Pelvic floor rehabilitation for defecation disorders.

Pelvic floor rehabilitation is frequently recommended for defecation disorders, in both constipation and fecal incontinence. However, the lack of patient selection, together with the variety of rehabilitation methods and protocols, often jeopardize the results of this approach, causing difficulty in evaluating outcomes and addressing proper management, and above all, in obtaining scientific evidence for the efficacy of these methods for specific indications. The authors represent different gastroenterological and surgical scientific societies in Italy, and their aim was to identify the indications and agree on treatment protocols for pelvic floor rehabilitation of patients with defecation disorders. This was achieved by means of a modified Delphi method, utilizing a working team (10 members) which developed the statements and a consensus group (15 members, different from the previous ones) which voted twice also suggesting modifications of the statements.

Rome IV. Gallbladder and Sphincter of Oddi Disorders.

The concept that motor disorders of the gallbladder, cystic duct and sphincter of Oddi can cause painful syndromes is attractive and popular, at least in the USA. However, the results of commonly performed ablative treatments (cholecystectomy and sphincterotomy) are not uniformly good. The predictive value of tests that are often used to diagnose dysfunction (dynamic gallbladder scintigraphy and sphincter manometry) is controversial. Evaluation and management of these patients is made difficult by the fluctuating symptoms and the placebo effect of invasive interventions. A recent stringent study has shown that sphincterotomy is no better than sham treatment in patients with post-cholecystectomy pain and little or no objective abnormalities on investigation, so that the old concept of sphincter of Oddi dysfunction (SOD) type III is discarded. ERCP approaches are no longer appropriate in that context. There is a pressing need for similar prospective studies to provide better guidance for clinicians dealing with these patients. We need to clarify the indications for cholecystectomy in patients with Functional Gallbladder Disorder (FGBD) and the relevance of sphincter dysfunction in patients with some evidence for biliary obstruction (previously SOD type II, now called "Functional Biliary Sphincter Disorder - FBSD") and with idiopathic acute recurrent pancreatitis.

Anal function after endoluminal locoregional resection by transanal endoscopic microsurgery and radiotherapy for rectal cancer.

AIM: In patients with rectal cancer, surgery and chemoradiotherapy may affect anal sphincter function. Few studies have evaluated anorectal function after neoadjuvant chemoradiotherapy (n-CRT) and/or transanal endoscopic microsurgery (TEM). The aim of this study was to evaluate the effects of n-CRT and TEM on anorectal function. METHOD: Thirty-seven patients with rectal cancer underwent anorectal manometry and Wexner scoring for faecal incontinence at baseline, after n-CRT (cT2-T3N0 cancer) and at 4 and 12 months after surgery. Water-perfused manometry measured anal tone at rest and during squeezing, rectal sensitivity and compliance. Twenty-seven and 10 patients, respectively, underwent TEM without (Group A) or with n-CRT (Group B). RESULTS: In Group A, anal resting pressure decreased from 68 ± 23 to 54 ± 26 mmHg at 4 months (P = 0.04) and improved 12 months after surgery (60 ± 30 mmHg). The Wexner score showed a significant increase in gas incontinence (59%), soiling (44%) and urgency (37%) rates at 4 months, followed by clinical improvement at 1 year (41%, 26% and 18%, respectively). In group B, anal resting pressure decreased from 65 ± 23 to 50 ± 18 mmHg at 4 months but remained stable at 12 months (44 ± 11 mmHg, P = 0.02 vs preoperative values - no significant difference compared with evaluation at 4 months). Gas incontinence, soiling and urgency were observed in 50%, 50%, 25% and in 38%, 12% and 12% of cases, respectively, 4 and 12 months after treatment. CONCLUSION: TEM does not significantly affect anal function. Instead, n-CRT does affect anal function but without causing major anal incontinence.

Position paper on transanal irrigation in chronic non-organic constipation.

The practice of recto-colonic water irrigation to treat constipation has been used since ancient times with different, uncontrolled, and variably performing methods which have been considered interchangeably all alike. The use of better-performing devices with a standardized methodology is relatively recent, and the term Trans Anal Irrigation (TAI) defines a methodology performed with devices able to control the timing, volume, and pressure of the water introduced into the rectum and colon utilizing a catheter or a cone through the anus. Such practice has been implemented with favorable responses in patients with refractory chronic constipation secondary to neurological diseases. However, since the role of Trans Anal Irrigation as a therapeutic aid in chronic functional constipation and functional evacuation disorders is not yet fully clarified and standardized, a group of clinical investigators with recognized expertise in these clinical conditions intends to clarify the elements that characterize a TAI procedure that can benefit patients with functional constipation and functional defecation disorders defined according to the lastly updated Rome Diagnostic Criteria. Finally, the paper deals with adherence and practical implementation of TAI.

