive or non-erosive esophagitis this test is frequently abnormal, suggesting an altered gastric function. The aim was to evaluate the water load test score before and after Nissen fundoplication in reflux patients. METHODS: Thirty-one patients (16 men, 15 women, mean age 46.5 y) were studied before and 3 months after Nissen fundoplication by stationary esophageal manometry, wireless Bravo pH system monitoring (48 hours), and water load test. A dyspepsia symptom questionnaire was also completed before and after surgery. Data were compared with those of 35 controls. RESULTS: All patients had pH-monitoring positive for pathological acid exposure and/or related-reflux symptoms in the absence of motility disorders. Basal symptoms scores were higher in patients compared to controls and improved after surgery, except than postprandial fullness, early satiation, and bloating, that were significantly increased. At baseline, all patients ingested significantly lower water volumes than controls, with a tendency to early onset of fullness and nausea, respectively. After surgery, the water volumes were significantly lower than presurgery. CONCLUSIONS: In patients with reflux-related symptoms, with or without esophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. Nissen fundoplication is associated with a relatively higher incidence of bloating, epigastric pain and fullness. These preliminary data could explain the incomplete resolution of symptoms after surgery in some patients, and suggest the use of additional studies to explore the gastric function in presurgical evaluation.

A SIGE-SINGEM-AIGO technical review on the clinical use of esophageal reflux monitoring.

Patients with esophageal symptoms potentially associated with gastroesophageal reflux disease such as heartburn, regurgitation, chest pain, or cough represent one of the most frequent reasons for referral to gastroenterological evaluation. The utility of esophageal reflux monitoring in clinical practice is: (1) to accurately define reflux burden, (2) to segregate patients according to reflux monitoring results as true GERD, reflux hypersensitivity and functional heartburn, and (3) to establish a treatment plan. With this in mind, in the last decade, investigations and technical advances, with the introduction of impedance-pH monitoring and wireless pH capsule, have enhanced our understanding and management of GERD. The following recommendations were discussed and approved after a comprehensive review of the medical literature pertaining to reflux testing techniques and their recent application. This review created under the auspices of the Società Italiana di Gastroenterologia ed Endoscopia Digestiva (SIGE), Società Italiana di Neuro-Gastro-Enterologia e Motilità (SINGEM) and Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) is intended to help clinicians in applying reflux studies in the most fruitful manner within the context of their patients with esophageal symptoms.

Microscopic colitis: a narrative review with clinical approach.

Microscopic colitis (MC) is diagnosed in presence of microscopic alterations of colonic mucosa, in patients without macroscopic lesions who referred for chronic diarrhea. The two types of MC are lymphocytic colitis (LC) and collagenous colitis (CC), but it is unclear whether these are the different expression of one unique disease or if they are distinct conditions. Today, although MC represents a consistent health problem, being responsible for a large part of gastroenterological consultations for diarrhea, it remains often underestimated. The detailed pathogenesis of MC has not been determined yet. Probably, it is the result of an interaction between individual, environmental and genetic factors. The most relevant risk factor for the development of MC is the use of certain drugs (such as non-steroidal anti-inflammatory drugs [NSAIDs], proton pump inhibitors [PPIs], selective serotonin reuptake inhibitors, beta-blockers, statins). Smoking is another relevant factor reported as associated with the development of MC. Diagnosis needs the execution of a colonoscopy in patients complaining about chronic diarrhea and abdominal pain. The crucial role is played by histology: MC is characterized by the presence of colonic mucosal lymphocytic infiltrate, with intraepithelial lymphocytes ≥20 per 100 enteric surface cells, in CC there is a typical subepithelial collagen layer, whose thickness is ≥10 µm. We carried out a review of the current literature to rule out what is new on epidemiology, diagnosis and therapy of MC.

Ski/SnoN expression in the sequence metaplasia-dysplasia-adenocarcinoma of Barrett's esophagus.

