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.

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.

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.

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.

I-SCAN targeted versus random biopsies in Barrett's oesophagus.

BACKGROUND: The accuracy and effectiveness of targeted oesophageal biopsies in Barrett's oesophagus to detect dysplasia using new magnification techniques are unknown. Aim of this study was to investigate whether the combined use of acetic acid, magnification and electronic filters allows the same accuracy as the four-quadrant random biopsies pattern; pathologist interobserver agreement both in low grade and high grade dysplasia was also assessed. METHODS: Fifty-four consecutive patients newly diagnosed with Barrett's oesophagus were enrolled in a prospective study from a single endoscopy unit. Biopsies were evaluated by the local pathologist and by an expert pathologist from another pathology unit. MAIN OUTCOME MEASUREMENT: Dysplasia detection rate and interobserver agreement for the histologic diagnosis of dysplasia. RESULTS: The use of acetic acid, magnification and electronic filters showed an unacceptably low dysplasia detection rate by the two pathologists (9.2% and 5.5% for targeted biopsies, respectively). The interobserver agreement for low grade dysplasia between pathologists was low (Cohen's K weighted=0.45). CONCLUSIONS: In an average setting, the standard four-quadrant method should still be preferred, along with the implementation of a routine second evaluation by an expert pathologist.

Symptom patterns can distinguish diverticular disease from irritable bowel syndrome.

BACKGROUND: Diverticular disease (DD) and irritable bowel syndrome (IBS) share a similar symptom pattern. However, comparative studies are flawed by different age at onset of symptoms. We aimed to verify whether clinical features distinguish DD from IBS. MATERIALS AND METHODS: Patients with DD or IBS, matched for age and gender (1/1) were consecutively recruited. Data on demographic parameters, voluptuary habits, inheritance of disease and symptoms were collected. Moreover, the association between pain > 24 h, and clinical parameters were evaluated. RESULTS: Ninety patients with DD and 90 patients with IBS (DD: F/M: 46/44; age: 50.9 years; IBS: 46/44; 50.4) were selected from an overall population of 1275 patients. Only nine patients with DD (10%) fulfilled the criteria for IBS diagnosis. Abdominal pain > 24 h was more prevalent in SDD than in patients with IBS (20 vs. 6 patients; P < 0.01). Furthermore, compared with IBS, patients with DD showed more episodes of pain > 24 h requiring medical attention (80% vs. 33%; P < 0.01). CONCLUSIONS: Abdominal pain lasting for more than 24 h discriminates patients with DD compared with those with IBS. Identifying this symptom could be an appropriate strategy to define the diagnosis and management.

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.

Education improves colonoscopy appropriateness.

BACKGROUND: Appropriateness in GI endoscopy is critical to face the rising amount of demands. Education of physicians has been advocated to reduce the level of inappropriateness. OBJECTIVE: Our purpose was to assess the effectiveness of an educational program in determining a reduction of inappropriate colonoscopies in an open access system. DESIGN: Prospective study. SETTING: A single endoscopy unit in Italy. PATIENTS: A total of 495 consecutive outpatients referred to our endoscopy unit by family physicians for diagnostic colonoscopy before the educational course and 522 after its completion, for a total of 1017 patients. MAIN OUTCOME MEASUREMENTS: Inappropriate colonoscopy reduction rates, cost savings, and reduction of waiting lists were evaluated. RESULTS: With regard to inappropriate colonoscopies, the post-course group rate of inappropriateness was significantly lower than that of the pre-course group (P < or = .001). The economic savings for 1 year was estimated to be euro19,000. The reduction of the waiting list was about 15% of the original value. CONCLUSIONS: Education has a high incidence in reducing inappropriate colonoscopies in an open-access system determining reduction of costs and waiting lists.

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.

Concomitant chemotherapy and external radiotherapy plus brachytherapy for locally advanced esophageal cancer: results of a retrospective multicenter study.

AIMS AND BACKGROUND: In October 1995, the Piedmont AIRO (Italian Society of Radiation Oncology) Group started a multi-institutional study of radiochemotherapy on locally advanced esophageal cancer, characterized by external radiotherapy followed by an intraluminal high dose-rate brachytherapy boost. Most patients were re-evaluated for surgery at the end of the program. The primary aim of the study was to assess efficacy of curative radiochemotherapy regarding overall survival and local control rates. The secondary aim was to evaluate the ability of radiochemotherapy to make resectable lesions previously considered inoperable. METHODS AND STUDY DESIGN: Between January 1996 and March 2000, 75 patients with locally advanced esophageal cancer were enrolled. All were treated with definitive radiotherapy; due to age or high expected toxicity, chemotherapy was employed only in 53 of them. Treatment schedule consisted of 60 Gy external radiotherapy (180 cGy/d, 5 days/week for 7 weeks) concomitant with two 5-day cycles of chemotherapy with cisplatin and fluorouracil (weeks 1 and 5). One or two sessions of 5-7 Gy intraluminal high dose-rate brachytherapy were carried out on patients whose restaging showed a major tumor response. Surgery was performed in 14 patients. RESULTS: At the end of radiotherapy, dysphagia disappeared in 46/75 cases (61%), and in 20/75 (27%) a significant symptom reduction was recorded. Complete objective response at restaging after radiotherapy was obtained in 33% of patients and a partial response in 53%. At the end of the multimodal treatment program, including esophagectomy, complete responses were 34 (45%); 4 of 14 (28.5%) cases proved to be disease free (pT0) at pathological examination. No G3-G4 toxicity was recorded. Two- and 5-year overall survival rates of all patients were, respectively, 38% and 28%; 2- and 5-year local control rates were, respectively, 35% and 33%. In a subgroup of 20 nonsurgical patients in complete response after radiochemotherapy, the overall survival rate at 3 and 5 years was 65% and the local control rate at 3 and 5 years was 75%. According to multivariate analysis, prognostic factors for survival were Karnofsky index and esophagectomy. CONCLUSIONS: For patients with locally advanced disease, radiochemotherapy showed improved clinical and pathologic tumor response and survival compared to surgery or radiotherapy alone. Intraluminal brachytherapy with a small fraction size allows an increased dose to the tumor without higher toxicity. Esophagectomy following radiochemotherapy could improve survival rates compared to definitive radiochemotherapy, but it is necessary to optimize selection criteria for surgery at the re-evaluation phase.