Chronic constipation in hemiplegic patients.

AIM: To assess the prevalence of bowel dysfunction in hemiplegic patients, and its relationship with the site of neurological lesion, physical immobilization and pharmacotherapy. METHODS: Ninety consecutive hemiplegic patients and 81 consecutive orthopedic patients were investigated during physical motor rehabilitation in the same period, in the same center and on the same diet. All subjects were interviewed >= 3 mo after injury using a questionnaire inquiring about bowel habits before injury and at the time of the interview. Patients' mobility was evaluated by the Adapted Patient Evaluation Conference System. Drugs considered for the analysis were nitrates, angiogenic converting enzyme (ACE) inhibitors, calcium antagonists, anticoagulants, antithrombotics, antidepressants, anti-epileptics. RESULTS: Mobility scores were similar in the two groups. De novo constipation (OR = 5.36) was a frequent outcome of the neurological accident. Hemiplegics showed an increased risk of straining at stool (OR: 4.33), reduced call to evacuate (OR: 4.13), sensation of incomplete evacuation (OR: 3.69), use of laxatives (OR: 3.75). Logistic regression model showed that constipation was significantly and independently associated with hemiplegia. A positive association was found between constipation and use of nitrates and antithrombotics in both groups. Constipation was not related to the site of brain injury. CONCLUSION: Chronic constipation is a possible outcome of cerebrovascular accidents occurring in 30% of neurologically stabilized hemiplegic patients. Its onset after a cerebrovascular accident appears to be independent from the injured brain hemisphere, and unrelated to physical inactivity. Pharmacological treatment with nitrates and antithrombotics may represent an independent risk factor for developing chronic constipation.

Relationship between gastrointestinal and extra-gastrointestinal symptoms and delayed gastric emptying in functional dyspeptic patients.

AIM: Delayed gastric emptying and an enlarged fasting gastric antrum are common findings in functional dyspepsia but their relationship with gastrointestinal (GI), and the frequently associated extra-GI symptoms remains unclear. This study evaluated the relationship between GI and extra-GI symptoms, fasting antral volume and delayed gastric emptying in functional dyspepsia. METHODS: In 108 functional dyspeptic patients antral volume and gastric emptying were assessed with ultrasonography (US). Symptoms were assessed with standardized questionnaire. The association of symptoms and fasting antral volume with delayed gastric emptying was estimated with logistic regression analysis. RESULTS: Delayed gastric emptying was detected in 39.8% of the patients. Postprandial drowsiness (AOR 11.25; 95%CI 2.75-45.93), nausea (AOR 3.51; 95%CI 1.19-10.32), fasting antral volume (AOR 1.93; 95%CI 1.22-3.05), were significantly associated with delayed gastric emptying. Symptoms, mainly the extra-GI ones as postprandial drowsiness and nausea, combined with fasting antral volume predicted the modality of gastric emptying with a sensitivity and specificity of 78%. CONCLUSION: In functional dyspeptic patients, (1) an analysis of fasting antral volume and of symptoms can offer valuable indication on the modality of gastric emptying, and (2) it seems appropriate to inquire on postprandial drowsiness that showed the best correlation with delayed gastric emptying.

A randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of long-term treatment with prucalopride.