Barrett's esophagus (BE) is a precancerous condition. However, the mechanisms underlying the transformation from metaplastic to dysplastic to adenocarcinomatous epithelium are still poorly understood. As loss of transforming growth factor-beta growth inhibition is considered a hallmark of several human neoplasms, we evaluated the expression of Ski and SnoN (proteins that antagonize transforming growth factor-beta signaling through physical interaction with Smad complex and by recruiting histone deacetylases), as markers of the transforming growth factor-beta signaling pathway, in BE with and without dysplasia. Biopsy samples from 37 patients (26 men, aged 60 +/- 8 years) with histologically proven BE were evaluated; 10 patients had concomitant low-grade dysplasia, 7 high-grade dysplasia (HGD), and 6 HGD associated with adenocarcinoma. Ski and SnoN expression was assessed immunohistochemically. Neither Ski nor SnoN was expressed in normal esophageal epithelium, but both were strongly expressed in BE tissue, with intense cytoplasmic positivity. Expression of these proteins decreased markedly in dysplastic areas in patients with low-grade dysplasia and was absent in those with HGD or HGD/adenocarcinoma. Ski and SnoN proteins are overexpressed in BE and may be involved in abnormal signaling elicited by transforming growth factor-beta in this epithelium, enhancing the tumorigenesis process. These observations might help to elucidate the molecular mechanisms involved in the BE tumorigenesis process.

Gastroenterology today: between certainties and news.

This special article reports on two crucial issues discussed during a meeting. The first was the updated management of Helicobacter pylori (H. pylori) infection. This was approached taking into account the recent European Guidelines, with a focus on novelties in treatment. In particular, considering the increasing H. pylori antibiotic resistance to clarithromycin, in countries with a high clarithromycin resistance rate, the bismuth-containing quadruple therapies should be preferred. The new formulation, with bismuth, metronidazole, and tetracycline contained in a single capsule (three-in-one), has shown exciting results both in naive and in non-responder patients. Levofloxacin- and rifabutin-containing triple therapies should be proposed to patients who experienced H. pylori treatment failures. Another key message on H. pylori management was that, after one or more failures, standard antimicrobial susceptibility testing should be considered before prescribing a further treatment. The second issue concerned the novelties on dysbiosis of intestinal microbiota and its clinical consequences. Among the latter, the focus was on both constipation-predominant irritable bowel syndrome (IBS-C) and microscopic colitis. Since the number of microorganisms inhabiting the gastrointestinal (GI) tract is estimated to be about 10 times higher than that of human cells, it is not surprising to foresee the clinical consequences of dysbiosis. However, to date the role of dysbiosis in IBS-C and in microscopic colitis is poorly known and major efforts are needed to understand if manipulating microbiota could improve the treatment of these and other diseases both within and outside the GI tract. At a meeting held in Turin, Italy, on May 27, 2017 two crucial issues of modern gastroenterology were discussed: the updated management of Helicobacter pylori (H. pylori) infection and the novelties regarding the dysbiosis of intestinal microbiota and its clinical consequences. Among the latter, a focus was made on both constipation-predominant irritable bowel syndrome (IBS-C) and microscopic colitis. In this special article we report the most recent salient advances discussed during this meeting.

Appropriateness of colonoscopy: diagnostic yield and safety in guidelines.