BACKGROUND: Randomized trials have confirmed the efficacy of prucalopride for the treatment of chronic constipation up to 12 weeks. This study aimed to assess the efficacy of prucalopride over a 24-week period (ClinicalTrials.gov: NCT01424228). METHODS: Adults with chronic constipation and ≤2 spontaneous complete bowel movements (SCBMs)/week were randomized to receive prucalopride 2 mg or placebo daily for 24 weeks. The primary endpoint was the proportion of patients achieving a mean of ≥3 SCBMs/week over the treatment period, assessed using daily e-diaries. Secondary outcomes and safety parameters were assessed throughout the study. KEY RESULTS: Overall, 361 patients were randomized and received prucalopride or placebo. Baseline characteristics were similar in the prucalopride (N = 181) and placebo (N = 180) groups. Mean age was 48.9 years (standard deviation, 16.0) and most patients were women. The proportion of participants achieving the primary endpoint was not statistically different between the prucalopride and placebo groups (25.1% vs 20.7%; p = 0.367). There was also no statistically significant difference between groups over the first 12-week period (prucalopride, 25.1%; placebo, 20.1%; p = 0.341). There were no statistically significant differences between groups for most secondary endpoints. No new safety concerns were identified. CONCLUSIONS & INFERENCES: This trial did not show statistically significant improvements in primary or secondary outcomes with prucalopride compared with placebo over 24 or 12 weeks. This is in contrast to the results of four previous 12-week trials, which demonstrated prucalopride to be significantly more effective than placebo. An extensive evaluation did not provide an explanation for the null efficacy results of this study.

A cross-cultural investigation of attachment style, catastrophizing, negative pain beliefs, and symptom severity in irritable bowel syndrome.

BACKGROUND: Little information exists regarding whether psychosocial variables in irritable bowel syndrome (IBS) vary by geographic location. Adult attachment is an important psychological concept rooted in childhood relationship experience that has not been previously studied in IBS. Catastrophizing and negative pain beliefs have been described in IBS and may be affected by attachment. AIMS: In this cross-cultural study, we determined: (i) whether attachment differs between IBS patients and controls, (ii) whether geographic location has a significant effect on attachment style, catastrophizing and negative pain beliefs, and (iii) how all three variables correlate with IBS symptom severity. METHODS: 463 IBS patients, with moderate to severe symptom scores, and 192 healthy controls completed validated questionnaires about attachment, catastrophizing, negative pain beliefs and IBS-SSS in nine locations, USA (New York, Los Angeles), Mexico, Italy (Rome, Bari), Romania, Iran, India, and China. KEY RESULTS: Attachment anxiety and avoidance scores were significantly higher in IBS patients than in controls (p < 0.001). This was particularly true for the fearful-avoidant attachment category, especially in China and Romania. Path analysis showed that attachment anxiety and avoidance had indirect effects on IBS-SSS through catastrophizing (p < 0.0001) and negative pain beliefs (p = 0.005). All three psychosocial measures varied significantly depending on location. CONCLUSIONS & INFERENCES: In the IBS population studied, attachment style was significantly different in IBS compared to a control population. Geographic differences in attachment, catastrophizing and negative pain beliefs were documented and their correlation with symptom severity and thus, research of psychosocial variables in IBS should take into account the location of the population studied.

Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome.

Appropriate guidelines for clinical trials in irritable bowel syndrome are needed because of the inadequacy of previously performed trials, the use of new and more adequate patient definition, new emerging pathophysiological models and the unique requirements related to the assessment of treatment outcome that, in the absence of a biological marker, can rely only on the evaluation of clinical manifestations. This consensus report highlights the following points. (a) A 4-week period is considered to be adequate to assess drug efficacy for the control of symptoms. (b) For the cyclic and non-life-threatening nature of the disease, a long-term study of 4-6 months or more of active treatment to establish efficacy is considered to be inappropriate in the large majority of patients. (c) In the initial assessment phase of drug efficacy, the withdrawal effect of treatment can be ascertained during a follow-up period prolonged for a sufficient time (4-8 weeks) after stopping treatment. Subsequent trials with proper withdrawal phase design and duration can then ascertain the drug post-treatment benefit. (d) Considering the intermittent clinical manifestations of irritable bowel syndrome, designing trials with on-demand or repeated cycles of treatment could be envisaged. However, the lack of a definition of what constitutes an exacerbation is a major obstacle to the design of such trials. In the absence of an established gold standard, appropriately justified novel trial designs are welcome. (e) Patients eligible for inclusion should comply with the Rome II diagnostic criteria for irritable bowel syndrome. (f) The main efficacy outcome of the treatment should be based on one primary end-point. (g) The primary efficacy end-point could combine, in a global assessment, the key symptoms (abdominal pain, abdominal discomfort, bowel alterations) of irritable bowel syndrome or rate any single symptom for drugs considered to target specific symptoms. (h) A 50% improvement in the primary efficacy end-point seems to be a reasonable definition of a responder.

Quantitative determination of faecal fat, nitrogen and water by means of a spectrophotometric technique: near infrared reflectance analysis (NIRA). Assessment of its accuracy and reproducibility compared with chemical methods.

Measurement in faeces of the principal nutrients, fat (F), water (W) and nitrogen (N) is useful to assess digestive and absorptive functions and thus to monitor patients' progress and response to therapy in malabsorption/maldigestion syndromes. Presently available techniques are not ideal in clinical practice for serial analysis as they are time-consuming and require unpleasant and prolonged handling of the stools. The present study aimed to evaluate the accuracy and precision of near infrared reflectance analysis (NIRA) in routine measurement of fat, nitrogen and water faecal contents compared with Van de Kamer (VDK), Kjeldahl (KJ) and gravimetric-by-lyophilization (LY) methods, respectively. Fat, nitrogen and water (n = 34), were measured in the 1-day faecal collections of 15 healthy subjects and 19 patients (10, coeliac disease; 6, chronic pancreatitis; 3, small-bowel Crohn's disease). A highly significant linear correlation was found between VDK, KJ, LY methods and NIRA analysis. Very low values of intra-assay coefficient of variation indicated a remarkable analytical precision of NIRA. A recovery test at different concentrations in the useful range was performed for all three nutrients, to assess the accuracy of NIRA. Quantitative recoveries were between 95 and 105%. Data from the present study show that NIRA analysis is reproducible, accurate and rapid (less than 1 min). These characteristics make NIRA serial analysis useful in clinical practice to monitor progress and response to therapy in patients with malabsorption/maldigestion syndromes.

Sphincter of Oddi dysfunction.

Biliary-like pain alone, or associated with a transient increase in liver or pancreatic enzyme, may be the clinical manifestations of sphincter of Oddi dysfunction. Since it is not always possible to dissociate functional conditions from subtle structural changes, the term sphincter of Oddi dysfunction is used to define motility abnormalities caused by 'sphincter of Oddi stenosis' and 'sphincter of Oddi dyskinesia'. Both sphincter of Oddi stenosis and sphincter of Oddi dyskinesia may account for obstruction to flow through the sphincter of Oddi and may thus induce retention of bile in the biliary tree and pancreatic juice in the pancreatic duct. Most of the clinical information concerning sphincter of Oddi dysfunction refers to post-cholecystectomy patients who have been arbitrarily classified according to clinical presentation, laboratory results and endoscopic retrograde cholangiopancreatography findings in: (a) biliary type I, (b) biliary type II, and (c) biliary type III. Prevalence of biliary-type of pain has been reported to vary from 1 to 1.5% in unselected postcholecystectomy people, to 14% in a selected group of patients complaining of postcholecystectomy symptoms. The frequency of sphincter of Oddi dysfunction, as shown by manometry, differs in the different clinical subgroups: 65-95% in biliary group I, mainly due to sphincter of Oddi stenosis; 50-63% in biliary type II, and 12-28% in biliary type III. In patients with idiopathic recurrent pancreatitis, sphincter of Oddi dysfunction varies from 39 to 90%. Diagnostic work-up of postcholecystectomy patients for suspected sphincter of Oddi dysfunction includes liver biochemistry and pancreatic enzymes, plus negative findings of structural abnormalities. Usually, this would include transabdominal ultrasound and endoscopic retrograde cholangiopancreatography. Depending on the available resources, endoscopic ultrasound and magnetic resonance cholangiography may precede endoscopic retrograde cholangiopancreatography in specific clinical conditions. Quantitative evaluation of bile transit from the hepatic hilum to the duodenum at choledochoscintigraphy appears valuable in the decision to undertake sphincter of Oddi manometry or to treat. Sphincterotomy is the standard treatment for sphincter of Oddi dysfunction. In biliary type I patients, the indication for endoscopic sphincterotomy is straightforward without the need of any additional investigation. Slow bile transit in biliary type II is an indication to undergo endoscopic sphincterotomy without sphincter of Oddi manometry. Slow bile transit in biliary type III patients is an indication to perform sphincter of Oddi manometry. Diagnostic work-up of patients with gallbladder in situ is part of the same diagnostic algorithm that has initially excluded the presence of a gallbladder dysfunction.

Prevalence of sexual and physical abuse and its relationship with symptom manifestations in patients with chronic organic and functional gastrointestinal disorders.