AIM: To evaluate if the guidelines for the appropriateness of performing colonoscopy by American Society for Gastrointestinal Endoscopy (AGSE) and Italian Society of Digestive Endoscopy (SIED) yield a good diagnostic efficacy and do not present risks of missing important colonic pathologies in an Italian population sample. METHODS: A total of 1017 consecutive patients (560 men and 457 women; mean age 64.4 +/- 16 years) referred to an open-access endoscopy unit for colonoscopy from July 2004 to May 2006 were evaluated according to ASGE and SIED guidelines for appropriateness of performing the procedure. Diagnostic yield was defined as the percentage of relevant colonic pathologies of the total number of colonoscopies performed. RESULTS: About 85.2% patients underwent colonoscopy that was considered appropriate based on at least one ASGE or SIED criterion, while it was considered inappropriate for 14.8% of patients. The diagnostic yield of colonoscopy was significantly higher for appropriate colonoscopies (26.94% vs 10.6%, P < 0.001) than for inappropriate colonoscopies (5.3%). There was no missed colorectal cancer following the ASGE/SIED criteria. CONCLUSION: ASGE/SIED guidelines have shown a good diagnostic yield and the rate of missing relevant colonic pathologies seems very low. Unfortunately, the percentage of inappropriate referrals for colonoscopy in an open-access endoscopy system is still high, despite the number of papers published on the issue and the definition of international guidelines. Further steps are required to update and standardize the guidelines to increase their diffusion and to promote educational programs for general practitioners.

Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis.

AIM: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC). METHODS: Gastric tissue from a patient with severe idiopathic gastroparesis unresponsive to medical treatment and requiring surgery was analyzed by conventional histology and immunohistochemistry. RESULTS: Gastric pacemaker cells expressing Kit receptor had completely disappeared while the local level of stem cell factor, the essential ligand for its development and maintenance, was increased. No signs of cell death were observed in the pacemaker region. CONCLUSION: These results are consistent with the hypothesis that a lack of Kit expression may lead to impaired functioning of ICC. Total gastrectomy proves to be curative.

Botulinum toxin treatment of oesophageal achalasia in the old old and oldest old: a 1-year follow-up study.

BACKGROUND: Intrasphincteric injection of botulinum toxin (BTX) has become one of the most frequent therapeutic approaches for the treatment of oesophageal achalasia. This treatment seems particularly effective in elderly patients who are not candidates for more invasive procedures. AIMS: There are few or no data on BTX treatment of achalasia in the old old and oldest old. Therefore, we evaluated BTX treatment in a group of patients with achalasia in the extreme age range who were too ill or frail to undergo surgery or pneumatic dilatation. PATIENTS AND METHODS: Twelve elderly achalasic patients (age range 81-94 years, average age 86 years) with American Society of Anesthesiologists (ASA) class III-IV status were recruited for the study. After baseline clinical and instrumental evaluations, BTX 100U was injected at time 0 and 1 month later. Clinical follow-up was carried out after 3, 6 and 12 months. RESULTS: A significant improvement in symptom score was documented at each follow-up step. On the basis of improvements in scores, approximately 70% of patients were considered responders at the end of follow-up. CONCLUSIONS: BTX treatment is an effective treatment in a substantial proportion of achalasic patients >80 years of age, in whom benefits are still detectable after 12 months. BTX is a therapeutic option in patients unsuitable for surgery or pneumatic dilatation.

Noncardiac chest pain of esophageal origin in patients with and without coronary artery disease.

BACKGROUND/AIMS: Non-cardiac chest pain is a frequent finding in patients admitted to emergency departments, and it has been shown that many of these patients may have an esophageal cause for their pain. However, little data are available on patients primarily referred to the cardiology unit, and especially those with coronary artery disease. The purpose of this study was to assess the role of esophageal dysfunction in chest pain patients with and without coronary artery disease. METHODOLOGY: Eighty-one patients referred from a cardiology unit for chest pain and no myocardial infarction entered the study. Sixty-one patients had no evidence of coronary artery disease, whereas 20 had coronary artery disease with chest pain at rest. After the cardiological evaluation, the patients underwent esophageal function testing by means of upper endoscopy, manometry, and 24-hour pH-monitoring. RESULTS: Overall, 10% of patients (2.5% in the coronary artery disease group) had evidence of endoscopic esophagitis, 46% of esophageal motor disorders (12% in the coronary artery disease group), and 10% abnormal pH-monitoring (1% in the coronary artery disease group). CONCLUSIONS: We report that the esophagus might be responsible for non-cardiac chest pain in patients with and without coronary artery disease. In our experience, esophageal motor disorders, and not an increased acid reflux, are the abnormalities most commonly found in these patients.