UNLABELLED: A history of physical and/or sexual abuse is a frequent occurrence in patients referred for chronic gastrointestinal disorders and it may predispose to the development of functional gastrointestinal disorders, and multiple medical complaints. This study was aimed to determine: (a) prevalence of abuse history in Italian patients with chronic gastrointestinal disturbances, and (b) relationship between abuse history and clinical manifestations. SUBJECTS AND METHODS: Consecutive gastrointestinal out-patients filled in a self-administered standardised questionnaire, made up of two separate sections: (1) a medical section enquiring on gastrointestinal and extra-gastrointestinal symptoms, and (2) a section on abuse enquiring on the presence and type of abuse suffered during their lifetime. Associations between number of symptoms and abuse history were evaluated using univariate and multivariate logistic models. RESULTS: Questionnaires were handed out to 260 patients; 13% of whom did not fill in the questionnaires. Functional gastrointestinal disorders were diagnosed in 72.5% of patients and organic gastrointestinal diseases in 27.5%. A total of 31% of patients with organic gastrointestinal diseases and 32% of those with functional gastrointestinal disorders referred to a history of sexual or physical abuse. Histories of physical plus sexual abuse, sexual abuse, childhood abuse and female gender, were statistically associated with an increased number of gastrointestinal and extra-gastrointestinal symptoms irrespective of functional or organic disorders, whereas there was no statistical association with physical abuse only. Furthermore, diagnosis of functional gastrointestinal disorders was associated with a significantly (p<0.001) greater number of gastrointestinal symptoms than the diagnosis of organic gastrointestinal diagnosis. A total of 10 patients met the diagnostic criteria of somatization disorder. Of these, eight reported a history of severe physical and sexual abuse that had occurred, in all but one, during childhood. CONCLUSIONS: A history of physical and/or sexual abuse has a high prevalence in Italian patients with chronic gastrointestinal disorders, irrespective of organic or functional diagnosis. Abuse history has no relevant role in the pathogenesis of either functional or organic chronic gastrointestinal disorders but it can affect their clinical expression irrespective of functional or organic diagnosis. Severe physical and sexual abuse and childhood abuse were found in patients who met diagnostic criteria for somatization disorder, suggesting a role of abuse history in this subset of patients.

Contrast ultrasonography of the normal small bowel.

In basal conditions, the small bowel loops cannot be properly visualized by means of real-time ultrasound (US). Aims of this study were: 1. to assess whether an isosmolar solution containing a nondigestable, nonabsorbable and nonfermentable hydrophilic macro molecule, such as polyethylene glycol (PEG), can be profitably used as a contrast agent to visualize the entire small intestine with US (small intestine contrast ultrasonography, SICUS); and 2. to define the normal US values of wall thickness and luminal diameter of the jejunum, ileum and terminal ileum. Real-time ultrasonography was performed in 10 healthy volunteers with 4-and 5-MHz linear-array transducers in basal fasting conditions and after ingestion of an isosmolar PEG solution. In basal fasting conditions, only a few segments of jejunum and/or ileum could be visualized in some of the investigated subjects. After ingestion of the contrast solution, the entire small bowel could be visualized in any single subject. A contrast sonography of the entire small bowel could be satisfactorily performed with 200 mL-820 mL of contrast solution in a time period that did not exceed 65 min. Luminal diameter at the level of the jejunum (19 +/- 2.3 mm) and proximal ileum (18 +/- 1.8 mm) was significantly greater (p < 0.01) than at the level of distal ileum (16.4 +/- 2.8 mm). Wall thickness was greater at the level of the terminal ileum (2 +/- 0.4 mm) than of the jejunum (1.6 +/- 0.5 mm) but the difference did not reach statistical significance. Details such as valvulae conniventes and multilayered structure of the wall could be recognized. In conclusion, after the ingestion of an isosmolar PEG electrolyte balanced solution, it is possible to visualize with ultrasonography the entire small intestine and to measure wall thickness and luminal diameter of the jejunum, the ileum and the terminal ileum. Such a noninvasive, inexpensive method can be used to investigate the morphological aspects of the small bowel.

Small intestine contrast ultrasonography (SICUS) in the diagnosis of small intestine lesions.

After the ingestion of iso-osmolar polyethylene glycol solution, the small bowel can be visualized on ultrasonography. The aim of this study was to assess sensitivity and specificity of SICUS in diagnosis of small bowel lesions. A total of 53 consecutive patients with suspected intestinal pathology underwent a diagnostic workup, including a small bowel follow-through and SICUS performed by independent operators. The sonologist was unaware of the clinical data. Diagnostic sensitivity and specificity were assessed using radiologic findings. Diagnostic sensitivity of SICUS was 100%, with a specificity of 97%. The concordance index was 0.956 (p < 0.003, kappa statistics) and the conformity between SICUS and radiology was 1. The diagnostic accuracy of SICUS to detect small bowel lesions is comparable to that of small bowel follow-through. Results of this study support the use of noninvasive, widely available, inexpensive, and nondemanding SICUS as an initial investigation in patients with suspected small bowel disease.

Role of opioid ligands in the irritable bowel syndrome.

Endogenous opioid peptides - enkephalins, beta-endorphin and dynorphins - are located in specific sites of the brain, the spinal cord, the autonomic ganglia and the enteric nervous system. Endogenous opioids participate in the regulation of nervous visceral afference and sensitivity as well as of several visceral motor function induced by the central nervous system and through the enteroenteric and the myoenteric reflexes. Their final effect on gut physiology is the net and harmonically balanced result of their binding to mu, delta and kappa opioid receptor subtypes. Exogenous opioid receptor ligands with different affinities for the opioid receptor subtypes have been effectively used to modify and normalize altered gut functions. The mu receptor agonists - morphine and, to a greater extent, the meperidine congeners diphenoxylate and loperamide - have been shown to slow gastrointestinal transit by their effects on the circular and longitudinal muscle of the intestine. Diphenoxylate and, more efficiently, loperamide, for the lack of any effect on the central nervous system, have been usefully employed in the treatment of diarrhea in irritable bowel syndrome (IBS) patients. Unlike the mu receptor agonists morphine and loperamide, which invariably stimulate colonic motility, trimebutine, which has almost equal affinity for mu, delta and kappa receptors, has no effect on normal colonic activity but reduces the abnormal increase in postprandial motor activity in IBS patients and accelerates slow large bowel transit in constipated patients. Opioid ligands can be usefully employed to normalize altered visceral sensitivity in IBS patients. The kappa receptor agonist fedotozine exerts its antinociceptive effect by acting on peripheral nerve endings of sensory vagal and nonvagal afferent pathways. Fedotozine has been shown to increase the threshold of perception to colonic distension in experimental conditions and to affect favourably symptoms of IBS in clinical trials.

Octylonium bromide in the treatment of the irritable bowel syndrome: a clinical-functional study.

We investigated the effect of octylonium bromide on a number of symptoms and functional aspects of the irritable bowel syndrome. Seventy-two patients complaining mainly of abdominal pain were studied in a double-blind trial (octylonium bromide 40 mg tid for 4 weeks or placebo). Clinical parameters were: abdominal pain, bloating and bowel frequency. Sigmoid manometry with simultaneous recording of the thresholds for distension and/or pain upon graded inflation of an endoluminal balloon was performed before and at the end of treatment. In contrast to placebo, octylonium bromide significantly reduced pain and bloating, and significantly increased (p < 0.02) the pain threshold throughout the treatment period. However, comparison with the placebo group failed to show any relevant differences. Neither treatment influenced the frequency of bowel movement. Sigmoid motility during distension was significantly reduced after octylonium bromide (p < 0.05), but it did not change after placebo. In conclusion, octylonium bromide is capable of reducing symptoms and motor reactivity of the sigmoid in patients with irritable bowel syndrome.

Pressure relationships within the human bile tract. Normal and abnormal physiology.

Bile is secreted continuously, although at various rates, from the liver into the biliary tree; whether bile is then diverted into the gallbladder or the duodenum depends on the relative resistance to flow mainly determined by the contractile state of the gallbladder and the choledochoduodenal junction. The resistance of the sphincter of Oddi is considered the principal factor in the regulation of the intracholedochal pressure and, therefore, of the common bile duct-gallbladder pressure gradient; however, filling of the gallbladder may also take place after total sphincterotomy. During late phase II of the interdigestive period intragallbladder pressure increments favour flow of a small amount of bile into the bile duct and, through the sphincter of Oddi, into the duodenum. During phase III of the interdigestive period maximal frequency of sphincter of Oddi phasic contractions blocks bile flow into the duodenum. After a meal tonic active contraction of the gallbladder causes an increase of the intraluminal pressure followed shortly by volume reduction of the viscus and outflow of bile accompanied by an intracholedochal pressure increment. Gallbladder hypotonia is a relevant factor in the pathogenesis of gallbladder stones. The gallbladder acts as a reservoir, since intracholedochal pressure is higher after than before cholecystectomy, and this may explain post-cholecystectomy choledochal dilatation and biliary pain by obstructed bile flow due to either stenosis or dyskinesia of the sphincter of Oddi.

Patient with chest pain refractory to proton pump inhibitor: report of a case of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is the most common form of gastrointestinal disorders associated with eosinophilia. Typically, an inappropriate accumulation of eosinophils is found in the esophageal mucosa. EoE can be well managed and treated with several options that include an elimination diet, drug therapy (oral and topical steroids) and esophageal dilatations. We herein, report a case of a 49-year-old male affected by EoE associated to chest pain, treated with proton pump inhibitor without clinical response. The patient suffered from long lasting postprandial fullness and gastroesophageal reflux disease-like symptoms. He had a history of episodic asthmatic attacks and allergic rhinitis but had not dysphagia or food impaction. The patient recovered completely after an adequate treatment.

Contribution of intestinal smooth muscle to Crohn's disease fibrogenesis.

Mesenchymal cells transdifferentiation and extracellular matrix deposition are involved in the fibrotic process of Crohn's disease (CD). Mesenchymal smooth muscle cells (SMCs) de-differentiation, driven by Platelet-derived growth factor (PDGF) that counteracts Transforming growth factor (TGF-ß) has been studied in vascular muscle. The role of SMCs in intestinal fibrogenesis is still not clearly elucidated. Aim of the study was to evaluate the possible myogenic contribution to CD fibrotic process through the comparative analysis of histological, morphometric and molecular alterations occurring in human smooth muscle. Full thickness specimens were obtained from CD (non-involved and stenotic tracts) and healthy (control) ileum. Tissues were processed for histological and immunohistochemical (IHC) analyses and SMCs were isolated from the muscularis propria for morphofunctional and molecular (qPCR) analyses. CD stenotic ileum showed a significant increased thickness of all layers compared to CD non-involved and control ileum. IHC revealed an overexpression of α-smooth muscle actin and collagens I-III throughout all intestinal layers only in stenotic tracts. The two growth factors, PDGF and TGF-ß, showed a progressive increase in expression in the muscle layer from CD non-involved to stenotic tracts. Freshly isolated SMCs presented alterations in CD non-involved tracts that progressively increased in the stenotic tracts consisting in a statistical increase in mRNA encoding for PDGF-ß and collagen III, paralleled to a decrease in TGF-ß and Tribbles-like protein-3 mRNA, and altered morphofunctional parameters consisting in progressive decreases in cell length and contraction to acetylcholine. These findings indicate that intrinsic myogenic alterations occur in CD ileum, that they likely precede stricture formation, and might represent suitable new targets for anti-fibrotic interventions.

A four-country comparison of healthcare systems, implementation of diagnostic criteria, and treatment availability for functional gastrointestinal disorders: a report of the Rome Foundation Working Team on cross-cultural, multinational research.

BACKGROUND: Variations in healthcare provision around the world may impact how patients with functional gastrointestinal disorder (FGIDs) are investigated, diagnosed, and treated. However, these differences have not been reviewed. PURPOSES: The Multinational Working Team of the Rome Foundation, established to make recommendations on the conduct of multinational, cross-cultural research in FGIDs, identified seven key issues that are analyzed herein: (i) coverage afforded by different healthcare systems/providers; (ii) level of the healthcare system where patients with FGIDs are treated; (iii) extent/types of diagnostic procedures typically undertaken to diagnose FGIDs; (iv) physicians' familiarity with and implementation of the Rome diagnostic criteria in clinical practice; (v) range of medications approved for FGIDs and approval process for new agents; (vi) costs involved in treating FGIDs; and (vii) prevalence and role of complementary/alternative medicine (CAM) for FGIDs. Because it was not feasible to survey all countries around the world, we compared a selected number of countries based on their geographical and ethno-cultural diversity. Thus, we included Italy and South Korea as representative of nations with broad-based coverage of healthcare in the population and India and Mexico as newly industrialized countries where there may be limited provision of healthcare for substantial segments of the population. In light of the paucity of formal publications on these issues, we included additional sources from the medical literature as well as perspectives provided by local experts and the media. Finally, we provide future directions on healthcare issues that should be taken into account and implemented when conducting cross-cultural and multinational research in FGIDs.